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Are Calcium Channel Blockers Safe in Diabetic Hypertension?

Am Fam Physician. 1999 Jun 1;59(11):3202.

The leading cause of death among patients with diabetes is cardiovascular disease. Many diabetic patients also have hypertension. Calcium channel blockers have been shown to be effective for treating both hypertension and ischemic heart disease, as well as for preventing renal complications in patients with diabetes. Evidence suggests, however, that the dihydropyridine class of calcium channel blockers may actually provoke myocardial infarction in patients with coronary artery disease. To evaluate this, Tuomilehto and other investigators from the Systolic Hypertension in Europe (Syst-Eur) trial performed a post-hoc analysis of their data to determine the effect of nitrendipine, a calcium channel blocker, on long-term outcomes in diabetic and nondiabetic patients with hypertension.

Patients eligible for the trial had to be at least 60 years old and have a systolic blood pressure of 160 to 219 mm Hg and a diastolic pressure of less than 95 mm Hg. Diabetic patients were included only if their blood sugar levels were under good control. The patients were randomly assigned in a double-blind fashion to receive either nitrendipine or placebo. The dosage of the study medication was titrated to attain a systolic pressure of less than 150 mm Hg. If necessary, enalapril was added as a second-line drug and hydrochlorothiazide as a third-line drug for further blood pressure control. The end points that were evaluated included stroke, acute myocardial infarction, congestive heart failure and sudden death.

A total of 4,695 patients were randomized into the study, 492 of whom had diabetes. In the diabetic patients at randomization, the mean systolic blood pressure was 175 mm Hg, and the mean diastolic pressure was 86 mm Hg. The numbers were essentially the same in the nondiabetic patients. Approximately 66 percent of all patients were women, and 7 percent were smokers. The median duration of follow-up was two years. The overall antihypertensive treatments during this time were similar for both diabetic and nondiabetic patients.

After two years, systolic and diastolic blood pressures in the diabetic patients in the active treatment and placebo groups differed by 8.6 and 3.9 mm Hg, respectively. In the nondiabetic patients, these differences were 10.3 mm Hg systolic and 4.5 mm Hg diastolic. After adjusting for age, sex, smoking status and previous history of cardiovascular complications, the researchers found that the active-treatment group of diabetic patients had a 55 percent reduction in overall mortality, a 69 percent reduction in all cardiovascular events, a 76 percent reduction in cardiovascular mortality and a 73 percent reduction in fatal and nonfatal strokes. Nondiabetic patients who received hypertensive treatment had a 26 percent reduction in all cardiovascular events and a 38 percent reduction in fatal and non-fatal strokes. Collectively, the effect of active treatment on overall mortality and mortality associated with cardiovascular events was greater in the patients with diabetes than in patients without that disease.

The authors conclude that active treatment of systolic hypertension effectively reduces cardiovascular events, mortality associated with these events, and strokes. The benefits are even greater in patients who have diabetes. Furthermore, the authors believe this study shows that calcium channel blockers are a safe and effective therapy in patients with cardiovascular disease.

Tuomilehto J, et al. Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. N Engl J Med. March 4, 1999;340:677–84.


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