Fewer Cardiovascular Events When Statin Guidelines Apply More Broadly

01/02/18

By Will Boggs MD

NEW YORK (Reuters Health) - Guidelines that recommend statin use for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in a broader population of patients prevent more events than less-inclusive guidelines, according to a comparison of five major guidelines.

"Despite being founded on the same evidence originating from randomized statin trials, it was surprising to see the large heterogeneity between guidelines in the number of individuals qualifying for primary prevention with statins,” Dr. Borge Gronne Nordestgaard from Copenhagen University Hospital, Herlev, and University of Copenhagen, in Denmark, told Reuters Health by email.

Five organizations have published major guidelines or statements on statins for primary prevention of ASCVD since 2013: the American College of Cardiology/American Heart Association (ACC/AHA); the UK's National Institute for Health and Care Excellence (NICE); the Canadian Cardiovascular Society (CCS); the U.S. Preventive Services Task Force (USPSTF); and the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS). Their recommendations differ substantially.

Dr. Nordestgaard and Dr. Martin Bodtker Mortensen from Aarhus University Hospital, in Denmark, compared the value of these guidelines for primary prevention of ASCVD by applying them to 45,750 people ages 40 to 75 in the Copenhagen General Population Study. None were using statins or had ASCVD at baseline.

The findings were published online January 1 in Annals of Internal Medicine.

This population’s statin eligibility varied widely: 44% according to CCS guidelines, 42% with ACC/AHA guidelines, 40% with NICE, 31% with USPSTF, and 15% with ESC/EAS.

Fewer than 20% of people younger than 50 were eligible for statin therapy by all of the guidelines, and statin eligibility grew steadily with age to more than 75% in people older than 70 for all but the ESC/EAS guidelines.

If high-intensity statins were used for eligible individuals (assuming 50% reduction in LDL cholesterol), the potential reduction of all ASCVD events over 10 years was 34% for both CCS and ACC/AHA, 32% for NICE, 27% for USPSTF, and 13% for ESC/EAS. The potential reductions were lower for moderate-intensity statins (assuming 30% reduction in LDL cholesterol).

Using these figures, the researchers estimate that the CCS, ACC/AHA, and NICE guidelines each may prevent about 32 to 34 of 100 ASCVD events, the USPSTF guidelines about 27 of 100 events, and the ESC/EAS guidelines about 13 of 100 events.

“Our study clearly shows that the guidelines recommending statin therapy to 40% to 44% of individuals aged 40-75 have the potential for reducing the burden of atherosclerotic cardiovascular disease by a third - that is, if they are fully implemented and if high-dose statins are prescribed,” Dr. Nordestgaard said.

He added, “I wonder why many people, some doctors, and mainly European societies are not interested in the full implementation of this efficient method of prevention cardiovascular disease. . . . Statins are safe, inexpensive, and very effective in reducing atherosclerotic cardiovascular disease risk.”

Dr. G.B. John Mancini from the University of British Columbia, in Canada, who wrote a related editorial, told Reuters Health by email, "I think that among the top 3 performing guidelines, the fact that they all identified the same general level of risk even though they each used different risk algorithms was surprising to me. It raises the question whether all the debates on risk algorithms are material or not.”

“To me, (the findings indicate) that many patients in westernized societies would benefit from lipid lowering with safe drugs (i.e., statins in this modeling exercise) and that preventive efforts would be best with at least 50% lowering, even in primary prevention,” he said. “But the fact that the best-performing algorithms may be preventing only about a third of preventable events suggests that there is much more room to improve preventive efforts as long as one accepts that indications for lipid lowering would need to be liberalized further.”

“Guidelines are sociopolitical statements based on science, and so they will (and should) vary from country to country and from learned society to learned society,” Dr. Mancini said. “In this way we can learn from each other and perhaps ultimately adopt best practices more uniformly. But we must all recognize that these ‘best efforts’ still do not seem to prevent the majority of preventable events. Improvement of current lipid-based and risk-based algorithms may require incorporation of other factors including the mere presence of other, non-lipid cardiovascular risk factors/markers as used in some primary prevention randomized controlled trials (RCTs) or perhaps through RCTs based on imaging evidence of early atherosclerosis.”

Dr. Ariela Orkaby from VA Boston Healthcare System, Brigham and Women's Hospital, and Harvard Medical School, Boston, told Reuters Health by email, "Statins are excellent drugs for reducing the risk of CVD, though it is important to consider each guideline within the context of the population for which it was developed. However, it is striking to see the very significant difference in the number of people eligible between guidelines, particularly the much lower rates according to the European guidelines, and therefore the lower number of events prevented. Using any of the other guidelines to direct therapy, according to this population of largely white individuals, we would save many more lives by increasing the number of individuals to whom we prescribe statins.”

“None of these guidelines addresses how to treat older adults - the fastest-growing segment of the population who are often at the highest risk of a first cardiac event,” she said. “Further research is needed before we can make sweeping recommendations to prescribe statins to those over 75 where the risk of side effects, interaction with other medications, and time to benefit becomes increasingly problematic.”

“For patients at risk of CVD, I would first always encourage lifestyle changes, particularly smoking cessation,” Dr. Orkaby said. “Statins should also be part of every CVD risk prevention conversation.”

SOURCES: http://bit.ly/2qefxmg and http://bit.ly/2qaaVgV

Ann Intern Med 2018.

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