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

Lancet. 2000 Jul 29;356(9227):359-65. doi: 10.1016/s0140-6736(00)02526-5.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Aged
  • Antihypertensive Agents / therapeutic use*
  • Calcium Channel Blockers / therapeutic use*
  • Cardiovascular Diseases / mortality*
  • Cardiovascular Diseases / prevention & control*
  • Diltiazem / therapeutic use
  • Diuretics / therapeutic use*
  • Female
  • Humans
  • Hypertension / complications*
  • Hypertension / drug therapy*
  • Life Tables
  • Male
  • Middle Aged
  • Myocardial Infarction / mortality
  • Myocardial Infarction / prevention & control
  • Prospective Studies
  • Risk Factors
  • Single-Blind Method
  • Stroke / mortality
  • Stroke / prevention & control


  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Diuretics
  • Diltiazem