The effect of intensified lipid-lowering therapy on long-term prognosis in patients with peripheral arterial disease

Background. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are associated with improved outcome in patients with peripheral arterial disease. Statins may also have beneficial properties beyond their lipid-lowering effect. Methods. A prospective, observational cohort study was conducted at a university hospital from 1990 to 2005 to examine whether higher doses of statins and lower low-density lipoprotein (LDL) cholesterol levels are both independently associated with improved outcome in peripheral arterial disease. Enrolled were 1374 consecutive patients (age, 61 +/- 10 years, 73% male) with peripheral arterial disease (ankle-brachial index <= 0.90). They were screened for clinical risk factors, statin therapy, and LDL cholesterol levels. Serial LDL cholesterol levels were measured at 6 months and yearly after enrollment. The mean follow-up time was 6.4 +/- 3.6 years, and no patients were lost to follow-up. The primary end points were all-cause and cardiac mortality. The secondary end point was the progression to kidney failure. Results. Overall mortality, cardiac death, and progression to kidney failure occurred in 29%, 20%, and 5% of patients, respectively. Multivariate analysis revealed that higher doses of statins (per 10% increase) and lower 6-month LDL cholesterol levels (per 10 mg/dL decrease) were both independently associated with lower all-cause mortality (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.62 to 0.80; and HR, 0.96; 95% Cl, 0.93 to 0.98, respectively) and cardiac death (HR, 0.76; 95% CI, 0.67 to 0.86; and HR, 0.95; 95% CI, 0.92 to 0.98, respectively). Higher high-density lipoprotein cholesterol levels also correlated significantly with lower all-cause and cardiac mortality. Higher doses of statins (per 10% increase) were associated with less progression to kidney failure (HR, 0.69; 95% CI, 0.54 to 0.89). Conclusions. Higher doses of statins and lower LDL cholesterol levels are both independently associated with improved outcome in patients with peripheral arterial disease. These results support the view that statins have beneficial effects beyond their lipid-lowering properties and should be considered in all patients with PAD, irrespective of LDL cholesterol levels.