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Aims Heart failure is characterized by recurrent hospitalizations, but often only the first event is considered in clinical trial reports. In chronic diseases, such as heart failure, analysing all events gives a more complete picture of treatment benefit. We describe methods of analysing repeat hospitalizations, and illustrate their value in one major trial. Methods and results The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity ( CHARM)-Preserved study compared candesartan with placebo in 3023 patients with heart failure and preserved systolic function. The heart failure hospitalization rates were 12.5 and 8.9 per 100 patient-years in the placebo and candesartan groups, respectively. The repeat hospitalizations were analysed using the Andersen-Gill, Poisson, and negative binomial methods. Death was incorporated into analyses by treating it as an additional event. The win ratio method and a method that jointly models hospitalizations and mortality were also considered. Using repeat events gave larger treatment benefits than time to first event analysis. The negative binomial method for the composite of recurrent heart failure hospitalizations and cardiovascular death gave a rate ratio of 0.75 [95% confidence interval ( CI) 0.62-0.91, P = 0.003], whereas the hazard ratio for time to first heart failure hospitalization or cardiovascular death was 0.86 (95% CI 0.74-1.00, P = 0.050). Conclusions In patients with preserved EF, candesartan reduces the rate of admissions for worsening heart failure, to a greater extent than apparent from analysing only first hospitalizations. Recurrent events should be routinely incorporated into the analysis of future clinical trials in heart failure. [ABSTRACT FROM AUTHOR]

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]

Aims: Heart failure (HF) and chronic obstructive pulmonary disease are common partners. Bronchodilators are associated with adverse cardiovascular outcomes in patients with pulmonary disease. The outcome of patients with HF prescribed bronchodilators is poorly defined. [ABSTRACT FROM PUBLISHER]

Abstract: Trial of Preventing Hypertension (TROPHY) investigated whether pharmacological treatment of prehypertension prevents or postpones stage 1 hypertension. Hypertension was originally defined when a participant had blood pressure (BP) ≥140 and/or ≥90 mm Hg at any three clinic visits over 4 years. Contemporary guidelines define hypertension if the BP is ≥140 and/or ≥90 at two consecutive visits. TROPHY results were recalculated based on the current definition. Participants with repeated BP of 130 – 139 and/or 85 – 89 mm Hg were randomly assigned to 2 years of candesartan or placebo, followed by 2 years of placebo for all. All participants received lifestyle counseling at every visit. When participants reached hypertension, antihypertensive treatment was initiated. The 4-year incidence of hypertension was significantly (P < .001) lower than previously reported in the placebo (–11.3%) and candesartan (–11.0%) groups. During the first 2 years, hypertension developed in 162 placebo and 53 candesartan participants (relative risk reduction [RRR], 68%; P < .001; original report 66%; P < .001). After 4 years, hypertension occurred in 197 placebo and 165 candesartan participants (RRR, 18%; P < .009; original report 16%; P < .007). The new definition resulted in a lower incidence of hypertension, but the outcomes were remarkably similar with both definitions and confirmed our original findings. [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]

Context Angiotensin-converting enzyme (ACE) inhibitors reduce the risk of myocardial infarction (MI), but it is not known whether angiotensin receptor blockers have the same effect. Objective To assess the impact of the angiotensin receptor blocker candesartan on MI and other coronary events in patients with heart failure. Design, Setting, and Participants The Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program, a randomized, placebo-controlled study enrolling patients (mean age, 66 [SD, 11] years) with New York Heart Association class II to IV symptoms who were randomly allocated to receive candesartan (target dose, 32 mg once daily) or matching placebo given in addition to optimal therapy for heart failure. Patients were enrolled from March 1999 through March 2001. Of 7599 patients allocated, 4004 (53%) had experienced a previous MI, and 1808 (24%) currently had angina. At baseline, 3125 (41%) were receiving an ACE inhibitor; 4203 (55%), a β-blocker; 3153 (42%), a lipid-lowering drug; 4246 (56%), aspirin; and 6286 (83%), a diuretic. Main Outcome Measure The primary outcome of the present analysis was the composite of cardiovascular death or nonfatal MI in patients with heart failure receiving candesartan or placebo. Results During the median follow-up of 37.7 months, the primary outcome of cardiovascular death or nonfatal MI was significantly reduced in the candesartan group (775 patients [20.4%]) vs the placebo group (868 [22.9%]) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96; P = .004; number needed to treat [NNT], 40). Nonfatal MI alone was also significantly reduced in the candesartan group (116 [3.1%]) vs the placebo group (148 [3.9%]) (HR, 0.77; 95% CI, 0.60-0.98; P = .03; NNT, 118). The secondary outcome of fatal MI, sudden death, or nonfatal MI was significantly reduced with candesartan (459 [12.1%]) vs placebo (522 [13.8%]) (HR, 0.86; 95% CI, 0.75-0.97; P = .02; NNT, 59). Risk reductions in cardiovascular death or nonfatal MI were similar across predetermined subgroups and the component CHARM trials. There was no impact on hospitalizations for unstable angina or coronary revascularization procedures with candesartan. Conclusion In patients with heart failure, candesartan significantly reduces the risk of the composite outcome of cardiovascular death or nonfatal MI. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to explore the relationship between baseline resting heart rate and outcomes in patients with chronic heart failure (HF) according to baseline left ventricular ejection fraction (LVEF) and cardiac rhythm. Background: Elevated resting heart rate is associated with worse outcomes in patients with HF and reduced LVEF. Whether this association is also found in patients with HF and preserved LVEF is uncertain, as is the predictive value of heart rate in patients in atrial fibrillation (AF). Methods: Patients enrolled in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) Program were divided into groups by tertiles of baseline heart rate. Cox proportional hazard models were used to investigate the association between heart rate and pre-specified outcomes in the overall population as well as in subgroups defined according to LVEF (≤40% vs. >40%) and presence (or absence) of AF at baseline. Results: After adjusting for predictors of poor prognosis, patients in the highest heart rate tertile had worse outcomes when compared with those in the lowest heart rate group (e.g., for the composite of cardiovascular death or HF hospital stay hazard ratio: 1.23, 95% confidence interval: 1.11 to 1.36, p < 0.001). The relationship between heart rate and outcomes was similar across LVEF categories and was not influenced by beta-blocker use (p value for interaction >0.10 for both endpoints). However, amongst patients in AF at baseline, heart rate had no predictive value (p value for interaction <0.001). Conclusions: Resting heart rate is an important predictor of outcome in patients with stable chronic HF without AF, regardless of LVEF or beta-blocker use. [ABSTRACT FROM AUTHOR]