Serelaxin may be more effective for relieving dyspnea in heart failure with preserved ejection fraction (HFpEF) than reduced (HFrEF) during the first 24 hours, according to results from RELAX-AHF presented in a late breaking trial at the Heart Failure Congress 2013. Results were also presented from VIVIDD, the first trial of the anti-diabetes drug vildagliptin in patients with heart failure.
The Heart Failure Congress is the main annual meeting of the Heart Failure Association of the European Society of Cardiology and is being held 25-28 May in Lisbon, Portugal.
Many patients with acute heart failure (AHF) have preserved ejection fraction but there is a lack of evidence based therapies for this population. In a sub-group analysis, investigators of the Relaxin in Acute Heart Failure (RELAX-AHF) trial addressed the question of whether serelaxin was equally effective in AHF patients with HFpEF and HFrEF.
RELAX-AHF was a double blinded, randomised, placebo controlled trial in which 1161 AHF patients from 96 sites were randomised to 48 hour infusion of serelaxin or placebo within 16 hours of presentation. The primary efficacy endpoint was the effect on dyspnea in the short term (6, 12 and 24 hours) and at 5 days. Secondary efficacy endpoints were cardiovascular death or rehospitalisation for heart or renal failure, and days alive and out of hospital through day 60. All-cause death and cardiovascular death through day 180 were also evaluated.
Serelaxin induced similar dyspnea relief in HFpEF and HFrEF patients at day 5 but was more effective in the HFpEF group in the first 24 hours. There were no differences between HFpEF and HFrEF patients in the effect of serelaxin on the secondary endpoints. Serelaxin had similar benefits on mortality in patients with HFpEF and HFrEF.
Presenter Professor Gerasimos Filippatos (Greece) said: “RELAX-AHF is the first trial to give positive findings in patients with acute heart failure and preserved ejection fraction, a large population with unmet treatment needs. Seralaxin is at least as effective in AHF patients with HFpEF for relieving dyspnea during the first 24 hours and had a similar effect on rehospitalisation and survival in HFrEF and HFpEF patients.”
The Vildagliptin in Ventricular Dysfunction Diabetes (VIVIDD) trial investigated the effects of the DPP4 inhibitor vildagliptin in patients with type 2 diabetes and HFrEF (left ventricular ejection fraction [LVEF] <40%). It is the first study to test this class of anti-diabetes drugs in patients with heart failure.
Presenter Professor John McMurray (UK) said: “Diabetes and heart failure is a common dual problem and these patients have a particularly bad outlook. But, remarkably, patients with heart failure are excluded from most trials testing diabetes drugs. At the moment it’s not at all clear how clinicians should choose between the various anti-diabetes drugs when confronted with a heart failure patient.”
The primary objective of this randomised, double-blind, placebo controlled trial was to demonstrate that vildagliptin was non-inferior to placebo with respect to change in echocardiographic LVEF from baseline to 52 weeks. For the trial, 254 patients from 15 countries were randomised to 52 weeks treatment with placebo or vildagliptin 50mg bid.
The effect of vildagliptin on LVEF did not differ from placebo, confirming non-inferiority. But, unexpectedly, vildagliptin increased the size of the left ventricle with no decline in the contraction and emptying of the left ventricle and no change in B-type natriuretic peptide (BNP).
Professor McMurray said: “Normally an increase in the size of the left ventricle is associated with a decline in systolic function but we saw no change in ejection fraction and a fall rather than increase in BNP. We speculate that the surprising findings of VIVIDD indicate that this anti-diabetes drug may have improved the distensibility and compliance of the left ventricle.”
He concluded: “We don’t have enough studies investigating the effects of anti-diabetes drugs in patients with both diabetes and heart failure. The two diseases clearly interact in many ways and unless a drug is studied in these very vulnerable patients we will never know what effect it has.”
European Society of Cardiology