Combined angiotensin II receptor antagonism and angiotensin-converting enzyme inhibition further attenuates postinfarction left ventricular remodeling

Background-ACE inhibition (ACEI) attenuates post-myocardial infarction (MI) LV remodeling, but the effects of angiotensin II type 1 receptor (AT(1)) a ntagonism alone or in combination with ACEI are unclear. Accordingly, we in vestigated the effects of AT(1) antagonism, ACEI, and their combination in a well-characterized ovine postinfarction model. Methods and Results-Beginning 2 days after transmural anteroapical MI, 62 s heep were treated with 1 of 5 treatment regimens: no therapy (control, n=12 ), standard-dose ACEI (sACEI; ramipril 10 mg/d, n=14), high-dose ACEI (hACE I; ramipril 20 mg/d, n=8), AT(1) blockade (losartan 50 mg/d, n=13), and com bination therapy with sACEI+AT, blockade (CT; ramipril 10 mg/d+losartan 50 mg/d, n=15). MRI was performed before and 8 weeks after MI to quantify chan ges in LV end-diastolic and end-systolic volume indices (Delta EDVI, Delta ESVI) and ejection fraction (Delta EF). Change in regional percent intramyo cardial circumferential shortening in noninfarcted segments adjacent to the infarct (Adj Delta %S) was measured by tagged MRI. CT resulted in the most marked blunting of LV remodeling: Delta ESVI (+1.0 +/-0.4, +0.7 +/-0.4, +0 .6 +/-0.3 dagger, +0.9 +/-0.5, and +0.4 +/-0.2* mL/kg); Delta EDVI (+0.9 +/ -0.4, +0.7 +/-0.5, +0.6 +/-0.5, +0.9 +/-0.5, and +0.4 +/-0.3 double dagger mL/kg); Delta EF (-24 +/-7, -18 +/-6, -14 +/-7 dagger, -18 +/- 10, and -11 +/-9* %); and Adj Delta %S (-8 +/-4, -7 +/-3, -5 +/-3, -5 +/-3, and -2 +/-3 * %) for Control, sACEI, hACEI, AT(1) blockade, and CT, respectively (*P <0 .04 versus sACEI, AT(1) blockade, and control; daggerP <0.05 versus control ; double daggerP <0.002 versus AT(1) blockade and control). EDVI and ESVI a t 8 weeks after MI were smallest with CT (P <0.02 versus all). Conclusions-Combination therapy with sACEI+AT(1) blockade shows promise in attenuating postinfarction LV remodeling but was not clearly superior to hA CEI in the present study.