Does the combination of an ace inhibitor and a calcium antagonist enhance cardioprotection?

Abstract

The combination of compounds with different modes of action, especially of ACE inhibitors and Ca’ antagonists, is gaining increasing importance in recent years in the treatment of hypertensive patients [1], as both efficacy and responder rates are enhanced. Modern therapy of hypertension, however, does not only require effective and safe control of elevated blood pressure, but additional cardiovascular and renal protection is mandatory for optimal treatment. In many experimental models it was shown that phenylalkylamine Ca’ antagonists like verapamil protect the heart against ischemia-induced myocardial damage [2]. This positive effect of verapamil has also been confirmed recently by clinical trials, DAVIT II [3] showing verapamil’s potential in secondary prevention, as well as in VAS [4], in which the patients receiving verapamil experienced significantly less late reocclusion after PTCA than the group under standard therapy. ACE inhibitors are the agents most able to induce regression of hypertension-induced left ventricular hypertrophy, as was shown in experimental [5] and clinical trials [6]. In addition, trandolapril[7]has been shown to positively influence ventricular remodelling in rats with healed myocardial infarction, as did captopril in an earlier study [8]. Clinical studies in post-MI patients confirmed this positive effect of trandolapril in humans as well (TRACE [9]). Experiments were therefore designed to test 1) if a combination of verapamil plus trandolapril was more potent in certain aspects of cardioprotection than either monotherapy, and 2) if a combination of subthreshold doses of the two substances would lead to a potentiation of some cardioprotective effects.