Lancet. 2000 Jul 29;356(9227):366-72. Brown MJ， Palmer CR， Castaigne A， de Leeuw PW， Mancia G， Rosenthal T， Ruilope LM. Clinical Pharmacology Unit， University of Cambridge， UK. morris.brown@cai.cam.ac.uk

BACKGROUND: The efficacy of antihypertensive drugs newer than diuretics and beta-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 > or = 150/95 mm Hg， or > 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 mg [corrected] 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.