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Combined Angiotensin II Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition Further Attenuates Postinfarction Left Ventricular Remodeling

2001; Lippincott Williams & Wilkins; Volume: 103; Issue: 23 Linguagem: Inglês

10.1161/01.cir.103.23.2845

1524-4539

Sunil Mankad, Thomas A. d’Amato, Nathaniel Reichek, Walter McGregor, Jeff Chien-Fu Lin, Deepak Singh, Walter J. Rogers, Christopher M. Kramer,

Cardiac Structural Anomalies and Repair

Background —ACE inhibition (ACEI) attenuates post–myocardial infarction (MI) LV remodeling, but the effects of angiotensin II type 1 receptor (AT 1 ) antagonism alone or in combination with ACEI are unclear. Accordingly, we investigated 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 sheep 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 (hACEI; ramipril 20 mg/d, n=8), AT 1 blockade (losartan 50 mg/d, n=13), and combination therapy with sACEI+AT 1 blockade (CT; ramipril 10 mg/d+losartan 50 mg/d, n=15). MRI was performed before and 8 weeks after MI to quantify changes in LV end-diastolic and end-systolic volume indices (ΔEDVI, ΔESVI) and ejection fraction (ΔEF). Change in regional percent intramyocardial circumferential shortening in noninfarcted segments adjacent to the infarct (Adj Δ%S) was measured by tagged MRI. CT resulted in the most marked blunting of LV remodeling: ΔESVI (+1.0±0.4, +0.7±0.4, +0.6±0.3†, +0.9±0.5, and +0.4±0.2* mL/kg); ΔEDVI (+0.9±0.4, +0.7±0.5, +0.6±0.5, +0.9±0.5, and +0.4±0.3‡ mL/kg); ΔEF (−24±7, −18±6, −14±7†, −18±10, and −11±9* %); and Adj Δ%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; † P <0.05 versus control; ‡ P <0.002 versus AT 1 blockade and control). EDVI and ESVI at 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 hACEI in the present study.