Statin Therapy In Heart Failure Research Articles

Impact of Statin Therapy in Heart Failure Patients: Results of a Large Real-World Experience

BackgroundThe use of statins in patients with heart failure (HF) is controversial. In patients without HF, statins reduce atherosclerotic cardiovascular disease (ASCVD) risk, including HF-related events. However, in some large studies, no benefit was seen in statin-treated HF patients. ObjectivesThe purpose of this study was to determine the impact of statin therapy in HF with reduced ejection fraction (HFrEF). MethodsIntermountain Healthcare medical records identified patients with a HF diagnosis and an ejection fraction of ≤40%. Patients prescribed and not prescribed a statin were compared for major adverse cardiovascular events (MACE) (death, myocardial infarction, stroke) (median of 4.5 years follow-up). Statin use was defined as use at or after a HF diagnosis but at least 60 days before MACE or end of follow-up. Cox proportional hazards regression was used to determine the relationship between statin use and outcomes. ResultsA total of 15,010 patients (n = 9,641 [64%] on statins) were studied. Statin use was associated with more frequent ASCVD risk factors yet a lower risk of MACE risk (adjusted HR: 0.53; 95% CI: 0.51-0.56; P < 0.0001). Benefit was similar for primary and secondary prevention patients and for prior and new statin prescriptions. Using time-varying hazard ratio analysis, the longer the patient was on a statin, the greater the reduction in risk of MACE (P < 0.0001). ConclusionsThese results suggest a potential benefit of selective statin use in the real-world management of HFrEF patients with ASCVD or at high ASCVD risk.

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

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.

Comparison of Effects of Statin Use on Mortality in Patients With Heart Failure and Preserved Versus Reduced Left Ventricular Ejection Fraction

Randomized trials showed no survival benefit with statin therapy in heart failure (HF) patients with reduced ejection fraction (HFrEF). Whether these results are generalizable to HF patients with preserved ejection fraction (HFpEF) or with mid-range ejection fraction is unclear. In a cohort of 13,440 patients with HF, 9,903 (73.7%) were treated with statins. The association between statin use and all-cause mortality was assessed with Cox proportional hazard regression models and survival time inverse probability weighting propensity scores analyses. Multivariable Poisson regression models with robust error variance were applied to estimate the rate ratios (RR) for hospitalization. The association between statin treatment and clinical outcomes differed by ejection fraction group. In patients with HFpEF, statin use was associated with reduced mortality (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.66 to 0.81, p <0.001; average treatment effect [ATE] 0.48, 95% CI 0.13 to 0.84, p = 0.007) and reduced all-cause hospitalization (RR 0.82, 95% CI 0.76 to 0.89, p <0.001). In contrast, in patients with HFrEF, no significant association was observed between statin use and mortality (HR 0.86, 95% CI 0.74 to 1.0, p = 0.054; ATE 0.41, 95% CI -0.09 to 0.93, p = 0.11) or hospitalization (RR 0.92, 95% CI 0.82 to 1.04, p = 0.17). Similarly, in patients with mid-range ejection fraction, there was no significant association with reduced mortality (HR 0.76, 95% CI 0.60 to 0.95, p = 0.02, ATE 0.3, 95% CI -0.84 to 1.43, p = 0.61) or hospitalization (RR 1.07, 95% CI 0.9 to 1.27, p = 0.44). In conclusion, statin use was associated with improved clinical outcomes in patients with HFpEF but not in patients with HFrEF or mid-range ejection fraction.

Statin Therapy in Heart Failure: For Good, for Bad, or Indifferent?

Statins are effective in the prevention of coronary events and the treatment of acute coronary syndromes. However, their efficacy and safety in patients with heart failure (HF) is still a matter of debate. On the basis of literature evidence from subgroup analysis, retrospective, prospective cohort studies, and randomized controlled trials, in this review we try to answer the following question: Is statin therapy in HF patients for good, for bad, or indifferent? Some studies showed a negative impact of low cholesterol levels in patients with severe HF (endotoxin-lipoprotein hypothesis and coenzyme Q10 hypothesis). On the other hand, a large amount of literature demonstrates that in patients with HF, statins have a positive impact on survival and other outcomes, regardless of whether the HF was of ischemic or nonischemic origin, which is related to a combination of mechanisms (pleiotropic effects and cholesterol reduction). Much of this evidence, however, comes from observational and retrospective studies and subgroup analyses of statin use in patients with HF. Randomized clinical trials examining the efficacy of statins in HF (GISSI-HF and CORONA) did not show a benefit in mortality for patients with HF randomized to receive statins. Nevertheless, a meta-analysis found that statin therapy does not decrease all-cause or cardiovascular mortality but significantly decreases the rate of hospitalization for worsening HF and increased left ventricular ejection fraction compared with placebo.

Long-Term Statin Therapy in Patients With Systolic Heart Failure and Normal Cholesterol: Effects on Elevated Serum Markers of Collagen Turnover, Inflammation, and B-Type Natriuretic Peptide

BackgroundThe role of statin therapy in heart failure (HF) is unclear. The amino-terminal propeptide of procollagen type III (PIIINP) predicts outcome in HF, and yet there are conflicting reports of statin therapy effects on PIIINP. ObjectivesThis study determined whether there was an increase in serum markers of inflammation, fibrosis (including PIIINP), and B-type natriuretic peptide (BNP) in patients with systolic HF and normal total cholesterol and determined the effects of long-term treatment with atorvastatin on these markers. MethodsFifty-six white patients with systolic HF and normal cholesterol levels (age 72 [13] years; 68% male; body mass index 27.0 [7.3] kg/m2; ejection fraction 35 [13]%; 46% with history of smoking) were randomly allocated to atorvastatin treatment for 6 months, titrated to 40 mg/d (A group) or not (C group). Age- and/or sex-matched subjects without HF (N group) were also recruited. Biomarkers were measured at baseline (all groups) and 6 months (A and C groups). ResultsSerum markers of collagen turnover, inflammation, and BNP were significantly elevated in HF patients compared with normal participants (all P < 0.05). There were correlations between these markers in HF patients but not in normal subjects. Atorvastatin treatment for 6 months caused a significant reduction in the following biomarkers compared with baseline: BNP, from median (interquartile range) 268 (190–441) pg/mL to 185 (144–344) pg/mL; high-sensitivity C-reactive protein (hs-CRP), from 5.26 (1.95 –9.29) mg/L to 3.70 (2.34–6.81) mg/L; and PIIINP, from 4.65 (1.86) to 4.09 (1.25) pg/mL (all P < 0.05 baseline vs 6 months). Between-group differences were significant for PIIINP only (P = 0.027). There was a positive interaction between atorvastatin effects and baseline hs-CRP and PIIINP (P < 0.01). ConclusionsLong-term statin therapy reduced PIIINP in this small, selected HF population with elevated baseline levels. Further evaluation of statin therapy in the management of HF patients with elevated PIIINP is warranted. ClinicalTrials.gov identifier: NCT00795912.

Low-density lipoprotein in the setting of congestive heart failure: Is lower really better?

Hypercholesterolemia is a risk factor for coronary artery disease (CAD), CAD mortality, and incident heart failure (HF). Lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been shown to reduce the risk of developing HF in patients with CAD. However, in patients with chronic established HF, hypercholesterolemia has not been associated with an increased risk of mortality. Several studies have demonstrated that higher lipid and lipoprotein levels, including total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides, are associated with significantly improved outcomes in HF of both ischemic and nonischemic etiologies. In light of the association between high cholesterol levels and improved survival in HF, statin or other lipid-lowering therapy in HF remains controversial. To date, large outcome trials of statin therapy in HF of multiple etiologies have not demonstrated mortality benefit.

Statin Therapy and Clinical Outcomes in Heart Failure: A Propensity-Matched Analysis

Background The influence of statin therapy in heart failure (HF) has been of considerable interest. The objective of this study was to determine if statins are associated with improved outcomes in patients discharged after hospitalization for HF. Methods Patients admitted to Ontario hospitals between 1999 and 2001 with HF were identified in the Enhanced Feedback For Effective Cardiac Treatment study. Propensity score methods were used to assess 5-year outcomes in the overall cohort as well as in 4 subgroups: those with coronary artery disease (CAD) or without (NoCAD), and those with preserved ejection fraction (HFPEF) or with reduced ejection fraction (HFREF). Of the 6451 HF patients, 1121 were discharged with a prescription for a statin. Results In propensity analysis stratified on matched pairs in a Cox proportional hazards model, statins were associated with improved mortality at 5 years overall (hazard ratio [HR] 0.85, P = .05) and in those with CAD (HR 0.79, P = .008). Similarly, statins were associated with lower risk of the combined end point in the CAD group (HR 0.85, P = .045). Conclusions Among patients with HF discharged from hospital, statin therapy was associated with improved outcomes, particularly in patients with CAD. Stratification by ejection fraction did not differentially impact the effect of statins in patients with HF.

Statin therapy in heart failure: Prognostic effects and potential mechanisms

The use of statins as therapy for heart failure remains controversial. Nevertheless, many of the pleiotropic effects of statins are potentially applicable in heart failure. Although early statin trials excluded patients with heart failure because of concerns that lowering serum cholesterol could worsen an already poor prognosis, statin treatment has not been shown to have adverse effects on either cardiovascular events or mortality, and recent experimental and clinical studies have shown promise of benefit. Two large, ongoing trials should provide definitive evidence of the value of statin therapy for patients with heart failure. Pending those results, it is reasonable to follow current National Cholesterol Education Program guidelines in this high-risk population.

Potential Role of Statin Therapy in Heart Failure, Atrial Fibrillation and Aortic Stenosis

3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, or statins, are widely prescribed throughout the world, and considerable evidence has indicated their powerful effects in ischemic forms of cardiovascular disease. Recently, several trials have demonstrated that statins have pleiotropic effects beyond their lipid-lowering capacities. These findings may play a role in the use of statins to manage forms of cardiovascular disease that may or may not have an ischemic etiology: congestive heart failure, atrial fibrillation and aortic stenosis.

Statin therapy in heart failure

The 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors, or statins, have been shown to reduce cardiovascular morbidity and mortality among a wide spectrum of patients with established atherosclerotic vascular disease. Mounting experimental and clinical evidence also suggest a potential benefit as well as theoretical harm of statin therapy in patients with heart failure. This article briefly summarizes the therapeutic properties of statins that may be of benefit to patients with heart failure and the theoretical adverse effects of cholesterol reduction in this group of patients. A number of nonrandomized clinical studies over the past several years have shown an association between statin use and reduced overall mortality. Several large-scale randomized studies designed to confirm these findings are currently under way. Statin therapy appears to improve clinical outcomes in patients with both ischemic and nonischemic cardiomyopathy independently of their cholesterol-lowering properties. The theoretical adverse properties of statins in heart failure patients have not been substantiated in small to medium-sized clinical trials. Although the encouraging results of these preliminary studies suggest a role for statin therapy in heart failure, larger studies are needed to validate these findings. Several ongoing randomized trials are currently under way to evaluate the effect of statin therapy on cardiovascular outcomes in heart failure patients. The results of these studies, expected in the next several years, should provide scientific evidence for the role of statins in the treatment of failure.

Statin therapy in heart failure

Congestive heart failure (CHF) affects up to2% of the population, and recent data indicatedramatic increases in its incidence and preva-lence, especially in western societies. It is a verydisabling and debilitating illness. Over the past10 to 20 years there have been dramaticchanges in the management of CHF, based onlarge-scale, randomized, controlled trials. Cur-rently, angiotensin-converting enzyme inhibi-tors,