Riesgo en Enfermedad Arterial Periférica (EAP) Profesor Curt Diehm, Karlsbad Clinic Academic Teaching Hospital University of Heidelberg

Introducción: patogénesis de EAP

Arteria dorsalis pedis ¿Qué es la EAP? Enfermedad vascular oclusiva afectando a: Arterias que irrigan los miembros, o Arterias periféricas Estenosis  claudicación intermitente Hipoperfusión  ulceración isquémica y gangrena Aorta abdominal Arteria ilíaca Arteria femoral Arteria poplítea Arteria tibial Arteria dorsalis pedis Peripheral arterial disease (PAD) refers to any pathological process causing obstruction of blood flow in arteries exclusive of the coronary and cerebral arteries.1 In this context PAD describes atherosclerotic disease in the arteries supplying the limbs and in the peripheral arteries themselves. These include the femoral, tibial, popliteal and iliac arteries and the aorta. The classical symptom is intermittent claudication (i.e. discomfort in the calves, thighs or buttocks) that occurs during exercise and is relieved with rest within 10 minutes. Intermittent claudication is the most common presenting symptom of PAD but many patients with PAD remain asymptomatic. Intermittent claudication is usually seen as a response to a mismatch between oxygen demand and supply in the muscles of the lower limb. However, many pathophysiological factors are involved in claudication, including muscular (metabolic), neurological and inflammatory effects.2 Ouriel K. Peripheral arterial disease. Lancet 2001;358:1257–1264. Stewart KJ, Hiatt WR, Regensteiner JG, et al. Exercise training for claudication. N Engl J Med 2002;347:1941–1951.

La EAP es indicativa de enfermedad vascular sistémica Enfermedad cerebrovascular Enfermedad carotidea Enfermedad arterial coronaria Enfermedad aórtica Estenosis arterial renal Enfermedad arterial visceral EAP claudicación intermitente Isquemia crítica de miembros (dolor en reposo, gangrena) It is well accepted that PAD is indicative of systemic atherosclerotic disease. The principal reason for identifying and diagnosing PAD patients is to ascertain those who are at risk of atherothrombotic disease and those who would most benefit from CV risk reduction.1 PAD patients are at high risk of atherothrombotic events – even higher than patients with a history of myocardial infarction (MI).2 Local complications (e.g. ischaemic leg ulceration or need for amputation) affect only a small percentage of PAD patients.1 Ouriel K. Peripheral arterial disease. Lancet 2001;358:1257–1264. Steg PG, Bhatt DL, Wilson PWF et al. 55th Annual Scientific Session of the ACC, 2006. Available at: http://acc06online.acc.org/Lectures.aspx?sessionId=30&date=12. Accessed 28/06/06.

Progresión de la aterotrombosis Ateroesclerosis Angina inestable IM Ictus isquémico/AIT Isquemia crítica de miembros Muerte CV Atherosclerosis is the common underlying disease process leading to MI, ischaemia and PAD.1 Unstable atherosclerotic plaques may rupture, leading to the formation of a platelet-rich thrombus that partially or completely occludes the artery and causes acute ischaemic symptoms (atherothrombosis). Stable atherosclerotic plaques may encroach on the lumen of the artery and cause chronic ischaemia, resulting in (stable) angina pectoris or intermittent claudication, depending on the vascular bed affected. Resolution of thrombi that do not result in ischaemic symptoms (silent or sub-clinical atherothrombosis) can lead to plaque growth. Atherosclerosis, thrombosis and vasoconstriction of the arteries all lead to decreased blood flow in the periphery.2 Ischaemia may lead to painful symptoms that can increase in severity as the demand for oxygen increases in response to muscular activity. Painful symptoms at rest are signs of progressive disease. Fuster V. Atherothrombosis: Mechanisms and Clinical Therapeutic Approaches. Vasc Med 1998;3:231–239. Ross R. Atherosclerosis – an inflammatory disease. N Engl J Med 1999;340:115–126. Angina estable/claudicación intermitente CV: cardiovascular; IM: infarto de miocardio; AIT: ataque isquémico transitorio Libby P. Circulation 2001;104:365–372.

La activación plaquetaria es un paso clave en la aterotrombisis Desarrollo de la placa Erosión y ruptura de la placa Trombosis Oclusión parcial o completa Episodio aterotrombótico (ej. ICM, SCA, ictus, etc.) Síntomas isquémicos Activación y agregación plaquetaria Estable Inestable ICMI, isquemia crítica de miembros; SCA: síndrome coronario agudo

Características de la claudicación intermitente Malestar muscular en miembro inferior que se repite con el mismo nivel de ejercicio sobre el mismo grupo muscular y se supera tras 10 minutos de descanso1 Reproducible La posición del cuerpo no tiene ningún efecto Las zonas de dolor incluyen la pantorrilla, el muslo y/o los glúteos The primary cause of pain in claudication is ischaemia on exertion, but other metabolic, neurological and inflammatory effects have important roles in the pathophysiology of this condition.1 The classical symptom of intermittent claudication is muscle discomfort in the lower limb that occurs on the same level of exercise and is relieved within 10 minutes of rest.2 Importantly, the pain of intermittent claudication is reproducible and body position has no effect on the onset or duration of pain. Patients may complain of muscle fatigue, aching or cramping on exertion. The calf is the most common site of pain but it may occur also in the thigh or buttocks. Stewart KJ, Hiatt WR, Regensteiner JG, et al. Exercise training for claudication. N Engl J Med 2002;347:1941–1951. Norgren L, Hiatt WR (eds) et al. Inter-society consensus for the management of peripheral arterial disease. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1-S75. 1. Norgren L, Hiatt WR (eds) et al. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1-S75.

La EAP es asintomática habitualmente Una de cada 5 personas con edad ≥65 años, que visita al médico de AP padece EAP (definida como ITB <0,9) Sólo 1 de cada 10 de estos pacientes presentarán síntomas clásicos de claudicación intermitente In the observational German Epidemiological Trial on Ankle Brachial Index (getABI), 6880 patients (aged ≥ 65 years) were evaluated for PAD using the ankle-brachial index (ABI), the ratio of the systolic pressures at the ankle and the brachial artery.1 An ABI of <0.9 allows diagnosis of PAD. Using the Word Health Organization (WHO) Intermittent Claudication Questionnaire, intermittent claudication was reported by 2.8% of the total population and 11.1% of patients with PAD (as diagnosed using the ABI). Therefore, approximately one in 10 people with PAD experience intermittent claudication. If a clinician were to rely solely on intermittent claudication as a sign of PAD, he or she would fail to identify and diagnose many patients who could benefit from treatment. Diehm C, Schuster A, Allenberg JR, et al. High prevalence of peripheral arterial disease and co-morbidity in 6880 primary care patients: cross-sectional study. Atherosclerosis 2004;172:95–105. Si se confía únicamente en los síntomas clásicos de la claudicación intermitente, muchas EAP pueden pasar desapercibidas ITB, índice tobillo-brazo Diehm C et al. Atherosclerosis 2004;172:95–105.

Modulo 1: EAP – prevalencia, detección y riesgo

Sr. X: varón con múltiples factores de riesgo Presentación caso clínico hipotético El Sr. X, de 59 años de edad, va a consulta de AP para un reconocimiento médico. Aunque no tiene síntomas de EAP, tiene varios factores de riesgo Evaluación de los factores de riesgo Fumador durante 10 años; lo dejó hace 1 Diabetes: Sí; Glucemia en ayunas: 9,0 mmol/L (162,16 mg/dL) IMC: 23 PA: 158/92 mm Hg Valores lipídicos: CT: 6,2 mmol/L (239,4 mg/dL) HDL: 1,5 mmol/L (57,9 mg/dL) LDL: 4,1 mmol/L (158,3 mg/dL) TG: 1,8 mmol/L (159,3 mg/dL) Tratamiento actual Ninguno PA, Presión arterial; IMC, índice de masa corporal; CT, colesterol total; HDL, lipoproteínas de alta densidad; LDL, lipoproteínas de baja densidad; TG, triglicéridos.

Paciente con múltiples factores de riesgo: valoración del riesgo Este paciente es asintomático. ¿Es probable que padezca EAP? ¿Por qué el médico de AP debe preocuparse por la posible presencia de EAP? ¿Qué factores de riesgo de EAP están presentes? ¿Cuál es riesgo de este paciente para un episodio aterotrombótico futuro?

La prevalencia de EAP aumenta con la edad Mujer Hombre 50 39,2 40 Prevalencia (%) 30 27,2 27,8 25,0 25,0 20,9 20 17,1 17,5 14,6 11,5 10 <70 70–74 75–79 80–84 85+ In the German getABI study, 344 primary care physicians measured the ABI in 6880 patients aged 65 years and above.1 The prevalence of PAD as indicated by an ABI <0.9 was 19.8% in men and 16.8% in women. The prevalence of PAD increased with increasing age. Diehm C, Schuster A, Allenberg JR, et al. High prevalence of peripheral arterial disease and co-morbidity in 6880 primary care patients: cross-sectional study. Atherosclerosis 2004;172:95–105. Edad Diehm C et al. Atherosclerosis 2004;172:95–105.

El conocimiento de la EAP por los médicos es relativamente bajo 83 49 10 20 30 40 50 60 70 80 90 Conocimiento de los pacientes los médicos Pacientes (%) In the PAD Awareness, Risk and Treatment: New Resources for Survival (PARTNERS) study, the prevalence of PAD (defined as ABI <0.9) was 29% in 6979 at-risk patients in US primary care clinics.1 At the time of screening, 83% of patients with prior PAD were aware of their diagnosis, whereas only 49% of primary care physicians had recognised the PAD diagnosis (p<0.01). Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 2001;286:1317–1324. PARTNERS, PAD Awareness, Risk and Treatment: New Resources for Survival Hirsch AT et al. JAMA 2001;286:1317–1324.

Factores de riesgo de EAP 1 2 3 4 Edad (por cada 10 años) Diabetes Fumador Hipertensión Dislipemia Proteína C-reactiva (PCR) Odds ratio Insuficiencia renal Sexo masculino (vs. femenino) Hiperhomocisteinemia Age is a risk factor for declining ABI in healthy individuals and a strong predictor of PAD.1 Mean ABI is lower, and prevalence of PAD is higher, in people of African descent compared with those of European descent. Race is an independent predictor of lower ABI and the presence of PAD after adjusting for age and conventional risk factors.2 Smoking increases the risk of PAD by 2–6 times and the risk of intermittent claudication by 3–10 times.1,3–5 Smoking increases the risk of PAD more than the risk of coronary heart disease.3 Hyperhomocysteinaemia is associated with a 2- to 3-fold increased risk for developing atherosclerotic arterial disease, including PAD.6,7 Male gender, diabetes, hypertension and dyslipidaemia are also established risk factors for PAD.1,3–5 Kennedy M, Solomon C, Manolio TA, et al. Risk factors for declining ankle-brachial index in men and women 65 years or older: the Cardiovascular Health Study. Arch Intern Med 2005;165:1896–1902. Kullo IJ, Bailey KR, Kardia SL, et al. Ethnic differences in peripheral arterial disease in the NHLBI Genetic Epidemiology Network of Arteriopathy (GENOA) study. Vasc Med 2003;8:237–242. Fowkes FG, Housley E, Riemersma RA, et al. Smoking, lipids, glucose intolerance, and blood pressure as risk factors for peripheral atherosclerosis compared with ischemic heart disease in the Edinburgh Artery Study. Am J Epidemiol 1992;135:331–340. Bowlin SJ, Medalie JH, Flocke SA, et al. Epidemiology of intermittent claudication in middle-aged men. Am J Epidemiol 1994;140:418–430. Meijer WT, Hoes AW, Rutgers D, et al. Peripheral arterial disease in the elderly: The Rotterdam Study. Arterioscler Thromb Vasc Biol 1998;18(2):185–192. Boushey CJ, Beresford SA, Omenn GS, et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 1995;274:1049–1057. Graham IM, Daly LE, Refsum HM, et al. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA 1997;277:1775–1781. Raza (asiática/hispana/negra vs. blanca) Norgren L, Hiatt WR (eds) et al. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1-S75.

La población con EAP tiene un alto riesgo de episodios aterotrombóticos: resultados del estudio REACH a 1 año Muerte CV/ IM/ictus / hospitalización* 25 Muerte CV IM no mortal Ictus No mortal Muerte CV/ IM/ictus Episodios (%) p<0,001 Casi 1 de cada 5 pacientes con sólo EAP, fallecerán debido a causas CV, sufren un IM o ictus, o requieren hospitalización durante el 1er año 1,5 1,4 0,9 3,1 13,3 1,2 1 0,6 2,3 18,2 5 10 15 20 EAC solo EAP solo The REACH registry enrolled 67,888 patients aged 45 years or older from 44 countries.1 These patients had either established CAD, cerebrovascular disease, PAD, or three or more risk factors. Steg PG, Bhatt DL, Wilson PWF et al. 55th Annual Scientific Session of the ACC, 2006. Available at: http://acc06online.acc.org/Lectures.aspx?sessionId=30&date=12. Accessed 28/06/06. *AIT, angina inestable u otro episodio arterial isquémico incluyendo empeoramiento de EAP REACH: Reduction of Atherothrombosis for Continued Health EAC: Enfermedad coronaria Steg PG et al. 55th Annual Scientific Session of the ACC, 2006. Available at: http://acc06online.acc.org/Lectures.aspx?sessionId=30&date=12. Accessed 28/06/06.

REACH: índice de episodios el primer año según diagnóstico principal % pacientes con episodios 1,8 1,5 1,4 3,8 1 3,6 5,3 2,4 1,3 1,7 4,3 2 3 4 5 6 Muerte CV IM no mortal Ictus no mortal Muerte/IM/ictus Enfermedad Coronaria Enfermedad Cerebrovascular EAP At 1 year, the event rate for atherothrombotic events (CV death, MI or stroke) was 4.3% in patients in whom the primary diagnosis was PAD and 3.8% in patients diagnosed with CAD.1 Steg PG, Bhatt DL, Wilson PWF et al. 55th Annual Scientific Session of the ACC, 2006. Available at: http://acc06online.acc.org/Lectures.aspx?sessionId=30&date=12. Accessed 28/06/06. Tasas ajustadas según edad y factores de riesgo Steg PG et al. 55th Annual Scientific Session of the ACC, 2006. Available at: http://acc06online.acc.org/Lectures.aspx?sessionId=30&date=12. Accessed 28/06/06.

Malos resultados en pacientes SCA con EAP Resultados hospitalarios en pacientes con SCA en un periodo de 5 años OR ajustado 1,17; 95% CI: 1,08–1,26 OR ajustado 1,18; 95% CI: 1,09–1,28 40 No EAP 36,7 35 EAP 30,1 30,7 30 25,6 25 OR ajustado 1,19; 95% CI: 1,02–1,39 20 OR ajustado 1,11; 95% CI: 0,93–1,33 Pacientes (%) 15 OR ajustado 0,83; 95% CI: 0,56–1,24 The Global Registry of Acute Coronary Events (GRACE) included 41,108 patients aged 18 years and above who presented to hospital with acute coronary syndrome (ACS) over a 5-year period.1 Of these patients, 9.7% had prior PAD and these patients were more likely to present with non-ST-segment elevation MI (NSTEMI) than those without PAD. PAD patients were under-treated and had low treatment rates with medications such as angiotensin-converting enzyme (ACE) inhibitors, aspirin, beta-blockers and lipid-lowering agents. Compared with patients without prior PAD, the composite endpoint of death, cardiogenic shock, recurrent angina and stroke was more common in patients with prior PAD. Froehlich JB, Mukherjee D, Avezum A, et al. Association of peripheral artery disease with treatment and outcomes in acute coronary syndromes. The Global Registry of Acute Coronary Events (GRACE). Am Heart J 2006;151:1130–1135. 10 7,7 5 5,6 4,2 5 0,9 0,8 Muerte Ictus Shock Angina Variable cardiogénico recurrente compuesta Froehlich JB et al. Heart J 2006;151:1130–1135.

Índice de mortalidad a los 5 años con EAP comparado con otras situaciones 10 20 30 40 50 60 70 80 90 100 Cáncer de mama1 Enfermedad de Hodgkin's 1 Claudicación intermitente2 EAP3 Cáncer colorectal1 Post-primer IM4 pulmón1 Pacientes (%) A study of 1582 patients aged 55–74 years in Scotland found that the 5-year mortality for patients with intermittent claudication was 19.2%.1 Severe PAD is reported to have a 5-year mortality rate higher than that reported for breast cancer and Hodgkin’s disease.2,3 Leng GC, Lee AJ, Fowkes FG et al. Int J Epidemiol 1996. 25 (6): 1172–1181. American Cancer Society. Cancer facts and figures 1997. Kampozinski RP, Bernard VM. In: Rutherford RB (ed). Vascular surgery. Philadelphia: WB Saunders, 1989: chapter 53. Gráfico adaptado de Criqui MH. Vasc Med. 2001;6(3 Suppl):3-7. American Cancer Society. Cancer facts and figures 1997. Leng GC et al. Int J Epidemiol 1996. 25 (6): 1172–1181. Kampozinski RP, Bernard VM. In: Rutherford RB (ed). Vascular surgery. Philadelphia: WB Saunders, 1989: chapter 53. Capewell S et al. Eur Heart J 2000. 21 (22): 1833–1840.

El riesgo de pérdida de miembros es eclipsado por el riesgo de episodios aterotrombóticos Predicción de resultados a 10 años en pacientes que presentan claudicación intermitente 20 40 60 80 100 1 2 3 4 5 6 7 8 9 10 Tiempo (años) Pacientes (%) Supervivencia Intervención Amputación IM The risk of limb loss is much lower than that of atherothrombotic disease.1 The predicted survival curves given in this slide are based on a 6.8% annual risk of mortality, a 2% risk of MI, a 1% risk of intervention and a 0.4% risk of amputation. Ouriel K. Peripheral arterial disease. Lancet. 2001;358:1257–1264. Ouriel K. Lancet 2001;358:1257–1264.

Paciente con múltiples factores de riesgo: resumen de valoración del riesgo Sr. X presenta múltiples factores de riego de EAP, incluyendo hipertensión, diabetes, hiperlipidemia, sexo masculino y antecedentes de tabaquismo El registro REACH muestra que la EAP está asociada con un alto riesgo de muerte CV, IM no mortal o ictus en el primer año La mayoría de los pacientes con EAP podrían diagnosticarse en AP

Módulo 2: diagnóstico realizado en la consulta

Paciente con múltiples factores de riesgo: diagnóstico ¿Qué información clínica adicional sería útil para ayudar al diagnóstico? ¿Qué preguntas debería realizar el médico de AP al Sr. X durante la consulta? ¿Qué otras pruebas deben ser realizadas?

Guía para el diagnóstico Primer paso Determinar los factores de riesgo del paciente Historia familiar Tabaquismo Diabetes Edad Hipertensión Dislipemia Antecedentes de enfermedad aterotrombótica Determinar los síntomas de la pierna Claudicación intermitente Síntomas atípicos Herramientas: listado de EAP, cuestionario Edinburgh Segundo paso Auscultación Si hay sospecha de EAP, medir ITB para confirmar el diagnóstico Herramienta: Doppler

Identificar la EAP La mayoría de los pacientes son asintomáticos El síntoma clásico es la claudicación intermitente Los síntomas atípicos, incluyen:1,2 Dolor que no se alivia en reposo Dolor generalizado Calor, quemazón en los pies Pies fríos Tener en cuenta la duración de los síntomas Los pacientes de EAP pueden tener síntomas silentes, como:1 Andar despacio Disminución del equilibrio de pie Levantarse lentamente desde un asiento Los pacientes pueden atribuir estos síntomas a la edad2 Only approximately one in 10 patients with PAD complain of intermittent claudication, yet a much larger proportion have some kind of lower limb dysfunction. Ostensibly, asymptomatic PAD patients may have subtle signs of limb impairment, such as slow walking speed, poor standing balance, and slow time to arise from a seated position.1 Some patients may attribute such signs to the normal ageing process.2 The impairment may go unnoticed in very elderly patients or those with co-morbidities that limit activity, such as congestive heart failure, severe pulmonary disease, or musculoskeletal disease. In some patients, it is the spouse, carer or other family member who identifies the impairment. Patients at risk of PAD should be questioned about their walking habits and a history of walking impairment should be included in a review of other symptoms.2 A number of instruments have been used in epidemiological studies to identify limb impairment and permit recording of atypical leg pain. These include the Walking Impairment Questionnaire and the San Diego Claudication Questionnaire. McDermott MM, Greenland P, Liu K, et al. Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment. JAMA 2001;286:1599–1606. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. J Am Coll Cardiol 2006;47:1239–1312. McDermott MM et al. JAMA 2001;286:1599–1606. Hirsch AT et al. J Am Coll Cardiol 2006;47:1239–1312.

Examen físico: guías TASC II Los individuos con riesgo de EAP o los pacientes con función reducida en los miembros, se les debe realizar una historia clínica vascular para evaluar los síntomas de claudicación u otros síntomas de los miembros que limiten su capacidad de caminar A los pacientes con riesgo de EAP o pacientes con reducción funcional de los miembros se les debe realizar una examen vascular para evaluar los pulsos periféricos TASC, Transatlantic Inter-Society Consensus Norgren L, Hiatt WR (eds) et al. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1-S75.

Examen físico del paciente con EAP Puede que no se detecten resultados anormales Los pulsos femoral, poplíteo, tibial posterior y dorsalis pedis, pueden estar ausentes o disminuidos Confiar en la ausencia de los pulsos del pie conduce a un posible error en el diagnóstico Las alteraciones pueden ser evidentes solamente después de ejercicio Pueden estar presentes soplos femorales Physical examination in patients with suspected PAD should assess the entire circulatory system; this involves measuring systemic blood pressure (BP) and identification of any cardiac murmurs, gallops or arrhythmias.1,2 Abdominal aortic aneurysm must be ruled out. There may be no abnormal findings. True claudication may be associated with diminished pulses in the femoral, popliteal, posterior tibial and dorsalis pedis arteries.1,2 Pulses may be graded on a scale of 0–2, where 0 signifies it is absent and 2 signifies it is normal. Aorto-iliac occlusive disease that reduces inflow may be associated with a diminished femoral pulse; disease in which inflow is preserved may be indicated by an absent pedal pulse. Pulses should be assessed in both legs. Reliance on the absence of pedal pulses leads to over-diagnosis and disease at certain locations may have no effect on pulses (e.g. occlusion of an internal iliac artery).1,2 Femoral bruits may be present owing to turbulence from focal stenoses but the absence of a bruit does not exclude PAD. Bruits in the carotid and renal arteries are signs of systemic atherosclerosis. PAD may be associated with superficial changes in the feet and legs, such as changes in colour and temperature of the skin, muscle atrophy, decreased hair growth, and hypertrophied, slow-growing toenails.2 Norgren L, Hiatt WR (eds) et al. Inter-society consensus for the management of peripheral arterial disease. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1-S75. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. J Am Coll Cardiol 2006; 47:1239–1312. Norgren L, Hiatt WR (eds) et al. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1-S75.

Palpación del pulso en la pierna: arteria femoral Palpando ambas femorales simultáneamente Palpando una sola arteria, utilizando una mano para el pulso y la otra para hacer presión Fotografías cortesía del Profesor Curt Diehm, Karlsbad Clinic, Academic Teaching Hospital, University of Heidelberg y del Dr John Pittard, Staines Thameside Medical Centre and St. Peter’s Hospital, UK

Palpación del pulso en la pierna : arteria poplítea Fotografía cortesía del Profesor Curt Diehm, Karlsbad Clinic, Academic Teaching Hospital, University of Heidelberg

Palpación del pulso en el pie Arteria dorsalis pedis Arteria Tibial posterior Fotografía cortesía del Profesor Curt Diehm, Karlsbad Clinic, Academic Teaching Hospital, University of Heidelberg

Diagnóstico de la EAP: el ITB El ITB es el cociente entre la presión arterial sistólica en el tobillo y en la arteria braquial Se utilizan las presiones más altas del tobillo y del brazo ya que valores más bajos aumentan la probabilidad de falsos positivos ITB derecho= Presión sistólica más alta del tobillo derecho (tibial posterior o dorsal del pie) en mm Hg Presión sistólica más alta del brazo (dcho o izqdo) en mm Hg ITB izquierdo= Presión sistólica más alta del tobillo izquierdo (tibial posterior o dorsal del pie) en mm Hg ABI > 1.29: abnormal: suspect diabetes ABI 1.00–1.29: normal. ABI 0.91–0.99: equivocal – may indicate the need for further testing, depending on symptoms. ABI 0.41–0.90: mild-to-moderate PAD. Symptomatic disease is unusual if ABI >0.5 and there are many asymptomatic patients in this group who are currently undiagnosed. ABI 0.0–0.40: severe PAD in which amputation may be indicated.

Interpretación del ITB > 1,29 Valorar presencia de diabetes 1,00–1,29 Normal 0,91–0,99 Indeterminado 0,41–0,90 EAP leve a moderada 0,0–0,40 EAP grave ABI 1.00–1.29: normal. ABI 0.91–0.99: equivocal – may indicate the need for further testing, depending on symptoms. ABI 0.41–0.90: mild-to-moderate PAD. Symptomatic disease is unusual if ABI >0.5 and there are many asymptomatic patients in this group who are currently undiagnosed. ABI 0.0–0.40: severe PAD in which amputation may be indicated. A reduced ABI in symptomatic patients confirms the existence of haemodynamically significant occlusive disease between the heart and the ankle, with a lower ABI indicating a greater haemodynamic severity of occlusive disease.1 Hirsch AT et al. ACC/AHA Guidelines for the Management of Patients with Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic). Available at: http://www.acc.org/clinical/guidelines/pad/index.pdf. Accessed 05/04/06. Hirsch AT et al. ACC/AHA Guidelines for the Management of Patients with Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic). Available at: http://www.acc.org/clinical/guidelines/pad/index.pdf. Accessed 05/04/06.

El ITB tiene un gran valor diagnóstico El ITB es una medida sensible y específica para el diagnóstico de la EAP1,2 El ITB es una forma rápida y coste/efectiva para establecer o refutar el diagnóstico de EAP3 Las guías TASC II recomiendan el ITB como una medida de rutina en AP4 1. Fowkes FG et al. Int J Epidemiol 1988;17:248–254. 2. Feigelson HS et al. Am J Epidemiol 1994;140:526–534. 3. Hirsch AT et al. J Am Coll Cardiol. 2006;47:1239–1312. 4. Norgren L, Hiatt WR (eds) et al. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1–S75.

TASC II: medida del ITB El ITB debe medirse en todos los pacientes: Con síntomas en la pierna durante el ejercicio Con una edad entre 50 y 69 años, con factores de riesgo CV (especialmente tabaquismo y diabetes) Edad ≥70 años, independientemente de la presencia de factores de riesgo Norgren L, Hiatt WR (eds) et al. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1–S75.

ITB y mortalidad: una relación lineal 70 Mortalidad por todas las causas Mortalidad por enfermedad CV 60 50 40 Porcentaje 30 20 10 The Strong Heart Study (SHS) investigated the relationship between ABI and all-cause and CV mortality among 4393 American-Indian patients.1 ABI was measured at baseline and patients were followed up over a period of 8.3±2.2 years. ABI was related to mortality. The relationship was linear in patients with ABI <1.10. In patients with higher ABI values, increasing ABI was related to increasing mortality, and overall, the study revealed U-shaped relationships between baseline ABI and all-cause mortality and between baseline ABI and CV mortality. Resnick HE, Lindsay RS, McDermott MM, et al. Relationship of high and low ankle brachial index to all-cause and cardiovascular disease mortality: the Strong Heart Study. Circulation 2004;109:733–739. <0,60 (n=25) 0,60–<0,70 (n=21) 0,70–<0,80 (n=40) 0,80–<0,90 (n=130) 0,90–<1,0 (n=195) 1,0–<1,10 (n=980) ITB basal: media de seguimiento por paciente de 8,3 años Resnick HE et al. Circulation 2004;109:733–739.

ITB bajo y riesgo de muerte y episodios CV: getABI 6880 pacientes no seleccionados >65 años con un seguimiento de 3 años 1.0 1.0 0.9 0.9 0.8 ITB 0.8 Supervivencia (%) ≥1,1 Supervivencia libre de episodios (%) <1,1 – ≥0,9 0.7 0.7 <0,9 – ≥0,7 In this monitored prospective observational study, 6880 representative unselected patients aged 65 years were followed up over 3 years by 344 primary care physicians. Main outcome measures were mortality or a combined endpoint of mortality and severe vascular events. In total, 20,127 patient-years were observed. In the group of PAD patients (n=1230), 134 patients died; in the group without PAD (n=5591), 237 patients died [multivariate hazard ratio (HR) 2.0; 95% confidence interval 1.6–2.5, p<0.001]. Compared with an ABI ≥1.1, the risk of death increased linearly in the lower ABI categories: ABI 0.7–0.89, HR 1.7 (1.2–2.4, p<0.001); ABI <0.5, HR 3.6 (2.4–5.4, p<0.001). During follow-up, a total of 376 patients had died. Deaths were due to myocardial infarction (59 cases), stroke (28), coronary revascularisation (2), or other reasons (287). Nonfatal severe vascular events were coronary revascularisation (131 cases), myocardial infarction (84), ischaemic stroke (120), carotid revascularisation (18), revascularisation due to critical leg ischaemia (60), or leg amputation (7). The number of events in the PAD groups was more than 2.5-fold increased, and the corresponding HR was doubled after adjustment for other known risk factors. There was an inverse correlation between the ABI category and events: compared with individuals with an ABI ≥1.1, subjects with an ABI <0.5 had a more than fivefold increase in events and a nearly fourfold risk increase after adjustment for other risk factors. The risk increase in PAD patients observed in our study (HR 2.0 for death) is higher than in previous studies but may be explained by the higher average patient age in this study. An important finding was the almost linear inverse relationship between ABI and risk. The ABI range between 0.9 and 1.1 should be considered to indicate ‘borderline PAD’. 1. Diehm C, Lange S, Darius H, et al. Association of low ankle brachial index with high mortality in primary care. Eur Heart J 2006; 27:1743–1749. <0,7 – ≥0,5 0.6 <0,5 0.6 0.5 0.5 12 24 36 12 24 36 Tiempo (meses) Tiempo (meses) Los pacientes con un ITB bajo tienen un riesgo sustancialmente elevado de sufrir episodios CV y muerte Diehm C et al. Eur Heart J 2006; 27:1743–1749.

Un ITB bajo predice la mortalidad en poblaciones de edad avanzada Estudio getABI: mortalidad por todas las causas a 3 años en función del ITB 40 35,8 35 30 25 22,8 Índice de mortalidad (por 1000) 20 15 12,1 Overall mortality was 2.5 times higher in the PAD group than in the group without PAD. There was an inverse correlation between the ABI category and the all-cause mortality.1 The multivariate hazard ratio for patients with PAD (n=1230) versus patients without PAD (n=5591) was 2.02 (95% CI: 1.61–2.53; p<0.001). Diehm C. Lange S, Darius H, et al. Association of low ankle brachial index with high mortality in primary care. Eur Heart J 2006; 27:1743–1749. 10 8,2 7,0 5 <0,5 0,5–0,69 0,7–0,89 0,9–1,09  1,1 ITB Diehm C et al. Eur Heart J 2006:27:1743–1749.12

La EAP sintomática se asocia con un incremento significativo de la mortalidad De 4.352 pacientes entre 40–80 años, el 1,6% padecía EAP Riesgo relativo de los pacientes EAP vs. controles Mortalidad de todo tipo Mortalidad CV Episodios CV no mortales 10 4 6 2 4,0 7,8 3,1 15% de los pacientes con EAP murieron en las primeras 24 h p=0,006 8 p=0,014 p=0,005 PACE Study in Italy 4352 subjects aged 40–80 years from 7 GP practices 1.6% of subjects had PAD (i.e. ABI ≤0.9) After 24 months follow-up 15% of PAD patients had died The presence of PAD was associated with an increased risk of: all cause mortality – RR 4.03 (95%CI 1.50-10.84; p=0.006) cardiovascular mortality – RR (95%CI 1.51-40.16; p=0.014) non-fatal CV events – RR 3.11 (95%CI 1.41-6.80; p=0.005). 1. Brevetti G, Schiano V, Verdoliva S, et al. Peripheral arterial disease and cardiovascular risk in Italy. Results of the Peripheral Arteriopathy and Cardiovascular Events (PACE) study. J Cardiovasc Med 2006; 7:608–613. La EAP sintomática se asocia con un incremento 4x de la mortalidad y cerca de un 8x de la mortalidad cardiovascular Brevetti et al. J Cardiovasc Med 2006;7:608–613.

Guías Inter-sociedades TASC II para diagnosticar la EAP Edad 50–69 años + tabaquismo o diabetes; edad ≥70 años; síntomas con el ejercicio en la extremidad inferior o función física reducida en pierna ; examen vascular anormal en pierna; valoración del riesgo CV Medida de ITB >1,40 0,91–1,40 ≤0,90 IDB o VWF Dupplex Resultados normales: no EAP Resultados anormales ITB normal tras ejercicio rutinario: no EAP ¿Otras causas? ITB disminuido tras ejercicio EAP Síntomas de claudicación – ITB tras prueba de esfuerzo VWF: análisis de velocidad y duración de onda por Doppler IDB – Indice dedo – brazo. Norgren L, Hiatt WR (eds) et al. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1–S75.

Medida del ITB en la consulta Equipamiento necesario: Manguitos de PA de 10–12 cm Doppler manual a 5 o 10-mHz Medir la PA sistólica en ambas arterias braquiales, ambas dorsalis pedis y arterias tibiales posteriores tras permanecer el paciente en reposo 10 minutos en posición supina1 Extremidad objetivo: aquella con el ITB más bajo Medir la PA en ambos brazos; si no es igual, se usará el valor más alto Recoger la medida con dos decimales En algunos pacientes, puede haber un efecto “bata blanca” cuando se mida la presión arterial2 (y esto afectará al ITB) The ABI is carried out by measuring the systolic BP from both brachial arteries, and from both the dorsalis pedis and posterior tibial arteries after the patient has been at rest in the supine position for at least 10 minutes.1 Optimal recordings are obtained with 10–12 cm BP cuffs that are appropriately sized to the patient’s lower calf (immediately above the ankle) and systolic pressures are recorded with a handheld 5- or 10-mHz Doppler instrument. The index leg is defined as the leg with the lowest ABI.1 In normal individuals, there should be a minimal (less than 12 mm Hg) interarm systolic pressure gradient. Both arm pressures should be recorded. If the arm BPs are not equal, then the presence of a subclavian or axillary arterial stenosis is presumed present, and the higher BP is used. ABI values should be recorded to two decimal places. Interpretation of ABI values:1 ABI 1.00–1.29 is normal; ABI 0.91–0.99 is equivocal and may indicate the need for further testing, depending on symptoms; ABI 0.41–0.90 indicates mild-to-moderate PAD; ABI 0.0–0.40 indicates severe PAD in which amputation may be indicated. ABI > 1.29 is abnormal and the clinician should suspect diabetes. Norgren L, Hiatt WR (eds) et al. Inter-society consensus for the management of peripheral arterial disease. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1–S75. Norgren L, Hiatt WR (eds) et al. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1–S75. Pickering T et al. JAMA 1988; 259:225–228.

Otras herramientas diagnósticas IDB: el cociente de las presiones en el dedo del pie y la arteria braquial. IDB normal >0,70 Examinar la presión del segmento Registro del Volumen de pulso Ecografía Doppler de onda continua Ecografía Duplex Test de ejercicio en punta del dedo del pie Prueba de esfuerzo Angiografía por resonancia magnética Angiografía por tomografía computerizada Angiografía de contraste

Paciente con múltiples factores de riesgo: medida del ITB El médico de AP del Sr. X mide la ITB en la consulta PA braquial Derecha: 156/88 mm Hg Izquierda: 160/92 mm Hg Seleccionar la más elevada de las dos medidas ITB pierna dcha.: 160/160=1,00 ITB pierna iqda. : 100/160=0,63 Diagnostico: EAP moderada en la pierna izquierda 156 mm Hg 160 mm Hg Izquierda 100 mm Hg

Diagnóstico: puntos clave RECORDAR ACCIÓN Realizar una examen físico para detectar la EAP en pacientes con factores de riesgo asociados y/o síntomas atípicos Preguntar si el paciente sufre dolor en la pierna durante el ejercicio y problemas al caminar Utilizar una lista de diagnóstico para facilitar la detección de la EAP Confirme el diagnóstico con el ITB Muchos pacientes de alto riesgo pueden ser diagnosticados en la consulta de AP

Módulo 3: Modificación de factores de riesgo y tratamiento

Sr. X: varón diagnosticado de EAP El Sr. X fue diagnosticado de EAP moderada en pierna izquierda, hipertensión, diabetes y dislipemia El Sr. X tiene un riesgo total elevado de episodios aterotrombóticos ¿Cómo puede reducirse el riesgo?

Recomendaciones de las guías TASC II: modificación de factores de riesgo Modificación del estilo de vida: Abandono del tabaco Reducción de peso Control lipídico: EAP (no SCA): LDL <2,59 mmol/L (<100 mg/dL) EAP (y antecedentes de SCA): LDL <1,8 mmol/L (<70 mg/dL) Control de la Presión Arterial: EAP (sin diabetes o insuficiencia renal): <140/90 mm Hg EAP (con diabetes o insuficiencia renal): <130/80 mm Hg Control glucémico: HbA1c <7,0% Todos los pacientes con EAP debería recibir tratamiento antiagregante (ácido acetil salicílico o clopidogrel) The TASC II guidelines recommend that modification of atherosclerotic risk factors should be the primary strategy in patients with PAD.1 Lifestyle modification should be encouraged in all patients. The low-density lipoprotein (LDL) target for symptomatic and asymptomatic PAD patients with dyslipidaemia is <2.59 mmol/L.1 For patients with PAD and a history of ACS, the target is <1.8 mmol/L. Dietary modification should be the first-line treatment. Statins should be the primary agents in symptomatic PAD patients. Other lipid-modifying agents (e.g. nicotinic acid or fibrates) may be considered. The BP target for PAD patients with hypertension is <140/90 mm Hg or <130/80 mm Hg in diabetes or renal insufficiency.1 ACE inhibitors should be the initial agent to reduce BP in PAD. Treatment goals and therapy options should be the same, irrespective of whether or not the patient has claudication symptoms. Diabetic patients with PAD should receive aggressive control of blood glucose levels.1 The HbA1c goal is <7.0%. Insulin-sensitising agents (thiazolidinediones) may provide good blood glucose control and prevent CV events. Norgren L, Hiatt WR (eds) et al. Inter-society consensus for the management of peripheral arterial disease. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1–S75. Norgren L, Hiatt WR (eds) et al. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1–S75.

Recomendaciones ADA para la modificación de factores de riesgo en pacientes con EAP Abandono del tabaco HbA1c <7,0% PA <130/80 mm Hg LDL<2,59 mmol/L The American Diabetes Association (ADA) has published a consensus statement regarding the diagnosis and treatment of PAD in diabetic patients.1 Smoking cessation counselling is recommended. Tight glycaemic control (HbA1c <7.0%) is recommended to prevent microvascular complications, and hypertension should be treated aggressively to reduce CV risk, with a target BP of <130/80 mm Hg. No particular agent is recommended for BP reduction. Dyslipidaemia should be treated using statins and other agents as appropriate (target LDL level <2.59 mmol/L) to reduce the risk of CV death and to slow the progression of PAD. American Diabetes Association. Peripheral arterial disease in people with diabetes. Diabetes Care 2003;26:3333–3341. American Diabetes Association. Diabetes Care 2003;26:3333–3341.

Recomendaciones de las guías TASC II: ejercicio y rehabilitación Programa estructurado y supervisado 1 hora, tres veces a la semana Ciclo de ejercicio y descanso Los beneficios son resultado de la mejora en la eficiencia al caminar, en la función endotelial y las adaptaciones del músculo esquelético A structured, supervised exercise programme is recommended as the initial approach to the treatment of limb symptoms such as claudication.1 General, unstructured recommendations to exercise do not appear to have clinical benefit.1,2 However, supervised exercise programmes lasting 3 months or more lead to increases in treadmill exercise performance and a decrease in pain severity.2 These benefits may result from improved walking efficiency, improved endothelial function, and metabolic adaptations in skeletal muscle. Norgren L, Hiatt WR (eds) et al. Inter-society consensus for the management of peripheral arterial disease. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1–S75. Hiatt WR, Wolfel EE, Meier RH, et al. Superiority of treadmill walking exercise versus strength training for patients with peripheral arterial disease. Implications for the mechanism of the training response. Circulation 1994;90:1866–1874. Norgren L, Hiatt WR (eds) et al. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1–S75.

Recomendaciones de las guías TASC II: tratamiento de la claudicación Medidas iniciales: ejercicio estructurado En pacientes seleccionados, se recomienda farmacoterapia para tratar la limitación del ejercicio Un ciclo de 3 a 6 meses para determinar la eficacia del cilostazol debería ser la farmacoterapia de 1ª elección para mejorar los síntomas de claudicación, ya que la evidencia indica tanto mejoras en el desarrollo del ejercicio en tapiz rodante como en la calidad de vida. [A] También puede recomendarse naftidrofurilo en el tratamiento de los síntomas de claudicación [A] Cilostazol is a phosphodiesterase III inhibitor with vasodilator, metabolic and antiplatelet activity. Cilostazol has been shown to increase maximal treadmill walking distance and leads to increases in health-related quality of life, as measured by the Walking Impairment Questionnaire and the Medical Outcomes Study Short Form-36 (SF-36).1 Regensteiner JG, Ware JE Jr, McCarthy WJ, et al. Effect of cilostazol on treadmill walking, community-based walking ability, and health-related quality of life in patients with intermittent claudication due to peripheral arterial disease: meta-analysis of six randomized controlled trials. J Am Geriatr Soc 2002; 50:1939–1946. Norgren L, Hiatt WR (eds) et al. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1–S75.

Paciente diagnosticado de EAP: tratamiento Sr. X fue tratado según el siguiente esquema: Modificación del estilo de vida Reducción del peso Control de la PA Inhibidores de la enzima convertidora de la angiotensina, IECAs, (ramipril) Control de lípidos Dieta Estatinas (simvastatina) Control de glucemia Sulfonilurea (glibenclamida) Inhibición plaquetaria Ácido acetil salicílico (AAS)

Modificación de los factores de riesgo y tratamiento: puntos clave RECORDAR ACTUAR Lípidos: Sin SCA: LDL <2,59 mmol/L (<100 mg/dL) Con SCA: LDL <1,8 mmol/L (<70 mg/dL) PA: Sin diabetes o insuficiencia renal: <140/90 mm Hg Con diabetes o insuficiencia renal): <130/80 mm Hg Glucemia: HbA1c <7,0% Terapia antiagregante Si existiera, tratar la claudicación con: Ejercicio Terapia farmacológica Una acción temprana y agresiva frente a la EAP es importante para reducir el riesgo CV y episodios cerebrovasculares

Módulo 4: riesgo residual en EAP

Paciente diagnosticado de EAP: 1 año después Presentación Sr. X, ahora paciente de 60 años, dado de alta tras IM agudo Medicación actual Ramipril, simvastatina, glibenclamida, AAS

Sr. X: valoración del riesgo A pesar del tratamiento para reducir los factores de riesgo (incluyendo AAS), el Sr. X sufrió un episodio aterotrombótico ¿Cual es el riesgo de un episodio aterotrombótico recurrente?

Reducciones del riesgo de EAP: estatinas HPS: el tratamiento con estatinas permite reducir el riesgo un 25% después de 5 años In the Heart Protection Study (HPS), simvastatin therapy in 6748 patients with PAD resulted in a 25% reduction in the risk of CV death, MI, stroke or revascularisation after 5 years compared with placebo.1 Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22. Heart Protection Study (HPS) Group. Lancet 2002;360:7–22.

Reducciones del riesgo de EAP: IECAs Mortalidad CV, IM e ictus en pacientes con EAP tratados con ramipril HOPE: el tratamiento con ramipril consigue una reducción del riesgo del 27% tras 4,5 años en pacientes asintomáticos con ITB ≤0,9 0,3 Placebo Ramipril 0,2 0,1 EAP clínica 0,0 0,3 0,2 0,1 In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril therapy in 2118 asymptomatic PAD patients resulted in a reduction in the risk of CV death, MI or stroke of 27% after 4.5 years compared with placebo.1 Ostergren J, Sleight P, Dagenais G, et al. Impact of ramipril in patients with evidence of clinical or subclinical peripheral arterial disease. Eur Heart J 2004;25:17–24. EAP asintomatica ITB 0,9 0,0 Días de seguimiento HOPE, Heart Outcomes Prevention Evaluation Ostergren J et al. Eur Heart J 2004;25:17–24.

Reducciones del riesgo de EAP: tratamientos antihiperglicémicos UKPDS: un estricto control de la glucemia con sulfonilureas consiguen una reducción del 12% en las variables relacionadas con la diabetes a los 10 años, consecuencia de una reducción del 25% en el riesgo de episodios microvasculares1 El control de la glucemia con metformina en pacientes con sobrepeso, consigue una reducción del 42% en el riesgo de muerte relacionada con la diabetes (incluyendo muerte CV)2 In the UK Prospective Diabetes Study (UKPDS), tight glycaemic control was associated with a 12% reduction in diabetes-related endpoints but this was due to a 25% risk reduction in microvascular endpoints.1 The prevalence of PAD in this population was not reported. Intensive blood glucose control with metformin was associated with a 42% reduction in the risk of diabetes-related death (including CV death) and a 36% reduction in the risk of all-cause mortality compared with diabetes control using a primarily diet-based regimen.2 UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837–853. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854–865. 1. UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837–853. 2. UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854–865.

Resumen de la reducción relativa del riesgo Tratamiento Paciente RRR IECAs1 EAP asintomática (ITB≤0,9) 27% RRR en muerte CV, IM o ictus (comparado con placebo) Estatinas2 Pacientes con EAP (± otra enfermedad CV ± diabetes) 25% RRR en muerte CV, IM o ictus (comparado con placebo) Metformina3 Pacientes con sobrepeso y con diabetes (no exclusivamente pacientes con EAP) 32% en cualquier variable relacionada con diabetes (incluyendo muerte CV) (comparado con régimen de medidas dietéticas) Terapia antiagregamte4 Pacientes con enfermedad CV establecida o condiciones predisponentes 23% en muerte CV, IM o ictus (comparado con placebo) In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril therapy in 2118 asymptomatic PAD patients resulted in a reduction in the risk of CV death, MI or stroke of 27% after 4.5 years compared with placebo.1 The Heart Protection Study (HPS) investigated the efficacy and safety of simvastatin in 20,536 patients aged 40–80 years who had established atherosclerotic disease or diabetes.2 In the total population, simvastatin was associated with a 17% RRR for CV death, a 38% reduction for first non-fatal MI, and a 25% reduction for first stroke compared with placebo. Among 6748 patients with PAD, simvastatin therapy resulted in a 25% reduction in the risk of CV death, MI, stroke or revascularisation after 5 years compared with placebo.2 Among overweight patients with diabetes, intensive blood glucose control with metformin was associated with a 42% reduction in the risk of diabetes-related death (including CV death) and a 36% reduction in the risk of all-cause mortality compared with diabetes control using a primarily diet-based regimen.3 Meta-analysis of randomised trials of antiplatelet regimens (including aspirin, clopidogrel and dipyridamole) reveals that in patients with PAD antiplatelet therapy is associated with a 23% RRR in CV death, MI or stroke.4 Ostergren J, Sleight P, Dagenais G, et al. Impact of ramipril in patients with evidence of clinical or subclinical peripheral arterial disease. Eur Heart J 2004;25:17–24. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7–22. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854–865. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71–86. 1. Ostergren J et al. Eur Heart J 2004;25:17–24. 2. Heart Protection Study Group. Lancet 2002;360:7–22. 3. UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854–865. 4. Antithrombotic Trialists’ Collaboration. BMJ 2002;324:71–86.

Riesgo Residual Basado en la reducción del 25% del riesgo relativo (RRR) observado en pacientes con EAP tratados con simvastatina en el HPS 25 20 20 Reducción del riesgo con estatinas: 25% 15 15 Riesgo CV a los 10 años (%) 10 Riesgo residual del 15% 5 Risk-factor modification reduces total CV risk but the ‘residual risk’ that remains is unacceptably high. If a patient’s 10-year CV risk was 20%, then based on the results of the HPS, after 5 years of simvastatin therapy, this risk should be reduced by approximately 25%.1 The patient’s residual CV risk would therefore be 15% – a level of moderate risk. Based on the results of the HOPE study, ramipril therapy was associated with a risk reduction of approximately 25% for a similar period of time. However, evidence does not show that combined ACE inhibitor and statin therapy would have additive effects on the overall CV risk. Heart Protection Study Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7–22. Riesgo CV en el momento de consulta Riesgo CV tras tratamiento con simvastatina Heart Protection Study Group. Lancet 2002;360:7–22.

Índices de tratamiento en pacientes con EAP reclutados en el estudio REACH (incluyendo aquéllos con enfermedad polivascular) 28,7 92,4 81,7 85.6 70 20 40 60 80 100 Pacientes (%) Al menos un agente hipolipemiante Al menos un tratamiento antidiabético Al menos un agente antiagregante Al menos un antihipertensivo At baseline, the majority of PAD patients in REACH were receiving at least one lipid-lowering agent:1 64.2% were receiving a statin and 11.5% were receiving another type of lipid-lowering agent. A total of 85.6% of PAD patients were receiving at least one diabetes medication, the most common being insulin (37.8%), followed by sulphonylureas (36.4%), biguanides (31.0%), and thiazolidinediones (13.2%). Use of antiplatelet therapy was high: 81.8% were receiving at least one antiplatelet agent, the most common being aspirin (62.5%), with 34.5% receiving another antiplatelet agent and 14.9% receiving two antiplatelet agents. The majority of patients were also receiving at least one antihypertensive agent (92.4%), most commonly ACE inhibitors (47.2%). Bhatt DL, Steg PG, Ohman EM, et al. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA 2006;295:180–189. Cilostazol, pentoxifilina, buflomedilo o naftidrofuril Bhatt DL et al. JAMA 2006;295:180–189.

CT objetivo: ≤ 5,18 mmol/L (≤ 200 mg/dL) Tasas de control en pacientes con EAP reclutados en el estudio REACH (incluyendo aquéllos con enfermedad polivascular) Objetivo PA PA objetivo: ≤140/90 mmHg CT objetivo: ≤ 5,18 mmol/L (≤ 200 mg/dL) 19 alcanzado Objetivo CT 33.3 alcanzado Despite relatively high treatment rates, control rates in PAD patients at baseline were low, with substantial proportions of patients not achieving guideline-recommended targets in BP and cholesterol levels.1 This demonstrates that treatment is generally sub-optimal. In addition, 44.1% of symptomatic patients were obese (Men: waist circumference ≥102 cm; women: waist circumference ≥88 cm) and 40.3% of patients were overweight (body mass index [BMI] ≥25 kg/m2). A total of 50.9% were former smokers and 24.5% were current smokers. 1. Bhatt DL, Steg PG, Ohman EM et al. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA 2006;295:180–189. 20 40 60 80 100 % pacientes Bhatt DL et al. JAMA 2006;295:180–189.

La población con EAP tiene un alto riesgo de episodios aterotrombóticos: resultados del estudio REACH a 1 año 25 p<0,001 EAC solo EAP solo 20 18,2 Casi 1 de cada 5 pacientes con sólo EAP fallecen debido a causas CV, sufren un IM o ictus, o requieren hospitalización en el 1er año 15 13,3 Episodios (%) 10 5 3,1 The REACH registry enrolled 67,888 patients aged 45 years or older from 44 countries.1 These patients had either established CAD, cerebrovascular disease, PAD, or three or more risk factors. Steg PG, Bhatt DL, Wilson PWF et al. 55th Annual Scientific Session of the ACC, 2006. Available at: http://acc06online.acc.org/Lectures.aspx?sessionId=30&date=12. Accessed 28/06/06. 2,3 1,5 1,2 1,4 1 0,9 0,6 Muerte CV IM no mortal Ictus no mortal Muerte CV/ IM/ictus Muerte CV/ IM/ictus / hospitalización* EAC, enfermedad coronaria *AIT, angina inestable u otro episodio arterial isquémico incluyendo empeoramiento de EAP REACH: Reduction of Atherothrombosis for Continued Health Steg PG et al. 55th Annual Scientific Session of the ACC, 2006. Available at: http://acc06online.acc.org/Lectures.aspx?sessionId=30&date=12. Accessed 28/06/06.

REACH: tasa de episodios a 1 año según diagnóstico principal 6 5,3 5 Enfermedad Coronaria 4,3 Enfermedad Cerebrovascular 4 3,8 3,6 EAP % pacientes con episodios 3 2,4 2 1,8 1,8 1,7 1,5 1,4 1,3 At 1 year, the event rate for atherothrombotic events (CV death, MI or stroke) was 4.3% in patients in whom the primary diagnosis was PAD and 3.8% in patients diagnosed with CAD.1 Steg PG, Bhatt DL, Wilson PWF et al. 55th Annual Scientific Session of the ACC, 2006. Available at: http://acc06online.acc.org/Lectures.aspx?sessionId=30&date=12. Accessed 28/06/06. 1 1 Muerte CV IM no mortal Ictus no mortal Muerte/IM/ictus Tasas ajustadas según edad y factores de riesgo Steg PG et al. 55th Annual Scientific Session of the ACC, 2006. Available at: http://acc06online.acc.org/Lectures.aspx?sessionId=30&date=12. Accessed 28/06/06.

EAC + EAP + Enf. cerebrovascular REACH: tasa de episodios a 1 año en pacientes con enfermedad polivascular EAC sólo EAP sólo EAC + EAP EAC + EAP + Enf. cerebrovascular Índice de Episodios (%) 1,5 1,4 0,9 3,1 13,3 1,2 1 0,6 2,3 18,2 2,9 1,3 4,8 23,3 3,6 1,8 4 7,4 26,9 5 10 15 20 25 30 Muerte CV IM no mortal Ictus no mortal Muerte CV/ IM/ Ictus Ictus u hospitalización In REACH, patients who had PAD and CAD were at high risk of a recurrent atherothrombotic event. A total of 23.3% of such patients suffered an atherothrombotic event or were hospitalised for a TIA, unstable angina or other ischaemic event.1 Steg PG, Bhatt DL, Wilson PWF et al. 55th Annual Scientific Session of the ACC, 2006. Available at: http://acc06online.acc.org/Lectures.aspx?sessionId=30&date=12. Accessed 28/06/06. EAC = enfermedad coronaria. EAP = enfermedad arterial periférica Steg PG et al. 55th Annual Scientific Session of the ACC, 2006. Available at: http://acc06online.acc.org/Lectures.aspx?sessionId=30&date=12. Accessed 28/06/06.

Riesgo residual: puntos clave RECORDAR ACTUAR A pesar de el tratamiento con IECAs, estatinas y AAS, los pacientes con EAP continúan en riesgo de episodios aterotrombóticos. Tras un episodio, los pacientes están en riesgo permanente de padecer un episodio recurrente Gestionar los factores de riesgo de forma intensiva Optimizar el tratamiento para reducir el riesgo residual

Módulo 5: Terapia antiagregante y optimización del tratamiento para reducir el riesgo residual

Paciente diagnosticado de EAP con IM previo: optimización del tratamiento ¿Cómo puede optimizarse el tratamiento del Sr. X? Al Sr. X se le había prescrito previamente AAS. ¿Qué alternativas consideraría?

La activación plaquetaria es un paso clave en la aterotrombosis Platelet activation involves the release of a variety of substances including thrombin, serotonin, adenosine diphosphate (ADP) and thromboxane A2 (TXA2).1 Platelets secrete a variety of agonists that augment activation. They also undergo a structural change that involves flattening and the formation of pseudopodia resulting in an increase in the number of activated glycoprotein (GP) IIb/IIIa receptor molecules on the platelet surface. This conformational change is thought to augment the binding of fibrinogen in the bloodstream to the GP IIb/IIIa receptors of adjacent platelets, which results in platelet aggregation. Platelet activation may be thought of as the crucial step in atherothrombosis and the development of an atherothrombotic event. Ouriel K. Peripheral arterial disease. Lancet 2001;358:1257–1264. Forma espinosa, esférica de plaquetas activadas Forma lisa, discoide, de plaquetas no activadas Adaptado de www.akh-wien.ac.at/biomed-research/htx/anatomy.htm. Accessed 31 October, 2002. (Con permiso del Center of Biomedical Research, University of Vienna).

Modo de acción de los fármacos antiagregantes Vía del ADP ADP Clopidogrel Es un inhibidor potente y específico de la agregación plaquetaria dependiente del ADP C Receptor ADP PLAQUETA COX AAS es un inhibidor de la enzima COX y de la agregación plaquetaria dependiente del tromboxano A2 Receptor TXA2 Clopidogrel and aspirin inhibit different pathways of platelet activation. Aspirin acts by a mechanism independent of the ADP receptor and inhibits the cyclooxygenase (COX) enzyme, preventing the production of prostaglandin and TXA2 from arachidonic acid. TXA2 activates the GP IIb/IIIa binding site on the platelet, allowing fibrinogen to bind.1 Clopidogrel is a potent, non-competitive inhibitor of ADP-induced platelet aggregation, irreversibly inhibiting the binding of ADP to its platelet membrane receptors.1,2 This inhibition is specific and, unlike that induced by aspirin, does not significantly affect COX or arachidonic acid metabolism.3 ADP binding is necessary for activation of the GP IIb/IIIa receptor, which is the binding site for fibrinogen. Fibrinogen links different platelets together thus forming the platelet aggregate.1 Clopidogrel ultimately inhibits the activation of the GP IIb/IIIa receptor and its binding to fibrinogen. Schafer AI. Antiplatelet therapy. Am J Med 1996;101:199–209. Clopidogrel Prescribing Information, US, February 2006. Schrör K. The basic pharmacology of ticlopidine and clopidogrel. Platelets 1993;4:252–261. TXA2 Vía del TXA2 TXA2 = tromboxano A2 ADP = adenosín difosfato COX = ciclooxigenasa Schafer AI. Am J Med 1996;101:199–209.

La terapia antiagregante es necesaria para prevenir la activación de las plaquetas Muchas de las estrategias dirigidas a reducir el riesgo total de un episodio aterotrombótico implican una demora de la aterogénesis La terapia antiagregante es clave para una estrategia coherente de la reducción del riesgo, porque la activación plaquetaria es una etapa que conduce a la trombosis y, posiblemente, a un episodio aterotrombótico

Recomendaciones clave sobre antiagregantes en las guías TASC II A todos los pacientes sintomáticos, con o sin antecedentes de otra enfermedad cardiovascular, se les debería prescribir un tratamiento antiagregante a largo plazo para reducir el riesgo de morbilidad y mortalidad cardiovasculares [A] AAS es eficaz en los pacientes con EAP que también presentan evidencias clínicas de otros tipos de enfermedad cardiovascular (coronaria o carotídea) [A] Puede considerarse el uso del AAS en pacientes con EAP sin evidencias clínicas de otros tipos de enfermedad cardiovascular [C] Clopidogrel es eficaz en la reducción de episodios cardiovasculares en pacientes con EAP sintomática, con o sin otras evidencias clínicas de enfermedad cardiovascular [B] Norgren L, Hiatt WR (eds) et al. Eur J Vasc Endovasc Surg 2007;33(Suppl. 1):S1–S75.

Mejor terapia antiagregante Peor terapia antiagregante La terapia antiagregante reduce el riesgo de episodios aterotrombóticos en EAP con independencia de los síntomas o la intervención empleada % odds ratio Mejor terapia antiagregante Peor terapia antiagregante % Reducción de riesgo Claudicación intermitente Injerto periférico Angioplastia periférica Todos 23 (9) 22 (16) 29 (35) 23 (8) 1,0 1,5 2,0 0,5 The Antithrombotic Trialists’ Collaboration carried out a collaborative meta-analysis of randomised trials of antiplatelet agents in high-risk patients.1 The meta-analysis included 287 studies involving 135,000 patients in comparisons of antiplatelet therapy versus a control, and 77,000 patients in comparisons of different antiplatelet regimens. A total of 42 trials that included patients with PAD were available (encompassing 9214 patients). Overall, a 23% proportional reduction in serious vascular events (CV death, non-fatal MI and non-fatal stroke) associated with antiplatelet therapy was observed. Similar results were seen among patients with intermittent claudication, those having peripheral grafting, and those having peripheral angioplasty. The slide shows the odds ratio for these groups and for all PAD patients. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71–86. Antithrombotic Trialists’ Collaboration. BMJ 2002;324:71–86.

Recomendaciones de ADA para la terapia antiagregante en pacientes diabéticos Las recomendaciones de la ADA son: “Los pacientes diabéticos deberían estar con un agente antiagregante (por ej. AAS o clopidogrel) de acuerdo con las guías actuales” “Aquellos pacientes con diabetes y EAP pueden beneficiarse más con la administración de clopidogrel” American Diabetes Association. Diabetes Care 2003;26:3333–3341.

CAPRIE: datos de clopidogrel en pacientes con diabetes* Incidencia de IM, ictus, muerte vascular u hospitalización por episodios isquémicos o hemorrágicos AAS 325 mg/día Clopidogrel 75 mg/día Todos pacientes CAPRIE¹ Diabetes² Diabetes tratada con insulina2 11† 21† 38† 137 177 215 126 156 50 100 150 200 250 300 Incidencia por 1000 pacientes/año n=1914 n=1952 n=9553 n=9546 Sin datos p=0,042 p=0,106 p=0,011 In the CAPRIE Trial, 3837 patients had co-existing diabetes.1 These patients are at higher risk of MI, ischaemic stroke, vascular death or hospitalisation for ischaemic events/bleeding (17.7% diabetic versus 12.7% non-diabetic patients in the aspirin group; 15.6% diabetic versus 11.8% non-diabetic in the clopidogrel group).2,3 The annual event rate per 1000 patients was reduced in the clopidogrel group compared with the aspirin group by 38 in patients receiving insulin at baseline and by 21 in diabetic patients who were not receiving insulin. These reductions compare favourably with the reduction of 11 in the overall CAPRIE population. As the CAPRIE trial was not powered to evaluate efficacy of individual subgroups, it is not clear whether the differences in event rate across qualifying conditions are real or a result of chance. 1. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329–1339. 2. Jarvis B, Simpson K. Clopidogrel: a review of its use in the prevention of atherothrombosis. Drugs 2000;60:347–377. 3. Bhatt DL, Marso SP, Hirsch AT et al. Superiority of clopidogrel versus aspirin in patients with a history of diabetes mellitus. J Am Coll Cardiol 2000;35(Suppl A):409. *Como CAPRIE no estaba diseñado para evaluar la eficacia de subgrupos individuales, no está claro si las diferencias en la RRR según las condiciones de si son reales o producto del azar. †Episodios prevenidos por 1000 pacientes/año con AAS (reducción absoluta del riesgo) Bhatt DL. Am Heart J 2000;140:67–73; Jarvis B and Simpson K. Drugs 2000;60:347–377.

Aumentar la dosis de AAS no implica un incremento de la eficacia 500–1500 mg día 160–325 mg día 75–150 mg día <75 mg día Cualquier dosis de AAS 0.0 0.5 1.0 1.5 Mejor AAS Mejor control % reducción riesgo* 23%2 (p<0,0001) The results of the meta-analysis performed by the Antithrombotic Trialists’ Collaboration failed to find any significant difference between the different aspirin regimens:1 no particular range of aspirin dose was preferable for the prevention of CV death, non-fatal MI or non-fatal stroke. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71–86. *Episodios vasculares: IM, ictus o muerte vascular Antithrombotic Trialists’ Collaboration. BMJ 2002;324:71–86.

CAPRIE: RRR del 8,7% en la población total tratada con clopidogrel Tasa acumulada de episodios tras 3 años de seguimiento (IM, ictus isquémico o muerte vascular) RRR 8,7%* (95% CI: 0,3 a 16,5) 16 12 Aspirina RRR adicional al 23% de RRR correspondiente a AAS solo Tasa acumulada de episodios (%) 8 Clopidogrel 4 CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events) investigated the relative efficacy and safety of clopidogrel compared with aspirin in 19,185 patients with either recent MI, recent ischaemic stroke or symptomatic PAD.1 Clopidogrel was significantly more efficacious than aspirin, with a relative risk reduction (RRR) of 8.7% in the combined risk of MI, ischaemic stroke or CV death (p=0.043). This improvement was observed over and above the effect of aspirin (25% odds reduction reported previously for aspirin using a similar outcome cluster of all-cause stroke, MI and CV death).2 The cumulative event rate curves for clopidogrel and aspirin diverged early during the follow-up period and continued to diverge throughout the full treatment period of 3 years.1 CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329–1339. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71–86. p=0,043; n=19.185 3 6 9 12 15 18 21 24 27 30 33 36 *Análisis ITT Meses de seguimiento CAPRIE, Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events CAPRIE Steering Committee. Lancet 1996;348:1329–1339; Antithrombotic Trialists’ Collaboration. BMJ 2002;324:71–86.

CAPRIE: RRR 23,8% en EAP con clopidogrel 4,86 3,71 1 2 3 4 5 6 AAS (pacr=5.797) Clopidogrel (pacr=5.795) Índice de Episodios/año (%) Tasas de IM, ictus o muerte CV RRR*: 23,8% (95% CI: 8,9–36,2) p=0,0028 As the CAPRIE trial was not powered to evaluate efficacy of individual subgroups, it is not clear whether differences in RRR across qualifying conditions are real or a result of chance. *Como el ensayo CAPRIE no fue diseñado para evaluar la eficacia de subgrupos individuales, no está claro si las diferencias en RRR por las condiciones de calificación son reales o un producto del azar pacr: pacientes/año en riesgo CAPRIE Steering Committee. Lancet 1996;348:1329–1339.

CAPRIE: RRR 22.7% en pacientes con enfermedad polivascular Tasas de IM, ictus o muerte CV 12 10,74 RRR*: 22,7% (95% CI: 4,9–37.2) 10 8,35 8 Tasa de episodios/año (%) 6 4 2 In patients with either PAD or stroke who also had a previous MI, clopidogrel was associated with a 22.7% RRR for the composite endpoint of MI, non-fatal stroke and CV death.1 As the CAPRIE trial was not powered to evaluate efficacy of individual subgroups, it is not clear whether differences in RRR across qualifying conditions are real or a result of chance. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329–1339. AAS (pacr=1.825) Clopidogrel (pacr=1.963) *Como el ensayo CAPRIE no fue diseñado para evaluar la eficacia de subgrupos individuales, no está claro si las diferencias en RRR por las condiciones de calificación son reales o un producto del azar pacr: pacientes/año con riesgo CAPRIE Steering Committee. Lancet 1996;348:1329–1339.

CAPRIE: seguridad y tolerabilidad Pacientes (%) Clopidogrel (n=9.599) AAS* (n=9.586) Hemorragia GI 2,0 2,7 Hospitalización debida a hemorragia GI 0,7 1,1 Úlceras GI 1,2 Hemorragia intracraneal 0,4 0,5 Neutropenia severa 0,04 0,02 Aunque el riesgo de aparición de mielotoxicidad es baja, esta posibilidad debería considerarse cuando un paciente en tratamiento con clopidogrel tiene fiebre o signos de infección * Del estudio CAPRIE se excluyeron los pacientes con antecedentes de intolerancia a AAS GI: gastrointestinal CAPRIE Steering Committee. Lancet 1996;348:1329–1339.

Pacientes con EAP diagnosticada e IM previo: optimización del tratamiento El tratamiento con AAS se sustituyó por clopidogrel Las dosis de IECAs y estatinas se aumentaron de forma adecuada Se dieron indicaciones sobre cambios del estilo de vida: reducción de peso y control de los lípidos

Optimización del tratamiento: puntos clave RECORDAR ACTUAR La terapia antiagregante es clave en la prevención de episodios aterotrombóticos La optimización del tratamiento implica asegurar que cada paciente recibe el tratamiento más apropiado y eficaz Incluir un agente antiagregante (AAS o clopidogrel) en la estrategia global para reducir el riesgo Clopidogrel es eficaz en pacientes con EAP1 1. CAPRIE Steering Committee. Lancet 1996;348:1329–1339.

Diapositivas de Back-up

Papel de la enfermera especializada en la consulta Valoración del paciente Preparación para exploración y pruebas diagnósticas (ej. ITB) Educación y consejo al paciente Manejo de lesiones The role of the vascular nurse is becoming increasingly important in primary care and in specialist settings, including: Diabetic foot clinics Palliative care/hospice Limb centres Private hospitals Nursing homes In the clinic, vascular nurses may be involved in: Patient assessment Preparation for examination and diagnostic tests (e.g. ABI) Patient education and counselling (e.g. regarding medication, dose adjustment, exercise training) Management of lesions/wounds The vascular nurse may also: Manage staff Conduct and coordinate research and development Be involved in patient education initiatives Encourage best practice initiatives and continuing professional development Desarrollado conShiela Dugdill, Freeman Hospital, Newcastle, UK

Papel de la enfermera especializada fuera de la consulta Gestión del personal Investigación y desarrollo (ej. nuevos procedimientos o intervenciones) Iniciativas de educación al paciente Iniciativas para las buenas prácticas y desarrollo profesional continuado Control clínico: asegurarse que su práctica clínica diaria está basada en la evidencia y que se ajusta a los protocolos recomendados Desarrollado conShiela Dugdill, Freeman Hospital, Newcastle, UK

La presencia de EAP es un predictor de mortalidad hospitalaria en pacientes con IM Sin EAP (n=2745) EAP (n=301) 30 60 90 120 150 180 210 240 270 300 330 360 80 82 84 86 88 92 94 96 98 100 p<0,0001 Días Supervivencia (%) Among 3716 patients with acute MI who underwent emergency catheterisation with planned primary angioplasty, 394 (10.6%) had PAD, defined as either:1 history of intermittent claudication abnormal lower extremity arteriographic findings with previous stroke or TIA. Compared with those without PAD, PAD patients had a two-fold increase in in-hospital mortality (5.3% versus 2.6%, p=0.0021). This difference was significant at 1 month, 6 months and at 1 year.1 History of PAD was an independent predictor of in-hospital mortality at 1 year (odds ratio: 1.64, 95% CI: 1.04–2.57, p=0.032). Guerrero M, Harjai K, Stone GW, et al. Usefulness of the presence of peripheral vascular disease in predicting mortality in acute myocardial infarction patients treated with primary angioplasty (from the Primary Angioplasty in Myocardial Infarction Database). Am J Cardiol. 2005;96:649–654. Guerrero M et al. Am J Cardiol 2005;96:649–654.

Costes sanitarios por paciente con EAP y año (USA) * Hospitalización 75% Angioplastia 3% Laboratorio/diagnóstico 1% Consultas externas Agentes antiagregantes + fármacos para tratamiento de IC 2% Agentes antihipertensivos 5% Bypass arterial 4% Agentes hipolipemiantes Urgencias Embolectomía, aterectomía Stent Número de pacientes: 6,67 millones Gasto total atribuible a EAP: 5.955 $ por paciente y año In a large, managed-care database of 6.67 million people enrolled between 1999 and 2003, 30,561 people had had an intervention for PAD or had claimed for cilostazol or pentoxifylline.1 The prevalence of PAD defined in this way was 1.18% but note this does not take into account asymptomatic patients or untreated symptomatic patients. The total average annualised cost of PAD-related care was US$5,955 per PAD patient per year. Hospitalisations for MI, stroke, TIA and amputations accounted for 75% of the total healthcare costs. PAD-related, non-coronary procedures accounted for 12.2% of the costs. The total PAD-related pharmacy claims accounted for 10.2% of the costs. Note that antiplatelet medications did not include over-the-counter aspirin. Clopidogrel was the most commonly prescribed antiplatelet agent, accounting for 41% of prescribed agents. Margolis J, Barron JJ, Grochulski WD. Health care resources and costs for treating peripheral artery disease in a managed care population: results from analysis of administrative claims data. J Manag Care Pharm 2005;11:727–734. Margolis J et al. J Manag Care Pharm 2005;11:727–734. *IM, ictus, AIT o amputación

EAC = Enfermedad coronaria EAC estaba presente en la mayoría de los pacientes con EAP en una clínica de cirugía vascular con fines académicos 65 70 60 54 n=561 50 40 Pacientes (%) 25 30 20 10 In a population of 561 patients followed in an academic vascular surgery clinic, the prevalence of co-morbid CAD was 65%. Intermittent claudication was a complaint in 54%, and 21% were asymptomatic but with an ABI <0.9. A total of 138 (25%) had undergone vascular surgery or amputation. Hypertension was present in 69%, diabetes in 40%, and high LDL levels in 64%. A total of 79% were either current smokers or former smokers. The majority of patients (89%) were receiving either aspirin or clopidogrel. All intermittent claudication patients were receiving cilostazol or pentoxifylline. Sukhija R, Yalamanchili K, Aronow WS, et al. Clinical characteristics, risk factors, and medical treatment of 561 patients with peripheral arterial disease followed in an academic vascular surgery clinic. Cardiol Rev 2005;13:108–110. EAC Claudicación Cirugía vascular o intermitente amputación EAC = Enfermedad coronaria Sukhija R et al. Cardiol Rev. 2005;13:108–110.

La EAP se asocia a niveles elevados de marcadores de inflamación Fibrinógeno Refleja el proceso inflamatorio sistémico de la ateroesclerosis No está claro si reduciendo los marcadores (ej. con ejercicio) se alcanza una menor incidencia y se disminuye la progresión de EAP 10,66 10,7 10,5 10,3 10,16 μmol/L 10,1 9,9 9,7 EAP (n=107) No EAP (n=848) IL-6 PCR 1,8 1,65 40 1,6 31,8 1,37 1,4 30 25,6 1,2 1 mg/L 20 pg/mL 0,8 0,6 10 0,4 0,2 EAP (n=107) No EAP (n=848) EAP (n=107) No EAP (n=848) McDermott MM et al. Am Heart J 2005;150:276–281.

Uso de Beta-bloqueantes (%) Mejora en los índices de tratamiento en Holanda en un periodo de 22 años 45 AAS 45 Estatinas 40 40 35 35 32 30 27 27 30 26 Uso de AAS (%) 25 21 Uso de estatinas (%) 25 20 20 15 15 15 13 14 10 10 5 5 1983–1989 1990–1994 1995–1999 2000–2004 1983–1989 1990–1994 1995–1999 2000–2004 IECAs Beta-bloqueantes 45 45 40 40 40 35 35 30 30 30 30 28 Uso de IECAS (%) Feringa et al.1 conducted a prospective observational cohort study in 2420 PAD patients treated in the Erasmus Medical Centre, Rotterdam, during the period 1983–2005. PAD was defined as ABI ≤9.0.1 The graphs show the prescriptions of various drug classes in patients who were included in different periods of time. Feringa HH, van Waning VH, Bax JJ, et al. Cardioprotective medication is associated with improved survival in patients with peripheral arterial disease. J Am Coll Cardiol 2006;47:1182–1187. 25 22 Uso de Beta-bloqueantes (%) 25 21 20 20 17 15 12 15 10 10 5 5 1983–1989 1990–1994 1995–1999 2000–2004 1983–1989 1990–1994 1995–1999 2000–2004 Feringa HHH et al. J Am Coll Cardiol 2006;47:1182–1187.

Existe una relación inversa entre el ITB y un indicador de agregación plaquetaria Correlación entre pequeños agregados plaquetarios e ITB 0,0 0,2 0,4 0,6 0,8 1,0 1,2 1,4 ITB 5,0 7,0 9,0 11,0 13,0 Log pequeños agregados plaquetarios p<0,0001 r=–0,42 n=130 La formación de pequeños agregados plaquetarios es un indicador del proceso de agregación La propensión a formar agregados es mayor cuando el ITB es bajo Teóricamente, esto supondría un incremento del riesgo de aterotrombosis (aunque no se haya estudiado aquí) Platelet activation (and subsequent aggregation) is the key step to progression from atherosclerosis to atherothrombosis. Kudoh et al.1 used laser-light scattering to detect the formation of small platelet aggregates, an indicator of the initial stages of platelet aggregation. A total of 130 patients were tested, 42 of whom had concomitant PAD and CAD, 56 of whom had CAD only, and 32 of whom had neither CAD nor PAD. There was an inverse correlation between log small platelet aggregates and ABI. (r=-0.422, p<0.001). Low ABI was found to be an independent predictor of increased levels of small platelet aggregates. These results suggest that systemic atherosclerosis in PAD patients leads to changes platelet activity, making platelets more prone to aggregation. This would theoretically lead to an increased risk of atherothrombosis (although this was not studied here). Kudoh T, Sakamoto T, Miyamoto S, et al. Relation between platelet microaggregates and ankle brachial index in patients with peripheral arterial disease. Thromb Res 2006;117:263–269. r: coeficiente de correlación Kudoh T et al. Thromb Res 2006;117:263–269.

Los pacientes con ITB bajo y PCR alta tienen el riesgo más alto de un episodio aterotrombótico 30 ITB <0,9 25 ITB ≥0,9 20 ITB <0,9 Episodios (%) 15 10 ITB ≥0,9 Among 110 patients (mean age: 62 years), C-reactive protein (CRP) was highest in those with PAD.1 Those with highest levels of CRP and lowest ABI were at greatest risk of an atherothrombotic event (MI or stroke) or death. The risk of stroke, MI or death was fourfold greater in patients who had PAD and higher CRP levels (≥1 mg/L) than in those who had neither PAD nor high CRP levels. Beckman JA, Preis O, Ridker PM, et al. Comparison of usefulness of inflammatory markers in patients with versus without peripheral arterial disease in predicting adverse cardiovascular outcomes (myocardial infarction, stroke, and death). Am J Cardiol 2005;96:1374–1378. 5 PCR >1 mg/L PCR <1 mg/L n=110 Seguimiento medio: 2,25 años Episodio: muerte, IM e ictus Beckman JA et al. Am J Cardiol 2005;96:1374–1378.