Angiotensin-receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors reduce afterload and improve cardiac output. ACE inhibitors have clear benefits when used to treat patients with chronic heart failure and high-risk acute myocar-dial infarction; this is possibly because they inhibit production of inflammatory cytokines by angiotensin II. The American College of Cardiology/American Heart Association guidelines recommend the use of ACE inhibitors over ARBs in patients with heart failure, but note that ARBs may be used in patients who cannot tolerate ACE inhibitors. Other respected medical organizations, including the Joint Commission on Accreditation of Healthcare Organizations and the Centers for Medicare and Medicaid Services, also encourage the use of ACE inhibitors in patients with ejection fractions of less than 0.40 (without making any comment about ARBs).
Lee and associates used a meta-analysis of 24 randomized, controlled studies evaluating the use of ARBs in patients with chronic heart failure and high-risk acute myocardial infarction using outcomes of all-cause mortality and heart failure hospitalization. The studies used the following ARBs: losartan (Cozaar; n = 9), candesartan (Atacand; n = 7), valsartan (Diovan; n = 5), eprosartan (Teveten; n = 1), irbesartan (Avapro; n = 1) and telmisartan (Micardis; n = 1). Follow-up periods ranged from four weeks to 41 months, with all 24 studies reporting all-cause mortality and 11 studies reporting heart failure hospitalization rates.
Studies comparing ARBs with placebo demonstrated a nonsignificant reduction in all-cause mortality and a significant decrease in heart failure hospitalizations. When ARBs and ACE inhibitor therapy were compared, no difference was found for either of the endpoints. The combination of an ARB and an ACE inhibitor reduced heart failure hospitalizations when compared with ACE inhibitor therapy alone.
Only two randomized, controlled studies of patients with high-risk myocardial infarction met the criteria for inclusion. These were the Valsartan in Acute Myocardial Infarction (VALIANT) and the Optimal Trial in Myocardial Infarction with the Angiotensin II Antagonist Losartan (OPTIMAAL) trials. These two studies compared the efficacy of ACE inhibitors versus ARBs. The results of these studies could not be pooled because of heterogeneity, but the OPTIMAAL study came close to showing the superiority of ACE inhibitors for both of the studied endpoints, whereas the VALIANT trial showed that ARBs had a nonstatistically significant advantage for both endpoints.
The authors conclude that ARBs are legitimate alternatives to ACE inhibitors for patients with congestive heart failure or high-risk acute myocardial infarction. ARBs are associated with a significant decrease in all-cause mortality in patients with chronic heart failure and a nonstatistically significant decrease in heart failure hospitalizations. No significant difference was noted when endpoints were compared in patients taking an ACE inhibitor or an ARB. Updated meta-analyses are encouraged to continually evaluate new data on ARB efficacy.