Statin Therapy and Risks for Death and Hospitalization in Chronic Heart Failure

Department of Medicine, University of California, San Francisco, San Francisco, California, United States
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 12/2006; 296(17):2105-11. DOI: 10.1001/jama.296.17.2105
Source: PubMed


Whether statin therapy has beneficial effects on clinical outcomes in patients with heart failure is unclear.
To evaluate the association between initiation of statin therapy and risks for death and hospitalization among adults with chronic heart failure.
Propensity-adjusted cohort study of adults diagnosed with heart failure who were eligible for lipid-lowering therapy but had no previous known statin use, within an integrated health care delivery system in northern California between January 1, 1996, and December 31, 2004. Statin use was estimated from filled outpatient prescriptions in pharmacy databases.
All-cause death and hospitalization for heart failure during a median of 2.4 years of follow-up. We examined the independent relationships between statin therapy and risks for adverse events overall and stratified by the presence or absence of coronary heart disease after multivariable adjustment for potential confounders.
Among 24,598 adults diagnosed with heart failure who had no prior statin use, those initiating statin therapy (n = 12,648; 51.4%) were more likely to be younger, male, and have known cardiovascular disease, diabetes, and hypertension. There were 8235 patients who died. Using an intent-to-treat approach, incident statin use was associated with lower risks of death (age- and sex-adjusted rate of 14.5 per 100 person-years with statin therapy vs 25.3 per 100 person-years without statin therapy; adjusted hazard ratio, 0.76 [95% confidence interval, 0.72-0.80]) and hospitalization for heart failure (age- and sex-adjusted rate of 21.9 per 100 person-years with statin therapy vs 31.1 per 100 person-years without statin therapy; adjusted hazard ratio, 0.79 [95% confidence interval, 0.74-0.85]) even after adjustment for the propensity to take statins, cholesterol level, use of other cardiovascular medications, and other potential confounders. Incident statin use was associated with lower adjusted risks of adverse outcomes in patients with or without known coronary heart disease.
Among adults diagnosed with heart failure who had no prior statin use, incident statin use was independently associated with lower risks of death and hospitalization among patients with or without coronary heart disease.

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    • "If cholesterol levels increase by 30%, the risk of cardiovascular disease doubles [14]. In order to properly control hyperlipidemia, various recommendations have been made that include receiving lipid-lowering drugs along with maintaining a healthy diet and getting ample exercise [14-19]. "
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    ABSTRACT: The rapid growth of prescription drug expenditures is a major problem in South Korea. Accordingly, the South Korean government introduced a positive listing system in 2006. They also adopted various price reduction policies. Nevertheless, the total expenditure for lipid-lowering drugs have steadily increased throughout South Korea. The present study explores the factors that have influenced the increased expenditures of lipid-lowering drugs with a particular focus on the effects of statins in this process. This paper investigates the National Health Insurance claims data for prescribed lipid-lowering drugs collected between January 1, 2005 and December 31, 2009. We specifically focused on statins and assessed the yearly variation of statin expenditure by calculating the increased rate of paired pharmaceutical expenditures over a 2 year period. Our study classified statins into three categories: new entrants, core medicines and exiting medicines. For core medicines, we further examined influencing factors such as price, amount of drugs consumed by volume, and prescription changes (substitutes for other drug). Statin expenditure showed an average annual increase of 25.7% between 2005 and 2009. Among the different statins, the expenditure of atorvastatin showed a 36.6% annual increase rate, which was the most dramatic among all statins. Also we divided expenditure for core medicines by the price factor, volume factor, and prescription change. The result showed that annual weighted average prices of individual drug decreased each year, which clearly showed that price influenced statin expenditure in a negative direction. The use of generic drugs containing the same active ingredient as name-brand drugs increased and negatively affected statin expenditure(Generic Mix effect). However, the use of relatively expensive ingredients within statin increase, Ingredient Mix effect contributed to increased statin expenditure (Ingredient Mix effect). In particular, the volume effect was found to be critical for increasing statin expenditure as the amount of statin consumed increased steadily throughout the study period. The recent rapid increase in statin expenditure can largely be attributed to an increase in consumption volume. In order to check drug expenditures effectively in our current situation, in which chronic diseases remain steadily on the rise, it is necessary to not only have supply-side initiatives such as price reduction, but also demand-side initiatives that could control drug consumption volume, for example: educational programs for rational prescription, generic drug promotional policies, and policies providing prescription targets.
    Full-text · Article · Mar 2014 · BMC Health Services Research
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    • "Nonetheless, it is still unclear whether statins are beneficial in patients with established heart failure. A number of non-randomised studies have shown statin therapy improves clinical outcomes in patients with HF [6-10]. Likewise, small-scale RCTs have shown improved cardiac function and reduced inflammation and mortality outcomes in HF [11-14]. "
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    ABSTRACT: Background: Statins are known to reduce cardiovascular morbidity and mortality in primary and secondary prevention studies. Subsequently, a number of nonrandomised studies have shown statins improve clinical outcomes in patients with heart failure (HF). Small randomised controlled trials (RCT) also show improved cardiac function, reduced inflammation and mortality with statins in HF. However, the findings of two large RCTs do not support the evidence provided by previous studies and suggest statins lack beneficial effects in HF. Two meta-analyses have shown statins do not improve survival, whereas two others showed improved cardiac function and reduced inflammation in HF. It appears lipophilic statins produce better survival and other outcome benefits compared to hydrophilic statins. But the two types have not been compared in direct comparison trials in HF. Methods/design: We will conduct a systematic review and meta-analysis of lipophilic and hydrophilic statin therapy in patients with HF. Our objectives are:1. To determine the effects of lipophilic statins on (1) mortality, (2) hospitalisation for worsening HF, (3) cardiac function and (4) inflammation.2. To determine the effects of hydrophilic statins on (1) mortality, (2) hospitalisation for worsening HF, (3) cardiac function and (4) inflammation.3. To compare the efficacy of lipophilic and hydrophilic statins on HF outcomes with an adjusted indirect comparison meta-analysis.We will conduct an electronic search of databases for RCTs that evaluate statins in patients with HF. The reference lists of all identified studies will be reviewed. Two independent reviewers will conduct the search. The inclusion criteria include:1. RCTs comparing statins with placebo or no statin in patients with symptomatic HF.2. RCTs that employed the intention-to-treat (ITT) principle in data analysis.3. Symptomatic HF patients of all aetiologies and on standard treatment.4. Statin of any dose as intervention.5. Placebo or no statin arm as control.The exclusion criteria include:1. RCTs involving cerivastatin in HF patients.2. RCTs with less than 4 weeks of follow-up. Discussion: We will perform an adjusted indirect comparison meta-analysis of lipophilic versus hydrophilic statins in patients with HF using placebo or no statin arm as common comparator.
    Full-text · Article · Apr 2013 · Systematic Reviews
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    • "Of note, there were no formulary restrictions for use of these β-blockers at KPCO during the study period. We used automated pharmacy data on filled outpatient prescriptions to determine the dose and timing, and estimate the duration of receipt of β-blockers based on the days supplied per prescription and refill patterns using a previously established approach [11-13]. The KPCO pharmacy benefit offered prescriptions for a nominal co-payment (typically $5 for a month supply) and prescriptions were conveniently filled at the site of clinical encounters or mailed directly to patients, thus providing a strong incentive to fill prescriptions within the KPCO system. "
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    ABSTRACT: In response to the short-term negative inotropic and chronotropic effects of β-blockers, heart failure (HF) guidelines recommend initiating β-blockers at low dose with gradual uptitration as tolerated to doses used in clinical trials. However, patterns and safety of β-blocker intensification in routine practice are poorly described. We described β-blocker intensification among Kaiser Colorado enrollees with a primary discharge diagnosis of HF between 2001-2009. We then assessed β-blocker intensification in the 30 days prior to first hospital readmission for cases compared to the same time period following index hospitalization for non-rehospitalized matched controls. In separate analysis of the subgroup initiated on β-blocker after index hospital discharge, we compared adjusted rates of 30-day hospitalization following initiation of high versus low dose β-blocker. Among 3,227 patients, median age was 76 years and 37% had ejection fraction ≤ 40% (LVSD). During a median follow up of 669 days, 14% were never on β-blocker, 21% were initiated on β-blocker, 43% were discharged on β-blocker but never uptitrated, and 22% had discharge β-blocker uptitrated; 63% were readmitted and 49% died. β-blocker intensification occurred in the 30 days preceding readmission for 39 of 1,674 (2.3%) readmitted cases compared to 27 (1.6%) of matched controls (adjusted OR 1.36, 95% CI 0.81-2.27). Among patients initiated on therapy, readmission over the subsequent 30 days occurred in 6 of 155 (3.9%) prescribed high dose and 9 of 513 (1.8%) prescribed low dose β-blocker (adjusted OR 3.10, 95% CI 1.02-9.40). For the subgroup with LVSD, findings were not significantly different. While β-blockers were intensified in nearly half of patients following hospital discharge and high starting dose was associated with increased readmission risk, the prevailing finding was that readmission events were rarely preceded by β-blocker intensification. These data suggest that β-blocker intensification is not a major precipitant of hospitalization, provided recommended dosing is followed.
    Full-text · Article · Jun 2012 · BMC Cardiovascular Disorders
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