Statin therapy associated with reduced mortality in patients with HFpEF

Determinants of the survival benefit associated with statins in patients with acute heart failure

Literature - Park CS, Hwang IC, Park JJ et al. - ESC Heart Fail. 2021. doi: 10.1002/ehf2.13637.

Introduction and methods

Aim of the study

Inflammation and endothelial dysfunction are considered as potential targets for therapeutic interventions in HF [1,2]. Besides the well-known lipid-lowering effects, statins have anti-inflammatory properties and exert positive effects on endothelial function [3-6]. Studies have shown varying results on the effects of statins on mortality in patients with HF [7-9]. This study aimed to investigate the effect of statin therapy on 5-year mortality in patients with acute HF, stratified according to the etiology (ischemic vs. non-ischemic) and type of HF (HFrEF vs. HFpEF).

Study design

Patients hospitalized for acute HF were recruited between 2009 and 2016 from three university hospitals. A total of 3837 patients who underwent baseline echocardiography were included in the analysis. Of these patients, 1680 received statins and 2157 did not receive statins. 18.8% had ischemic HFrEF, 33.9% non-ischemic HFrEF, 14.9% had ischemic HFpEF and 33.4% had non-ischemic HFpEF.

Primary outcome

The primary outcome was 5-year all-cause mortality.

Main results

  • Statin therapy was independently and significantly associated with reduced 5-year mortality in patients with HFpEF (aHR 0.781, 95% CI 0.621-0.981, P=0.034), but not in patients with HFrEF (aHR 0.881, 95% CI 0.721-1.090, P=0.244).
  • When comparing patients with an ischemic etiology of HF vs a non-ischemic etiology of HF, it was found that statin treatment was significantly associated with a reduced 5-year mortality in patients with ischemic HF, but not in those with non-ischemic HF (HR 0.775, 95% CI 0.607-0.989, P=0.040 vs. HR 0.895, 95% CI 0.734-1.092, P=0.275).
  • A Cox regression analysis showed that the relative magnitude of survival benefit with statin treatment increased with increasing LVEF and LV-global longitudinal strain (GLS). This association was more pronounced in those with ischemic HF than in those with non-ischemic HF.
  • The relative magnitude of survival benefit with statin therapy decreased as RV-fractional area change (FAC) and RV-GLS increased.
  • Subgroup analyses showed a significant interaction between statin therapy and age for mortality in patients with ischemic HF. Statin therapy was associated with a greater mortality reduction in patients ≤75 years than in older patients.

Conclusion

This study in patients with acute HF found that statin therapy was associated with reduced 5-year mortality in those with HFpEF and in those with an ischemic etiology of HF. The authors suggest that identification of HF subgroups based on clinical features and echocardiographic assessment may help to select HF patients who could potentially benefit from statin therapy.

References

1. Dick SA, Epelman S. Chronic heart failure and inflammation: what do we really Know? Circ Res 2016; 119: 159–176.

2. Marti CN, Gheorghiade M, Kalogeropoulos AP, Georgiopoulou VV, Quyyumi AA, Butler J. Endothelial dysfunction, arterial stiffness, and heart failure. J Am Coll Cardiol 2012; 60: 1455–1469.

3. Node K, Fujita M, Kitakaze M, Hori M, Liao JK. Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation 2003; 108:839–843.

4. Ridker PM, Luscher TF. Anti-inflammatory therapies for cardiovascular disease. Eur Heart J 2014; 35: 1782–1791.

5. Rikitake Y, Liao JK. Rho GTPases, statins, and nitric oxide. Circ Res 2005;97: 1232–1235.

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8. Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, Lucci D, Nicolosi GL, Porcu M, Tognoni G, Investigators GH. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, doubleblind, placebo-controlled trial. Lancet 2008; 372: 1231–1239.

9. Lee MS, Duan L, Clare R, Hekimian A, Spencer H, Chen W. Comparison of effects of statin use on mortality in patients with heart failure and preserved versus reduced left ventricular ejection fraction. Am J Cardiol 2018; 122:405–412.

Find this article online at ESC Heart Fail.

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