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Serelaxin in acute heart failure patients with preserved left ventricular ejection fraction: results from the RELAX-AHF trial.

Filippatos G, Teerlink JR, Farmakis D, Cotter G, Davison BA, Felker GM, Greenberg BH, Hua T, Ponikowski P, Severin T, Unemori E, Voors AA, Metra M - Eur. Heart J. (2013)

Bottom Line: We compared the effects of serelaxin on efficacy endpoints, safety endpoints, and biomarkers of organ damage between preserved (≥50%) and reduced (<50%, HFrEF) EF.Similar safety and changes in biomarkers (high-sensitivity troponin T, cystatin-C, and alanine/aspartate aminotransferases) were found in both groups.In AHF patients with HFpEF compared with those with HFrEF, serelaxin was well tolerated and effective in relieving dyspnoea and had a similar effect on short- and long-term outcome, including survival improvement.

View Article: PubMed Central - PubMed

Affiliation: Athens University Hospital Attikon, Athens, Greece.

ABSTRACT

Aims: Serelaxin is effective in relieving dyspnoea and improving multiple outcomes in acute heart failure (AHF). Many AHF patients have preserved ejection fraction (HFpEF). Given the lack of evidence-based therapies in this population, we evaluated the effects of serelaxin according to EF in RELAX-AHF trial.

Methods and results: RELAX-AHF randomized 1161 AHF patients to 48-h serelaxin (30 μg/kg/day) or placebo within 16 h from presentation. We compared the effects of serelaxin on efficacy endpoints, safety endpoints, and biomarkers of organ damage between preserved (≥50%) and reduced (<50%, HFrEF) EF. HFpEF was present in 26% of patients. Serelaxin induced a similar dyspnoea relief in HFpEF vs. HFrEF patients by visual analogue scale-area under the curve (VAS-AUC) through Day 5 [mean change, 461 (-195, 1117) vs. 397 (10, 783) mm h, P = 0.87], but had possibly different effects on the proportion of patients with moderately or markedly dyspnoea improvement by Likert scale at 6, 12, and 24 h [odds ratio for favourable response, 1.70 (0.98, 2.95) vs. 0.85 (0.62, 1.15), interaction P = 0.030]. No differences were encountered in the effect of serelaxin on short- or long-term outcome between HFpEF and HFrEF patients including cardiovascular death or hospitalization for heart/renal failure through Day 60, cardiovascular death through Day 180, and all-cause death through Day 180. Similar safety and changes in biomarkers (high-sensitivity troponin T, cystatin-C, and alanine/aspartate aminotransferases) were found in both groups.

Conclusions: In AHF patients with HFpEF compared with those with HFrEF, serelaxin was well tolerated and effective in relieving dyspnoea and had a similar effect on short- and long-term outcome, including survival improvement.

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Kaplan–Meier curves for cardiovascular death or hospitalization for heart/renal failure through Day 60 according to LVEF. HR, hazard ratio.
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EHT497F2: Kaplan–Meier curves for cardiovascular death or hospitalization for heart/renal failure through Day 60 according to LVEF. HR, hazard ratio.

Mentions: The effect of treatment (serelaxin vs. placebo) on several efficacy endpoints in HFrEF and HFpEF patients is presented in Table 2. Serelaxin induced a similar dyspnoea relief in HFpEF and HFrEF patients through Day 5 according to VAS-AUC (mean AUC change, 461 vs. 397 mm × h, respectively, P for interaction = 0.8683; Figure 1A). A nominally statistically significant interaction was found for the proportion of patients with moderately or markedly improved dyspnoea at 6, 12, and 24 h on Likert scale (odds ratio 1.70 vs. 0.85, P for interaction = 0.030), which was not reflected at each individual time point (Figure 1B). Regarding short- and long-term outcome, serelaxin had a similar effect in HFpEF and HFrEF patients on cardiovascular death or hospitalization for heart or renal failure through Day 60 (hazard ratio, 1.08 vs. 1.10, P for interaction = 0.97, Figure 2), days alive and out of hospital through Day 60 (−1.28 vs. 0.86, P for interaction = 0.19), cardiovascular death through Day 180 (0.59 vs. 0.64, P for interaction = 0.87, Figure 3). While serelaxin appeared to reduce the risk of cardiovascular mortality by roughly the same extent in both HFpEF and HFrEF (Figure 3), the rate of rehospitalization for HF/RF was higher in the serelaxin group in both EF groups, particularly in patients with HFrEF, reflected in an apparently greater detrimental serelaxin effect on the composite outcome in the HFrEF group (Figure 2); however, given the smaller size of the HFpEF group, the role of chance in these findings cannot be ruled out. There was no difference between HFpEF and HFrEF patients in the effects of serelaxin on all additional endpoints such as total dose of intravenous loop diuretics to Day 5, change in weight through Day 5, and length of hospital stay or days in ICU/CCU (Table 2). An analysis reclassifying nine HFpEF patients with biventricular pacing and/or implantable cardiac defibrillator as HFrEF showed nearly identical results.Table 2


Serelaxin in acute heart failure patients with preserved left ventricular ejection fraction: results from the RELAX-AHF trial.

Filippatos G, Teerlink JR, Farmakis D, Cotter G, Davison BA, Felker GM, Greenberg BH, Hua T, Ponikowski P, Severin T, Unemori E, Voors AA, Metra M - Eur. Heart J. (2013)

Kaplan–Meier curves for cardiovascular death or hospitalization for heart/renal failure through Day 60 according to LVEF. HR, hazard ratio.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3992428&req=5

EHT497F2: Kaplan–Meier curves for cardiovascular death or hospitalization for heart/renal failure through Day 60 according to LVEF. HR, hazard ratio.
Mentions: The effect of treatment (serelaxin vs. placebo) on several efficacy endpoints in HFrEF and HFpEF patients is presented in Table 2. Serelaxin induced a similar dyspnoea relief in HFpEF and HFrEF patients through Day 5 according to VAS-AUC (mean AUC change, 461 vs. 397 mm × h, respectively, P for interaction = 0.8683; Figure 1A). A nominally statistically significant interaction was found for the proportion of patients with moderately or markedly improved dyspnoea at 6, 12, and 24 h on Likert scale (odds ratio 1.70 vs. 0.85, P for interaction = 0.030), which was not reflected at each individual time point (Figure 1B). Regarding short- and long-term outcome, serelaxin had a similar effect in HFpEF and HFrEF patients on cardiovascular death or hospitalization for heart or renal failure through Day 60 (hazard ratio, 1.08 vs. 1.10, P for interaction = 0.97, Figure 2), days alive and out of hospital through Day 60 (−1.28 vs. 0.86, P for interaction = 0.19), cardiovascular death through Day 180 (0.59 vs. 0.64, P for interaction = 0.87, Figure 3). While serelaxin appeared to reduce the risk of cardiovascular mortality by roughly the same extent in both HFpEF and HFrEF (Figure 3), the rate of rehospitalization for HF/RF was higher in the serelaxin group in both EF groups, particularly in patients with HFrEF, reflected in an apparently greater detrimental serelaxin effect on the composite outcome in the HFrEF group (Figure 2); however, given the smaller size of the HFpEF group, the role of chance in these findings cannot be ruled out. There was no difference between HFpEF and HFrEF patients in the effects of serelaxin on all additional endpoints such as total dose of intravenous loop diuretics to Day 5, change in weight through Day 5, and length of hospital stay or days in ICU/CCU (Table 2). An analysis reclassifying nine HFpEF patients with biventricular pacing and/or implantable cardiac defibrillator as HFrEF showed nearly identical results.Table 2

Bottom Line: We compared the effects of serelaxin on efficacy endpoints, safety endpoints, and biomarkers of organ damage between preserved (≥50%) and reduced (<50%, HFrEF) EF.Similar safety and changes in biomarkers (high-sensitivity troponin T, cystatin-C, and alanine/aspartate aminotransferases) were found in both groups.In AHF patients with HFpEF compared with those with HFrEF, serelaxin was well tolerated and effective in relieving dyspnoea and had a similar effect on short- and long-term outcome, including survival improvement.

View Article: PubMed Central - PubMed

Affiliation: Athens University Hospital Attikon, Athens, Greece.

ABSTRACT

Aims: Serelaxin is effective in relieving dyspnoea and improving multiple outcomes in acute heart failure (AHF). Many AHF patients have preserved ejection fraction (HFpEF). Given the lack of evidence-based therapies in this population, we evaluated the effects of serelaxin according to EF in RELAX-AHF trial.

Methods and results: RELAX-AHF randomized 1161 AHF patients to 48-h serelaxin (30 μg/kg/day) or placebo within 16 h from presentation. We compared the effects of serelaxin on efficacy endpoints, safety endpoints, and biomarkers of organ damage between preserved (≥50%) and reduced (<50%, HFrEF) EF. HFpEF was present in 26% of patients. Serelaxin induced a similar dyspnoea relief in HFpEF vs. HFrEF patients by visual analogue scale-area under the curve (VAS-AUC) through Day 5 [mean change, 461 (-195, 1117) vs. 397 (10, 783) mm h, P = 0.87], but had possibly different effects on the proportion of patients with moderately or markedly dyspnoea improvement by Likert scale at 6, 12, and 24 h [odds ratio for favourable response, 1.70 (0.98, 2.95) vs. 0.85 (0.62, 1.15), interaction P = 0.030]. No differences were encountered in the effect of serelaxin on short- or long-term outcome between HFpEF and HFrEF patients including cardiovascular death or hospitalization for heart/renal failure through Day 60, cardiovascular death through Day 180, and all-cause death through Day 180. Similar safety and changes in biomarkers (high-sensitivity troponin T, cystatin-C, and alanine/aspartate aminotransferases) were found in both groups.

Conclusions: In AHF patients with HFpEF compared with those with HFrEF, serelaxin was well tolerated and effective in relieving dyspnoea and had a similar effect on short- and long-term outcome, including survival improvement.

Show MeSH
Related in: MedlinePlus