Final outcome results of the multicenter isradipine diuretic atherosclerosis study (MIDAS) - A randomized controlled trial

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 SEP 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.