Prosarcopenic Effects of Statins May Limit Their Effectiveness in Patients with Heart Failure

Bielecka‐Dąbrowa, Agata; Fabiś, Jarosław; Mikhailidis, Dimitri P.; Haehling, Stephan von; Sahebkar, Amirhossein; Rysz, Jacek; Banach, Maciej

doi:10.1016/j.tips.2018.02.003

Cited by 22 publications

(25 citation statements)

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“…Available knowledge has indicated that statins might be potentially harmful in HF due to decreased endotoxin defense, diminishing thereby the potentially beneficial pleiotropic effects. There is some suggestive evidence that statins might reduce muscle strength and alter energy metabolism during aerobic exercise [38]. Based on our recent hypothesis this pro-sarcopenic effect of statins might be responsible of their limited efficacy in HF patients [38].…”

Section: Discussionmentioning

confidence: 99%

Association of statin use and clinical outcomes in heart failure patients: a systematic review and meta-analysis

et al. 2019

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BackgroundThe 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.MethodsWe 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.ResultsFinally 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.ConclusionsIn 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.

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Section: Discussionmentioning

confidence: 99%

Association of statin use and clinical outcomes in heart failure patients: a systematic review and meta-analysis

et al. 2019

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“…Along with the main effect of cholesterol lowering, statins have some ancillary actions that may be relevant to sarcopenia. The potential mechanisms of statin-mediated muscle dysfunction involve IGF-1, inflammation, the UPS, apoptosis, and myostatin 97.…”

Section: Treatmentsmentioning

confidence: 99%

New insights into the pathogenesis and treatment of sarcopenia in chronic heart failure

et al. 2019

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Sarcopenia is an age-related geriatric syndrome that is characterized by a progressive loss of muscle mass, strength and function. Chronic heart failure (CHF), the final stage of various cardiovascular diseases, may be closely correlated with the occurrence of sarcopenia. Accumulating evidence has demonstrated that CHF can promote the development of sarcopenia through multiple pathophysiological mechanisms, including malnutrition, inflammation, hormonal changes, oxidative stress, autophagy, and apoptosis. Additionally, CHF can aggravate the adverse outcomes associated with sarcopenia, including falls, osteoporosis, frailty, cachexia, hospitalization, and mortality. Sarcopenia and CHF are mutually interacting clinical syndromes. Patients with these two syndromes seem to endure a double burden, with no particularly effective way to hinder their progression. However, the combination of physical exercise, nutritional supplements, and drug therapy may counteract the development of these maladies. In this review, we will summarize the latest progress in the pathogenesis and treatment of sarcopenia in patients with CHF.

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“…The beneficial effects of statins on cerebral ischemia were not evident in eNOS gene knockout mice, confirming that these effects are mediated by NO [66]. However, there are controversies regarding beneficial effects of statins in HF [67][68][69].…”

Section: Heart Failurementioning

confidence: 99%

Statin-Induced Nitric Oxide Signaling: Mechanisms and Therapeutic Implications

Gorabi

Kiaie

Hajighasemi

et al. 2019

JCM

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In addition to their cholesterol-lowering effects, statins are associated with pleiotropic effects including improvements in heart failure (HF), reduced blood pressure, prevention of the rupture of atherosclerotic plaques and improved angiogenesis. In addition to these cardiovascular benefits, statins have been implicated in the treatment of neurological injuries, cancer, sepsis, and cirrhosis. These cholesterol-independent beneficial effects of statins are predominantly mediated through signaling pathways leading to increased production and bioavailability of nitric oxide (NO). In this review, the mechanistic pathways and therapeutic effects of statin-mediated elevations of NO are described and discussed.

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Prosarcopenic Effects of Statins May Limit Their Effectiveness in Patients with Heart Failure

Cited by 22 publications

References 218 publications

Association of statin use and clinical outcomes in heart failure patients: a systematic review and meta-analysis

Association of statin use and clinical outcomes in heart failure patients: a systematic review and meta-analysis

New insights into the pathogenesis and treatment of sarcopenia in chronic heart failure

Statin-Induced Nitric Oxide Signaling: Mechanisms and Therapeutic Implications

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