Heart illustration
Heart illustration
A two-drug combination for lowering cholesterol could save hundreds of thousands of lives worldwide each year, according to a major new study released Monday in Mayo Clinic Proceedings.
The findings challenge current medical practice, suggesting doctors shouldn’t wait to see if statins alone work before adding a second medication for high–risk patients with clogged arteries.
Researchers found that immediately combining statins with a drug called ezetimibe reduced overall death risk by 19% compared to treating patients with high-dose statins alone. The combination also cut deaths from cardiovascular causes by 16% and lowered the occurrence of major heart events and strokes by 18% and 17% respectively.
“This study confirms that combined cholesterol lowering therapy should be considered immediately and should be the gold standard for treatment of very high-risk patients after an acute cardiovascular event,” said Peter Toth, co-author and Professor of Clinical Family and Community Medicine at the University of Illinois.
Largest Study of Its Kind
The meta-analysis examined 108,353 patients across 14 studies, making it the most comprehensive investigation of its kind. All participants were at very high risk of heart attack or stroke, or had already experienced one of these events.
Currently, many doctors start high-risk patients on statins first and monitor cholesterol levels for at least two months before considering additional medication. This approach, the researchers argue, misses a critical window for prevention.
When researchers conducted a network meta-analysis—allowing direct comparison between different treatment approaches—the results were even more striking. This showed a 49% reduction in deaths from all causes and a 39% reduction in major adverse cardiovascular events with the combination therapy compared to statins alone.
“Simply adding ezetimibe to statin therapy, without waiting for at least two months to see the effects of statin monotherapy, which is suboptimal in many patients, is associated with more effective LDL-C goal achievement and is responsible for significant incremental reductions in cardiovascular health problems and deaths,” Toth explained.
How It Works
Statins reduce “bad” cholesterol (LDL-C) by limiting its production in the liver, while ezetimibe works differently—it blocks cholesterol absorption in the intestines. The dual approach pushed cholesterol levels significantly lower than statins alone, reducing LDL-C by an additional 13mg per deciliter of blood.
This increased patients’ chances of reaching the ideal goal of less than 70mg/dL of LDL-C by 85%.
Importantly, the study found that patients tolerated the combination treatment just as well as statins alone. In fact, the network meta-analysis showed a significant 44% reduction in therapy discontinuation rates with the combination approach versus high-dose statins.
Global Implications
Cardiovascular disease remains the world’s leading killer, claiming approximately 20 million lives annually. Eastern Europe and Central Asia see the highest death rates attributed to elevated LDL-C, with 4.5 million deaths worldwide linked to high cholesterol in 2020.
“Based on our previous analysis, we estimate that if combination therapy to reduce LDL-C was included in all treatment guidelines and implemented by doctors everywhere for patients with high cholesterol levels, it would prevent over 330,000 deaths a year among patients who have already suffered a heart attack, and almost 50,000 deaths alone in the USA,” said Maciej Banach, the study’s lead author and Professor of Cardiology at the John Paul II Catholic University of Lublin, Poland.
Banach, who also serves as Adjunct Professor at the Ciccarone Center for the Prevention of Cardiovascular Disease at Johns Hopkins University, led the international team that conducted the analysis.
Cost-Effective Approach
Unlike many medical advances that require significant new investments, this approach could actually reduce healthcare costs.
“This approach does not require additional funding or reimbursement of new expensive drugs. In fact, it may translate into lower rates of first and subsequent heart attacks and stroke, and their complications like heart failure, which are extremely costly for all healthcare systems,” Toth noted.
The findings underscore two critical principles in cardiovascular care, according to the researchers: “the lower for better for longer” and “the earlier the better” when treating high-risk patients.
“We recommend combination therapy should be considered the gold standard of treatment for these patients and included in all future treatment guidelines,” Banach concluded.
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