Statins Stave Off Death for Chronic Heart Failure Patients

OAKLAND, Calif., Nov. 1 -- Statins appear to be beneficial in reducing death and hospitalizations in heart failure patients, according to researchers here.

In chronic heart failure patients who started statin therapy, the drugs were associated with a reduction in the relative risk of death by 24% and hospitalization by 21% compared with those who did not take them, reported Alan S. Go, M.D., of Kaiser Permanente of Northern California, and colleagues, in the Nov. 1 issue of the Journal of the American Medical Association.

The role of statins in patients with heart failure has been unclear. Clinical trials of statins have largely excluded them, and some epidemiological studies have indicated that if heart failure patients have low levels of LDL cholesterol, they may be at a higher risk of adverse events. Also, there has been concern that statins could indirectly impair cardiac muscle and function and interact with medications such as digoxin.

Dr. Go and colleagues reported results of an observational study of 24,598 adults insured by Kaiser Permanente Northern California and diagnosed with heart failure. The study included only patients who had no prior statin use but were eligible for it on the basis of the National Cholesterol Education Program's Adult Treatment Panel III guidelines.

In an intent-to-treat analysis, the investigators found:

• Incident statin use was associated with a lower rate of death after adjustment for age and sex (14.5 versus 25.3 per 100 person-years, P<0.001),
• Patients who started statin therapy had a lower risk of all-cause mortality after adjustment for age and sex (hazard ratio 0.76, 95% confidence interval 0.72 to 0.80),
• Statin use reduced the rate of hospitalization for heart failure even after adjustment for age and sex (21.9 versus 31.1 per 100 person-years P<0.001), and
• The risk of hospitalization for heart failure was lower in patients who started statin therapy compared with those who did not (adjusted hazard ratio 0.79, 95% CI 0.74 to 0.85) even after adjustment for the propensity to take statins, cholesterol level, use of other cardiovascular medications, and other potential confounders.

A little more than half of the participants did begin statin therapy (12,648, 51.4%). Compared with those who did not initiate statin treatment, they were more likely to be younger, male, and have known cardiovascular disease, diabetes, and hypertension at baseline. Patients initiating statin therapy also had more pre- and post-study visits to a cardiologist and higher total cholesterol and LDL levels.

The investigators analyzed the Kaiser Permanente databases for statin use estimated from filled outpatient prescriptions. The researchers defined chronic heart failure as having one or more hospitalizations with a principal diagnosis of heart failure, two hospitalizations with a secondary diagnosis of heart failure and a related principal diagnosis, three or more hospitalizations with secondary diagnosis of heart failure, two or more outpatient diagnoses, three or more emergency department visit diagnoses, or two or more inpatient secondary diagnoses and one outpatient diagnosis.

Over the median 2.4 years of follow-up, 8,235 participants died. The study population was sociodemographically diverse and had equal access to healthcare.

Secondary analyses looking at timing and duration of exposure to statins "suggested even greater benefit," Dr. Go and colleagues said. The time-varying use findings were:

• There was an even lower adjusted risk of death while patients were taking statins compared with periods when they were not taking them (adjusted hazard ratio 0.64, 95% CI 0.60 to 0.68), and
• The risk of hospitalization for heart failure was likewise reduced during on-drug periods (0.75, 95% CI 0.70 to 0.79).

The lower risk of adverse outcomes was unaffected by whether patients had known coronary heart disease. The researchers reported:

• The risk of death was not significantly different for patients with compared to without coronary heart disease (time-varying statin use adjusted hazard ratio 0.66 versus 0.60), and
• The risk of hospitalization was similar between patients with and without coronary heart disease (time-varying statin use adjusted hazard ratio 0.73 versus 0.74).

The researchers said there may be benefits for patients with heart failure beyond just lipid lowering, such as reduced inflammatory factors and detrimental cytokines, improved endothelial function, and stabilized coronary plaque.

They cautioned that as an observational study, residual confounding and selection bias could not be completely excluded. They concluded that future randomized controlled trials involving clinical outcomes-particularly among patients with nonischemic heart failure not otherwise recommended to receive lipid lowering therapy-are needed to clarify the role of statins in heart failure.

The study was funded by a grant from Amgen. Some of the authors received research support from Amgen, Novartis and Wyeth.