Effect of Candesartan on Cause-Specific Mortality in Heart Failure Patients

Abstract

Background-Patients with heart failure are at increased risk of sudden death and death attributed to progressive pump failure. We assessed the effect of candesartan on cause-specific mortality in patients enrolled in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program. Methods and Results-The CHARM program consisted of 3 component trials that enrolled patients with symptomatic heart failure: CHARM-Alternative (nϭ2028; LVEFՅ40% and ACE intolerant), CHARM-Added (nϭ2548; LVEFՅ40%, already on ACE inhibitors), and CHARM-Preserved (nϭ3023; LVEF Ͼ40%). Patients were randomized to candesartan, titrated to 32 mg QD, or placebo and were followed up for a median of 37.7 months. All deaths were reviewed by a blinded adjudication committee and categorized according to prespecified definitions on the basis of a narrative and source documentation. The number and rate of deaths by cause were calculated for each of the component trials and the overall program. Of all the patients, 8.5% died suddenly, and 6.2% died of progressive heart failure.

2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death

“…Komorowe zaburzenia rytmu występują u większości pacjentów z HF, a nagłe zgony są częste w tej populacji [1, 8,295,296]. Występowanie i ciężkość arytmii komorowej zwiększają się wraz z ciężkością HF, ale wartość tych zaburzeń rytmu jako wskaźnika predykcyjnego nagłych zgonów pozostaje niejasna [297][298][299][300].…”

Outcomes for COPD pharmacological trials: from lung function to biomarkers

“…As a matter of fact, only one study [196] was found in the COPD literature where a methodology for the adjudication of the actual cause of death was described. In contrast, adjudication committees for the cause of death and a description of their methods are frequent in cardiovascular trials [253,254]. The discrepancy between the original and the adjudicated cause of death in some of those studies has reached 20% [196].…”

Sudden Cardiac Death in Heart Failure

“…24 Although for a long time patients with diastolic HF were thought to be at low risk for SCD, recent studies have shown an increased risk in this population as well. In the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-PRE-SERVE) trial 25 and the Candesartan in Heart Failure Assessment of Reduction in Mortality (CHARM) Preserved study, 26 a little more than a quarter of the deaths were deemed to be arrhythmic SCD, highlighting the need for strategies to prevent the high burden of SCD in these patients with diastolic HF.…”