When it comes to reducing low-density lipoprotein cholesterol (LDL-C) levels in patients age 75 or older, simvastatin perhaps shouldn’t be used alone. A study in JAMA Cardiology showed that a combination of ezetimibe (10 mg/d) and simvastatin (40 mg/d) yielded the best results in lowering LDL-C levels in this cohort without compromising safety. The findings could set a precedent on new guideline recommendations to reduce LDL-C levels in elderly individuals with atherosclerotic cardiovascular disease (CVD).
“Although randomized trials have shown that high-intensity treatment to lower lipid levels reduces CVD events for patients after an ACS whose mean age is approximately 60 years, the evidence supporting the benefit of intensive therapy to lower lipid levels among elderly patients is more limited,” observed the authors. For this reason, a lack of uniform guidelines exists for elderly patients regarding therapy.
A general concern has been that older patients might suffer adverse effects from a more intensive therapy regimen. To evaluate this clinical scenario, investigators of the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) sought to compare two types of regimens: ezetimibe combined with simvastatin, and simvastatin combined with placebo (simvastatin monotherapy) in more than 18,000 patients from 1,147 sites in 39 countries. Among these patients, 2,798 were 75 years or older, 5,173 were 65 to 74 years old, and 10,173 were under age 65.
Investigators randomly assigned the participants to a daily dose of simvastatin (40 mg) plus ezetimibe (10 mg) or simvastatin (40 mg) plus placebo, conducting follow-ups after 1 month, 4 months, and every 4 months after that for 6 years. Mortality due to CVD, myocardial infarction, stroke, unstable angina requiring hospitalization, and coronary revascularization after 30 days comprised the study’s primary end points. Additional analyses took place on individual adverse ischemic and safety end points and lipid variables.
Overall, the two-statin combination yielded lower rates in the primary end points—0.9% and 0.8% for patients younger than 65 years and those 65 to 74 years of age, respectively, than the simvastatin monotherapy. In the 75-plus cohort, the combination therapy yielded the greatest absolute risk reduction (8.7%) in the primary end points or outcomes. Among older and younger patients, the two-statin approach did not lead to higher rates of adverse events. “Treatment of only 11 patients 75 years or older with simvastatin-ezetimibe appeared to be needed to prevent 1 event,” the investigators reported.
The findings suggest that elderly patients could benefit from this higher intensity statin regime to lower bad cholesterol following acute coronary syndrome without worrying about safety issues.
The IMPROVE-IT trial “provided additional confirmation of the LDL hypothesis and showed that lower is better in terms of LDL-C level reduction,” wrote Antonio M. Gotto Jr., MD, DPhil, a professor at Weill Cornell Medicine, in a related editorial. “The mean LDL-C level in the placebo group was approximately 69 mg/dL after 1 year, while the treatment arm reached a mean level of 53 mg/dL. Importantly, IMPROVE-IT showed that lowering LDL-C levels that were already below threshold values could produce further reductions in cardiovascular events.” The results offer valuable information for patients and clinicians alike, he continued. “They strongly support the benefit of intensive therapy to reduce LDL-C levels in elderly individuals with atherosclerotic cardiovascular disease,” suggested Gotto.
Another ongoing study, Statin Therapy for Reducing Events in the Elderly (STAREE), should offer additional insights regarding statin use in healthy older patients. STAREE “is evaluating the effects of statin therapy (atorvastatin, 40 mg/d) on overall survival and disability-free survival in 18,000 participants in Australia, with results expected in 2020,” Gotto reported.