18 Jul Older Patients May Benefit from Combination of Simvastatin-Ezetimibe After Acute Coronary Syndrome
MedicalResearch.com Interview with:
Richard G. Bach, MD FACC
Professor of Medicine
Washington University School of Medicine
Director, Cardiac Intensive Care Unit
Director, Hypertrophic Cardiomyopathy Center
St. Louis, MO 63110
MedicalResearch.com: What is the background for this study?
Response: Elderly patients represent the largest group of those hospitalized for an acute coronary syndrome, and age is an important marker of increased risk. The risk of death and recurrent cardiovascular events is greatest among the elderly. High intensity lipid lowering by statins has been shown to reduce the incidence of recurrent cardiovascular events after an acute coronary syndrome in general, but there remains limited data on efficacy and safety of that treatment in the elderly, and guidelines do not routinely advocate higher intensity treatment for patients older than 75 years. In practice, older age has been associated with a lower likelihood of being prescribed intensive lipid lowering therapy. IMPROVE-IT evaluated the effect of higher-intensity lipid lowering with ezetimibe combined with simvastatin compared with simvastatin-placebo among patients after ACS, and observed that ezetimibe added to statin therapy incrementally lowered LDL-cholesterol level and improved CV outcomes. IMPROVE-IT enrolled patients with no upper age limit, which gave us the opportunity to examine the effect of age on outcome on the benefit of more intensive lipid lowering with ezetimibe combined with simvastatin vs. simvastatin monotherapy.
MedicalResearch.com: What are the main findings?
Response: A total of 18,144 patients were enrolled in IMPROVE-IT, of whom 10,173 (56%) were <65 years of age; 5173 (29%) were age 65 to 75 years; and 2798 (15%) were ≥75 years at randomization. Note that by the end of the trial, the median age of the group of patients ≥75 years at baseline was 85 years. In IMPROVE-IT, we observed that higher-intensity lipid lowering by adding ezetimibe to simvastatin provided a similar LDL reduction and a lower rate of cardiovascular events across all age groups. For patients age 75 years and older, treatment with simvastatin monotherapy at 1 year reduced the mean LDL-C level to 66 mg/dl, while ezetimibe combined with simvastatin reduced the mean LDL-C level to 49 mg/dl.
At 7 years of follow-up in IMPROVE-IT, when compared with younger patients, the absolute risk reduction for the primary endpoint of CV death, major adverse cardiac event, or non-fatal stroke, was substantially greater for patients 75 years of age or older. While patients younger than 75 years of age treated with ezetimibe-simvastatin showed about a 0.8% to 0.9% absolute risk reduction compared with simvastatin monotherapy, for patients age 75 years and older, treatment by ezetimibe-simvastatin resulted in about a 9% absolute risk reduction compared with simvastatin monotherapy. As a result, among patients ≥75 years of age only 11 patients ≥75 years of age need to be treated with simvastatin-ezetimibe to prevent one adverse ischemic event. Importantly, simvastatin-ezetimibe was well tolerated across all age groups. We concluded that in IMPROVE-IT, patients after ACS derived benefit from higher-intensity lipid-lowering therapy with simvastatin-ezetimibe compared with simvastatin monotherapy, with the greatest absolute risk reduction among patients ≥75 years of age, and that addition of ezetimibe to simvastatin was not associated with any significant increase in safety issues among older age patients.
MedicalResearch.com: What should readers take away from your report?
Response: Our data show that elderly patients after an acute coronary syndrome may derive significant benefit with preserved safety from higher-intensity lipid-lowering therapy with ezetimibe-simvastatin versus simvastatin alone. In light of these observations, continuing to treat elderly patients after an ACS with moderate rather than higher-intensity lipid-lowering therapy will represent a missed opportunity to incrementally improve long-term outcomes for this high-risk population. Given that older age is both a marker of increased risk and of a lower likelihood of being prescribed intensive lipid lowering therapy, with these data supporting significant benefit yet excellent safety and tolerability, clinicians can be more confident that they can benefit their elderly patients by prescribing higher intensity lipid lowering, and that combined statin and ezetimibe may be an excellent choice for achieving that goal.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: With more options for reducing lipid levels now available, more prospective clinical trial research is needed among elderly patients at increased risk of adverse cardiovascular events regarding the efficacy and safety of different agents and of the target goals of higher intensity lipid lowering therapy.
MedicalResearch.com: Is there anything else you would like to add?
Response: Our study adds to a growing body of evidence that older age is a powerful marker for increased risk of recurrent cardiovascular events that may be modifiable with important interventions available to the clinician, such as higher-intensity lipid-lowering therapy, that are currently less likely to be prescribed to older versus younger patients.
Bach RG, Cannon CP, Giugliano RP, et al. Effect of Simvastatin-Ezetimibe Compared With Simvastatin Monotherapy After Acute Coronary Syndrome Among Patients 75 Years or Older: A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. Published online July 17, 2019. doi:10.1001/jamacardio.2019.2306
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