Statins for Heart Failure

Abstract & Commentary

By Jonathan Abrams, MD, Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque. Dr. Abrams serves on the speaker's bureau for Merck, Pfizer, and Parke-Davis.

Synopsis: 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.

Source: Go AS, et al. Statin Therapy and Risks for Death and Hospitalization in Chronic Heart Failure. JAMA. 2006;296:2105–2111.

Yet another observational study has been published that strongly suggests the value of concomitant statin treatment in a medical condition that is not clearly related to dyslipidemia. Because of prior reports in the literature regarding the favorable effect of statin utilization in patients with heart failure (in non-randomized or prospective trials), Go and colleagues from the Kaiser Permanente of Northern California Group, initiated an elaborate observational protocol in an attempt to identify whether statin treatment in patients with congestive heart failure is or is not beneficial. The medical records of almost 10,000 patients were carefully reviewed and a wide variety of potential confounding factors, ie, drug therapy, socio-economic status, were collected. The study only utilized data regarding the incidence in statin use in patients who were not receiving a statin at the study entry date, and who were eligible for treatment based on the national guidelines. The authors controlled for a wide variety of medications used in the treatment of heart failure; data on race and ethnicity were included. Renal dysfunction and multiple other diagnoses were assessed using ICD-9 codes, laboratory data, etc. Left ventricular function was obtained from health plan databases. Reduced left ventricular systolic function was defined as of an LV ejection fraction of < 40% or a designation of moderate or severely reduced systolic function; preserved LV function was defined by an LVEF of > 40% or a qualitative statement of only mildly reduced systolic function." Enrollment in the database could occur at any time during the 9 year window. A wide variety of statistical techniques were utilized, and many baseline demographic characteristics were identified.

Twenty-five thousand adults with CHF and no prior statin use were identified and considered eligible for lipid-lowering therapy. During follow-up, half of these individuals initiated statin therapy; these patients tended to be younger and male, but no other clinical differences were noted. There was a higher prevalence of coronary heart disease (CHD), diabetes, and hypertension in those individuals initiating statin therapy during the observational period. Baseline use of multiple drugs used for heart failure therapy and other lipid-lowering drugs were also higher among patients who initiated therapy during the study period.

Results: Median follow-up was 2.4 years, during which time 8,200 patients died and 9,200 patients were hospitalized for CHF. Age- and gender-adjusted rate of death was substantially lower in the statin therapy group, 14.5 per 100 person years vs 25.3 per 100 person years. Known CHD did not affect the data. Rates of hospitalization for heart failure were lower in those who began statin therapy vs those who did not, 21.9 per 100 person years vs 31.1 per 100 person years, P < 0.001. In the primary analysis (intention to treat analysis), incident statin use was associated with a 24% lower relative risk of death compared to patients not taking a statin, even after adjustment for multiple co-morbidities, socio-economic factors, etc. In a secondary, time-dependant, exposure analysis, the risk of death was even greater than in the primary analysis, with a hazard ratio of 0.66. Hospitalizations for CHF were 21% lower using the intent-to-treat approach.

The authors comment on theoretical benefits as well as adverse effects of statins. Two studies are cited that come to the same conclusion. However, the present study attempts to overcome many…methodological challenges" that are related to the wide variability of data collection in other reports. The authors emphasize that the Kaiser population was large and socio-demographically diverse," including patients diagnosed with CHF in and out of the hospital. Efforts were made to improve the power of this observational study. Overall, statin therapy remained a robust predictor of improved outcomes." The authors stress that they could not exclude residual confounding or selection bias, despite a wide number of adjustments for many population characteristics. They note that limited other experimental data are available, and that randomized trials have utilized relatively small sample sizes and had mixed results. They point out that several very large prospective randomized trials will be available in the future to resolve this issue and to clarify the role of statins in the management of heart failure."

Commentary

This study fits in with many reports in a variety of conditions indicate that individuals who are on a statin have lower morbidity and mortality rates than those not exposed to a statin. These data sets are observational in nature. It is unclear whether overall physician treatment in statin-treated patients is different (ie, better) compared to those not exposed to statins. The increased use of appropriate congestive heart failure therapy in the statin group suggests that this may be a factor; that is, that care in general was better and more evidence-based in the statin group. There are a variety of intracellular effects of HMG CoA reductase therapy, known as pleiotropic actions. Thus, endothelial function and nitric oxide availability are improved, cytokines and other inflammatory markers are diminished, and coronary plaque may be stabilized by statins. This report adds to a wide variety of data in the literature that come to the same conclusion, although with

widely disparate diagnoses. Clearly, at the very least, physicians should pay particular attention to current lipid guidelines, and make sure that congestive heart failure patients are appropriately treated, particularly for LDL cholesterol lowering, and that individuals with heart failure should not to be considered ineligible or poor statin candidates because of their primary illness.