The cardiovascular (CV) benefits of therapy with hydroxymethylglutaryl-CoA reductase inhibitors (statins) are well established. In a prospective meta-analysis of over 90,000 patients in 14 randomized trials statin therapy decreased total mortality by 19%.1 The average LDL-cholesterol (LDL-C) at the end of the trials was 105 mg/dL representing a 29% reduction. A more recent meta-analysis of 7 randomized controlled trials of different intensities of statin therapies (29,395 patients) supported the use of more intensive statin regimens in patients with known coronary heart disease (CHD).2 Mortality was not decreased in patients with chronic ischemic heart disease but was significantly decreased in patients with acute coronary syndromes. There was insufficient evidence to support particular target LDL-C values or the use of combination therapies to achieve these targets. Investigators continue to search for convincing evidence supporting the hypothesis that greater reductions in LDL-C translate into greater reductions in CV morbidity and mortality.
Rahilly-Tierney and colleagues used the Veteran’s Affairs (VA) National Patient Care Database and northeast regional healthcare databases to perform a retrospective cohort study.3 The primary inclusion criteria for the cohort were at least 1 diagnosis that placed the subject at high risk for acute coronary events. These included diabetes mellitus, ischemic heart disease, or peripheral vascular disease. The study group was limited to male patients with 2 or more LDL-C measurements documented before the date of their first CV event [acute myocardial infarction, coronary artery bypass graft (CABG), or percutaneous transluminal angioplasty (PTCA)]. Patients with no outcomes were included if they had 2 or more LDL-C levels before the last date of available laboratory data or the date of their death. The cohort was also limited to patients with initial LDL-C values of ≥ 100 mg/dL.
For each patient the investigators calculated the reduction in LDL-C by determining the difference between the first documented LDL-C level and the level closest to but not on the date of the first CV outcome or death. LDL-C reduction was categorized as follows: an achieved reduction between 10 and 40 mg/dL was considered small, between 40 and 70 mg/dL was moderate, and a reduction ≥ 70 mg/dL was considered large. The reference group consisted of patients whose LDL-C decreased ≤ 10 mg/dL or increased. Additional patient data included age, body mass index (BMI), current smoking status, cholesterol-modifying therapy, and other medications used such as angiotensin-converting enzyme inhibitors, aspirin, and beta-blockers. The primary outcome was combined acute myocardial infarction, PTCA, or CABG, whichever occurred first.
The authors identified 20,132 subjects meeting the study criteria. The mean time to their first event was 0.98 years. The mean age was 67.7 years. The cohort consisted of patients with diabetes mellitus (39.5%), peripheral vascular disease (59.2%), and ischemic heart disease (61.5%). The mean initial LDL-C level was 137.8 mg/dL. Statin therapy was prescribed to 76.7% of the cohort and 15.9% were prescribed non-statin cholesterol-modifying therapy. Among the statin users, 62% received simvastatin, 30.7% lovastatin, and 5.5% atorvastatin. The mean ...