Lancet. 2000 Jul 29;356(9227):359-65. Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study. Hansson L， Hedner T， Lund-Johansen P， Kjeldsen SE， Lindholm LH， Syvertsen JO， Lanke J， de Faire U， Dahlof B， Karlberg BE. Department of Public Health and Social Sciences， University of Uppsala， Sweden.

BACKGROUND: Calcium antagonists are a first-line treatment for hypertension. The effectiveness of diltiazem， a non-dihydropyridine calcium antagonist， in reducing cardiovascular morbidity or mortality is unclear. We compared the effects of diltiazem with that of diuretics， beta-blockers， or both on cardiovascular morbidity and mortality in hypertensive patients.

METHODS: In a prospective， randomised， open， blinded endpoint study， we enrolled 10，881 patients， aged 50-74 years， at health centres in Norway and Sweden， who had diastolic blood pressure of 100 mm Hg or more. We randomly assigned patients diltiazem， or diuretics， beta-blockers， or both. The combined primary endpoint was fatal and non-fatal stroke， myocardial infarction， and other cardiovascular death. Analysis was done by intention to treat.

FINDINGS: Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups (reduction 20.3/18.7 vs 23.3/18.7 mm Hg; difference in systolic reduction p<0.001). A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group (16.6 vs 16.2 events per 1000 patient-years; relative risk 1.00 [95% CI 0.87-1.15]， p=0.97). Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group (6.4 vs 7.9 events per 1000 patient-years; 0.80 [0.65-0.99]， p=0.04) and fatal and non-fatal myocardial infarction in 183 and 157 patients (7.4 vs 6.3 events per 1000 patient-years; 1.16 [0.94-1.44]， p=0.17).

INTERPRETATION: Diltiazem was as effective as treatment based on diuretics， beta-blockers， or both in preventing the combined primary endpoint of all stroke， myocardial infarction， and other cardiovascular death.