The American Heart Association estimates one in three adults in the United States have cardiovascular disease (CVD).1 As the leading cause of mortality in the Western world, CVD creates a considerable health care burden.2 Current clinical trials and meta-analyses support the use of hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) for secondary prevention of CVD and for primary prevention in individuals with cardiovascular risk factors. Although statin use has been proven effective in CVD, recent debate centers on determining the ideal treatment approach to lower coronary artery disease (CAD) risk. A new, tailored approach to statin therapy has emerged to challenge the current strategy adopted by the NCEP (National Cholesterol Education Program) III guidelines.3 This novel treatment approach would stratify patients to lipid-modifying therapy based on CAD risk without targeting set low-density lipoprotein (LDL) cholesterol goals. Questions then arise as to whether or not statin therapy is safe and effective in patients with substantial CAD risk but low LDL-cholesterol levels.
In the retrospective cohort study conducted by Nicholas J. Leeper and colleagues at the Palo Alto VA Medical Center in Palo Alto, CA, researchers examined the safety and clinical outcomes of statin therapy in patients with LDL cholesterol levels below 60 mg/dL.4 The primary end point was total mortality. Secondary endpoints included ischemic heart disease hospitalization, congestive heart failure hospitalization, myocardial infarction, cerebrovascular accident, de novo malignancy, rhabdomyolysis liver dysfunction, and renal failure. The final analysis included 4,295 individuals with a mean age of 65 years old and average LDL cholesterol of 49.3 ± 9.8 mg/dL. Individuals on statin therapy were compared with those not receiving statin therapy. Patients were considered to be on statin therapy if they filled a prescription for a statin within 150 days after the recorded low LDL cholesterol value. In all, 2,564 patients were treated with statin therapy (59.7%).
During the mean 2.0 ± 1.4 year follow-up period, 258 (10%) deaths occurred in the statin therapy group compared with 252 (14.6%) deaths in the group not receiving statin therapy (p < 0.001). Both adjusted and unadjusted proportional hazards demonstrated a statistically significant decrease in mortality between patients on statin therapy versus those not receiving a statin [(unadjusted: hazard ratio [HR], 0.81; 95% confidence interval [CI] 0.68 to 0.96) (adjusted: HR, 0.65; 95% CI 0.53 to 0.80)]. Patients on statin therapy did have a higher incidence of ischemic events (myocardial infarction or unstable angina admission); however, after adjustment for baseline characteristics, a trend towards reduced admission for ischemic events was observed (adjusted odds ratio, 0.79; 95% CI, 0.60 to 1.05). In terms of safety, statin use was not associated with a statistically significant increase in malignancy, rhabdomyolysis, transaminase elevation, or stroke.
As new discoveries are made in CAD prevention, treatment strategies will evolve and recommendations for statin therapy may change. Based on the study of statin therapy in patients with extremely low LDL levels, statin use appears to be safe and efficacious. Although encouraging, these finding are based on a short follow-up period, observational data, and two cohort groups with substantially different baseline characteristics. Further research is therefore needed, preferably utilizing prospective randomized studies, to confirm the positive findings in patients with low LDL cholesterol levels.
1. American Heart Association. Heart disease and stroke statistics 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009,119:e21–e181.
2. Brugts JJ, Yetgin T, Hoeks SE, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ 2009,338:b2376.
3. Hayward RA, Drumholz HM, ...