Trial | Interventions | N | Important outcomes |
---|---|---|---|
Hypertension trials | |||
HAPPHY trial10 | Diuretic (bendrofluazide or hydrochlorothiazide) versus BB (atenolol or metoprolol) | 6569 | No difference between groups in terms of: Fatal/non-fatal CAD (10.62/1000 patient years vs 9.48/1000 patient years, respectively, OR=0.88, 95% CI 0.68 to 1.14) Fatal/non-fatal stroke (2.58/1000 patient years vs 3.35/1000 patient years, respectively, OR=1.29, 95% CI 0.82 to 2.04) All deaths (7.73/1000 patient years vs 8.25/1000 patient years, respectively, OR=1.06, 95% CI 0.80 to 1.41) |
LIFE trial14 | Atenolol versus losartan | 9193 | Primary composite end point (CV death and stroke) was significantly less (11% vs 13%, HR=0.87, 95% CI 0.77 to 0.98, p=0.021) in the losartan group Stroke (5% vs 7%, HR=0.75, 95% CI 0.63 to 0.89, p=0.001) and new-onset diabetes (6% vs 8%, HR=0.75, 95% CI 0.63 to 0.88, p=0.001) was lower in the losartan group CV mortality (4% vs 5%, HR=0.89, 95% CI 0.73 to 1.07, p=0.206), MI (4% vs 4%, HR=1.07, 95% CI 0.88 to 1.31, p=0.491) and total mortality (8% vs 9%, HR=0.90, 95% CI 0.78 to 1.03, p=0.128) did not show any significant differences between the two groups |
CAPP trial20 | Captopril versus conventional treatment (diuretic or BB or both) | 10 985 | CV mortality (0.77, p=0.092) and the incidence of type 2 diabetes was found to be lower in the captopril group (RR=0.79; p=0.007) as compared with conventional treatment group Fatal and non-fatal strokes showed a higher incidence with captopril treatment (1.25, p=0.044) Fatal and non-fatal MI had similar incidences between the two groups (0.96, p=0.68) |
INVEST trial21 | Verapamil versus atenolol | 23 000 | Verapamil-treated patients had a significantly lower incidence of new-onset diabetes versus atenolol (15% lower risk; RR=0.85, 95% CI 0.77 to 0.95) |
ASCOT-BPLA trial22 | Atenolol versus amlodipine | 19 257 | Atenolol increased CV mortality (P=0.001), all-cause mortality (p=0.025), and the development of diabetes (p<0.0001) compared with amlodipine |
AMI trials | |||
ISIS-166 | Atenolol versus control | 16 027 | Vascular mortality was significantly reduced with atenolol versus placebo at 1 year (10.7% vs 12.0%), but this did not reach significance at trial end (12.5% vs 13.4%, p=0.07). The combined end point (death, cardiac arrest or reinfarction) was significantly reduced with atenolol (p=0.0002) |
Goteborg67 | Metoprolol versus placebo | 1395 | Significant 36% reduction in mortality with metoprolol (p<0.03) |
MIAMI68 | Metoprolol versus placebo | 5778 | No significant reduction in all-cause mortality with metoprolol versus placebo (4.3% vs 4.9%, p=0.29) |
LIT69 | Metoprolol versus placebo | 2395 | Compared with placebo there was no significant reduction in all-cause mortality with metoprolol at 1 year (65 vs 62, p=non-significant) |
COMMIT trial63 | Metoprolol versus placebo | 45 852 | No statistically significant reduction in the primary composite end point of death, reinfarction or cardiac arrest (OR=0.96, 95% CI 0.90 to 1.01, p=0.10) or death alone (OR=0.99, 95% CI 0.92 to 1.05, p=0.69) Cardiogenic shock occurred in 5.0% of the patients randomised to metoprolol and 3.9% in the placebo group (OR=1.30, 1.19 to 1.41; p<0.00001) Reinfarction (2.0% vs 2.5%, OR=0.82, 95% CI 0.72 to 0.92, p=0.001) and ventricular fibrillation (2.5% vs 3.0%, OR=0.83, 95% CI 0.75 to 0.93, p=0.001) were less frequently seen in the metoprolol-treated group |
Basu et al70 | Carvedilol versus placebo | 151 | Compared with placebo, carvedilol significantly reduced cardiac events (fatal and non-fatal, 45% reduction p=0.02), ‘hard’ cardiac events (42% reduction, p<0.03) and serious cardiac events (death, reinfarction, unstable angina, CHF and ventricular tachycardia) in patients with a LVEF <45% at baseline (5 vs 13, p=0.04) |
CAPRICORN trial64 | Carvedilol or placebo | 1959 | All-cause mortality was lower in the carvedilol group compared with placebo (116 (12%) vs 151 (15%), 0.77 (0.60 to 0.98), p=0.03). Carvedilol caused a 76% reduction in arrhythmias (ventricular tachycardia and fibrillation/flutter, p<0.0001), a 52% reduction in supraventricular arrhythmias (p=0.0015) and a 26% reduction in sudden cardiac death (p=0.098) compared with placebo |
CAMIS65 | Carvedilol versus atenolol | 232 | No difference in the LVEF between the two groups and no significant reduction in the occurrence of a first serious CV event with carvedilol versus atenolol (RR=0.88, 95% CI 0.59 to 1.30, p=0.524) |
HF trials | |||
MERIT-HF trial40 | Metoprolol, placebo | 3991 | Metoprolol significantly reduced all-cause mortality by 34% (RR=0.66, 95% CI 0.53 to 0.81, p=0.00009) Increase in mortality with metoprolol versus placebo in the US geographical region (HR=1.05, 95% CI 0.71 to 1.56) |
COMET71 | Carvedilol versus metoprolol | 3029 | Compared with metoprolol, carvedilol significantly reduced all-cause mortality (17% reduction, p=0.0017), CV mortality (20% reduction, p=0.0009), sudden death (23% reduction, p=0.0073), fatal stroke (63% reduction, p=0.0027), fatal or non-fatal MI (29% reduction, p=0.03), stroke or MI (25% reduction, p=0.015), fatal MI or fatal stroke (54% reduction, p=0.0002) and death after non-fatal MI or stroke (44% reduction, p=0.0086) |
COPERNICUS trial49 50 | Carvedilol or placebo | 2289 | The annual mortality rate in the carvedilol group was reduced by 35% (12.8% vs 19.7%, p=0.00013) and risk of death or hospitalisation was reduced by 24% (p=0.00004) as compared with the placebo group Lower incidence of hospitalisations due to HF (17.1% vs 23.7%, p=0.0001), for a CV reason (21.3% vs 27.7%, p=0.0003) or for any reason (32.2% vs 38.1%, p=0.003) in the carvedilol group Reduced incidence of all adverse effects (39.0% vs 45.5%, p=0.002), HF (p<0.0001), sudden death (p=0.016), ventricular tachycardia (p=0.019) and cardiogenic shock (p=0.003) with carvedilol |
US Carvedilol HF study51 | Carvedilol, placebo | 1094 | The mortality rate in the carvedilol group was reduced by 65% (3.2% vs 7.8%, 95% CI 39% to 80%, p<0.001) The risk of hospitalisation for CV causes was reduced by 27% (14.1% vs 19.6%, p=0.036) in the carvedilol group The combined risk of hospitalisation and death was reduced by 38% (24.6% vs 15.8%, p<0.001) in the carvedilol group Greater decrease in the mean heart rate with the carvedilol group as compared with placebo (12.6±12.8 vs 1.4±12.2 bpm, p<0.001) |
Australia-New Zealand HF trial52 | Carvedilol, placebo | 415 | 5.3% increase in the LVEF (p<0.0001) and decrease in the end-diastolic and end-systolic heart dimensions by 1.7 mm (p=0.06) and 3.2 mm (p=0.001) in the carvedilol The incidence of death or hospitalisation was also lower in the carvedilol group as compared with the placebo group (104 vs 131, RR=0.74, 95% CI 0.57 to 0.95) |
CIBIS I42 | Bisoprolol versus placebo | 641 | Compared with placebo, bisoprolol significantly reduced hospitalisations for cardiac decompensation (61 vs 90, p<0.01) with significantly more patients improving by at least one NYHA functional class (68 vs 48, p=0.04). No significant reduction in mortality with bisoprolol (53 vs 67, RRR=0.80, 95% CI 0.56 to 1.15, p=0.22) |
CIBIS II43 | Bisoprolol versus placebo | 2647 | Compared with placebo, bisoprolol significantly reduced all-cause mortality (11.8% vs 17.3%, HR=0.66, 95% CI 0.54 to 0.81, p<0.0001) and sudden death (3.6% vs 6.3%, HR=0.50, 95% CI 0.39 to 0.80, p=0.0011) |
SENIORS57 | Nebivolol versus Placebo | 2128 | Compared with placebo, nebivolol significantly reduced the composite end point (all-cause mortality or CV hospital admission) (14% reduction, p=0.039) |
AMI, acute myocardial infarction; ASCOT-BPLA, Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm; BB, β-blocker; CAD, coronary artery disease; CAMIS, Carvedilol Acute Myocardial Infarction Study; CAPP, Captopril Prevention Project; CAPRICORN, Carvedilol Post Infarction Survival Control in Left Ventricular Dysfunction; CIBIS, Cardiac Insufficiency Bisoprolol Study; COMET, Carvedilol Or Metoprolol European Trial; COMMIT, Clopidogrel and Metoprolol in Myocardial Infarction Trial; COPERNICUS, Carvedilol Prospective Randomized Cumulative Survival; CV, cardiovascular; HF, heart failure; HAPPHY, Heart Attack Primary Prevention in Hypertension; INVEST, International Verapamil-Trandolapril Study; ISIS-1, First International Study of Infarct Survival; LIFE, Losartan Intervention For Endpoint Reduction; LIT, Lopressor Intervention Trial; LVEF, left ventricular ejection fraction; MERIT-HF, Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure; MIAMI, Metoprolol in Acute Myocardial Infarction; NYHA, New York Heart Association; RRR, relative risk reduction; SENIORS, Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure.