BENEFICIOS DEL TRATAMIENTO DE LA HIPERTENSIÓN ARTERIAL PROF. DR. JORGE RESK HOSPITAL NACIONAL DE CLINICAS UNIVERSIDAD NACIONAL DE CORDOBA PROF. DR. JORGE RESK HOSPITAL NACIONAL DE CLINICAS UNIVERSIDAD NACIONAL DE CORDOBA

BLOOD PRESSURE, STROKE, AND CORONARY HEART DISEASE The Lancet 1990; 335: TCTCTCTCTC Total numbers of individuals affected STROKECHD REMAINING VASCULAR DEATHS* ALL VASCULAR DEATHS* ALL OTHER DEATHS T = TREATMENT C = CONTROL = FATAL EVENTS = NON FATAL EVENTS ALL AVAILABLE EVIDENCE FROM RANDOMISED ANTIHYPERTENSIVE DRUG TRIALS (mean DBP difference 5-6 mmHg for 5 years) % reduction in odds 2P-value 42% SD 6 < % SD 5 <0.01<0.0002

BENEFICIOS DEL TRATAMIENTO ANTIHIPERTENSIVO 1.Reducción significativa de la morbilidad y mortalidad cardiovascular. 2.Reducción menos significativa sobre todas las causas de muerte. 3.Los beneficios se observan en individuos de edad avanzada, incluso en pacientes con hipertensión arterial sistólica aislada. 4.Reducción del riesgo cardiovascular en hombres y mujeres. 5.Hay mayor reducción del riesgo de ACV (30 a 40%) que de ECo (20%). 6.Probablemente produce una reducción significativa en la incidencia de insuficiencia cardíaca. 1.Reducción significativa de la morbilidad y mortalidad cardiovascular. 2.Reducción menos significativa sobre todas las causas de muerte. 3.Los beneficios se observan en individuos de edad avanzada, incluso en pacientes con hipertensión arterial sistólica aislada. 4.Reducción del riesgo cardiovascular en hombres y mujeres. 5.Hay mayor reducción del riesgo de ACV (30 a 40%) que de ECo (20%). 6.Probablemente produce una reducción significativa en la incidencia de insuficiencia cardíaca.

ADVERSE OUTCOMES IN PLACEBO-CONTROLLED TRIALS WITH FIRST-LINE THIAZIDE OR  -BLOCKERS WRIGHT JM ET AL. CMAJ 1999; 161: OUTCOMETHIAZIDEPLACEBO RR (95% CI) STROKE * ( ) CAD * ( ) ANY CV EVENT * ( ) DEATH * ( ) TOTAL OF PATIENTS TREATMENT, Nº OF PATIENTS * P <0.05

RANDOMIZED CONTROLLED TRIALS IN HYPERTENSION: FIRST DRUG THERAPY PSATY BM, SMITH NL, SISCOVICK DE, ET AL. JAMA 1997; 277: STROKECHDCHF CV MORTALITY HIGH DOSE DIURETIC ( mg) 0,490,990,170,78 LOW DOSE DIURETIC ( mg) 0,660,720,580,76 BETA-BLOCKER0,710,930,580,89 CHD: CORONARY HEART DISEASE CHF: CONGESTIVE HEART FAILURE RELATIVE RISK VS PLACEBO

LANCET 2003; 362: THE BLOOD PRESSURE LOWERING TREATMENT TRIALISTS’ COLLABORATION  BP mmHg RR (95% CI) STROKE-8 / ( ) CHD-8 / * ( ) HEART FAILURE-8 / ( ) MAJOR CV EVENTS-8 / ( ) CALCIUM CHANNEL BLOCKERS vs PLACEBO * BORDERLINE STATISTICAL SIGNIFICANCE.

LANCET 2003; 362: THE BLOOD PRESSURE LOWERING TREATMENT TRIALISTS’ COLLABORATION CALCIUM CHANNEL BLOCKERS vs DIURETICS /  -BLOCKERS  BP mmHg RR (95% CI) STROKE0 / ( ) CHD0 / ( ) HEART FAILURE0 / 01.34* ( ) MAJOR CV EVENTS0 / ( ) * HIGHLY STATISTICAL SIGNIFICANCE.

LANCET 2003; 362: THE BLOOD PRESSURE LOWERING TREATMENT TRIALISTS’ COLLABORATION  BP mmHg RR (95% CI) STROKE-5 / ( ) CHD-5 / * ( ) HEART FAILURE-5 / ( ) MAJOR CV EVENTS-5 / ( ) ANGIOTENSIN CONVERTING ENZIME INHIBITORS vs PLACEBO * HIGHLY STATISTICAL SIGNIFICANCE.

LANCET 2003; 362: THE BLOOD PRESSURE LOWERING TREATMENT TRIALISTS’ COLLABORATION ACE-INHIBITORS vs DIURETICS /  -BLOCKERS  BP mmHg RR (95% CI) STROKE2 / ( ) CHD2 / ( ) HEART FAILURE2 / ( ) MAJOR CV EVENTS2 / ( )

LANCET 2003; 362: THE BLOOD PRESSURE LOWERING TREATMENT TRIALISTS’ COLLABORATION ACE-INHIBITORS vs CALCIUM CHANNEL BLOCKERS  BP mmHg RR (95% CI) STROKE1 / ( ) CHD1 / ( ) HEART FAILURE1 / 10.82* ( ) MAJOR CV EVENTS1 / ( ) * HIGHLY STATISTICAL SIGNIFICANCE.

EFECTOS DEL TRATAMIENTO ANTIHIPERTENSIVO ANTAGONISTAS DE LOS RECEPTORES DE ANGIOTENSINA VS OTROS TRATAMIENTOS ARCH INTERN MED 2005; 165: RR (95% IC)Valor p ACV0.87 ( )0.05 Enfermedad coronaria1.00 ( )0.37 Insuficiencia cardíaca0.79 ( )0.002 Eventos CV mayores0.90 ( )0.94 Muerte CV1.00 ( )0.79 Mortalidad total0.95 ( )0.55

ADVERSE OUTCOMES IN PLACEBO-CONTROLLED TRIALS WITH FIRST-LINE THIAZIDE OR  -BLOCKERS WRIGHT JM ET AL. CMAJ 1999; 161: OUTCOME  -BLOCKER PLACEBO RR (95% CI) STROKE ( ) CAD ( ) ANY CV EVENT ( ) DEATH ( ) TOTAL OF PATIENTS TREATMENT, Nº OF PATIENTS

PRIMARY AND SECONDARY OUTCOMES LosartanAtenololRRp (n=4605)(n=4588)(%) Primary composite ** CV mortality Stroke MI Total mortality LosartanAtenololRRp (n=4605)(n=4588)(%) Primary composite ** CV mortality Stroke MI Total mortality Adjusted * * For degree of LVH and Framingham risk score at randomization ** CV mortality, stroke and MI; patients with a first primary event * For degree of LVH and Framingham risk score at randomization ** CV mortality, stroke and MI; patients with a first primary event LIFE STUDY LANCET 2002; 359:

Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) LANCET 2005; 366: STROKE TOTAL CV EVENTS

Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) LANCET 2005; 366: CV MORTALITY TOTAL MORTALITY

FINDINGS: –When the effect of  -blockers was compared with that placebo or no treatment, the relative risk of stroke was reduced by 19% (7-29%), about half that expected from previous hypertension trials. –There was no difference for myocardial infarction or mortality. FINDINGS: –When the effect of  -blockers was compared with that placebo or no treatment, the relative risk of stroke was reduced by 19% (7-29%), about half that expected from previous hypertension trials. –There was no difference for myocardial infarction or mortality. Should  -Blockers Remain First Choice in the Treatment of Primary Hypertension? A Meta-Analysis LANCET 2005; 366:

CONCLUSIONS: –Hence, we believe that  -blockers should not remain first choice in the treatment of primary hypertension. CONCLUSIONS: –Hence, we believe that  -blockers should not remain first choice in the treatment of primary hypertension. Should  -Blockers Remain First Choice in the Treatment of Primary Hypertension? A Meta-Analysis LANCET 2005; 366:

HOW STRONG IS THE EVIDENCE FOR USE OF  -BLOCKERS AS FIRST LINE THERAPY FOR HYPERTENSION? SYSTEMATIC REVIEW AND META-ANALYSIS J HYPERTENS 2006; 24:  -BLOCKERS VS PLACEBO RR (95% IC) STROKE0.80 ( ) TOTAL CV EVENTS0.88 ( ) TOTAL MORTALITY0.99 ( ) CHD0.93 ( ) CV MORTALITY0.93 ( )

HOW STRONG IS THE EVIDENCE FOR USE OF  -BLOCKERS AS FIRST LINE THERAPY FOR HYPERTENSION? SYSTEMATIC REVIEW AND META-ANALYSIS J HYPERTENS 2006; 24: STROKE RR (95% IC)  -BLOCKERS VS CCBs 1.24 ( )  -BLOCKERS VS RAS INHIBITORS 1.30 ( )

CONCLUSIONS: –  -blockers are inferior to CCBs and to RAS inhibitors for reducing several important hard end points. –Compared with diuretics, they had similar outcomes, but were less will tolerated. –Hence,  -blockers are generally suboptimal first- line antihypertensive drugs. CONCLUSIONS: –  -blockers are inferior to CCBs and to RAS inhibitors for reducing several important hard end points. –Compared with diuretics, they had similar outcomes, but were less will tolerated. –Hence,  -blockers are generally suboptimal first- line antihypertensive drugs. HOW STRONG IS THE EVIDENCE FOR USE OF  -BLOCKERS AS FIRST LINE THERAPY FOR HYPERTENSION? SYSTEMATIC REVIEW AND META-ANALYSIS J HYPERTENS 2006; 24:

INTERVENTIONS GOAL BLOOD PRESSURE WAS LESS THAN 140/90 mm Hg DOSE (mg/d) n n STEP 1 DRUGS CHLORTHALIDONE 12.5 TO AMLODIPINE 2.5 TO LISINOPRIL 10 TO STEP 2 DRUGS ATENOLOL 25 TO 100 RESERPINE 0.05 TO 0.2 CLONIDINE 0.1 TO 0.3 STEP 3 DRUG HYDRALAZINE 25 TO 100 ALLHAT JAMA Dec 2002; 288:

PRIMARY OUTCOME RR 95% CI AMLODIPINE vs CHLORTHALIDONE 0,98 0,90-1,07 LISINOPRIL vs CHLORTHALIDONE 0,99 0,91-1,08 ALLHAT JAMA Dec 2002; 288: FATAL CHD OR NON-FATAL MYOCARDIAL INFARCTION

RR 95% CI AMLODIPINE vs CHLORTHALIDONE HEART FAILURE 1,38 1,25-1,52 LISINOPRIL vs CHLORTHALIDONE COMBINED CV DISEASE 1,10 1,05-1,16 STROKE 1,15 1,02-1,30 HEART FAILURE 1,19 1,07-1,31 ALLHAT JAMA Dec 2002; 288: SECONDARY OUTCOME

IN ANY CASE, THE ABOVE QUOTED META-ANALYSIS OF BETA BLOCKERS INITIATED TRIALS WELL ILLUSTRATE THE DIFFICULTIES INHERENT IN MANY RECENT TRIALS IN WHICH COMBINATION THERAPY HINDERS THE ATTRIBUTION OF EITHER BENEFITS OR HARMS TO INDIVIDUAL COMPOUNDS GUIDELINES FOR THE MANAGEMENT OF ARTERIAL HYPERTENSION (ESH/ESC)

EFECTOS DEL TRATAMIENTO ANTIHIPERTENSIVO MAS INTENSO VS MENOS INTENSO ARCH INTERN MED 2005; 165: RR (95% IC)Valor p ACV0.76 ( )0.11 Enfermedad coronaria0.95 ( )0.14 Insuficiencia cardíaca0.82 ( )0.28 Eventos CV mayores0.87 ( )0.03 Muerte CV0.93 ( )0.02 Mortalidad total0.89 ( )0.06

2007 Guidelines for Management of Arterial Hypertension (J Hypertens 2007; 25: ) CONCLUSIONES: –Hay un efecto beneficioso sobre la morbilidad y mortalidad cardiovascular cuando el tratamiento es iniciado con un diurético, bloqueante beta, calcio antagonista o inhibidor de la enzima de conversión. –La disminución de la presión arterial parece ser el determinante más importante para reducir la incidencia del accidente cerebrovascular y eventos coronarios. CONCLUSIONES: –Hay un efecto beneficioso sobre la morbilidad y mortalidad cardiovascular cuando el tratamiento es iniciado con un diurético, bloqueante beta, calcio antagonista o inhibidor de la enzima de conversión. –La disminución de la presión arterial parece ser el determinante más importante para reducir la incidencia del accidente cerebrovascular y eventos coronarios.

2007 Guidelines for Management of Arterial Hypertension (J Hypertens 2007; 25: ) CONCLUSIONES: –Algunos agentes antihipertensivos pueden ejercer un efecto beneficioso sobre determinados eventos en forma independiente al descenso de la presión arterial (calcio antagonistas sobre ACV e inhibidores ECA sobre eventos coronarios), aunque este efecto es definitivamente más pequeño que el efecto protector dominante ejercido por el descenso de la presión arterial. CONCLUSIONES: –Algunos agentes antihipertensivos pueden ejercer un efecto beneficioso sobre determinados eventos en forma independiente al descenso de la presión arterial (calcio antagonistas sobre ACV e inhibidores ECA sobre eventos coronarios), aunque este efecto es definitivamente más pequeño que el efecto protector dominante ejercido por el descenso de la presión arterial.

2007 Guidelines for Management of Arterial Hypertension (J Hypertens 2007; 25: ) CONCLUSIONES: –En general se ha reportado una menor protección de los calcio antagonistas en la prevención de nuevo comienzo de insuficiencia cardíaca independiente de las diferencias en la presión arterial. –Una disminución más intensa de la presión arterial produce una reducción mayor del ACV y de todos los eventos cardiovasculares, particularmente en pacientes diabéticos. –Los bloqueantes de los receptores de angiotensina también son efectivos para reducir los eventos cardiovasculares. CONCLUSIONES: –En general se ha reportado una menor protección de los calcio antagonistas en la prevención de nuevo comienzo de insuficiencia cardíaca independiente de las diferencias en la presión arterial. –Una disminución más intensa de la presión arterial produce una reducción mayor del ACV y de todos los eventos cardiovasculares, particularmente en pacientes diabéticos. –Los bloqueantes de los receptores de angiotensina también son efectivos para reducir los eventos cardiovasculares.

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