Promptly prescribing a combination of cholesterol-lowering medications with statins and ezetimibe to patients with acute coronary syndrome (ACS) could substantially decrease their risk of death.
Research published in the Journal of the American Heart Association reported that patients with ACS, including those who have experienced a heart attack or unstable angina, are 47% less likely to die within 3 years if they start that drug regimen in comparison with only with high level dose of statin.
The study was led by Maciej Banach, MD, PhD, professor of Cardiology at the Medical University of Lodz, Poland, and associate professor at the Ciccarone Center for the Prevention of Cardiovascular Diseases at the Johns Hopkins University School of Medicine in Baltimore.
“Patients with acute coronary syndrome, such as those who have already had a heart attack, face a much higher risk of further heart problems. Current guidelines, including prevention guidelines from the European Society of Cardiology, recommend a gradual approach, first offering only a statin,” Dr. Banach said. "This study shows that if we act quickly and decisively to lower patients’ cholesterol with this combination of treatments, we can dramatically reduce the risk of death."
The study team sought to compare statin monotherapy and initial combination therapy of statins and ezetimibe in patients with ACS and included consecutive patients in the PL-ACS (Polish Registry of Acute Coronary Syndromes), which is a prospective observational registry, in course, multicenter and national that is mandatory for patients with ACS hospitalized in Poland.
After propensity score matching, the researchers analyzed two groups: 768 patients on statin monotherapy (atorvastatin or rosuvastatin) and 768 who received initial combination therapy of statin and ezetimibe. “The difference in mortality between the groups was significant during follow-up and was present in 1 (5.9% versus 3.5%; P = 0.041), 2 (7.8% versus 4.3%; P = 0.019 ) and 3 (10.2% versus 5.5%; P = 0.024) years of follow-up in favor of the initial combination therapy as well as during the overall period,” the study reported.
"For treatment, rosuvastatin significantly improved prognosis compared with atorvastatin (odds ratio [OR], 0.790 [95% CI, 0.732-0.853])," the authors added. “Upfront combination therapy was associated with a significant reduction in all-cause mortality compared with statin monotherapy (OR, 0.526 [95% CI, 0.378-0.733]), with an absolute risk reduction of 4. 7% after 3 years (number needed to treat = 21).”
The investigators concluded that initial combination lipid-lowering therapy is superior to statin monotherapy for all-cause mortality in patients with ACS. "These results suggest that in high-risk patients, this approach should be recommended, rather than stepwise therapy," they advised.
The risk of death was found to be lower after just 52 days of treatment, and the results suggested that for every 21 patients who took the double treatment for 3 years, one death was avoided.
"Every year about seven million people suffer from acute coronary syndrome and most cases are related to high cholesterol and the buildup of fat in the blood vessels," Dr. Banach said. "We have effective cholesterol-lowering treatments, but we need to make sure the people who need them are taking them."
Conclusions Initial combination lipid-lowering therapy is superior to statin monotherapy for all-cause mortality in patients with ACS. These results suggest that this approach, rather than a stepwise treatment approach, should be recommended in high-risk patients. |
Clinical perspective
What’s new?
The objective was to evaluate which strategy, monotherapy versus initial combined lipid-lowering treatment of statin and ezetimibe, is superior in the context of reducing all-cause mortality in patients with acute coronary syndrome.
It is the first analysis of its kind to present results based on real-world data.
We confirmed that already after 1.5 months, the difference in the reduction in all-cause mortality was significant, with an absolute risk reduction of 4.7% after 3 years (number needed to treat = 21).
What are the clinical implications?
Because the lipid-lowering treatment strategy recommended in European guidelines has not been sufficient to increase the percentage of patients achieving the low-density lipoprotein cholesterol target (only one third in Europe), in 2021, the International Panel of Lipid Experts recommended introducing initial combination therapy in a selected group of patients with very high and extremely high cardiovascular risk. However, the initial combination therapy approach has had limited data to support it.
In this analysis, initial combination lipid-lowering therapy was shown to be superior to statin monotherapy for all-cause mortality, calling into question the recommended stepwise approach.
