In patients with coronary heart disease (CHD) and type 2 diabetes, percutaneous coronary intervention (PCI) was associated with reductions in major adverse cardiac or cerebrovascular events (MACCE) only when a low-density lipoprotein (LDL) cholesterol level below 70 mg/dL was achieved, a recent study found.
Researchers performed a patient-level pooled analysis of three randomized clinical trials in patients with established CHD and type 2 diabetes to determine how LDL cholesterol levels affected cardiovascular events after PCI or coronary artery bypass grafting (CABG) plus optimal medical therapy or after optimal medical therapy alone. Patients were enrolled in the trials between 1999 and 2010 and, for the current study, were classified according to LDL cholesterol levels one year after randomization (<70 mg/dL, 70 to <100 mg/dL, or ≥100 mg/dL). The primary end point was MACCE (a composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke). The study was funded by a research grant from Gilead Science as well as U.S. and Canadian government agencies. Results of the study were published Nov. 10 by the Journal of the American College of Cardiology.
Overall, 4,050 patients were followed for a median of 3.9 years after the initial assessment. Mean baseline age before study randomization for the whole cohort was 62.8 years, 27.0% of patients were women, and mean LDL cholesterol level at one year was 83.1 mg/dL. At one year, 1,398 patients (34.5%) had LDL cholesterol levels below 70 mg/dL, 1,711 (42.2%) had levels between 70 and below 100 mg/dL, and 941 (23.2%) had levels of 100 mg/dL or higher. Overall, 1,348 (33.3%) patients were assigned to optimal medical therapy, 990 (24.4%) to CABG and optimal medical therapy, and 1,712 (42.3%) to PCI and optimal medical therapy.
Over the 3.9-year follow-up, patients with a one-year LDL cholesterol level at or above 100 mg/dL had a higher cumulative risk of MACCE (17.2%) versus those with LDL levels of 70 to less than 100 mg/dL (13.3%) and less than 70 mg/dL (13.1%). Patients who had PCI plus optimal medical therapy had a reduction in MACCE versus optimal medical therapy alone only when their LDL level at one year was below 70 mg/dL (hazard ratio, 0.61; 95% CI, 0.40 to 0.91; P=0.016). CABG plus optimal medical therapy, however, was associated with improved outcomes at all categories of LDL cholesterol at one year. Among patients whose LDL cholesterol level at one year was 70 mg/dL or greater, those undergoing CABG had lower MACCE rates than those undergoing PCI.
The authors noted that interventions to reduce LDL cholesterol levels during the first year of follow-up were not systematically analyzed, that data on adherence to prescribed therapy were not available, and that medical technology and therapies have advanced since the study was conducted, among other limitations. They concluded that in patients with CHD and type 2 diabetes, control of LDL cholesterol levels in the first year after coronary revascularization is important for risk reduction. Patients with LDL cholesterol levels at or above 100 mg/dL had higher rates of MACCE and subsequent revascularization than patients with LDL levels below 70 mg/dL at one year. “Additionally, LDL-C [cholesterol]-lowering seems to be particularly important in patients with [type 2 diabetes] undergoing PCI, because when compared with [optimal medical therapy] alone, MACCE reductions in this group were observed only with 1-year LDL-C levels <70 mg/dl,” the authors wrote. They noted that optimal control of LDL cholesterol levels may be key to achieving optimal outcomes after PCI and called for further study of this issue.
An accompanying editorial said that the current study and previous research support the use of an individual treatment strategy that accounts for patients' individual LDL cholesterol levels when estimating outcomes and treatment effects. LDL levels of 100 mg/dL or greater are associated with the highest-risk profile, the editorialists noted. “The findings of the present study are relevant for clinical practice and may pave the way toward the generation of novel personalized medicine models that can optimize care of patients with [type 2 diabetes]. These models will ultimately integrate the treatment effects from coronary revascularizations and lipid-lowering interventions with baseline and 1-year LDL-C thresholds,” they wrote. “This research is a much welcomed deeper foray into this important area and should increase the pace of future investigations to further unravel the so-far neglected association among LDL-C thresholds, outcome, and expected treatment effects in all high-risk subjects.”