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The associations of a history of hypertension with subsequent outcomes after acute myocardial infarction have not been examined in propensity-matched studies. Of the 6,632 patients with acute myocardial infarctions and left ventricular systolic dysfunction in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), 4,407 had histories of hypertension. Propensity scores for a history of hypertension, estimated for each patient using 64 baseline characteristics, were used to match 1,990 pairs of patients with and without hypertension. Matched Cox regression models were used to estimate associations between hypertension and outcomes during a mean of 16 months of follow-up. Heart failure (HF) hospitalization occurred in 11.9% and 8.8% of patients, respectively, with and without hypertension (hazard ratio [HR] for hypertension vs no hypertension 1.36, 95% confidence interval [CI] 1.10 to 1.68, p = 0.004). The association between a history of hypertension and HF hospitalization was significant only in patients without previous HF (n = 3,495, HR 1.48, 95% CI 1.18 to 1.84, p = 0.001), but not in those with previous HF (n = 485, HR 1.09, 95% CI 0.73 to 1.62, p = 0.688, p for interaction = 0.179). A history of hypertension was not associated with all-cause mortality (HR 1.02, 95% CI 0.86 to 1.22, p = 0.790) or cardiovascular hospitalization (HR 1.08, 95% CI 0.92 to 1.27, p = 0.339). In conclusion, a history of hypertension was associated with subsequent HF hospitalization after acute myocardial infarction, especially in patients without histories of HF, suggesting that hypertension increased the risk for hospitalization with incident HF but did not affect hospitalization for worsening HF symptoms in those with prevalent HF. [Copyright &y& Elsevier]

Post hoc analyses of the Digitalis Investigation Group (DIG) trial indicate that digoxin at low (0.5 to 0.9 ng/ml) serum digoxin concentration (SDC) reduces mortality, which is eliminated at higher (≥1 ng/ml) SDC, and that low-dose digoxin (≤0.125 mg/day) predicts low SDC. In the DIG trial, patients with ambulatory chronic systolic and diastolic heart failure (HF) (n = 7,788) in normal sinus rhythm receiving angiotensin-converting enzyme inhibitors and diuretics were randomized to receive placebo (n = 3,899) or digoxin (n = 3,889). The median dose of digoxin (0.25 mg/day) and the target SDC (0.8 to 2.5 ng/ml) were higher than what are currently recommended, which in part may explain the lack of long-term mortality benefit of digoxin in the DIG trial. To test this hypothesis, we examined the effect of digoxin on short-term outcomes; 1-year all-cause mortality occurred in 392 and 448 patients respectively in the digoxin and placebo groups (hazard ratio for digoxin 0.87, 95% confidence interval [CI] 0.76 to 0.995, p = 0.043). Respective hazard ratios for cardiovascular and HF deaths were 0.87 (95% CI 0.76 to 1.01, p = 0.072) and 0.66 (95% CI 0.52 to 0.85, p = 0.001). All-cause hospitalization occurred in 1,411 and 1,529 patients receiving digoxin and placebo respectively (hazard ratio 0.89, 95% CI 0.83 to 0.96, p = 0.002). Respective hazard ratios for cardiovascular and HF hospitalizations were 0.82 (95% CI 0.75 to 0.89, p <0.0001) and 0.59 (95% CI 0.52 to 0.66, p <0.0001). In conclusion, digoxin reduced 1-year mortality and hospitalization in patients with chronic HF receiving angiotensin-converting enzyme inhibitors and diuretics. Randomized clinical trials are needed to determine the effect of low-dose digoxin in contemporary patients with chronic HF. [Copyright &y& Elsevier]

Heart failure continues to significantly impact morbidity and mortality after acute myocardial infarction (AMI), especially when associated with left ventricular systolic dysfunction (LVSD). Therefore, routine use of optimal therapy for patients with heart failure after AMI is needed in the future. Data from the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) has demonstrated that addition of eplerenone to standard therapy in patients with LVSD and clinical heart failure post-AMI significantly improves outcomes in these patients, providing the basis for acceptance of aldosterone blockade as an integral component of therapy. However, further studies are needed to more broadly explore the usefulness of aldosterone blockade in heart failure therapy. As research clarifies the many complex pathophysiologic processes involved in post-AMI remodeling, treatment should continue to move beyond symptom-targeted therapies to disease- and mechanism-targeted therapies that will further improve outcomes in the setting of heart failure post-AMI and beyond. [Copyright &y& Elsevier]