Table 2.
Outcome trials using calcium channel blockers
| Study | Design/drug | Patient population | Key result |
|---|---|---|---|
| ACCOMPLISH (2008) [48•] | Double-blind, randomized trial. Benazepril + amlodipine or benazepril + hydrochlorothiazide. Mean follow-up 36 months. | 11,506 patients with hypertension at high risk of CV events. | Compared with benazepril + hydrochlorothiazide, fewer individuals on benazepril + amlodipine had a primary endpoint (death from CV causes, nonfatal MI, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization) HR, 0.80; 95 % CI, 0.72 to 0.90; P < 0.001. For the secondary endpoint of death from CV causes, nonfatal MI, and nonfatal stroke, HR 0.79; 95 % CI, 0.67 to 0.92; P = 0.002. |
| ASCOT-BPLA (2005) [47•] | Open-label, randomized trial. Amlodipine ± perindopril-based regimen or atenolol ± bendroflumethiazide-based regimen. Mean 5.5 year follow-up. | 19,257 patients with hypertension and ≥3 additional CV risk factors. | Compared with the atenolol-based regimen, fewer individuals on the amlodipine-based regimen had a primary endpoint (nonfatal MI and fatal CHD) HR, 0.90; 95 % CI, 0.79 to 1.02; P = 0.1052; fatal and nonfatal stroke, HR, 0.77; 95 % CI, 0.66 to 0.89; P = 0.0003; total CV events and procedures, HR, 0.84; 95 % CI, 0.78 to 0.90; P < 0.0001; all-cause mortality, HR, 0.89; 95 % CI, 0.81 to 0.99; P = 0.025. |
| CAMELOT (2004) [46] | Double-blind, placebo-controlled, randomized trial. Amlodipine, enalapril, or placebo. 24 month follow-up. | 1,991 patients with CAD and DBP <100 mm Hg. | Compared with placebo, there was a 31 % reduction in CV events in the amlodipine group (P = 0.003) and a 15 % reduction in the enalapril group (P = 0.16). In the amlodipine group, IVUS showed evidence of slowing atherosclerosis progression. |
| VALUE (2004)[45] | Double-blind, parallel-group, randomized trial. Valsartan or amlodipine. Mean follow-up 4.2 years. | 15,245 patients with hypertension at high risk of cardiac events. | No difference in the primary outcome (cardiac mortality and morbidity) between treatment groups, HR 1.04; 95 % CI, 0.94 to 1.15; P = 0.49. BP reduced by both treatments, but amlodipine had greater effect especially in the early period. Amlodipine was superior to valsartan at preventing MI and angina. |
| INVEST (2003)[44] | Open-label, blinded endpoint, randomized trial. Verapamil or atenolol. Mean follow-up 2.7 years. | 22,576 patients with hypertension and CAD. | No difference in the primary outcome (first occurrence of all-cause mortality, nonfatal MI or nonfatal stroke) between treatment groups, RR 0.98; 95 % CI 0.90-1.06. |
| CONVINCE (2003)[43] | Double-blind, randomized trial. Verapamil versus atenolol or hydrochlorothiazide. Mean follow-up 3 years. | 16,602 patients with hypertension and ≥1 additional CV risk factor. | No difference in the primary outcome (first occurrence of stroke, MI, or CV-related death) between treatment groups, HR 1.02; 95 % CI, 0.88 to 1.18; P = 0.77. |
| ALLHAT (2002)[42] | Double-blind, randomized trial. 3 treatment groups: chlorthalidone; amlodipine; lisinopril. Mean follow-up 4.9 years. | 33,357 patients with hypertension and ≥1 additional CHD risk factor. | No difference in the primary outcome (fatal CHD or nonfatal MI) between treatment groups. Compared with chlorthalidone: RR for amlodipine 0.98; 95 % CI, 0.90 to 1.07; lisinopril 0.99; 95 % CI, 0.91 to 1.08. |
| NORDIL (2000)[40] | Open-label, blinded endpoint, randomized trial. Diltiazem or diuretics ± beta-blockers. Mean follow-up 4.5 years. | 10,881 patients with DBP ≥100 mm Hg. | No difference in the primary outcome (fatal and non-fatal stroke, MI, CV death) between the 2 groups, RR 1.00; 95 % CI, 0.87 to 1.15; P = 0.97. |
| INSIGHT (2000)[39] | Double-blind, randomized trial. Nifedipine or co-amilozide. Follow-up 3 years after recruitment of the last patient. | 6,321 patients with hypertension and ≥1 additional CV risk factor. | No difference in the primary outcome (CV death, MI, heart failure, or stroke) between the 2 groups, RR, 1.10; 95 % CI, 0.91 to 1.34; P = 0.35. |
| PREVENT (2000) [41] | Double-blind, placebo-controlled, randomized trial. Amlodipine or placebo. 36-month follow-up. | 825 patients with CAD. | No difference in coronary stenosis between the amlodipine and placebo group. Amlodipine slowed the progression of carotid artery atherosclerosis (IMT: amlodipine −0.0126 versus placebo +0.033; P = 0.007) and was associated with fewer hospitalizations for unstable angina and coronary revascularization. |
| SYST-EUR (1997) [38] | Double-blind, placebo-controlled, randomized trial. Nitrendipine or placebo. Median follow-up 2 years. | 4695 patients with isolated systolic hypertension (SBP ≥160 mmHg and DBP <95 mmHg). | Compared with placebo, nitrendipine reduced the total rate of stroke by 42 % (P = 0.003); nonfatal stroke by 44 % (P = 0.007) and all fatal and nonfatal cardiac events by 26 % (P = 0.03). |
| MIDAS (1996) [37] | Double-blind, randomized trial. Isradipine or hydrochlorothiazide. 3 year follow-up. | 883 patients with hypertension | No difference in the rate of progression of mean maximum IMT (P = 0.68) between treatment groups. Higher (but non-significant, P = 0.07) incidence of major vascular events (MI, stroke, heart failure, angina, sudden death) in the isradipine versus the hydrochlorothiazide group (25 vs 14 events). |
ACCOMPLISH Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension study; ASCOT-BPLA Anglo-Scandinavian Cardiac Outcomes Trial – Blood Pressure Lowering Arm; CAMELOT Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis study; VALUE, Valsartan Antihypertensive Long-term Use Evaluation; INVEST, The International Verapamil-Trandolapril Study; CONVINCE, Controlled Onset Verapamil Investigation of Cardiovascular End Points; ALLHAT, The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; NORDIL, the Nordic Diltiazem study; INSIGHT, Intervention as a Goal in Hypertension Treatment; PREVENT Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial; SYS-EUR, Systolic Hypertension in Europe; MIDAS, Multicenter Isradipine Diuretic Atherosclerosis Study.
CAD coronary artery disease; CHD coronary heart disease; CI confidence interval; CV cardiovascular; DBP diastolic blood pressure; HR hazard ratio; IMT intimal-media thickness; IVUS intravascular ultrasound; MI myocardial infarction; SBP, systolic blood pressure