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Higher-Intensity Lipid Lowering After ACS Seems Beneficial in Patients 75+

July 22, 2019

By Marilynn Larkin

NEW YORK (Reuters Health) - In patients 75 and older with acute coronary syndrome (ACS), adding ezetimibe to a statin for higher-intensity lipid lowering may be beneficial and safe, a secondary analysis of IMPROVE-IT suggests.

The multicenter randomized trial, which enrolled patients with no upper age limit, found that ezetimibe combined with simvastatin incrementally lowered low-density lipoprotein cholesterol and improved cardiovascular disease outcomes compared with simvastatin monotherapy.

"In practice, older age has been associated with a lower likelihood of being prescribed intensive lipid-lowering therapy (and) guidelines do not routinely advocate higher-intensity treatment for patients older than 75 years," Dr. Richard Bach of Washington University School of Medicine in St. Louis told Reuters Health by email.

The secondary analysis of IMPROVE-IT "gave us the opportunity to examine the effect of age on the benefit of more intensive lipid-lowering," he said.

Dr. Bach and colleagues analyzed IMPROVE-IT data from 10,173 patients under age 65 (76% men) at the time of randomization; 5,173 ages 65 to 74 (73% men); and 2,798 ages 75 or older (66% men).

The primary composite endpoint was death due to cardiovascular disease, myocardial infarction, stroke, unstable angina requiring hospitalization, and coronary revascularization after 30 days. Patients were followed for about seven years.

"By the end of the trial, the median age of the group of patients 75 and older at baseline was 85," Dr. Bach noted.

As reported online July 17 in JAMA Cardiology, treatment with simvastatin-ezetimibe resulted in lower rates of the primary endpoint than simvastatin-placebo: 0.9% lower for patients under 65 (hazard ratio, 0.97); 0.8% lower for those 65 to 74 (HR, 0.96); and the greatest absolute risk reduction of 8.7% for those aged 75 or older (HR, 0.80).

"Among patients 75 and older, only 11 ...need to be treated with simvastatin-ezetimibe to prevent one adverse ischemic event," Dr. Bach said. By contrast, the number needed to treat to prevent an adverse event in patients under age 75 is 125.

Further, the rate of adverse events did not increase with simvastatin-ezetimibe among younger or older patients.

Dr. Bach said, "Although adding any medication will be associated with increased cost, given that ezetimibe is now generic, adding it to statin therapy should not be cost-prohibitive. And when one considers the added costs of serious cardiovascular events that may be prevented, the balance may still be considered highly favorable."

"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," he concluded.

Dr. Antonio Gotto, Dean Emeritus of Weill Cornell Medicine in New York City and author of a related editorial, commented by email, "We have known that age is a very significant risk factor for cardiovascular disease. In the most recent AHA/ACC cholesterol guidelines, many individuals over age 75 would qualify for statin therapy just based on age. But there has been a paucity of evidence testing benefit (and) the guidelines did not recommend intensive therapy for this group."

"The greatest surprise to me in the (study) was that the absolute risk reduction was 10 times greater in individuals over 75 than those under 75," he told Reuters Health. "These results have to be considered good news for older patients at high cardiovascular risk."

"Lifestyle remains an important part of the therapy," he added, "and the decision to use high-intensity lipid lowering therapy should be a joint one between the physician and patient."

Merck funded the study and Dr. Bach and seven coauthors have received fees from the company.


JAMA Cardiol 2019.

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