Table 7.
The Impact of Angiotensin Receptor Blocker Therapies on Cardiovascular Outcomes
| Study and Year | ARB (n) | Comparator (n) | Primary Outcome | Main Results | Comments | |
|---|---|---|---|---|---|---|
| Hypertension primary outcome trials | ||||||
| LIFE 2001 (89) | Losartan 100 mg/day (4,605) | Atenolol (4,588) | Death, myocardial infarction, or stroke | Losartan reduced cardiovascular morbidity and death more than atenolol (RR 0.87, p=0.021) | Similar reduction in BP achieved between two groups with left ventricular hypertrophy | |
| VALUE 2003 (90) | Valsartan 160 mg/day (7,649) | Amlodipine 10mg/day (7,596) | Cardiovascular mortality and morbidity | No difference between valsartan and amlodipine (HR 1.04, p=0.49) | Amlodipine treatment resulted in greater BP reduction compared to valsartan causing potential confounding in high risk patients | |
| SCOPE 2003 (91) | Candesartan 16 mg/day (2477) | Placebo* (2460) | Cardiovascular death, non-fatal stroke and non-fatal myocardial infarction | No difference between candesartan and placebo (p=0.19). | Candesartan reduced non-fatal stroke by 27.8% (p=0.04) | |
| Renal Disease | ||||||
| ONTARGET (86) | Telmisartan 80 mg/day (8,541) | Telmisartan/ramipril combination 80/10 mg/day (8,502) Ramipril 10 mg/day (8.576) |
Composite of dialysis, doubling of serum creatinine, and death | Composite primary renal outcome was similar between telmisartan (HR 1.00, 95% CI 0.92–1.09), but increased with combination therapy (HR 1.09, 1·01–1.18; p=0·037) | Patients were aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. | |
| IRMA-2 2001 (93) | Irbesartan 150 mg/day (195)/Irbesartan 300 mg/day (194) | Placebo* (201) | Progression to diabetic nephropathy based on increases in proteinuria | Reduction of progression to diabetic nephropathy (IRB 300mg HR 0.30, p< 0.001; IRB 150mg HR 0.61 p=0.08) | The effect of irbesartan was independent of its antihypertensive effect | |
| RENAAL 2001 (95) | Losartan 100 mg/day (751) | Placebo* (762) | Doubling of the baseline serum creatinine, development of end- stage renal disease, or death from any cause | Losartan reduced the incidence of doubling of serum creatinine (25% risk reduction, p=0.006) and incidence of end-stage renal disease (ESRD) (28% risk reduction, p=0.002) versus placebo | Losartan showed no ESRD mortality benefit | |
| IDNT 2001 (96) | Irbesartan 300 mg/day (579) | Amlodipine 10 mg/day (567) Placebo* (569) |
Doubling of the serum creatinine, development of ESRD, or death from any cause. | Irbesartan reduced the incidence of doubling of serum creatinine versus amlodipine (37% risk reduction, p<0.001) and placebo (33% risk reduction, p=0.003) | Irbesartan was associated with 23% lower incidence of ESRD versus placebo and amlodipine (both p=0.07). | |
| Heart Failure | ||||||
| ELITE II 2000 (97) | Losartan 50 mg/day (1,578) | Captopril 150 mg/day (1,574) | All cause mortality, and sudden death or resuscitated arrest | No significant differences in all-cause mortality with average annual mortality of 11.7% in the losartan arm versus 10.4% in the captopril arm (HR 1.13, p= 0.16) | Losartan was better tolerated than captopril | |
| CHARM-Alternative 2003 (101) | Candesartan 32 mg/day (1,013) | Placebo (1,015) | Composite of cardiovascular death or hospital admission for CHF | Candesartan reduced cardiovascular death and hospitalization for CHF versus placebo (adjusted HR 0.70, p<0.0001) | ACE inhibitor intolerant patients | |
| CHARM-Added 2003 (102) | Candesartan 32 mg/day (1,276) | Placebo^ (1,272) | Composite of cardiovascular death or hospital admission for CHF | Candesartan reduced cardiovascular death and hospitalization for CHF versus placebo (unadjusted HR 0.85, p=0.011). | Patients were on background of lisinopril, enalapril, captopril or ramipril; ARB+ACE inhibitor had higher withdrawal rate due to prespecified doubling of creatinine and hyperkalemia | |
| CHARM-Preserved 2003 (103) | Candesartan 32 mg/day (1,514) | Placebo (1,509) | Composite of cardiovascular death or hospital admission for CHF | Trend towards reduction in cardiovascular mortality and morbidity versus placebo but not statistically significant (adjusted HR 0.86, p=0.051). | ||
| ValHeFT 2001 (104) | Valsartan 320 mg/day (2,511) | Placebo^ (2,499) | Combined end point of mortality and morbidity | Valsartan reduced mortality and morbidity versus placebo (RR 0.87, P=0.009) | Valsartan was associated with improvement in NYHA class, LVEF and quality of life versus placebo. | |
| I-PRESERVE 2008 (105) | Irbesartan 300mg/day (2,061) | Placebo (2,067) | Composite of death from any cause or hospitalization for a cardiovascular cause (heart failure, myocardial infarction, unstable angina, arrhythmia, or stroke) | No difference between the two groups. (HR Irbesartan vs placebo, 0.95; p=0.35) | Patients with preserved LV function | |
| Post-Myocardial Infarction | ||||||
| VALIANT 2003 (98) | Valsartan 320mg/day (4,909) |
|
All-cause mortality | No difference between three groups (HR VAL vs captopril, 1.00, p=0.98; HR VAL+captopril vs captopril 0.98, p=0.73) | Higher adverse effects with combined therapy | |
| OPTIMAAL 2002 (99) | Losartan 50mg/day (2,744) | Captopril 150mg/day (2,733) | All-cause mortality | No difference between valsartan and captopril (RR 1.13 [95% p=0.07). | Losartan was more tolerated than captopril | |
| Stroke Prevention | ||||||
| LIFE 2001 (89) | Losartan 100 mg/day (4,605) | Atenolol (4,588) | Nonfatal and fatal stroke | Favored losartan over atenolol showing a 24.9% relative risk reduction compared with atenolol (p=0·001). | Similar reduction in BP achieved between two groups with left ventricular hypertrophy | |
| PRoFESS (130) | Telmisartan 80mg/day (10,146) | Placebo | Recurrent Stroke | No difference between telmisartan and placebo. (HR 0.95, p=0.023). | ||
LIFE Losartan Intervention for Endpoint Reduction in Hypertension. SCOPE Study on Cognition and Prognosis in the Elderly. VALUE Valsartan Antihypertensive Long-term Use Evaluation. RENAAL Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan. IDNT Irbesartan Diabetic Nephropathy Trial. MARVAL Microalbuminuria Reduction With Valsartan in Patients With Type 2 Diabetes Mellitus. IRMA 2 Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria. ELITE II Losartan Heart Failure Survival Study. VALHEFT Valsartan Heart Failure Trial. CHARM Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity). I-PRESERVE Irbesartan in Patients with Heart Failure and Preserved Ejection Fraction. VALIANT Valsartan in Acute Myocardial Infarction. OPTIMAAL (Optimal Trial in Myocardial Infarction with the Angiotensin II Antagonist Losartan). PRoFESS Prevention Regimen for Effectively Avoid Second Strokes. ONTARGET Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk.
*
Other antihypertensive medications allowed;
^
Patients allowed to use ACE inhibitors and beta blockers