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Aims: It is unknown whether there is an interaction between aspirin and angiotensin receptor blockers on outcomes in patients with heart failure (HF). [ABSTRACT FROM PUBLISHER]

Abstract: Background: The efficacy and safety of adding an angiotensin receptor blocker (ARB) in heart failure (HF) patients already taking an angiotensin-converting enzyme-inhibitor (ACE-I) plus an aldosterone antagonist is uncertain (especially if taking a beta blocker as well). The CHARM-Added trial describes the largest experience of using multiple inhibitors of the renin–angiotensin–aldosterone system (RAAS) together. Methods and results: 2548 HF patients, taking an ACE-I (936 no spironolactone/no beta blocker; 1175 no spironolactone/beta blocker; 199 spironolactone/no beta blocker; 238 sprionolactone/beta blocker), were randomized to placebo or candesartan and followed for 41 months (median). The primary outcome was cardiovascular death or HF hospitalization. In patients taking both a beta blocker and spironolactone (in addition to an ACE-I) at baseline, the candesartan:placebo hazard ratio was 0.85(95% CI 0.56, 1.29), compared to 0.85(95% CI 0.75, 0.96) in all randomized patients (interaction p value 0.49). The relative risk of discontinuation of candesartan (compared to placebo) because of hypotension, increased serum creatinine or hyperkalemia was not increased in patients taking spironolactone at baseline. Conclusions: An ARB may provide added benefit, at acceptable risk, in HF patients already taking spironolactone as well as an ACE-I and beta blocker. These findings must be confirmed in a prospective randomized trial before this approach can be recommended, routinely. [Copyright &y& Elsevier]

Abstract: Background: Bundle branch block (BBB) is a powerful independent predictor of cardiovascular mortality in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). The prognostic implications in HF with preserved systolic function (HF–PSF) are less well understood. Methods: The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme randomised 7599 patients with symptomatic HF to receive candesartan or placebo. The primary outcome comprised cardiovascular death or HF hospitalisation. The relative risk conveyed by BBB relative to a normal electrocardiogram was examined. Results: The prevalence of BBB was significantly lower in patients with preserved compared with reduced systolic function (CHARM-Preserved 14.4%, Alternative 29.6%, Added 30.5%), p <0.0001. Overall, the adjusted hazard ratio for the primary outcome was 1.48 (95% confidence interval 1.22–1.78), p <0.0001, reflecting increased risk in patients with reduced LVEF (1.72 [1.28–2.31], p =0.0003). The apparently more modest risk among patients with HF–PSF was significant in unadjusted (1.80 [1.37–2.37], p <0.0001) but not adjusted analysis (1.16 [0.88–1.54], p =0.2897). However, no formal statistical difference was observed between the two cohorts, and interpretation is limited by the unknown prevalence of left and right BBB morphologies in each. Comparing BBB presence with absence yielded qualitatively similar results. Conclusion: The simple clinical finding of BBB is a powerful independent predictor of worse clinical outcomes in patients with HF and reduced LVEF. It is less frequent, with a more modest predictive effect, in patients with preserved systolic function. [Copyright &y& Elsevier]

Abstract: Background: Limited comparative studies assessing the health-related quality of life (HRQL) in heart failure (HF) patients with preserved vs. low ejection fraction (LVEF) have been disparate. Aims: The aims of this study were a) to characterize HRQL in a large population of HF patients with preserved and low LVEF and b) to determine the factors associated with worse HRQL. Methods: Patients with symptomatic HF (NYHA Class II–IV) enrolled in the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) HRQL study completed the Minnesota Living with Heart Failure questionnaire at randomization. Patients were stratified into 2 HF cohorts: preserved LVEF (>40%) and low LVEF (≤40%). Results: In 2709 of the eligible 2744 (98.6%) patients, the summary scores ranged from 0 to 105 (mean 40.9). There were no differences in overall responses of HF patients with preserved vs. low LVEF (41.1 vs. 40.8). Independent factors associated with worse HRQL in both populations included female gender, younger age, higher body mass index, lower systolic blood pressure, greater symptom burden, and worse functional status. Conclusions: In symptomatic HF patients, HRQL is equally impaired in both preserved and low LVEF populations. Targeting improvement in symptoms and HRQL is an important treatment objective in all HF patients. [Copyright &y& Elsevier]