Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT)

Background The efficacy of antihypertensive drugs newer than diuretics and β-blockers has not been established. We compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in high risk patients with hypertension. Methods We did a prospective, randomised, double-blind trial in Europe and Israel in 6321 patients aged 55–80 years with hypertension (blood pressure ≥150/95 mm Hg, or ≥160 mm Hg systolic). Patients had at least one additional cardiovascular risk factor. We randomly assigned patients nifedipine 30 mg in a long-acting gastrointestinal-transport-system (GITS) formulation (n=3157), or co-amilozide (hydrochlorothiazide 25 μg plus amiloride 2·5 mg; n=3164). Dose titration was by dose doubling, and addition of atenolol 25–50 mg or enalapril 5–10 mg. The primary outcome was cardiovascular death, myocardial infarction, heart failure, or stroke. Analysis was done by intention to treat. Findings Primary outcomes occurred in 200 (6·3%) patients in the nifedipine group and in 182 (5·8%) in the co-amilozide group (18·2 vs 16·5 events per 1000 patient-years; relative risk 1·10 [95% CI 0·91–1·34], p=0·35). Overall mean blood pressure fell from 173/99 mm Hg (SD 14/8) to 138/82 mm Hg (12/7). There was an 8% excess of withdrawals from the nifedipine group because of peripheral oedema (725 vs 518, p<0·0001), but serious adverse events were more frequent in the co-amilozide group (880 vs 796, p=0·02). Deaths were mainly non-vascular (nifedipine 176 vs co-amilozide 172; p=0·81). 80% of the primary events occurred in patients receiving randomised treatment (157 nifedipine, 147 co-amilozide, difference 0·33% [−0·7 to 1·4]). Interpretation Nifedipine once daily and co-amilozide were equally effective in preventing overall cardiovascular or cerebrovascular complications. The choice of drug can be decided by tolerability and blood-pressure response rather than long-term safety or efficacy.