Nifedipine and diltiazem combine well with propranolol against angina But diltiazem + propranolol may have negative electrophysiological effects

There are significant differences between calcium antagonists in their effects on the cardiovascular system, and so diltiazem and nifedipine were compared when added to propranolol therapy in 12 patients with chronic stable angina Patients received propranolol 40 or 80mg tid, sufficient for beta blockade, underwent exercise and ECG tests, and then were randomised to nifedipine 10 or 20mg tid or diltiazem 60 or 120mg tid for 2-week double-blind crossover periods.

Maximal exercise time Increased significantly with both nifedipine and diltiazem (vs propranolol monotherapy), whereas time to onset of angina was significantly increased by addition of diltiazem but not with nifedipine. Systolic BP and rate pressure products were comparable with all regimens. Peak exercise HR was decreased with addition of diltiazem but unchanged with nifedipine. Minimal and maximal HR were lower with diltiazem combination therapy than other regimens, and AV conduction time was reduced, though this did not reach significance. Time to 1 mm of ST segment depression was increased significantly with both agents and maximal ST segment depression was decreased significantly with diltiazem but not nifedipine (vs propranolol monotherapy). There were nonsignificant decreases in the number and duration of ST segment depressions with both agents. One-hour serum propranolol levels were unchanged by nifedipine but were significantly increased (vs nifedipine combination therapy) with diltiazem.

The authors concluded that both nifedipine and diltiazem are effective in combination with propranolol as antianginal therapy, but with ' ... the possibility of an additive negative e/ectrophysiologic interaction when diltiazem and a ,8-blocker are administered together' and a possible biochemical effect of diltiazem on serum propranolol levels. Robinson K. K"kler S. K"kler DM Comparallve sludy of the effect of mfedlpine versus dlltlazem on exerCise performance. serum propranolol levels and ST·segment abnormalities in patients With chronic stable angina taking propranolol. Ame"can Journal of Cardiology 64: 27F·30F. 19 Sep 1989 ".,

0156-2703/89/1111-0007/0$01.00/0 © ADIS Press INPHARMA ' 11 Nov 1989 7