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Candesartan provides similar benefit for patients with mid-range ejection fraction as those with reduced ejection fraction

New results from the CHARM (Candesartan in heart failure: assessment of reduction in mortality and morbidity) trial, which was presented at a Late Breaking Trials session on chronic heart failure, indicate that the angiotensin receptor blocker (ARB) candesartan provides a similar benefit in patients with mid-range ejection fraction heart failure (HFmrEF) as it does in patients with reduced ejection fraction heart failure (HFrEF).



Study investigator Professor Lars H Lund (Karolinska Institute, Stockholm, Sweden) told Heart Failure 2017 Congress News that patients with HFmrEF—according to the 2016 European Society of Cardiology definition—have “symptoms and signs of heart failure, elevated levels of natriuretic peptides, and some evidence of structural or functional heart disease”. He added that the category of HFmrEF (40–49% ejection fraction) sits between HFrEF (ejection fraction <40%) and heart failure with preserved ejection (ejection fraction ≥50%). Prior to this clinical update, the characteristics, outcomes, and treatment effect in patients in the HFmrEF category had not previously been studied—the original CHARM trial programme only divided patients into HFrEF and HFpEF.

Therefore, the aim of the present study was to evaluate the use of candesartan in patients who come under this novel category of HFmEf.

Prof. Lund said: “The rationale for this trial was that normal ejection fraction is above 50%. Yet current heart failure therapy is effective at reducing morbidity and mortality only with ejection fraction less than 40%. This leaves an obvious gap of ejection fraction 40–49%, where ejection fraction is not normal but there also is no evidence-based therapy.”

Patients included in the original CHARM study were aged 18 or older, were in New York Health Association (NYHA) class II–IV heart failure symptoms of at least four weeks’ duration, and had a history of hospital admission for a cardiac reason. They could fall anywhere on the ejection fraction spectrum (ie. from HFpEF to HFrEF). Of the 7,598 patients who participated in the trial, 1,322 (17%) were in the HFmrEF category and they were intermediate between HFrEF (n=4,323; 57%) and HFpEF (n=1,953; 26%) in terms of their history of hypertension, NYHA class, and body mass index. However, HFmrEF patients resembled HFrEF patients in regard to most other characteristics, including 
age, systolic blood pressure, gender, previous myocardial infarction, and atrial fibrillation.

The primary endpoint was time to composite of cardiovascular death or first hospitalisation for heart failure, and secondary endpoints were cardiovascular death, first heart failure hospitalisation, recurrent heart failure hospitalisation, all-cause death, and all-cause hospitalisations. Over a mean follow-up of 2.9 years, the rates of the primary outcome declined with increasing ejection fraction up to ejection fraction approximately 50%. The effect of candesartan on the primary outcome in the HFmrEF range was similar to that in the HFrEF range. The results were consistent for time to first and for recurrent heart failure hospitalisation.

Prof. Lund said that researchers needed to develop a greater understanding of HFmrEF, commenting: “We know very little about the natural history of these patients. We know that the rates of outcomes such as heart failure hospitalisation are intermediate between HFrEF and HFpEF, but we know very little about how ejection fraction changes over time. This is currently an area of intense study.” He added: “There is little data from randomised trials on treatment effect across the entire ejection fraction spectrum. Determining potential treatment efficacy of existing heart failure drugs in HFmrEF will require new prospective randomised trials.”

Late Breaking Trials II: Focus on chronic heart failure

Sunday 30 April 08:30 - 10:00, room HUGO

VIEW THE PROGRAMME