The largest study to date suggests that patients at high risk for heart attacks and strokes should begin immediate treatment with a combination of a statin and ezetimibe.
The largest study to date examining how best to lower “bad” cholesterol in patients with blocked arteries has found that starting treatment with a combination of a statin and the drug ezetimibe is significantly more effective than using statins alone. This approach could prevent thousands of deaths each year from heart attacks, strokes, and other cardiovascular conditions.
Published in Mayo Clinic Proceedings, the meta-analysis included data from 14 clinical trials involving 108,353 high-risk patients, those who had either experienced a heart attack or stroke or were at high risk of doing so. The results showed that combining ezetimibe with a high-dose statin led to a 19% reduction in all-cause mortality, a 16% reduction in cardiovascular deaths, and an 18% and 17% reduction in major cardiovascular events and strokes, respectively, compared to high-dose statin therapy alone.
The combination therapy also achieved significantly better cholesterol control, lowering LDL-C (low-density lipoprotein cholesterol) by an additional 13 mg/dL compared to statins alone. This improvement made it 85% more likely for patients to reach the recommended LDL-C target of less than 70 mg/dL.
Enhanced Outcomes with Network Meta-Analysis
“These results were even more pronounced in the network meta-analysis, which enables a direct comparison of different therapy regimens used in the study. This showed a 49% reduction in all-cause mortality and a 39% reduction in major adverse cardiovascular events, when compared to high dose statin therapy alone,” said the first author of the study, Maciej Banach, Professor of Cardiology at the John Paul II Catholic University of Lublin, Poland, and Adjunct Professor at the Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, who also leads the International Lipid Expert Panel and the Blood Pressure Meta-analysis Collaboration group that carried out the study.
“The combination therapy is safe and efficacious; the risk of adverse events and the therapy discontinuation rate was comparable between groups. In the network meta-analysis, we showed a significant 44% reduction in the risk of discontinuation in those treated with moderately high-dose statin therapy plus ezetimibe versus a high-dose statin alone.”
Challenging Current Guidelines on Cholesterol Treatment
Until now, there have been inconsistent findings about whether or not combined cholesterol lowering therapy should be given to high risk patients immediately, even before they suffer a heart attack or stroke, or whether doctors should start these patients on a high dose statin first and monitor the effects on cholesterol levels after at least two months before deciding if the patients need ezetimibe as well.
Co-author of the study, Peter Toth, Professor of Clinical Family and Community Medicine, University of Illinois, and Adjunct Associate Professor of Medicine at Johns Hopkins University, USA, said: “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. 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.
“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.”
According to the data from the Global Burden of Disease and the American Heart Association, deaths occurring as a result of high LDL-C alone are highest in Eastern Europe and Central Asia, and 4.5 million deaths worldwide were attributed to it in 2020.
Global Health Implications and Future Guidelines
Prof. Banach said: “Cardiovascular disease kills around 20 million people a year worldwide. 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. We recommend combination therapy should be considered the gold standard of treatment for these patients and included in all future treatment guidelines.”
Statins have been used safely for years. They help to lower LDL-C by reducing the production of it by the liver. Ezetimibe reduces the amount of cholesterol that the body takes from food by inhibiting the absorption of it in the intestines. Some patients do not respond adequately to statins and are prescribed ezetimibe in combination with a statin. High doses of statins are known as ‘high intensity’ statins and moderately high doses are known as ‘moderate intensity’ or ‘medium intensity’ statins.
Prof. Toth said: “Our findings underline the importance of the adages ‘the lower for better for longer’ but also the equally important ‘the earlier the better’ for treating patients at high risk of cardiovascular conditions and to avoid further medical complications and deaths.”
A strength of the study is its large size, as it includes the greatest number of patients studied so far. The patients were included in 14 studies, 11 of which were randomised controlled trials and three of which were cohort studies. Limitations relate mainly to the type of studies that were included in the meta-analysis, including their size and the observational nature of some of them.
Reference: “Impact of Lipid-Lowering Combination Therapy With Statins and Ezetimibe vs Statin Monotherapy on the Reduction of Cardiovascular Outcomes: A Meta-analysis” by Maciej Banach, Vikash Jaiswal, Song Peng Ang, Aanchal Sawhney, Novonil Deb, Pierre Amarenco, Dan Gaita, Zeljko Reiner, Ivan Pećin, Carl J. Lavie, Peter E. Penson and Peter P. Toth, 23 March 2025, Mayo Clinic Proceedings.
DOI: 10.1016/j.mayocp.2025.01.018
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9 Comments
This has been know for over a decade. They are just reissuing the information to boost the VERY lucrative statin sales. There is a better option, and that is to let the body operate as it was intended to do. I have been on a PCSK9 blocker for over 15 years because my 300+ cholesterol almost killed me. I went on the PCSK9 blocker and Ezetimibe and my cholesterol is now 140 and has been for the last 15 years. The reason they wont pursue the development of a PCSK9 blocker in pill form is that it would kill the statin industry. The way the PCSK9 works is that your body starts to make this enzyme and it blocks the receptors in the liver that collects excess cholesterol in the blood and coverts it to bile to be pooped out. I believe our bodies developed this enzyme to help thin out the older members and give the heard a better shot at survival (evolution). The blocker attaches to the enzyme and modifies it to not be able to attach to the cholesterol receptors in the liver and allows the liver to operate they way it was designed. Statins, on the other hand, stops cells from absorbing cholesterol and also the intestine from absorbing cholesterol into the blood stream. Thats all good, but now the cells don’t have what they need to build fibrous tissue (muscle attaching) and you weaken the muscles and cause many other issues. Then your doctor feeds you more pills and the pharma companies make more money. Why would they research a drug that will cure high cholesterol and make you strong again so you don’t need more drugs. You do the math. Read about PCSK9 blockers and make you own decisions. It’s sad the mighty dollar rules over human life.
All the stations are generic, off patent and cheap. The sales are not lucrative, only mildly profitable.
Clean up water systems and food and you won’t have to come out with better drugs. Teach the human how to eat well and the human won’t need drugs. Worry more about the toxic environment and treat it back into health. But you won’t because money…if you don’t keep the human’s sick then you can’t profit from them.
Unfortunately the most effective way to determine whether a coronary problem exists is something rarely used. I’m HeFH and have always had extreme total lipids and LDL–as high as 600 and 500, respectively. So, of course I believed I had to do everything I could to lower my cholesterol, but had very limited success. Starting at age 30 I “knew” I’d not live to 60. That all changed at age 50 when I had my first coronary calcium scan and discovered I had zero coronary calcium. Zero! Multiple tests have confirmed this, so I quit all treatments to lower my lipids. Twenty nine years later, now 79, I still have no plaque and no coronary issues of any kind. It is crazy to medicate (or do anything) for elevated lipids without first imaging whether arteries have developed plaque; various estimates suggest about 50% of people considered at risk for plaque buildup may never have significant plaque. A coronary calcium scan is non-invasive, absolutely painless, takes 15 minutes and provides direct information about the state of heart arteries. As my cardiologist said, it is one of the great tragedies of medicine that calcium scans are not done as routinely as breast exams.
You know what else works? And is much less expensive and has no adverse side effects? The diet promoted by Esselstyn and Ornish over 30 years ago.
Put the pills down and pick up some dark leafy greens.
https://www.dresselstyn.com/site/articles-studies/
Why Prevent Disease when it can be Treated it with an RX.
Big Pharma needs its money!
This is tolally and utterly Bull S***.
The risk of side effects outweighs the minuscule benefit.
In terms of “real risk”, the benefit is less than 1%.
300 people need to be treated to prevent 1 non-fatal CV incident.
Dozens will experience side effects.
There is no big pharma in this case. Statins, Ezetimibe and aspirin are all off patent, generic and cheap. And very effective in this combination. And safe. All 3 of these drugs have been taken by huge populations for decades with minimal to no side effects.
Utter nonsense, just an advertisement for big pharma.
There is no big pharma for aspirin, Ezetimibe, or statins.