CURRENT STATUS OF COMBINATION THERAPY IN OTHER CARDIOVASCULAR-DISEASES

As in hypertension, the addition of a second active drug is believed t o enhance treatment efficacy; however, the extent to which a combinati on of two low-dose drugs outperforms conventional monotherapy remains uncertain. Established treatments of angina comprises nitrates compoun ds, beta-blockers and calcium antagonists, which are often given in co mbination. Beta-blockers are major players in this field as they inhib it the tachycardia induced by nitrates and calcium antagonists; there is therefore a pathophysiological justification for their use in combi nation therapy, supported by repeated confirmation of positive clinica l effect. The most widely chosen calcium antagonists are dihydropyridi nes; verapamil may impair conduction. However, it is not clear whether combination enhances the effects of the individual antianginal substa nces.Diuretics are for most clinicians the keystone treatment of heart failure; diuretics are often combined with other drugs, e.g. amilorid e and spironolactone. The latter also have a beneficial effect on myoc ardial structure (myocardium/collagen ratio). ACE-inhibitors are of pr oven clinical efficacy, and, in addition, have a beneficial effect on survival. They combine well with diuretics: because the diuretic stimu lates renin release, the ACE-inhibitor can be given at a lower dose (e nhancement of effect). There are, however, certain drawbacks (hypotens ion, hyperkalemia with antialdosterones). The results of combining ACE -inhibitors with calcium antagonists and beta-blockers await investiga tion. The ISIS studies demonstrated the advantages of combining beta-b lockers, thrombolysis and aspirin in acute infarction. ACE-inhibitors have recently been added to the regimen with a positive effect (extend ed survival), especially in the presence of a decreased ejection fract ion (SAVE, AIRE, GISSI 3 and ISIS 4 studies). However, as in angina, a n enhancement effect has not yet been conclusively demonstrated. To pr ove this last point, studies are mandatory, but they will be difficult , costly and require a large number of patients.