Under the new guidelines, 56 million Americans ages 40 to 75 are eligible to consider a statin; 43 million were under the old advice. Both numbers include 25 million people taking statins now.
"That is striking ... eye-opening," Dr. Daniel Rader of the University of Pennsylvania said of the new estimate.
But since too few people use statins now, the advice "has the potential to do much more good than harm," said Rader, a cardiologist who had no role in writing the guidelines.
Nearly half a million additional heart attacks and strokes could be prevented over 10 years if statin use was expanded as the guidelines recommend, the study estimates.
The guidelines, developed by the American Heart Association and American College of Cardiology at the request of the federal government, were a big change. They give a new formula for estimating risk that includes blood pressure, smoking status and many factors besides the level of LDL or "bad" cholesterol, the main focus in the past.
For the first time, the guidelines are personalized for men and women and blacks and whites, and they take aim at strokes, not just heart attacks. Partly because of that, they set a lower threshold for using statins to reduce risk.
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The guidelines say statins do the most good for people who already have heart disease, those with very high LDL of 190 or more, and people over 40 with Type 2 diabetes.
They also recommend considering statins for anyone 40 to 75 who has an estimated 10-year risk of heart disease of 7.5 percent or higher, based on the new formula. (This means that for every 100 people with a similar risk profile, seven or eight would have a heart attack or stroke within 10 years.)
Under this more nuanced approach, many people who previously would not have qualified for a statin based on LDL alone now would, while others with a somewhat high LDL but no other heart risk factors would not.
The Duke researchers gauged the impact of these changes by using cholesterol, weight and other measurements from health surveys by the Centers for Disease Control and Prevention. They looked at how nearly 4,000 people in these surveys would have been classified under the new and old guidelines, and projected the results to the whole country.
The biggest effect was on people 60 and older, researchers found. Under the new guidelines, 87 percent of such men not already taking a statin are eligible to consider one; only 30 percent were under the old guidelines. For women, the numbers are 54 percent and 21 percent, respectively.
Dr. Paul Ridker and Nancy Cook of Brigham and Women's Hospital in Boston have criticized the risk formula in the guidelines. Ridker declined to be interviewed, but in a statement, he and Cook noted that most people newly suggested for statins do not have high cholesterol but smoke or have high blood pressure. Those problems and lifestyle changes should be addressed before trying medications -- which the guidelines recommend -- they write.
Dr. Neil Stone, the Northwestern University doctor who helped lead the guidelines work, stressed that the guidelines just say who should consider a statin, and they recommend people discuss that carefully with a doctor.
"We think we're focusing the attention for statins on those who would benefit the most," Stone said.
Dr. Harlan Krumholz, a Yale University cardiologist who has long advocated this approach, agreed.
"The guidelines provide a recommendation, not a mandate" for statin use, he said.
Pencina, the leader of the Duke study, said his own situation motivated him to look at the guidelines more closely. His LDL was nearing a threshold to consider a statin under the old guidelines, but under the new formula for gauging risk, "I'm fine," he said.