When ACE inhibitors are started later after MI among individuals with LV dysfunction and continued long term, their benefits are even more robust; mortality rates have been reduced by 20% to 25% in long-term trials evaluating ACE inhibitors in these high-risk subgroups.205,206 5.3.5. Angiotensin Receptor Blockers ARBs are a useful alternative to ACE inhibitors in patients with anACEinhibitorcontraindicationorintolerance.TheVALIANT randomized patients with LV dysfunction or HF within 10 days after acute MI to additional therapy with valsartan, capto- pril, or the combination of the two. Valsartan was as effective as captopril for reducing cardiovascular events in these high- risk patients through 2 years of follow-up. However, combin- ing valsartan with captopril increased the rate of adverse events without improving survival. On the other hand, OPTIMAAL showed a trend toward increased mortality in patients receiving losartan 50 mg once daily over patients receiving captopril 50 These negative results may have been attrib- utable to inadequate dosing of losartan. In summary, because of the larger and more consistent evidence base for ACE inhibi- tors, these agents are preferred over ARBs for patients who can tolerate them, but ARBs are a first-line alternative for ACE inhibitor intolerant patients. 5.3.6. Aldosterone Antagonists Aldosterone, which is incompletely suppressed even among individuals on high doses of ACE inhibitors, is thought to con- tribute to both adverse ventricular remodeling and myocar- dial fibrosis after MI. The EPHESUS trial112 patients with MI who had an LV ejection fraction 40% and either signs of HF or diabetes mellitus. Patients were random- ized to the selective aldosterone inhibitor eplerenone or pla- cebo, initiated 3 to 14 days after MI. Eplerenone reduced total mortality by 15% and cardiovascular mortality by 17%, with a reduction in sudden cardiac death of 21%. 