EFFECTS OF LONG-TERM MONOTHERAPY WITH ENALAPRIL, METOPROLOL, AND DIGOXIN ON THE PROGRESSION OF LEFT-VENTRICULAR DYSFUNCTION AND DILATION INDOGS WITH REDUCED EJECTION FRACTION

Background Recent clinical trials have suggested that therapy with ang iotensin-converting enzyme inhibitors in asymptomatic patients with re duced left ventricular (LV) function can significantly reduce the inci dence of congestive heart failure compared with patients receiving pla cebo. In the present study, we examined the effects of long-term monot herapy with enalapril, metoprolol, and digoxin on the progression of L V systolic dysfunction and LV chamber enlargement in dogs with reduced LV ejection fraction (EF). Methods and Results LV dysfunction was pro duced in 28 dogs by multiple sequential intracoronary microembolizatio ns. Embolizations were discontinued when LVEF was 30% to 40%. Three we eks after the last embolization, dogs were randomized to 3 months of o ral therapy with enalapril (10 mg twice daily, n=7), metoprolol (25 mg twice daily, n=7), digoxin (0.25 mg once daily, n=7), or no treatment (control, n=7). As expected, in untreated dogs, LVEF decreased (36+/- 1% versus 26+/-1%, P<.001) and LV end-systolic volume (ESV) and end-di astolic volume (EDV) increased during the 3-month follow-up period (39 +/-4 versus 57+/-6 mL, P<.001, and 61+/-6 versus 78+/-8 mL, P<.002, re spectively). In dogs treated with enalapril or metoprolol, LVEF remain ed unchanged or increased after therapy compared with before therapy ( 35+/-1% versus 38+/-3% and 35+/-1% versus 40+/-3%, respectively, P<.05 ), whereas ESV and EDV remained essentially unchanged. In dogs treated with digoxin, EF remained unchanged but ESV and EDV increased signifi cantly. Conclusions In dogs with reduced LVEF, long-term therapy with enalapril or metoprolol prevents the progression of LV systolic dysfun ction and LV chamber dilation. Therapy with digoxin maintains LV systo lic function but does not prevent progressive LV enlargement.