ANGIOTENSIN-CONVERTING ENZYME-INHIBITION DURING THROMBOLYTIC THERAPY IN ACUTE MYOCARDIAL-INFARCTION - THE CAPTOPRIL AND THROMBOLYSIS STUDY

The adjunctive use of angiotensin-converting enzyme (ACE) inhibitors with thrombolytic therapy early during acute myocardial infarction offers theoretic advantages. In the acute phase, captopril may scavenge free radicals, blunt the catecholamine response, elicit coronary vasodilation, and increase prostacyclin and bradykinin levels. In the chronic phase, remodeling may be attenuated. At present, a large number of controlled clinical trials mainly focusing on the effects of ACE inhibition in the chronic phase is underway. Only a few studies concentrate on the effect of acute intervention with ACE inhibitors in ischemia-reperfusion, i.e., thrombolysis in myocardial infarction. In the Captopril and Thrombolysis pilot Study (CAT pilot study), 3 and 6.25 mg of captopril was well tolerated as adjunctive therapy to intravenous streptokinase. The decrease in mean arterial blood pressure (36 +/- 11%) after 6.25 mg was comparable to the control group (30 +/- 7%). Furthermore, norepinephrine levels decreased dose dependently to 47 +/- 6 and 38 +/- 7% from baseline, respectively. These results prompted a large nationwide acute intervention trial with captopril in 300 patients receiving thrombolytic therapy: the Captopril and Thrombolysis Study (CATS). The primary hypothesis of CATS supposes a very early effect of converting enzyme inhibition on evolving myocardial damage due to ischemia and the consequences of early reperfusion. This will be evaluated by serial echocardiography, Holter monitoring, and neurohumoral measurements immediately upon thrombolysis and during the first year after myocardial infarction. Blinded data show a favorable blood pressure response, with systolic hypotension <100 mm Hg occurring in only 0.8% of patients.