Study warns of more heart attacks if statin guidance shifts

IIf millions of Americans no longer qualify for a statin or blood pressure drug based on a new calculator updated to better predict their risk, it could lead to 107,000 additional heart attacks and strokes over 10 years, a new study estimates .

The research paper, published Monday in JAMAis the second in two months to draw attention to commonly used drugs designed to prevent the leading cause of death in the United States.

The research is causing a stir in cardiology circles, as two medical associations formulate new guidelines to inform practice, weighing new risk models and existing thresholds that lead to prescriptions.

“This is concerning that we could be rolling back eligibility for many millions of Americans,” Raj Manrai, assistant professor of biomedical informatics at Harvard Medical School’s Blavatnik Institute and senior author of the new study, said in an interview. “We really need to reexamine the other side of the equation here, which is how these risk estimates will be used by patients and physicians to decide who and when individuals receive preventive care, especially statins and antihypertensive medications.”

Who exactly should take a statin is the focus of both research articles analyzing risk equations published in November 2023, called Predicting Risk of cardiovascular disease EVENTs (PREVENT). That fashion modeldeveloped by the American Heart Association, intended to improve on a 2013 version known as the Pooled Cohort Equations (PCE) and widely criticized for overestimate risk.

PREVENT used billing and electronic health record data from a more diverse real world population than the elderly population, including current statin use as well as metabolic and kidney diseases. The current guidelines used by primary care physicians are based on PCE, while the American Heart Association and the American College of Cardiology are reviewing the newer PREVENT model and finalizing new guidelines.

According to guidelines based on the 2013 calculator, most people with a 10-year risk of 7.5% or more of developing cardiovascular disease are advised to take a statin, while at a 5% risk they are only told to take a statin. and their doctors should do so. consider doing this. The threshold for treating hypertension is a blood pressure of 140/90 mmHg or higher or a blood pressure of 130/80 mmHg or higher, combined with a 10% risk for other reasons.

Rather than debate which risk calculator is better, some experts said resetting the thresholds they use is more urgent.

“It is a well-known fact that PCE overestimates risk by approximately twofold,” Sadiya Khan, a cardiologist and associate professor of medicine and preventive medicine at Northwestern University Feinberg School of Medicine, told STAT in an email. She was not involved in either study, but chaired the group that developed the study AVOID comparisons. “The PREVENT estimates are more in line with contemporary event rates and are therefore approximately half of the PCE estimate. So the question is not more deaths or events if the threshold is the same, but what the guidelines should consider the new threshold.”

Harvard’s Manrai agreed. “To me, the data really says that this is a very, very important and urgent conversation to have, whether that 7.5% is the magic number at which we should start on statins and that rests on a risk-benefit analysis that I think that it needs to be re-examined.”

Statins, which are available in the US for about $40 a year, work very well at lowering LDL, the “bad” cholesterol that clogs arteries. If that atherosclerotic condition gets bad enough, the heart or brain can become deprived of oxygen-rich blood, which can cause a heart attack or stroke. A variety of blood pressure medications, including low-cost ones, relax and open blood vessels that, when blocked, can lead to a heart attack or stroke.

The disadvantages of statins include a possible higher risk of type 2 diabetes. But the drugs have dramatically improved cardiovascular health, although about 40% of Americans who might benefit from statins according to current guidelines, do not use them.

“Even if we leave aside the question of what will be the best and most accurate model for our patients in 2024 (which I think is the first fundamental question), we still know that there is a huge gap in patients getting the right receiving treatment even if eligible,” Khan said.

Last months JAMA Internal Medicine Research used the newer PREVENT risk equations to determine that among 3,785 adults who were 40 to 75 years old in a 2017-2020 National Health and Nutrition Examination Survey survey, there was an overall estimated average 10-year risk of 4% was at developing cardiovascular disease, compared to the average ten-year risk of 8% previously predicted by the PCE. If implemented in doctors’ offices across the country, the study estimates, the number of adults recommended for statins could drop by 17.3 million.

Monday’s JAMA investigation similarly applied the PREVENT risk calculator to 7,765 adults aged 30 to 79 who answered the same national survey, but from 2011-2020 (also ending when the pandemic began in March), before concluding that 14.3 million fewer people would no longer be eligible for statins and 2.6 million fewer people would be eligible for blood pressure medication.

The authors then went on to predict what that could mean for heart attacks and strokes if new risk tools reduced the number of people advised to take statins or blood pressure medications. Their answer: 107,000 additional heart attacks and strokes over 10 years as people are reclassified to lower risk and thus no longer benefit from preventive medicine. Possibly more men than women would be affected, but a similar percentage of black and white adults. People determined not to be eligible for treatment had fewer risk factors, including lower rates of obesity, high blood pressure and chronic kidney disease.

“This estimate is based on the assumption that fewer people would be treated, which assumes the same threshold would be applied,” Khan said of the JAMA article. “I think we should expect that the threshold should and should change because we now have a more accurate model.”

Manrai said he was struck by the potential magnitude of changing the risk equation. “I think every time you see a number of 107,000 heart attacks and strokes, we’ve checked it a hundred times. We did 15 sensitivity analyzes on it,” he said. “I really think this is a pretty stunning projection of the potential impact of changing these equations in the US”

Timothy Anderson, a family physician and assistant professor of medicine at the University of Pittsburgh Medical Center, was an author of the June analysis. He thinks there will be a conversation in both the primary care and cardiology communities about what the appropriate risk threshold is.

“I’ve never seen a study that tells us that 5% is the perfect number, versus 7% versus 2% versus 20%. Ultimately, statins are safe drugs and they work very well,” he said in an interview. “For a lot of people, they’re willing to tolerate some level of risk and they’re also willing to think about maybe if I turn down that statin, I’ll work on exercise and weight loss and get my blood pressure under control.”

Manrai and his co-authors noted that there are drawbacks to both statins and blood pressure medications. There is an increased risk of type 2 diabetes in people treated with statins, possibly because the drugs interfere with insulin. So under the PREVENT model, which suggests less statin use, the researchers predict that over a ten-year period there would be 57,800 fewer new cases of type 2 diabetes. People taking blood pressure medications may experience sudden drops in blood pressure, decreased blood flow, or sexual dysfunction, side effects that factor into patient and physician decisions about costs and benefits.

“There is no perfect equation for risk assessment,” Jelani Grant, Chiadi Ndumele, and Seth Martin of Johns Hopkins wrote in an accompanying editorial. “These comparisons provide a starting point for risk discussions and shared decision-making in the primary prevention setting. Further risk assessment via risk factors and arterial imaging can help tailor individual treatment plans.”

Manrai has heard that cardiologists are already incorporating PREVENT values ​​into their risk estimates.

Not Steven Nissen, a cardiologist at the Cleveland Clinic. Nissen believes that problems arise with risk calculations when they are misinterpreted as mandates.

“In my humble opinion, there is no substitute for a well-informed doctor who knows what the current medical literature looks like, looks at the patient in front of him and takes into account everything we know,” he said in a speech. interview.

He has proven the value of statins across the lifespan leading an initiative in collaboration with AstraZeneca to make the 5-milligram dose of his drug Crestor (rosuvastatin). available without a prescription.

“What they’re trying to say here is that if we make a mistake with a risk calculator, it could be very costly,” Nissen said of the new JAMA article, in which he had no role. “I think they are right when we say that if we miss the mark, we will cause social damage. We need to take a more thoughtful approach to deciding who to treat, and not put all our emphasis on someone’s mathematical risk calculator.”

Khan said new thresholds for treatment would ideally be based on randomized clinical trials where people were followed to see how well the risk model predicted subsequent heart attacks or strokes. That would help determine at what level of risk the most benefit and least harm can be achieved from prescribing statins and blood pressure medications.

“Guidelines do not recommend a one-size-fits-all threshold,” she said. Instead, doctors and patients should discuss individual risk factors, such as a family member who had a heart attack at a young age or developed the dangerous condition preeclampsia during pregnancy, as well as imaging of calcium levels in the coronary arteries.

“One of the most important parts of this discussion is to ensure that patients do not stop their statins without talking to their doctor based on a new model until new guidelines are available that indicate when to start or stop therapy,” she said. Khan. .

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