Enhanced cholesterol reduction by simvastatin in diltiazem-treated patients

Aims To investigate whether an interaction between diltiazem and the 3-hydr oxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin m ay enhance the cholesterol-lowering response to simvastatin in diltiazem-tr eated patients. Methods One hundred and thirty-five patients attending tho Sheffield hypert ension clinic who started consecutively on simvastatin for primary or secon dary prevention of coronary heart disease (CHD) during the 2 years June, 19 96-May 1998 were surveyed. From the clinic records we extracted and recorde d absolute and percentage cholesterol responses to the starting dose of sim vastatin and coprescription of diltiazem. Results The cholesterol reduction for the 19 patients on diltiazem was 33.3 % compared with 24.7% in the remaining 116 patients (median difference 8.6% , 95% CI 1.1-12.2%, P<0.02). The interindividual variability of cholesterol response to simvastatin was greater for patients trot taking diltiazem tha n for those patients taking diltiazem. The ratio of the variances in respon se for the nondiltiazem group relative to the diltiazem group was 1.34 at 1 0 mg simvastatin daily (not significant, 95% CI 0.16-4.11), and 3.42 at 20 mg daily (P<0.01, 95% CI 1.26-7.18). Concurrent diltiazem therapy (P < 0.04 ), age (P = 0.001) and starting dose of simvastatin (P = 0.002) were found to be significant independent predictors of percentage cholesterol response . Conclusions Patients who take both simvastatin and diltiazem may need lower doses of simvastatin to achieve the recommended reduction in cholesterol. The pharmacokinetic and pharmacodynamic aspects of this interaction need fu rther study to confirm an enhanced effect on cholesterol reduction, and exc lude an increased risk of adverse events.