Aspirin for primary prevention? No clear guidance in 2015

ESTES PARK, COLO. – Physicians who choose not to recommend daily aspirin for primary prevention of cardiovascular disease have nothing to apologize for, even though their position is at odds with a current recommendation by the U.S. Preventive Services Task Force (USPSTF), Dr. David Tanaka declared at a conference on internal medicine sponsored by the University of Colorado.

Non-recommenders of aspirin for primary cardiovascular prevention have plenty of company, as highlighted in two recent large studies, noted Dr. Tanaka, a general internist at the university.

Dr. David Tanaka

In one study, investigators analyzed National Health and Nutrition Examination Survey data for 2011-2012. They determined that while 87% of U.S. men aged 45-79 years were potentially eligible for aspirin for primary prevention of cardiovascular events under the USPSTF grade-A recommendation, a minority (34%) had received guidance from their physician to adopt this measure.

Further, 16% of women aged 55-79 years were eligible for aspirin for primary cardiovascular prevention under the USPSTF recommendation. As was the case for eligible men, the clinical recommendation rate for this practice was low: 42% of women had been advised to take a daily aspirin (J Gen Intern Med. 2015 Feb;30:155-60. doi: 10.1007/s11606-014-2985-8).

Dr. Tanaka noted that the task force is in the process of reassessing its current recommendations on aspirin for primary prevention, issued in 2009; the revision was slated to be published in 2014, according to the task force website.

The other highly revealing recent study was an analysis of 119 U.S. cardiology practices participating in the American College of Cardiology’s National Cardiovascular Disease Registry Practice Innovation and Clinical Excellence Registry (PINNACLE), a quality-improvement project.

The registry did not employ the USPSTF standard for eligibility for aspirin as primary prevention, opting instead to utilize an estimated 10-year cardiovascular disease risk of 6% or higher. Among 68,808 registry patients on aspirin for primary prevention, investigators determined that usage was inappropriate in 11.6% because their 10-year cardiovascular disease risk was below 6%. The most interesting finding, Dr. Tanaka said, was the huge disparity between practices in terms of inappropriate aspirin prescribing; some cardiology practices had zero inappropriate use of aspirin for primary prevention, while in other groups the rate was as high as 72% (J Am Coll Cardiol. 2015 Jan 20;65:111-21. doi: 10.1016/j.jacc.2014.10.035).

“I think these studies show that all of us – cardiologists, general internists, family physicians, everybody – we really don’t know exactly what to do,” Dr. Tanaka observed.

That’s understandable. Current guidelines don’t offer a clear consensus as to what’s best practice. The current 2010 joint ADA/AHA/ACCF scientific statement sings a different tune than those jointly issued in 2006, which remain much more widely known. The American College of Chest Physicians guidelines of 2012, the European Society of Cardiology Working Group on Thrombosis guidelines of 2014...none are in harmony, he said.

“It’s no wonder that there’s a wide variety of recommendations, since the risks and benefits of aspirin for primary prevention are actually very close,” Dr. Tanaka added.

He cited a metaanalysis of nine large randomized, placebo-controlled clinical trials of aspirin for primary prevention totaling more than 100,000 participants. The metaanalysis, conducted by investigators at St. George’s University of London, concluded aspirin did not reduce cardiovascular mortality or stroke, but it did result in a 20% reduction in the risk of nonfatal MI compared with placebo. This was offset by a 31% increase in the risk of nontrivial bleeding, defined as a fatal bleeding event, retinal bleeding, intracerebral bleeding, or GI bleeding requiring hospitalization and transfusion. The risk of hemorrhagic stroke was increased in aspirin users by roughly 1 event per 1,000 patients over 5 years (Arch Intern Med. 2012 Feb 13;172:209-16).

“If you really need good, solid proof in order to use a therapy, you can say ‘I’m not going to use aspirin for primary prevention because it’s not going to decrease my patients’ risk of dying,’ and that’s OK,” Dr. Tanaka said.

Many physicians will want to take a more nuanced approach, though, by individualizing the risk/benefit assessment and engaging in shared decision-making with at-risk patients, he continued.

At present, in Dr. Tanaka’s view, the best tools for this purpose are the AHA/ACC risk calculator, available online and as an app, and the Qbleed score, developed and validated in the U.K. in 753 general practices, with a massive derivation cohort of 4.4 million patients and 16.4 million person-years and validation cohort of 1.4 million patients. The Qbleed is by far the most precise tool available today for estimating bleeding risk.

Using the example of a 60-year-old woman with hypertension, diabetes, and no cardiovascular symptoms, Dr. Tanaka plugged the patient data into the AHA/ACC risk calculator and Qbleed and determined that her baseline 10-year risk of a cardiovascular event is 10%, with a 10-year risk of GI bleeding of 1% and a 0.4% risk of intracranial bleeding. Based upon the metaanalysis results, taking aspirin for primary prevention would reduce her 10-year risk of a nonfatal MI to roughly 8% while increasing her risk of a serious GI bleed from to 1.3%. Thus, her net benefit through taking aspirin would be one or two fewer nonfatal cardiovascular events versus a risk of 1.3 serious GI bleeds and roughly 0.5 intracranial bleeds.