Combination Lipid-Lowering Therapy May Reduce Risk of Stroke More Effectively than Statins Alone

Combination lipid-lowering therapy (LLT) using a statin in conjunction with Zetia (ezetimibe; Merck & Co, Rahway, NJ) may improve cardiovascular outcomes compared with statin monotherapy, according to results of a meta-analysis published in Mayo Clinic Proceedings. The findings provide evidence supporting the use of combination LLT as an early intervention for achieving low-density lipoprotein cholesterol (LDL-C) goals to reduce major adverse cardiovascular events (MACE), including stroke, and cardiovascular disease (CVD) morbidity and mortality (CVM).

Researchers conducted a systematic literature search of the PubMed, Embase, and ClinicalTrials.gov databases to identify 14 published articles to include in the meta-analysis. These articles comprised 11 randomized controlled trials (RCTs) and 3 cohort studies, with a total of 108,373 participants included across the 14 studies who were aged a mean of 67 years. Of this population, 24,608 received combination LLT and 83,765 received statin monotherapy.

The primary endpoint of the meta-analysis was change in mean LDL-C level from baseline, which was met. Combination LLT was associated with a mean 12.96 mg/dL greater reduction in LDL-C level from baseline compared with statin monotherapy (95% CI, -17.27 to -8.65; P<.001). In terms of key secondary endpoints, significant reductions in the following outcomes were also associated with combination LLT vs statin monotherapy:

• All-cause mortality (odds ratio [OR], 0.81; 95% CI, 0.67 to 0.97; P=.02)
• MACE (OR, 0.82; 95% CI, 0.69 to 0.97; P=.02)
• Stroke incidence (OR, 0.83; 95% CI, 0.75 to 0.91; P=.001)

There were also numerical but statistically insignificant reductions in CVM (OR, 0.86; 95% CI, 0.65 to 1.12; P=.26), and rates of adverse events and therapy discontinuation were similar between the 2 treatment groups.