Heart failure – serelaxin

Up to 10% of all those over 65 in the developed world have some form of heart failure and the long-term prognosis remains poor

Patients with acute heart failure represent a serious public health problem in the developed world, with up to 10% of all those over 65 having some form of heart failure. The heart becomes unable to pump blood around the body efficiently, leading to symptoms ranging from swollen legs, shortness of breath and difficulty carrying out any form of exercise.

Drug treatments include diuretics and blood pressure lowering agents, but the long-term prognosis remains poor, with the inability to exercise leading patients to spiral into a decline, with acute episodes where symptoms are significantly exacerbated leading to hospitalisation becoming more frequent. Almost a quarter of those who are hospitalised with acute heart failure have died within a year.1

A new potential drug treatment, serelaxin, is being developed by Novartis, which is a recombinant form of the human hormone relaxin-2.2 The vasoactive peptide hormone is naturally present in both men and women, and it acts by relaxing the blood vessels, resulting in reduced stress on the heart and kidney. Levels rise during pregnancy, as it increases cardiac output, arterial compliance and renal blood flow to compensate for the impact of pregnancy on the woman’s physiology. These effects would all be positive in heart disease if they could be replicated in patients given doses of the hormone.

A double blind, placebo-controlled, parallel group, dose ranging study was carried out in 234 patients with acute failure, plus dyspnoea, increased brain natriuretic peptide, were given standard care plus 48-hour infusion of either placebo or hormone in doses of 10, 30, 100 or 250µg/kg/day.3 Dyspnoea improved compared with placebo in those patients given 30µg/kg doses, and the length of hospitalisation was 10 days in the treated patients, compared with 12 days for the placebo group. Cardiovascular death or readmission because of heart or kidney failure at day 60 was 2.6% in the treated group, and 17% in those given placebo. The incidence of serious side-effects was similar across all patients.

A double blind, placebo-controlled Phase III trial has also been carried out. A total of 1,161 patients admitted to hospital with acute heart failure were randomly assigned to receive standard care plus 48-hour infusions of either placebo or 30µg/kg serelaxin per day, within 16 hours of admission.4 Half were given active treatment.

Again, all had dyspnoea, increased brain natriuretic peptide, congestion as seen by chest X-ray, high blood pressure and renal insufficiency. Those given the hormone drug experienced an improvement in their symptoms of dyspnoea. While no other significant effects were seen on primary endpoints, or the secondary endpoints of cardiovascular death or readmission to hospital for either heart or kidney failure, or days alive out of hospital, those treated with serelaxin were more likely to meet various other endpoints, including fewer deaths at day 180, with 65 deaths in the placebo group and 42 in the treatment group.

References

1. V.P. Harjola et al. Eur. J. Heart Fail. 2010, 12, 239

2. K.P. Conrad et al. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2011, 301, R267

3. J.R. Teerlink et al. Lancet 2009, 373, 1429

4. J.R. Teerlink et al. Lancet 2013, 381, 29

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