Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial

JAMA. 1996 Sep 11;276(10):785-91.


Objective: To compare the rate of progression of mean maximum intimal-medial thickness (IMT) in carotid arteries, using quantitative B-mode ultrasound imaging, during antihypertensive therapy with isradipine vs hydrochlorothiazide.

Design: Randomized, double-blind, positive-controlled trial.

Setting: Nine medical center clinics.

Population: A total of 883 patients with baseline mean +/- SD systolic and diastolic blood pressure (SBP and DBP, respectively) of 149.7 +/- 16.6 and 96.5 +/- 5.1 mm Hg, age of 58.5 +/- 8.5 years, and maximum IMT of 1.17 +/- 0.20 mm.

Interventions: Twice daily doses of isradipine (2.5-5.0 mg) or hydrochlorothiazide (12.5-25 mg). MAIN OUTCOME MEASURE (PRIMARY END POINT): Rate of progression of mean maximum IMT in 12 carotid focal points over 3 years.

Results: There was no difference in the rate of progression of mean maximum IMT between isradipine and hydrochlorothiazide over 3 years (P=.68). There was a higher incidence of major vascular events (eg, myocardial infarction, stroke, congestive heart failure, angina, and sudden death) in isradipine (n=25; 5.65%) vs hydrochlorothiazide (n=14; 3.17%) (P=.07), and a significant increase in nonmajor vascular events and procedures (eg, transient ischemic attack, dysrhythmia, aortic valve replacement, and femoral popliteal bypass graft) in isradipine (n=40; 9.05%) vs hydrochlorothiazide (n=23; 5.22%) (P=.02). At 6 months, mean DBP decreased by 13.0 mm Hg in both groups, and mean SBP decreased by 19.5 mm Hg in hydrochlorothiazide and 16.0 mm Hg in isradipine (P=.002); the difference in SBP between the 2 groups persisted throughout the study but did not explain the increased incidence of vascular events in patients treated with isradipine.

Conclusion: The rate of progression of mean maximum IMT in carotid arteries, the surrogate end point in this study, did not differ between the 2 treatment groups. The increased incidence of vascular events in patients receiving isradipine compared with hydrochlorothiazide is of concern and should be studied further.

Publication types

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

MeSH terms

  • Aged
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Arteriosclerosis / diagnostic imaging
  • Arteriosclerosis / drug therapy*
  • Arteriosclerosis / pathology
  • Carotid Arteries / diagnostic imaging
  • Carotid Arteries / pathology*
  • Diastole
  • Disease Progression
  • Diuretics
  • Double-Blind Method
  • Enalapril / therapeutic use
  • Female
  • Humans
  • Hydrochlorothiazide / adverse effects
  • Hydrochlorothiazide / therapeutic use*
  • Isradipine / adverse effects
  • Isradipine / therapeutic use*
  • Likelihood Functions
  • Male
  • Middle Aged
  • Regression Analysis
  • Sodium Chloride Symporter Inhibitors / adverse effects
  • Sodium Chloride Symporter Inhibitors / therapeutic use*
  • Systole
  • Treatment Outcome
  • Tunica Intima / diagnostic imaging
  • Tunica Intima / pathology*
  • Ultrasonography
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / therapeutic use*


  • Antihypertensive Agents
  • Diuretics
  • Sodium Chloride Symporter Inhibitors
  • Vasodilator Agents
  • Hydrochlorothiazide
  • Enalapril
  • Isradipine