A Comparison of Antihypertensive Drug Effects on the Progression of Extracranial Carotid Atherosclerosis

Summary

Hypertension is a major risk factor for coronary heart disease (CHD) and is the primary risk factor for stroke. Drug trials lowering blood pressure by pharmacological means have demonstrated impressive reduction in both fatal and nonfatal stroke (33 to 50%) that are virtually identical to the predicted stroke reduction, considering the observed diastolic blood pressure change (5 to 6mm Hg). On the other hand, reduction of CHD risk has been less impressive in these same trials. Although statistically significant, the reduction in CHD risk is roughly one-half (14%) of that predicted (25%) when results from these drug trials are analysed in aggregate. Most trials have used moderate to high dosages of thiazide diuretics or β-blockers as therapies. Several factors may account for the disappointing results in CHD risk reduction. These drugs may induce metabolic disturbances in lipids, increased glucose tolerance, insulin resistance, or cause inadequate regression of left ventricular hypertrophy, thus attenuating the predicted reduction in CHD risk associated with pharmacological blood pressure lowering.

Isradipine is a new dihydropyridine calcium antagonist that is highly effective in lowering blood pressure. Isradipine also has antiatherogenic properties in animal models of atherosclerosis. The effect of isradipine on atherosclerosis in humans is unknown. The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) is a 3-year double-blind, randomised trial in over 800 men and women with hypertension, aged 40 years or older. The primary aim of MIDAS is to compare the efficacy of isradipine 2.5 to 5.0mg twice daily vs hydrochlorothiazide 12.5 to 25mg twice daily in retarding the progression of extracranial carotid atherosclerosis.

A sample of 883 men and women with hypertension and with demonstrated carotid plaque have been recruited and will be observed for at least 3 years. Participants are randomised into 2 parallel groups receiving either isradipine or hydrochlorothiazide. The primary end-point is intimai thickness and extent of plaque in the carotid arteries as measured by B-mode ultrasonography.