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Review
. 2019 Oct 31;18(1):188.
doi: 10.1186/s12944-019-1135-z.

Association of Statin Use and Clinical Outcomes in Heart Failure Patients: A Systematic Review and Meta-Analysis

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Free PMC article
Review

Association of Statin Use and Clinical Outcomes in Heart Failure Patients: A Systematic Review and Meta-Analysis

Agata Bielecka-Dabrowa et al. Lipids Health Dis. .
Free PMC article

Abstract

Background: The role of statins in patients with heart failure (HF) of different levels of left ventricular ejection fraction (LVEF) remains unclear especially in the light of the absence of prospective data from randomized controlled trials (RCTs) in non-ischemic HF, and taking into account potential statins' prosarcopenic effects. We assessed the association of statin use with clinical outcomes in patients with HF.

Methods: We searched PubMed, EMBASE, Scopus, Google Scholar and Cochrane Central until August 2018 for RCTs and prospective cohorts comparing clinical outcomes with statin vs non-statin use in patients with HF at different LVEF levels. We followed the guidelines of the 2009 PRISMA statement for reporting and applied independent extraction by multiple observers. Meta-analyses of hazard ratios (HRs) of effects of statins on clinical outcomes used generic inverse variance method and random model effects. Clinical outcomes were all-cause mortality, cardiovascular (CV) mortality and CV hospitalization.

Results: Finally we included 17 studies (n = 88,100; 2 RCTs and 15 cohorts) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (HR 0.77, 95% confidence interval [CI], 0.72-0.83, P < 0.0001, I2 = 63%), CV mortality (HR 0.82, 95% CI: 0.76-0.88, P < 0.0001, I2 = 63%), and CV hospitalization (HR 0.78, 95% CI: 0.69-0.89, P = 0.0003, I2 = 36%). All-cause mortality was reduced on statin therapy in HF with both EF < 40% and ≥ 40% (HR: 0.77, 95% Cl: 0.68-0.86, P < 0.00001, and HR 0.75, 95% CI: 0.69-0.82, P < 0.00001, respectively). Similarly, CV mortality (HR 0.86, 95% CI: 0.79-0.93, P = 0.0003, and HR 0.83, 95% CI: 0.77-0.90, P < 0.00001, respectively), and CV hospitalizations (HR 0.80 95% CI: 0.64-0.99, P = 0.04 and HR 0.76 95% CI: 0.61-0.93, P = 0.009, respectively) were reduced in these EF subgroups. Significant effects on all clinical outcomes were also found in cohort studies' analyses; the effect was also larger and significant for lipophilic than hydrophilic statins.

Conclusions: In conclusion, statins may have a beneficial effect on CV outcomes irrespective of HF etiology and LVEF level. Lipophilic statins seem to be much more favorable for patients with heart failure.

Keywords: Heart failure; Hospitalization; Meta-analysis; Mortality; Statins.

Conflict of interest statement

ABD, IB, JR, JJ, SvH, and AVH have no conflicts of interest to disclose; DPM has given talks and attended conferences sponsored by MSD, AstraZeneca and Libytec; SDA reports personal fees from Bayer, Boehringer Ingelheim, Vifor, Servier and Novartis, outside the submitted work; MB has served on the speakers bureau of Abbott/Mylan, Abbott Vascular, Actavis, Akcea, Amgen, Biofarm, KRKA, MSD, Sanofi-Aventis, Servier and Valeant, and has served as a consultant to Abbott Vascular, Akcea, Amgen, Daichii Sankyo, Esperion, Lilly, MSD, Resverlogix, Sanofi-Aventis; Grants from Sanofi and Valeant.

Figures

Fig. 1
Fig. 1
Flow chart of studies
Fig. 2
Fig. 2
Association of statin versus non-statin use with all-cause mortality in heart failure
Fig. 3
Fig. 3
Association of statin versus non-statin use with a) CV mortality, and b) CV hospitalizations
Fig. 4
Fig. 4
Association of statin versus non-statin use with all-cause mortality by type of heart failure
Fig. 5
Fig. 5
Association of statin versus non-statin use with CV mortality by type of heart failure
Fig. 6
Fig. 6
Association of statin versus non-statin use in HF patients with CV hospitalizations by LVEF value
Fig. 7
Fig. 7
Association of statin versus non-statin use with all-cause mortality by type of liposolubility
Fig. 8
Fig. 8
Association of statin versus non-statin use with CV mortality by type of liposolubility
Fig. 9
Fig. 9
Association of statin versus non-statin use with CV hospitalization by type of liposolubility

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