Effects of Combination Lipid Therapy on Coronary Stenosis Progression and Clinical Cardiovascular Events in Coronary Disease Patients with Metabolic Syndrome: A Combined Analysis of the Familial Atherosclerosis Treatment Study (FATS) the HDL-Atherosclerosis Treatment Study (HATS) and the Armed Forces Regression Study (AFREGS)

摘要

We examined the impact of metabolic syndrome (MS) on coronary stenosis progression and major cardiovascular (CV) events and investigated the mitigating effects of low-density lipoprotein cholesterol (LDL-C) lowering and LDL-C-lowering plus high-density lipoprotein cholesterol (HDL-C) raising. This analysis combined individual patient data from 445 subjects who participated in 3 double-blinded, randomized, placebo-controlled trials (FATS, HATS, and AFREGS) comparing intensive lipid therapy to placebos on coronary stenosis progression by quantitative coronary angiography and on major CV events. The primary endpoints were the change in mean proximal coronary diameter stenosis (Δ%Sprox) over 3 years and the frequency of the pre-defined composite of coronary artery disease (CAD) death, nonfatal myocardial infarction (MI), stroke and revascularization due to worsening ischemia. Patients with the MS had 50% more rapid coronary stenosis progression and 64% increased CV event frequency compared to those without. More rapid coronary stenosis progression was significantly and independently associated with 3.5-fold increased event risk (p<0.001). Combination lipid therapy significantly decreased stenosis progression by 83% (Δ%Sprox=0.5 vs. 2.9, p<0.001) in patients with MS, and induced a small net regression in those without (Δ%Sprox=−0.3 vs. 2.0, p<0.001). Combination therapy reduced the event rate by 54% (13 vs. 28%, p=0.03) in those with MS and by 82% (3 vs. 17%, p=0.002) without. On average, each 10% reduction in LDL-C or 10% increase in HDL-C was significantly associated with 0.3 Δ%Sprox reduction. Each 10% LDL-C-lowering or 10% HDL-C-raising was associated with 11% (p=0.02) or 22% (p<0.001) event risk reduction. In conclusion, patients with MS have significantly more rapid coronary stenosis progression and a higher frequency of CV events. Greater stenosis progression rate is associated with a higher event rate. LDL-C-lowering and HDL-C-raising therapies independently and significantly decrease coronary stenosis progression and reduce CV events.