Hypertension Treatment A TransAtlantic view Arterial Hypertension 2014 José R. González Juanatey Cardiology Department and ICCU University Hospital Santiago de Compostela. Spain

Disclosures: Research Grants: AZ, Boehringer Ingelheim, Pfizer, Novartis, Daichii-Sankyo, Sanofi-Aventis, Bayer, MSD. Consultant/Honorarium. AZ, Boehringer-Ingelheim, Bayer, Pfizer, BMS, MSD, Daichii-Sankyo, Servier.

J.R.G. JUANATEY C.H.U.Santiago HT A transAtlantic view Epidemiology HT and Risk Stratification New Guidelines and Therapeutic Objectives New Guidelines and Drug Selection

J.R.G. JUANATEY C.H.U.Santiago HT Epidemiology.30 – 45 % of adult population (> million persons)

J.R.G. JUANATEY C.H.U.Santiago Ezzati M et al. Global Burden of Disease and Risk Factors. WHO Mortalidad atribuible a HTA - OMS

J.R.G. JUANATEY C.H.U.Santiago World’s biggest killers – CVD retain top spot

J.R.G. JUANATEY C.H.U.Santiago Contribución de la mortalidad CV a la esperanza de vida en España de 1980 a 2009 Contribución de la mortalidad CV a la esperanza de vida en España de 1980 a 2009 García González JM, et al. Rev Esp Cardiol on line Mujeres Varones Estilo de Vida Prevención Organización asistencial Tratamiento INCORPORACIÓN INNOVACIÓN

J.R.G. JUANATEY C.H.U.Santiago HT A transAtlantic view Epidemiology HT and Risk Stratification New Guidelines and Therapeutic Objectives New Guidelines and Drug Selection

J.R.G. JUANATEY C.H.U.Santiago HTA Nuevas Guías Aspectos Epidemiológicos Las Nuevas Guías y la Evaluación del Riesgo Las Nuevas Guías y los Objetivos Terapéuticos Las Nuevas Guías y la Selección de Fármacos

J.R.G. JUANATEY C.H.U.Santiago Office and ambulatory HT mmHg Category SBPDBP Office ≥ 140y/o≥ 90 ABPM Day (activity) ≥ 135y/o≥ 85 Night (rest) ≥ 120y/o≥ hours ≥ 130y/o≥ 80 In-home ≥ 135y/o≥ 85 JNC VIII / ASHESC / ESH 2013

J.R.G. JUANATEY C.H.U.Santiago EVALUATING THE PATIENT History. Important previous events include: Stroke, TIA, CAD, HF or symptoms of left vemtricular dysfunction, CKD, Pripheral artery disease, Diabetes, Sleep apnea, ask about other risk factors and concurrent drugs. Physical Examination. Measuring BP; weight, height and BMI, waist circumference, signs of HF, neuro examination, optic fundi (if possible), peri-ocular xantomas, peripheral pulses. TESTS Blood Sample: electrolytes, Fasting glucose, serum creatinine and BUN, Lipids, Hb/hematocrit, liver function tests. Urine Sample: Albuminuria, red and white cells. ECG. All patients ECHOCARDIOGRAM., if available, can be helpful …., although this test is not routine in hypertensive patients 2013

J.R.G. JUANATEY C.H.U.Santiago Estratificación del Riesgo CVC en 4 Categorías Riesgo Añad. Muy Alto Riesgo Añad. Muy Alto Riesgo Añad. Muy Alto Riesgo Añadido Alto Riesgo Añad. Muy Alto Riesgo Añad. Muy Alto Riesgo Añadido Alto Riesgo Riesgo Añad. Moderado Riesgo Añad. Moderado Riesgo Añad. Moderado Riesgo Añadido Bajo Presión Arterial (mmHg) Otros Factores Riesgo, LOD o Enfermedad Grado 1 HT PAS o PAD Grado 2 HT PAS O PAD Grado 3 HT PAS ≥ 180 o PAD ≥ o mas Facts. Riesgo, SM, LOD o Diabetes Riesgo Añad. Muy Alto Riesgo Añad. Muy Alto Riesgo Añadido Alto Riesgo Añad. Moderado No Riesgo Añadido Riesgo Añadido Bajo Riesgo No Riesgo Añadido Normal PAS o PAD Normal Alta PAS o PAD SBP: systolic blood pressure; DBP: diastolic blood pressure; CV: cardiovascular; HT: hypertension. Low, moderate, high, very high risa refer to 10year risk of a CV fatal or non-fatal event. The term “added” indicates that in all categories risk is greater than average. OD: subclinical organ damage; MS: metabolic syndrome. No otros Factores R. 1-2 factores riesgo Established CV or renal disease Riesgo añadido bajo: 30% 8% (SCORE)

J.R.G. JUANATEY C.H.U.Santiago Test CV predictive value Availability Reproducibility Cost-effect ESC/ESH Guidelines Markers of organ damage

J.R.G. JUANATEY C.H.U.Santiago Factores de riesgo (FRCV) Lesión de órgano diana (LOD) Enfermedad cardiovascular (ECV ) No otros factores de riesgo 1 – 2 factores de riesgo ≥ 3 factores de riesgo LOD, IRC 3 o Diabetes ECV sintomática, IRC ≥ 4 o Diabetes con LOD/FRCV Presión arterial (mmHg) Normal alta PAS 130 – 139 o PAD HTA grado 1 PAS 140 – 159 o PAD HTA grado 2 PAS 160 – 179 o PAD HTA grado 3 PAS ≥ 180 o PAD ≥ 110 Bajo riesgo Alto riesgo Muy alto riesgo Moderado riesgo Moderado a alto riesgo Moderado a alto riesgo Alto a muy alto riesgo Bajo a moderado riesgo Moderado a alto riesgo JNC VIII / ASH ESC / ESH 2013

J.R.G. JUANATEY C.H.U.Santiago HTA Nuevas Guías Aspectos Epidemiológicos Las Nuevas Guías y la Evaluación del Riesgo Las Nuevas Guías y los Objetivos Terapéuticos Las Nuevas Guías y la Selección de Fármacos

J.R.G. JUANATEY C.H.U.Santiago HT A transAtlantic view Epidemiology HT and Risk Stratification New Guidelines and Therapeutic Objectives New Guidelines and Drug Selection

J.R.G. JUANATEY C.H.U.Santiago Objetivos del Tratamiento: Reducción de PA y Riesgo CVC Global Riesgo absoluto añadido de enfermedad CVC a 10 años : Normal PAS o PAD Normal Alta PAS o PAD Complicaciones CVC Clínicas 3 o mas FRC, o Diabetes o LOD 1 o 2 Fact. Riesgo Adicionales No otros Factores Riesgo Grado 3 PAS  180 o PAD  110 Grado 2 PAS o PAD Grado 1 PAS o PAD < 15% 15-20%15-20% 20-30%20-30% > 30% Framingham < 4% 4 – 5% 4 – 5% 5-8% 5-8% > 8% SCORE BP 178/106

J.R.G. JUANATEY C.H.U.Santiago JNC VIII / ASH ESC / ESH 2013 JAMA 2013 / AJH 2013 Eur Heart J / J Hypertens 2013 < 140/90 mmHg < 140/90 mmHg in diabetes and chronic renal failure “…it may be prudent to recommend lowering SBP/DBP to values < 140/90 mmHg in all hypertensive patients…” “…<140/85 mmHg in diabetes…”

J.R.G. JUANATEY C.H.U.Santiago Blood Pressure Goal in Patientes with HT RecomendacionesClaseNivel Presión arterial sistólica < 140 mmHg pacientes con riesgo cardiovascular bajo-moderadoIB pacientes con diabetesIA pacientes con ictus previo o ataque isquémico transitorioIIaB pacientes con cardiopatía isquémicaIIaB pacientes con insuficiencia renal, diabética o no diabéticaIIaB Ancianos (< 80 años) con PAS ≥ 160 mmHg, objetivo PAS entre 140 y 150 mmHg IA Ancianos (< 80 años) en buena forma física < 140 mmHgIIbC Ancianos (> 80 años) con PAS ≥ 160 mmHg, objetivo PAS entre 140 y 150 mmHg, si están en buenas condiciones IB Presión arterial diastólica < 90 mmHg; en diabéticos < 85 mmHg. Valores PAD mmHg son seguros y bien tolerados IA ESC / ESH 2013

J.R.G. JUANATEY C.H.U.SantiagoPatientsBP Adults Aged > 18 y > 140 / 90 mmHgOBP Age > 80 y > 150 / 90 mmHgOBP High Risk (DM, CKD) > 140 / 90 mmHgOBP 2013 Blood Pressure >140/90 in Adults Aged >18 years (For age >80 years, pressure >150/90 or >140/90 if high risk (DM, CKD Start Lifestyle Changes (Lose weight, reduce dietary salt and alcohol, stop smoking)

J.R.G. JUANATEY C.H.U.Santiago Recommendation 1 In the general population aged 60 years or older, initiate pharmacologic treatment to lower BP at SBP of 150 mm Hg or higher or DBP of 90 mm Hg or higher and treat to goal SBP lower than 150 mm Hg and goal DBP lower than 90 mm Hg. Strong recommendation – Grade A Recommendation 2 In the general population younger than 60 years initiate pharmacologic treatment to lower BP at DBP of 90 mm Hg or higher and treat to goal DBP of lower than 90 mm Hg For ages years: Strong recommendation – Grade A For ages years: Expert opinion – Grade E Recommendation 3 In the general population younger than 60 years initiate pharmacologic treatment to lower BP at SBP of 140 mm Hg or higher and treat to goal SBP of lower than 140 mm Hg Expert opinion – Grade E

J.R.G. JUANATEY C.H.U.Santiago Metaregression of Treatment-induced Systolic BP Changes with Stroke and Myocardial Infarction Reboldi, Gentile, Angeli, Ambrosio, Mancia, Verdecchia, 2010 StrokeMyocardial infarction Relative risk SBP difference between randomized groups (mmHg) ABCD-N More vs Less SYST-EUR Diab ACCORD BP UKPDS 38 FACET MOSES-Diab JMIC-B-Diab HOPE-Diab IDNT/CCB -PLB PROGRESS-Diab SHEP-Diab EUROPA-Diab ABCD-H More vs Less ACTION-Diab ABCD/Norm ABCD/HT IDNT/ARB-CCB IDNT/ARB-PLB ADVANCE ASCOT-Diab HOT-DM More vs Less DETAIL DETAIL ALLHAT/ACE-CCB-Diab STOP2/CCB-BB-Diab LIFE-Diab INVEST-Diab IINSIGHT-Diab ALLHAT/CCB-D-Diab STOP2/ACE-BB-Diab RENAAL DIABHYCAR CAPPP-Diab ALLHAT/ACE-D-Diab UKPDS 39 STOP2/ACE-CCB-Diab ABCD-N More vs Less ACCORD BP UKPDS 38 FACET JMIC-B-Diab HOPE-Diab IDNT/ARB-CCB EUROPA-Diab ACTION-Diab ABCD/Norm ABCD/HT IDNT/ARB-CCB IDNT/ARB-PLB ADVANCE ASCOT-Diab HOT-DM More vs Less DETAIL STOP2/CCB-BB-Diab LIFE-Diab INVEST-Diab STOP2/ACE-BB-Diab RENAAL DIABHYCAR CAPPP-Diab UKPDS 39 STOP2/ACE-CCB-Diab ATLANTIS/1.25 ATLANTIS/5 ABCD-H More vs Less

J.R.G. JUANATEY C.H.U.Santiago CV Event Incidence in Relation to Mean FU Systolic BP (up to 1st event) in VALUE Mancia et al., 2010 MIMIStrokeStroke < < < < < < <180≥180 SBP (mmHg) < < < < < < <180≥180 %

J.R.G. JUANATEY C.H.U.Santiago Incidence and Unadjusted CV Risk of Events in Deciles of In-treatment SBP Incidence and Unadjusted CV Risk of Events in Deciles of In-treatment SBP Unadjusted risk of events (%) HR (95% CI) On-treatment SBP (mmHg) Unadjusted risk of events (%) HR (95% CI) Myocardial infarction StrokeStroke Sleight, et al., J Hypert 2009; 27: On-treatment SBP (mmHg)

J.R.G. JUANATEY C.H.U.Santiago Association of BP and Its Evolving Changes with the Survival of Patients with Heart Failure Grigorian-Shamagian L et al. Journal of Cardiac Failure, 2008 Cause-specific death rates in subgroups of patients with chronic HF defined by the quartiles of the distribution of baseline SBP in the whole study group. The P value refers to the differ­ences of cause-specific mortality in the SBP subgroups % 26.6 % 14.3 % 39.3 % 38.5 % 30.8 % 46.4 % 40.9 % 26.7 % 30.7 % 46.7 % 13.6 % p = 0.02 >50%

J.R.G. JUANATEY C.H.U.Santiago What is the optimal blood pressure after Acute Coronary Syndomes? PROVE IT TIMI 22 Non-fatal Myocardial Infarction Nadir = mmHg Nadir = 83.8 mmHg SBP mmHg DBP mmHg “J” Curve Circulation 2010; 122:

J.R.G. JUANATEY C.H.U.Santiago Evaluating the Performance of the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines (CRUSADE) Bleeding Score in a Contemporary Spanish Cohort of Patients With Non–ST-Segment Elevation acute myocardial infarction. Emad Abu-Assi, José María Gracía-Acuña, Ignacio Ferreira-González, Carlos Peña-Gil, Pilar Gayoso-Diz, José Ramón González- Juanatey. Circulation. 2010;121:

J.R.G. JUANATEY C.H.U.Santiago Reference Tight BP control and CV outcomes among HT patients with Diabetes and Coronary Artery Disease. INVEST All-cause Mortality JAMA 2010; 304: 61-68

J.R.G. JUANATEY C.H.U.Santiago Look at the concomitant life-threatening conditions!! Look at the concomitant life-threatening conditions!! Messerli F, Mancia G, et al. Ann Intern Med 2006 Associated ConditionAchieved Diastolic Blood Pressure (mmHg) ≤ Heart Failure Class I-III Myocardial Infarction Diabetes Cancer

J.R.G. JUANATEY C.H.U.Santiago The “J curve” between Blood Pressure and Coronary Artery Disease Patients with revascularization Patients without revascularization DBP (mmHg) Hazard Ratio “J” Curve JACC 2009; 54:

J.R.G. JUANATEY C.H.U.Santiago In retrospective analyses of observational or randomized studies, an increased risk of events at low values of achieved BP (J-curve) may reflect the confounding effect of concomitant life-threatening conditions (i.e., CHF, cancer, liver disease, etc) that are able to lower BP, not the specific effect of BP control induced by life-style measures or antihypertensive drugs. What is the meaning of the J-Curve ? What is the meaning of the J-Curve ?