Experts debate optimal duration of DAPT after MI, stenting

BOSTON — Reflecting the wide range of current opinions on dual antiplatelet therapy after MI or coronary artery stenting, two experts at the Cardiometabolic Health Congress debated the pros and cons of extended vs. shortened duration of therapy.

Gregg W. Stone, MD, professor of medicine at Columbia University, director of cardiovascular research and education at the Center for Interventional Vascular Therapy at NewYork-Presbyterian Hospital/Columbia University Medical Center, and co-director of medical research and education at the Cardiovascular Research Foundation, maintained that the net effect of extended dual antiplatelet therapy (DAPT) is greater harm than good.

Gregg W. Stone

DAPT should not be employed in patients with stable CAD beyond 6 months and in patients with ACS beyond 12 months, but “may be considered for longer-term use in selected patients in whom the risks of recurrent ischemia are substantially greater than the risks of bleeding, although in most patients it is not necessary,” Stone said.

Results of a meta-analysis of 10 trials of extended DAPT after stenting revealed that MI was reduced by 25% in patients who received DAPT for longer than 12 months vs. those who did not (P < .01) and stent thrombosis was numerically reduced by 41% in those who received prolonged DAPT (P = .06); however, cardiac mortality was 8% higher, major bleeding was 72% higher (P < .0001), noncardiac mortality was 49% higher (P = .006) and all-cause mortality was 22% higher (P = .02) among those who received prolonged DAPT, Stone said.

“How do you weigh the balance?” he asked. “Maybe what you do is look at all-cause mortality. That may have been what led to the guideline recommendations saying in most patients, there’s a minimum short period, maybe 6 months in most patients and 12 months after ACS, and … that’s all you need. In an occasional rare patient, you will need longer DAPT, but shorter is [usually] better.”

Another factor is whether a first- or second-generation drug-eluting stent was used, according to Stone. He noted that in patients with newer DES prolonged DAPT confers only a modest reduction in stent thrombosis at the cost of an 80% increased risk for bleeding.

For stable patients with prior MI, in the PEGASUS TIMI-54 trial, DAPT with ticagrelor (Brilinta, AstraZeneca) for as long as 33 months was associated with a lower rate of CV death, MI or stroke vs. aspirin and placebo after 12 months. But Stone noted that “it was a small reduction; it was an absolute one out of 100 patients over about 3 years, about 0.3% to 0.4% per year. The trade-off here was a lot of bleeding; TIMI major bleeding was increased by threefold, minor bleeding was increased by fourfold and transfusions by sixfold.”

Extended DAPT with ticagrelor was also associated with increased risk for dyspnea and gout, and there was no difference between the groups in any metric of mortality, he noted.

“In general, 1 year for most patients seems like the right duration of DAPT,” Stone, a member of the Cardiology Today’s Intervention Editorial Board, said.

Kenneth W. Mahaffey, MD, vice chair of clinical research in the department of medicine at Stanford School of Medicine and director of the Stanford Center for Clinical Research, said that because 50% of lesions causing ischemic events were not previously intervened upon, “we really need to think of ways to continue aggressive therapy, because atherosclerotic disease is a chronic systemic disease that needs chronic systemic therapies.”

Kenneth W. Mahaffey

In a meta-analysis of six trials of long-term DAPT for secondary prevention of CV events in stable but high-risk patients with prior MI, DAPT extended beyond 12 months reduced risk for CV death, MI or stroke vs. aspirin alone after 12 months (RR = 0.78; 95% CI, 0.67-0.9), Mahaffey said. The meta-analysis data were published in European Heart Journal. “CV death alone was decreased by about 15% and was highly significant, with no effect on all-cause mortality,” he said.

The same analysis revealed that extended DAPT was associated with increased risk for major bleeding (RR = 1.73; 95% CI, 1.19-2.5). “Importantly, fatal bleeding and intracranial hemorrhage, two of the most important bleeding events, were not increased with more prolonged or potent [DAPT],” Mahaffey said.

Using the DAPT Score, which was developed in 2015, may help identify patients who are at high risk for major bleeding and should not receive extended DAPT, he said. Patients with a score of less than 2 are not recommended for extended DAPT (number needed to treat to prevent ischemia, 153; number needed to harm to cause bleeding, 64), while those with a score of 2 or more should receive extended DAPT (number needed to treat to prevent ischemia, 34; number needed to harm to cause bleeding, 272), he said.

Another analysis (Eisen A, Bhatt DL. Nat Rev Cardiol. 2015;doi:10.1038/nrcardio.2015.87) identified the following factors suggesting DAPT duration should be 12 months or less: stable CAD, history of or high risk for bleeding, short lesions, single-vessel disease and use of a second-generation DES. The analysis also identified the following factors suggesting DAPT should be extended: ACS, diabetes, renal dysfunction, congestive HF, previous stent thrombosis, peripheral artery disease, long lesions, small vessels, bifurcation lesions, complex anatomy, left main disease, first-generation DES, long stent or multiple stents, according to Mahaffey.

“It’s clear now that patients who have had a prior MI, a spontaneous event with plaque rupture, are at much higher risk for subsequent ACS, whether they had stenting or not,” he said. “There are a number of angiographic features that need to be considered, and the evolution of stents may fundamentally change the equation of the risks for stent thrombosis and bleeding.”

A focused update to U.S. guidelines now suggests that for patients who underwent PCI with stenting, extended DAPT beyond 1 month for those implanted with a bare-metal stent and 6 months for those implanted with a DES may be reasonable if there is no bleeding or high risk for it, and for patients with ACS, extended DAPT beyond 12 months may be reasonable in those who did not bleed and are not at high risk to bleed, he said.

“This brings us into the area of informed decision making with our patients, and the ultimate goal of personalize medicine,” Mahaffey said. – by Erik Swain

Reference:

Mahaffey KW, Stone GW. The Latest in Antithombotic Therapy: The Experts Take Sides. Presented at: Cardiometabolic Health Congress; Oct. 5-8, 2016; Boston.

Disclosure: Mahaffey reports receiving research funding from Amgen, AstraZeneca, Daiichi Sankyo, Johnson & Johnson, Medtronic, Merck, Sanofi and Tenax; receiving consultant fees from AstraZeneca, BAROnova, Bayer, Boehringer Ingelheim, Bio2 Medical, Bristol-Myers Squibb, Cubist, Eli Lilly, Elsevier, Epson, Forest, GlaxoSmithKline, Johnson & Johnson, Medtronic, Merck, MyoKardia, Omthera, Portola, Purdue, Springer, The Medicines Company, Theravance, Vindico and WebMD; and holding equity in BioPrint Fitness. Stone reports no relevant financial disclosures.