EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS

SNOWMASS, COLO. (FRONTLINE MEDICAL NEWS) Forthcoming guideline updates addressing the duration of dual-antiplatelet therapy will recommend shorter minimum durations following elective coronary stent placement for patients with stable ischemic heart disease in order to provide physicians with more room to exercise clinical judgment and individualize therapy.

“The American College of Cardiology and the American Heart Association have gone through a several month process of revising all recommendations with respect to antiplatelet therapy across six different guidelines. That should be published in the next few months. I suspect it will be similar to what the Europeans have been espousing,” Dr. Patrick T. O’Gara , ACC immediate past president, said at the Annual Cardiovascular Conference at Snowmass.

“If you look at the European Society of Cardiology guidelines, it’s as little as 30 days of DAPT [dual-antiplatelet therapy] following placement of a bare metal stent in a stable ischemic heart disease patient, 3 months for current generation drug-eluting stents, extending that out a little longer for the bioabsorbable stent platforms,” said Dr. O’Gara, professor of medicine at Harvard Medical School and director of clinical cardiology at Brigham and Women’s Hospital, Boston.

The impetus for the updated guidelines on DAPT duration, according to the cardiologist, was a growing appreciation of the trade-offs involved in this potent therapy, which reduces the risk of major adverse cardiovascular events at the price of a significant increase in major bleeding.

The new ACC/AHA recommendation calling for as little as 3 months of DAPT following placement of current generation drug-eluting stents in patients with stable ischemic heart disease (IHD) follows from the observation that the risks of late and very late stent thrombosis are extremely low with these devices, whereas the risk of bleeding remains higher, he continued.

The new, shorter recommended minimum DAPT durations are consistent with the underlying histopathology of stable IHD with intermittent claudication. Plaque rupture is unlikely to occur at that stage of atherosclerotic heart disease, in contrast to the inherent instability of the vulnerable plaque with a thin fibrous cap that’s present in an acute coronary syndrome (ACS). Patients with ACS have increased risks of recurrent ischemia or MI, stent thrombosis, bleeding, and death, compared with those with stable IHD.

“It’s just their biology,” Dr. O’Gara explained. “Think of ACS as a prothrombotic state which has a tail of activity over the next 6-12 months.”

That’s why a minimum of 12 months of DAPT featuring aspirin at 81 mg/day following stent placement in patients who present with ACS will continue to be recommended in the update. The same applies to patients who undergo coronary artery bypass grafting after presenting with ACS, although Dr. O’Gara said many surgeons appear to be unaware of this recommendation.

“You’re obligated to complete 12 months of DAPT in that situation. One of the common mistakes made in clinical practice is for surgeons to simply send those patients home on aspirin without a P2Y12 inhibitor,” according to Dr. O’Gara.

The positive outcomes seen with DAPT lasting for longer than 12 months after stent implantation in patients with ACS in the large DAPT trial and the more recent PEGASUS-TIMI 54 trial have put considerable pressure on guideline-writing committees to give a strong endorsement of extended DAPT. But the steep price paid in terms of major bleeding with this prolonged DAPT strategy, he said, gives one pause.

PEGASUS-TIMI 54 randomized more than 21,000 patients with a history of MI nearly 2 years earlier plus one additional high-risk factor such as diabetes to an average of 33 months of double-blind treatment with ticagrelor (Brilinta) at 60 or 90 mg/day or placebo on top of low-dose aspirin ( N Engl J Med. 2015 May 7;372[19]:1791-800 ).

“For every 1,000 patients treated with prolonged DAPT, there were four fewer major ischemic events but three additional major bleeding events per year. Is this a clear winner? For all the enthusiasm there’s been about PEGASUS, those numbers look relatively small. It gets back to the point that individual judgment trumps everything,” Dr. O’Gara said.

He noted that this theme of a close overall risk/benefit balance for prolonged DAPT received further support at last year’s annual meeting of the European Society of Cardiology, where Dr. Jay A. Udell of the University of Toronto presented a meta-analysis of six randomized trials of prolonged DAPT versus aspirin alone in more than 33,000 high-risk patients with a history of MI. The results, which were recently published, showed a 22% reduction in the relative risk of major adverse cardiovascular events with extended DAPT, but a 73% increase in the risk of major bleeding ( Eur Heart J. 2016 Jan 21;37[4]:390-9 ).

The DAPT trial investigators have developed a risk score in an effort to aid clinicians in deciding whether to extend DAPT for more than 12 months after stent placement for ACS in a given individual. The score, which utilizes eight clinical variables, was unveiled at last November’s AHA scientific sessions. For patients with a DAPT score of 2 or more, the number needed to treat for 18 additional months after the initial 12 months of DAPT in order to prevent one major adverse cardiovascular event was 34, with the number needed to harm in the form of major bleeding being 272. For patients with a DAPT score of less than 2, the number needed to treat was 153, and the number needed to harm was 64.

However, Dr. O’Gara said he doesn’t consider the DAPT score ready for use in daily clinical practice for a couple of reasons: It hasn’t yet been validated externally, and it hasn’t yet been published in a peer-reviewed journal.

“I suspect it’s going through a lot of editorial revisions in terms of its statistical underpinnings,” the cardiologist said.

He reported having no financial conflicts of interest regarding his presentation.

bjancin@frontlinemedcom.com

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