Many people wonder how effective statins are for preventing a heart attack in healthy people with high cholesterol. Even more important, do statins save lives in this population? There are few more controversial questions in medicine. That’s because tens of millions of people take statins, presumably to prevent heart attacks and lengthen their lives.
Has this promise been broken? A study in JAMA Internal Medicine (March 14, 2022) suggests that statins are not as great at preventing heart attacks as most patients and clinicians believe. A new study has also created more confusion and controversy (New England Journal of Medicine, Aug. 24, 2023). Many health professionals will challenge these findings, but these two journals are the most respected in medicine!
The Statin Promise:
Most doctors consider statins primary pillars for the prevention of heart attacks. At last count, over 23 million Americans swallow atorvastatin daily to lower LDL cholesterol. It is the number one most prescribed drug in the country. Another 10 million people take simvastatin.
Doctors who prescribe drugs such as atorvastatin, simvastatin and rosuvastatin do so with the implicit promise that statins will: 1) lower total cholesterol and LDL cholestesterol, 2) reduce the risk of developing heart disease or prevent it from getting worse and 3) prevent heart attacks and premature deaths.
There is no doubt that statins deliver on the first promise. The drugs dramatically lower both total and LDL cholesterol. How well do they prevent heart disease, heart attacks and premature deaths? The study in JAMA Internal Medicine suggests that the results are not as good as you might expect.
What They Did:
The authors of this meta-analysis reviewed 21 clinical trials involving over 130,000 participants. They were looking for outcomes that people really care about. The primary outcome was “all-cause mortality.” How well do statins score when it comes to prolonging life compared to placebo?
In plain English, do statins save lives? The secondary outcomes were heart attack (myocardial infarction) and stroke. How well do statins prevent these serious cardiovascular complications?
What They Found:
One of the most surprising findings of this study is that the association between LDL cholesterol (LDL-C) and heart disease is “weak or inconsistent.” The foundation of modern cardiology is built upon the belief that LDL cholesterol clogs coronary arteries and that if you lower this “risk factor” you can prevent heart disease, heart attacks and premature death. Guidelines that doctors follow are based on this premise.
Science Daily (March 14, 2022) summarizes the new analysis:
“The new findings contradict this theory, finding that this relationship was not as strong as previously thought. Instead, the research demonstrates that lowering LDL-C using statins had an inconsistent and inconclusive impact on CVD [cardiovascular disease] outcomes such as myocardial infarction (MI), stoke, and all-cause mortality.
“In addition, it indicates that the overall benefit of taking statins may be small and will vary depending on an individual’s personal risk factors.”
The authors of the study in JAMA Internal Medicine describe the difference between RRR [relative risk reduction] and ARR [absolute risk reduction]:
“The cardiovascular benefits of treatment with statins are sometimes reported as RRR. However, reporting RRR without the corresponding ARR or number-needed-to-treat of a treatment can be misleading. For example, in our analysis, the RRR for MI [heart attack] was 29%, whereas the ARR was 1.3%. In other words, 77 participants would need to be treated with a statin for roughly 4.4 years on average to prevent 1 MI.”
OK, that’s a bit inside baseball. What it means is that 77 people would have to take statins more than 4 years in order to prevent 1 heart attack. 76 people would not get any protection, but some might experience side effects.
As I look at Table 1. in this study I find that 0.8 deaths are prevented after four years. In other words, barely 1 person out of 100 will avoid premature death by taking a statin. If you only look at “primary” prevention, namely those who do not have heart disease, the absolute risk reduction of death falls to 0.6% after four years. According to my calculations that means 166 people would have to take a statin for four years to save one life.
An old friend, Dr. Nortin Hadler, suggests that when the NNT (the number needed to treat) is over 50 or 60, it begins to lose statistical meaning. Should you wish to learn more about such calculations, I encourage you to read Dr. John Abramson’s book: Sickening: How Big Pharma Broke American Health Care and How We Can Repair It.
The Latest Research on Statins in a High-Risk Population:
Here is another study of statins in high risk patients. (People with HIV are at higher risk for cardiovascular disease.) This reader points out that the study “only” lasted five years (much longer than most).
Q. I have been using a statin drug to lower my cholesterol for years. In a recent article, you wrote about a study in the New England Journal of Medicine (NEJM). That study was limited to HIV-positive people with a median age of 50. The trial was stopped early for efficacy, indicating that pitavastatin (Livalo) was beneficial for that population.
Other, larger studies have shown that statins can help prevent major adverse cardiovascular events (MACEs). The NEJM study only lasted five years; a 50-year-old person could live for 50 more years with plaques accumulating in their arteries and increasing their risk of a MACE. Someone reading your article might conclude that statins have very little benefit and then go on to suffer a MACE!Hopefully they will talk to their doctor and learn that statins do work.
A. Statins clearly lower cholesterol. No one disputes that. They also reduce the likelihood of heart attacks and stents, especially in people who have diagnosed heart disease. This is called secondary prevention, and we fully support this use of statins.
The benefits of statins for primary prevention are less striking. These are people who have not had heart attacks or other cardiovascular complications…yet.
In the study you cited, the investigators calculated that if 105 high risk individuals (because of HIV infection) took a statin for five years, one would avoid MACE (New England Journal of Medicine, Aug 24, 2023). A cardiologist we know considers that a BIG win.
Not everyone would agree, though. He insists, like you, that if the study had continued for 10 or 20 years the benefits would be much more apparent. We cannot disagree, but because the study did not go on for that length of time, we are less willing to speculate on the benefits or risks of statins over such a long timeline.
Doctors who believe in “evidence-based medicine” should be able to demonstrate that long-term statin use (for 10-20 years) does indeed produce more obvious benefits than 1 in 105. People considering a statin for primary prevention should discuss the benefits and risks with their physicians. We encourage them to ask this question:
How many people like me would need to take a statin for 4-5 years for one to avoid 1) a heart attack or 2) death?
Evidence-based medicine requires clear data and evidence-based answers to questions like those above. Patients deserve understandable answers to basic questions about a drug’s ability to prevent a heart attack or death!
Statins May Save Lives for Secondary Prevention:
Let’s make one thing absolutely clear. I have been talking mostly about primary prevention, not secondary prevention. What’s the difference between these two situations?
If someone has experienced a heart attack or has diagnosed cardiovascular disease, we think a case could be made for statins in what doctors call secondary prevention. That’s because people who have clearly defined heart disease or have had heart attacks or strokes may benefit from drugs like atorvastatin, simvastatin or rosuvastatin. The goal is to prevent a “secondary”event.
What follows is not about that. Instead, we are reporting on people who are otherwise healthy but might have elevated cholesterol levels. Guidelines often encourage doctors to prescribe statins to older people just because of their age. Even if their cholesterol levels are good and their blood pressure is under control, they may be prescribed statins “just in case.” This is called primary prevention.
Research Asks Whether Statins Save Lives:
A previous meta-analysis published in JAMA Internal Medicine (Nov. 16, 2020) shows that if 100 healthy people between 50 and 75 years of age take a statin for 2.5 years, there will be one less cardiovascular event among that group. The data do not show that statins save lives for primary prevention.
This research focused on people over 55 years of age. They located eight randomized controlled trials involving 65,383 adults. The researchers followed up the subjects for 2 to 6 years, on average.
Drilling Down on the Data:
The authors were looking for two major outcomes: A Major Adverse Cardiovascular Event (known to cardiologists as MACE) and mortality. Did statins save lives?
Here is what they found:
“In this meta-analysis, only 1 of 8 randomized trials found that statins decreased all-cause mortality when used for primary prevention. We found that 100 adults aged 50 to 75 years would need to be treated for 2.5 years to avoid 1 MACE. This result suggests that statin treatment is most appropriate for adults aged 50-75 years with a life expectancy of greater than 2.5 years. For those with a life expectancy of less than 2.5 years, the harms of statins may outweigh the benefits. These results reinforce the importance of individualizing statin treatment decisions by incorporating each patient’s values and preferences.”
OK, that’s pretty technical. But the authors make it relatively simple.
They state unequivocally in their conclusions:
“There is no evidence of a mortality benefit.”
That means that for primary prevention there is little, if any, evidence that statins save lives. The drugs will prevent 1 MACE [major adverse cardiovascular event] such as a heart attack out of 100 adults. It will take about 2.5 years for this benefit to show up. Another way of saying that is that 99 adults out of 100 will not avoid a MACE by taking a statin.
This finding will aggravate many health professionals. Please do not shoot the messenger. This is not our opinion. This is the conclusion of a meta-analysis published in a highly reputable publication, JAMA Internal Medicine (Nov. 16, 2020). You may want to print the abstract and show it to your prescriber. Better yet, suggest that she read the full article herself.
Do Statins Cause Side Effects?
There is also a growing effort to convince physicians and patients that statins do not cause side effects. This is not the first time.
An article in the European Journal of Preventive Cardiology (March 12, 2014) concluded:
“Only a small minority of symptoms reported on statins are genuinely due to the statins: almost all would occur just as frequently on placebo.”
Many doctors are unaware that statins can actually raise Lp(a) levels. That is not a good thing for your heart or your blood vessels. Of course we always recommend that you check with your prescriber before taking any actions. Never stop any medicine without careful consultation!
If you would like to read more about statins and other ways to prevent heart disease, you may find our eGuide to Cholesterol Control & Heart Health of interest. You can find it in our Health eGuides library.
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