A controversial new way to identify which patients should be treated for high cholesterol got some fresh validation Tuesday, with new research finding that strict adherence to 2013 guidelines for the use of cholesterol-lowering statin medications could prevent 41,000 to 63,000 heart attacks and strokes over 10 years.
Published Tuesday in JAMA, two studies suggest that updated treatment recommendations issued by the American College of Cardiology and the American Heart Assn. improve upon a set of 2004 guidelines in identifying healthy people who may nevertheless go on to suffer heart attack or stroke.
One of the studies, an analysis based on a "microsimulation model," concludes not only that implementing the new guidelines is cost-effective. It also finds that even more inclusive standards, which would draw still lower-risk patients into statin therapy, would yield economic benefits as well. That study was led by researchers at Harvard University's School of Public Health
The unveiling of the 2013 guidelines, which would expand the size of the U.S. population taking statins by as many as 10 million adults, was greeted with howls of complaint by physicians, and by critics who complained that the new standards would expose too many Americans to statins' risks without compensating benefits.
Physicians' principal concerns with the new guidelines -- that they did not support the goal of achieving specific cholesterol targets in their patients -- are not addressed by the two new studies.
Instead, the new research addresses a somewhat more technical complaint raised by some cardiologists and public health specialists: that the guidelines used an untested metric to identify which seemingly healthy patients were at elevated risk of developing cardiovascular disease and thus could benefit from statin therapy.
The new battery of measures used in the 2013 guidelines aimed to spot and treat healthy patients whose probability of suffering a heart attack or stroke in the next decade exceeded 7.5%.
Writing in a JAMA editorial in 2013, Dr. John P.A. Ioannidis fretted that the risk calculator used in the 2013 guidelines "would lead to massive use of statins at the population level; ie, 'statinization.'"
"It is uncertain whether this would be one of the greatest achievements or one of the worst disasters of medical history," added Ioannidis, a specialist in epidemiology and preventive medicine at Stanford University.
The first of the two studies, led by cardiologists from Harvard Medical School and Massachusetts General Hospital, suggests that widespread adoption of the new risk calculator would be a lifesaving achievement.
Researchers went back into the vaults of the Framingham Heart Study and selected 2,435 adult subjects who were healthy and not taking cholesterol-lowering medicine in 2002 to 2005, when they had their arteries scanned for calcium deposits. Applying both the 2004 guidelines for cholesterol treatment and those issued in 2013, the researchers set out to find out which was a better predictor of who would go on to develop heart disease over the next nine years.
Among those who would be considered for treatment with statins under the new guidelines, 6% of subjects went on the have a heart attack or stroke, fatal or nonfatal. Stroke or heart attack struck 1% of subjects among the much larger pool of subjects that the 2013 guideline considered not eligible for statins.
The 2004 standards for cholesterol-lowering treatment would have drawn in the 7% of subjects who did go on to have a heart attack or stroke. But 2% of the much-larger group of subjects who were not considered for such treatment went on to have a stroke or heart attack.
Extrapolating their findings to the approximately 10 million U.S. adults who are newly eligible for statins, the authors of the study calculated that treating all of those patients could prevent 41,000 to 63,000 incident heart attacks and strokes over 10 years.
The authors of the second study found that shifting the standards for treatment from the 2004 criteria to those of the 2013 guidelines would drive the share of American adults eligible for statin treatment from 44% to 48%. The additional cost of medicating so many Americans -- including many who would never go on to suffer a stroke or heart attack -- would be high. But for every quality-adjusted life-year (QALY) gained, the additional cost would be $37,000 -- "an acceptable cost-effectiveness profile," they said.
A QALY is a standardized measure of a policy's cost that takes into account the quantity and quality of life gained with its implementation.
If the criteria for treatment with statins were dropped further -- a shift that would make roughly two-thirds of the adult population eligible for statins -- the authors found the cost higher, but predicted it would avert an additional 125,000 to 160,000 heart attacks or strokes over 10 years.
In an editorial published alongside the studies in JAMA on Tuesday, two influential cardiologists wrote that the new research should lay to rest debate over the metric used in the 2013 guidelines.
To drive down the incidence of strokes and heart attacks, "there should now be fewer questions about how to treat and in whom," wrote Drs. Philip Greenland and Michael S. Lauer. Greenland is a senior editor of JAMA and cardiologist and preventive medicine specialist at Northwestern University's Feinberg School of Medicine. Lauer directs the National Heart, Blood and Lung Institute's cardiovascular sciences division.
Cedars-Sinai cardiologist Sanjay Kaul said the new studies offer "an endorsement of what the guidelines suggested." Although the 2013 treatment recommendations were "a work in progress" when they were publicly presented, Kaul said, "these studies provide reassurance these are guidelines we can rely on."
Other experts took a dimmer view of the latest research and its power to salvage the much-debated 2013 guidelines from abandonment by practicing physicians.
"I really can draw no conclusions from these about whether the guidelines are identifying the right people or not," said Cleveland Clinic cardiologist Dr. Steven Nissen. The study, led by Harvard Medical School cardiologists, followed 2,435 subjects, mostly white New Englanders, who had enrolled in the ongoing Framingham Heart Study.
Nissen said it would take a much larger trial, following a more representative group of American adults, to demonstrate the validity of the new risk calculator.
"In my view, the guidelines need to be rewritten. They are not being used by practicing physicians because they're frankly not viewed as being thoughtful and rational," Nissen said.
Meanwhile, physicians continue to struggle with, and routinely to ignore, the 2013 guidelines' recommendation against monitoring a patient's response to cholesterol-lowering drugs and escalating the use of those drugs if specific LDL ("bad" cholesterol) targets aren't met.
"It's time to move on and do a new set of guidelines," Nissen said.