Isradipine in Prediabetic Hypertensive Subjects

OBJECTIVE Investigators from the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) previously reported that the isradipine group had a higher incidence of cardiovascular disease (CVD) events than the diuretic group. The ultimate objective of the analyses presented here was to assess how indices of glycemia (specifically, serum glucose, serum insulin, and HbA_lc)might have influenced the effects of the two agents on blood pressure control and CVD events.

RESEARCH DESIGN AND METHODS Inclusion criteria included men and women ≥40 years of age with ultrasonographically confirmed carotid atherosclerosis and a diastolic blood pressure of >90 mmHg. Although insulin-dependent diabetic patients were excluded, the three glycemia indices had wide enough ranges to include patients who may be classified as prediabetic. A total of 883 patients were randomized either to the dihydropyridine calcium antagonist (CA) isradipine (2.5–5 mg twice a day) or to the diuretic hydrochlorothiazide (12.5–25 mg twice a day) and followed in double-blind fashion for 3 years.

RESULTS Both treatment groups had achieved comparable control of diastolic blood pressure, and there were no statistically significant differences in any of the glycemia indices, either at baseline or during follow-up. However, the excess isradipine events were noted to be clustered among those patients with elevated baseline levels of HbA_1c who also experienced greater blood pressure reductions during follow-up.

CONCLUSIONS The increased cardiovascular risk associated with dihydropyridine CAs in prediabetic patients may be an explanation for the overall CA debate.