Statins and symptomatic chronic systolic heart failure: A post-hoc analysis of 5010 patients enrolled in Val-HeFT

https://doi.org/10.1016/j.ijcard.2006.07.106Get rights and content

Abstract

Background

Statins prolong survival in patients at high risk for cardiovascular events, however little is known regarding their efficacy and safety in patients with established chronic heart failure (CHF). To address this, we retrospectively analyzed the Valsartan Heart Failure Trial (Val-HeFT) database to determine outcomes in CHF patients according to statin use at baseline.

Methods

Demographic characteristics of patients receiving statins at baseline (n = 1602) were compared with those who were not (n = 3048). A multivariate Cox proportional hazards model, with death as outcome, was used to assess the impact of statin therapy, with adjustment made for baseline differences in relevant parameters.

Results

Patients receiving statins at baseline were younger with fewer females, fewer in NYHA III-IV, more with an ischemic etiology, more diabetics, higher BMI, lower SBP, more on beta-blockers, but no difference in LVEF or ACEi use. Mortality over a mean 2-year follow-up was 17.9% on statins versus 20.3% without statins (p = 0.029). Cox-adjusted hazard ratio for statins was 0.81 [95% CI 0.70–0.94]. No statistically significant interaction was found between statins and valsartan for mortality. After 4 months, the only laboratory changes were a reduction in CRP and an attenuation of the rise in norepinephrine in the statin group.

Conclusions

In a large, contemporary sample of patients with CHF, statin use appeared to be associated with a lower 2-year mortality. These findings suggest a prognostic benefit for statins in established CHF, however prospective data are required to definitively address this issue.

Condensed abstract

We examined major cardiovascular outcomes in patients who were (n = 1602) and were not (n = 3048) receiving statins at baseline in the Val-HeFT cohort of patients with mild to moderate systolic chronic heart failure. Mortality was reduced in patients receiving statins compared to those who were not, without any significant interaction effect between statin treatment and valsartan. These findings suggest a prognostic benefit for statins in established heart failure, however prospective data are required to definitively address this issue.

Introduction

Statin therapy may be of potential benefit in patients with chronic heart failure (CHF) via reduction of coronary events through plaque stabilisation and restoration of endothelial function [1]. Even in patients who do not have CHF of an ischaemic etiology, pre-clinical studies have supported direct improvements in cardiac myocyte function, possibly via neo-vascularisation, down-regulation of angiotensin II (AT1) receptors, restoration of autonomic function and inhibition of pro-inflammatory cytokines [2].

However, there are also patho-physiological reasons why statins may not be of benefit in this setting [2].

Very few studies have reported efficacy and/or outcome of statins in CHF patients and all of those studies were non-randomised or post-hoc analyses of large clinical trial datasets [3], [4], [5].

Therefore, the objective of the present study was to assess the outcome of patients enrolled in the Valsartan Heart Failure Trial (Val-HeFT) [6] according to statin use at the time of randomisation to the angiotensin receptor blocker (ARB) valsartan or placebo.

Section snippets

Methods

This was a retrospective, post-hoc analysis of the Val-HeFT dataset. Details of the overall Val-HeFT results have been published elsewhere [6]. Baseline characteristics of patients on statin compared to the remainder of the population were analysed using Chi Square or Wilcoxon analysis, as appropriate. Baseline laboratory values and changes from baseline to endpoint were analyzed by analysis of covariance for ranks (Rank ANCOVA), adjusted for demographic, echocardiographic and clinical

Baseline characteristics

Baseline characteristics of the patient population are summarised in Table 1. Of the 5010 randomised patients in Val-HeFT, 1602 (32%) were taking a statin at randomisation. Patients on statins at randomisation were younger, with fewer females, fewer NYHA class III-IV, more with ischaemic etiology, lower LVIDd/BSA, higher BMI, slightly lower systolic blood pressure and more diabetics. Statin treated patients were receiving more beta-blockers. Patients on statins at baseline had lower total

Discussion

The present analysis has examined a large cohort of patients with systolic CHF for mortality and morbidity/mortality outcomes according to statin use at baseline. To our knowledge this is the largest non-randomised sample of patients with CHF ever studied in this way.

We observed lower mortality (− 19%) and morbidity/mortality (− 15%) in patients taking statins at randomisation in Val-HeFT compared to no statin patients. Particular benefit was observed in Val-HeFT patients of ischaemic etiology to

Cited by (60)

  • Plant Statins and Heart Failure

    2013, Bioactive Food as Dietary Interventions for Cardiovascular Disease
  • Plant Statins and Heart Failure

    2012, Bioactive Food as Dietary Interventions for Cardiovascular Disease: Bioactive Foods in Chronic Disease States
  • Statins in heart failure: The paradox between large randomized clinical trials and real life

    2012, Mayo Clinic Proceedings
    Citation Excerpt :

    Although large randomized trials found that statin treatment did not reduce the number of deaths in patients with HF,7,8 our study suggests that “real-life” patients taking statins have better survival than patients with HF who are not treated with them. Our results concur with previous data reported before the GISSI-HF and CORONA trials era.3-6 These 2 large, randomized, placebo-controlled trials were designed to evaluate the role of statins in the prognosis of HF.

View all citing articles on Scopus
View full text