Treatment of heart failure with preserved systolic function: a review of the evidence

The importance of heart failure with preserved systolic function (HF-PSF) has been increasingly recognised during the last decade. However, until recently there were no large, randomised, controlled clinical outcome trials in patients with this condition. Indeed, the best evidence of symptom improvement came from two very small studies with the rate-limiting calcium-channel blocker verapamil, in a total of fewer than 50 patients. The largest outcome trial was an ancillary study (with about 900 patients) of the Digitalis Investigators Group (DIG) trial, in which digoxin was reported to have a proportionately similar effect on morbidity to that seen in patients with reduced systolic function. Recently, the CHARM-Preserved study randomised over 3000 patients to placebo or candesartan. There was a trend to a reduction in cardiovascular death or hospitalisation for heart failure with candesartan (333 vs. 366 patients, unadjusted p = 0.118; co-variate adjusted p = 0.051), and clear reductions in the proportion of patients admitted (by 15% from 270 to 230 patients, p = 0.017) and the total number of hospital admissions for worsening heart failure (by 29% from 566 to 402 admissions, p = 0.014). Overall the results of the CHARM Programme showed that candesartan exerted a favourable effect across a broad spectrum of patients with heart failure, irrespective of left-ventricular function, co-morbidity, symptomatic class or concomitant treatment.