BENEFICIOS DEL TRATAMIENTO DE LA HIPERTENSI

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BENEFICIOS DEL TRATAMIENTODE LA HIPERTENSIÓN
ARTERIAL

• PROF. DR. JORGE RESK
• HOSPITAL NACIONAL DE CLINICAS
• UNIVERSIDAD NACIONAL DE CORDOBA

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BLOOD PRESSURE, STROKE, AND CORONARY HEART
DISEASE
1000
ALL AVAILABLE EVIDENCE FROM RANDOMISED
T TREATMENT
ANTIHYPERTENSIVE DRUG TRIALS
C CONTROL
(mean DBP difference 5-6 mmHg for 5 years)
FATAL EVENTS
NON FATAL EVENTS
771
800
671
613
600
489
484
Total numbers of individuals affected
401
396
400
289
356
316
200
97
160
86
87
0
T
C
T
C
T
C
T
C
T
C
STROKE
CHD
REMAINING
ALL
ALL
VASCULAR
VASCULAR
OTHER
reduction
DEATHS
DEATHS
DEATHS
in odds
42 SD 6
14 SD 5
2P-value
lt0.0001
lt0.01
lt0.0002

• The Lancet 1990 335 827-838.

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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.

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ADVERSE OUTCOMES IN PLACEBO-CONTROLLED TRIALS
WITH FIRST-LINE THIAZIDE OR b-BLOCKERS
TREATMENT, Nº OF
PATIENTS
RR
OUTCOME
THIAZIDE
PLACEBO
(95 CI)
0.59
STROKE
284
584
(0.51-0.68)
0.84
CAD
433
703
(0.75-0.95)
0.70
ANY CV EVENT
838
1512
(0.64-0.75)
0.90
DEATH
742
1097
(0.82-0.98)
TOTAL OF
12118
17233
PATIENTS
P lt0.05
WRIGHT JM ET AL. CMAJ 1999 161 25-32
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RANDOMIZED CONTROLLED TRIALS IN HYPERTENSION
FIRST DRUG THERAPY
RELATIVE RISK VS PLACEBO
CV
STROKE
CHD
CHF
MORTALITY
HIGH DOSE DIURETIC
0,49
0,99
0,17
0,78
(50-100 mg)
LOW DOSE DIURETIC
0,66
0,72
0,58
0,76
(12.5-25 mg)
BETA-BLOCKER
0,71
0,93
0,58
0,89
CHD CORONARY HEART DISEASE
CHF CONGESTIVE HEART FAILURE
PSATY BM, SMITH NL, SISCOVICK DE, ET AL. JAMA
1997 277 739-745.
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THE BLOOD PRESSURE LOWERING TREATMENT TRIALISTS
COLLABORATION
CALCIUM CHANNEL BLOCKERS vs PLACEBO
D BP mmHg RR (95 CI)
STROKE -8 / -5 0.62 (0.47-0.82)
CHD -8 / -5 0.78 (0.62-0.99)
HEART FAILURE -8 / -5 1.21 (0.93-1.58)
MAJOR CV EVENTS -8 / - 5 0.80 (0.69-1.92)
BORDERLINE STATISTICAL SIGNIFICANCE.
LANCET 2003 362 1527-35.
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THE BLOOD PRESSURE LOWERING TREATMENT TRIALISTS
COLLABORATION
CALCIUM CHANNEL BLOCKERS vs DIURETICS / b-BLOCKERS
D BP mmHg RR (95 CI)
STROKE 0 / 0 0.93 (0.86-1.01)
CHD 0 / 0 1.01 (0.94-1.08)
HEART FAILURE 0 / 0 1.34 (1.22-1.47)
MAJOR CV EVENTS 0 / 0 1.04 (0.99-1.08)
HIGHLY STATISTICAL SIGNIFICANCE.
LANCET 2003 362 1527-35.
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THE BLOOD PRESSURE LOWERING TREATMENT TRIALISTS
COLLABORATION
ANGIOTENSIN CONVERTING ENZIME INHIBITORS vs
PLACEBO
D BP mmHg RR (95 CI)
STROKE -5 / -2 0.72 (0.64-0.81)
CHD -5 / -2 0.80 (0.73-0.88)
HEART FAILURE -5 / -2 0.82 (0.69-0.98)
MAJOR CV EVENTS -5 / -2 0.78 (0.73-0.83)
HIGHLY STATISTICAL SIGNIFICANCE.
LANCET 2003 362 1527-35.
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THE BLOOD PRESSURE LOWERING TREATMENT TRIALISTS
COLLABORATION
ACE-INHIBITORS vs DIURETICS / b-BLOCKERS
D BP mmHg RR (95 CI)
STROKE 2 / 0 1.09 (1.00-1.18)
CHD 2 / 0 0.98 (0.91-1.05)
HEART FAILURE 2 / 0 1.07 (0.96-1.19)
MAJOR CV EVENTS 2 / 0 1.02 (0.98-1.07)
LANCET 2003 362 1527-35.
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THE BLOOD PRESSURE LOWERING TREATMENT TRIALISTS
COLLABORATION
ACE-INHIBITORS vs CALCIUM CHANNEL BLOCKERS
D BP mmHg RR (95 CI)
STROKE 1 / 1 1.12 (1.01-1.25)
CHD 1 / 1 0.96 (0.88-1.05)
HEART FAILURE 1 / 1 0.82 (0.73-0.92)
MAJOR CV EVENTS 1 / 1 0.97 (0.92-1.03)
HIGHLY STATISTICAL SIGNIFICANCE.
LANCET 2003 362 1527-35.
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EFECTOS DEL TRATAMIENTO ANTIHIPERTENSIVO ANTAGONIS
TAS DE LOS RECEPTORES DE ANGIOTENSINA VS OTROS
TRATAMIENTOS
RR (95 IC) Valor p
ACV 0.87 (0.70-1.08) 0.05
Enfermedad coronaria 1.00 (0.83-1.19) 0.37
Insuficiencia cardíaca 0.79 (0.66-0.95) 0.002
Eventos CV mayores 0.90 (0.84-0.97) 0.94
Muerte CV 1.00 (0.86-1.15) 0.79
Mortalidad total 0.95 (0.87-1.03) 0.55
ARCH INTERN MED 2005 165 1410-1419.
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ADVERSE OUTCOMES IN PLACEBO-CONTROLLED TRIALS
WITH FIRST-LINE THIAZIDE OR b-BLOCKERS
TREATMENT, Nº OF
PATIENTS
RR
b
-BLOCKER
OUTCOME
PLACEBO
(95 CI)
0.80
STROKE
98
243
(0.64-1.01)
0.92
CAD
183
393
(0.78-1.10)
0.89
ANY CV EVENT
297
661
(0.78-1.02)
1.01
DEATH
287
568
(0.88-1.15)
TOTAL OF
5505
10867
PATIENTS
WRIGHT JM ET AL. CMAJ 1999 161 25-32
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LIFE STUDY LANCET 2002 359995-1003.
PRIMARY AND SECONDARY OUTCOMES
Adjusted
Losartan Atenolol RR p (n4605) (n458
8) () Primary composite 508 588 -13
0.021 CV mortality 204 234 -11
0.206 Stroke 232 309 -25 0.001 MI 198 188 7
0.491 Total mortality 383 431 -10 0.128
For degree of LVH and Framingham risk score
at randomization CV mortality, stroke and
MI patients with a first primary event
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Anglo-Scandinavian Cardiac Outcomes Trial-Blood
Pressure Lowering Arm (ASCOT-BPLA)
STROKE
TOTAL CV EVENTS
LANCET 2005 366895-906.
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Anglo-Scandinavian Cardiac Outcomes Trial-Blood
Pressure Lowering Arm (ASCOT-BPLA)
CV MORTALITY
TOTAL MORTALITY
LANCET 2005 366895-906.
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Should b-Blockers Remain First Choice in the
Treatment of Primary Hypertension? A
Meta-Analysis

• FINDINGS
• When the effect of b-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.

LANCET 2005 3661545-1553.
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Should b-Blockers Remain First Choice in the
Treatment of Primary Hypertension? A
Meta-Analysis

• CONCLUSIONS
• Hence, we believe that b-blockers should not
  remain first choice in the treatment of primary
  hypertension.

LANCET 2005 3661545-1553.
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HOW STRONG IS THE EVIDENCE FOR USE OF b-BLOCKERS
AS FIRST LINE THERAPY FOR HYPERTENSION? SYSTEMATIC
REVIEW AND META-ANALYSIS
b-BLOCKERS VS PLACEBO RR (95 IC)
STROKE 0.80 (0.66-0.96)
TOTAL CV EVENTS 0.88 (0.79-0.97)
TOTAL MORTALITY 0.99 (0.88-1.11)
CHD 0.93 (0.81-1.07)
CV MORTALITY 0.93 (0.80-1.09)
J HYPERTENS 2006 24 2131-2141.
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HOW STRONG IS THE EVIDENCE FOR USE OF b-BLOCKERS
AS FIRST LINE THERAPY FOR HYPERTENSION? SYSTEMATIC
REVIEW AND META-ANALYSIS
STROKE RR (95 IC)
b-BLOCKERS VS CCBs 1.24 (1.11-1.40)
b-BLOCKERS VS RAS INHIBITORS 1.30 (1.11-1.53)
J HYPERTENS 2006 24 2131-2141.
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HOW STRONG IS THE EVIDENCE FOR USE OF b-BLOCKERS
AS FIRST LINE THERAPY FOR HYPERTENSION? SYSTEMATIC
REVIEW AND META-ANALYSIS

• CONCLUSIONS
• b-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, b-blockers are generally suboptimal
  first-line antihypertensive drugs.

J HYPERTENS 2006 24 2131-2141.
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ALLHATJAMA Dec 2002 288 2981-2997
INTERVENTIONS
GOAL BLOOD PRESSURE WAS LESS THAN 140/90 mm Hg
DOSE (mg/d)
n
STEP 1 DRUGS
12.5 TO 25
15255
CHLORTHALIDONE
2.5 TO 10
9048
AMLODIPINE
10 TO 40
9054
LISINOPRIL
STEP 2 DRUGS
25 TO 100
ATENOLOL
0.05 TO 0.2
RESERPINE
0.1 TO 0.3
CLONIDINE
STEP 3 DRUG
25 TO 100
HYDRALAZINE
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ALLHATJAMA Dec 2002 288 2981-2997
PRIMARY OUTCOME
FATAL CHD OR NON-FATAL MYOCARDIAL INFARCTION
RR
95 CI
0,98
0,90-1,07
AMLODIPINE
vs CHLORTHALIDONE
0,99
0,91-1,08
LISINOPRIL
vs CHLORTHALIDONE
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ALLHATJAMA Dec 2002 288 2981-2997
SECONDARY OUTCOME
RR
95 CI
AMLODIPINE
vs CHLORTHALIDONE
1,38
1,25-1,52
HEART FAILURE
LISINOPRIL
vs CHLORTHALIDONE
1,10
1,05-1,16
COMBINED CV DISEASE
1,15
1,02-1,30
STROKE
1,19
1,07-1,31
HEART FAILURE
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2007 GUIDELINES FOR THE MANAGEMENT OF ARTERIAL
HYPERTENSION (ESH/ESC)

• 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.

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EFECTOS DEL TRATAMIENTO ANTIHIPERTENSIVO MAS
INTENSO VS MENOS INTENSO
RR (95 IC) Valor p
ACV 0.76 (0.58-1.00) 0.11
Enfermedad coronaria 0.95 (0.78-1.16) 0.14
Insuficiencia cardíaca 0.82 (0.55-1.22) 0.28
Eventos CV mayores 0.87 (0.75-1.01) 0.03
Muerte CV 0.93 (0.70-1.24) 0.02
Mortalidad total 0.89 (0.71-1.10) 0.06
ARCH INTERN MED 2005 165 1410-1419.
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2007 Guidelines for Management of Arterial
Hypertension(J Hypertens 2007 25 1105-87)

• 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.

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2007 Guidelines for Management of Arterial
Hypertension(J Hypertens 2007 25 1105-87)

• 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.

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2007 Guidelines for Management of Arterial
Hypertension(J Hypertens 2007 25 1105-87)

• 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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G R A C I A S