Therapeutic Approaches. Cardiovascular risk factor reduction is advocated in patients with ALVD to decrease the risk of developing overt HF. Control of blood pressure and treatments that slow the progression of ischemic heart disease may have substantial benefit. (See Section 3 for more on the control of cardiovascular risk factors.)

A twelve-year follow up in SOLVD demonstrated that the initial benefit of enalapril was maintained.10 Survival curve analysis has confirmed an absolute 9.2-month benefit in life expectancy conferred by 40 months of treatment with an ACE inhibitor, a benefit conferred despite the fact that nearly all patients enrolled in SOLVD went on to receive ACE inhibitors after termination of the randomized portion of the trial. The likelihood of death after 12 years in the treatment group remained fairly constant at approximately 5% annually.

A substudy of the SOLVD trial found that administration of enalapril reduced the tendency to progressive LV enlargement in patients with ALVD.22 This beneficial effect on LV remodeling, in combination with prevention of MI, most likely explains the mechanism of reduction of both cardiovascular mortality and progression to HF observed in the SOLVD Prevention trial.23-25 Thus ACE inhibitors are indicated in patients with reduced LVEF, regardless of symptoms.

Randomized clinical trials of ARBs in asymptomatic patients with LV systolic dysfunction who are intolerant of ACE inhibitors have not been conducted. Despite the absence of definitive data, based on the results of the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM)-Alternative and the Valsartan Heart Failure Trial (Val-HeFT) and a variety of pathophysiologic and clinical considerations, it is reasonable to use an ARB in a patient with ALVD if the patient is intolerant to an ACE inhibitor.26,27 The addition of an ARB to an ACE inhibitor in asymptomatic patients with reduced LVEF has not been investigated.

Ischemic Heart Disease With ALVD. A strong rationale exists for the use of beta blocker therapy in the management of patients with ALVD from ischemic heart disease, based on the benefits seen in patients with cardiac dysfunction and no overt HF after acute MI. The Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) study examined the effects of carvedilol in asymptomatic patients with reduced LVEF after MI, with concomitant use of ACE inhibitors, aspirin, and statins in the majority of patients. Although there was no difference between the carvedilol and placebo groups in the number of patients meeting the primary endpoint of all-cause mortality or hospital admission, carvedilol use was associated with fewer deaths, as well as a reduction in the combined endpoint of death or recurrent MI, classical end points in previous studies of beta blockade after MI.28

Beta blockade has been shown to attenuate LV remodeling in patients with ALVD. The Reversal of Ventricular Remodeling with Toprol-XL (REVERT) Trial randomized 149 patients to metoprolol succinate 50 mg, 200 mg, or placebo for 12 months. LV end-systolic volume, end-diastolic volume, and LVEF were measured at baseline and 6 and 12 months. Patients randomized to metoprolol succinate 200 mg had a significant decrease in LV end-systolic volume index and a significant increase in LVEF as compared to baseline and placebo at 12 months.29 Approximately half of the patients in REVERT had a non-ischemic HF etiology.

Nonischemic Heart Disease With ALVD. No trial has specifically examined the effect of beta blockers on mortality in asymptomatic patients with reduced LVEF but no recent MI. Given the consistency of benefit observed with beta blockers across symptomatic populations, with and without ischemic heart disease, and in patients with prior MI, regardless of HF symptoms, it is reasonable to recommend use of these agents in asymptomatic patients with reduced LVEF in the absence of identifiable ischemic heart disease. See more about beta blockers in Section 7.

Aldosterone Antagonists in Patients With ALVD. Although aldosterone antagonists have been demonstrated to decrease morbidity and mortality in patients with moderate to severe symptoms of HF and reduced LVEF, there are currently no substantial data to suggest that these agents should be recommended as treatment for patients with ALVD. Studies are ongoing to determine the potential of aldosterone antagonists to impact the process of remodeling.