New DAPT data prominent at ESC 2015

LONDON — The European Society of Cardiology Congress featured several presentations on the optimal patient populations and duration for dual antiplatelet therapy in patients with ACS or stable CAD.

The topic has been much-debated and somewhat controversial in recent years. Here is some of the new information that came to light at the congress.

48-month DAPT with clopidogrel

Researchers found no significant benefit to extending clopidogrel-based DAPT to 48 months compared with 12 months in the OPTIDUAL trial.

Gérard Helft

The primary outcome was net adverse clinical events, a composite of death, MI, stroke or major bleeding. At follow-up, events occurred in 5.8% of the extended-DAPT group vs. 7.5% of the aspirin-only group (HR = 0.75; 95% CI, 0.5-1.28), Gérard Helft, MD, PhD, from the Institut de Cardiologie, Hôpital Pitié-Salpétrière, in Paris, France, said at a press conference.

Helft and colleagues determined, however, that ischemic outcomes, including death, MI or stroke, occurred in 4.2% of the extended-DAPT group vs. 6.4% of the aspirin-only group (HR = 0.64; 95% CI, 0.4-1.02), without increasing bleeding (2% vs. 2%; P = .95) or all-cause mortality.

Ischemic events and prior MI

Compared with aspirin alone, DAPT for more than 1 year was associated with a reduction in ischemic events in stable but high-risk patients with prior MI, according to the results of a meta-analysis.

Jacob A. Udell, MD, MPH, and colleagues found that long-term DAPT was linked to a higher rate of major bleeding, but not of fatal bleeding or non-CV death.

Compared with aspirin alone, DAPT beyond 1 year was associated with a lower risk for major adverse CV events (6.4% vs. 7.5%; RR = 0.78; 95% CI, 0.67-0.9) and CV death (2.3% vs. 2.6%; RR = 0.85; 95% CI, 0.74-0.98), and a similar risk for non-CV death (RR = 1.03; 95% CI, 0.86-1.23) and all-cause mortality (RR = 0.92; 95% CI, 0.83-1.03), Udell, from the University of Toronto, and colleagues found.

Bleeding risk with prasugrel/aspirin

In a substudy of the BASKET-PROVE II trial of DAPT with prasugrel (Effient, Daiichi Sankyo/Eli Lilly) in patients after stenting, researchers reported that prasugrel-based DAPT was as safe in patients with stable CAD as in patients with ACS.

Raban V. Jeger, MD, and colleagues also found that, when BASKET-PROVE II patients were compared with a historical control group from BASKET-PROVE, prasugrel-based DAPT was as safe as clopidogrel-based DAPT in patients with stable CAD.

However, Jeger, from University Hospital Basel, Switzerland, and colleagues found that patients at high risk for bleeding (those older than 75 years and those weighing less than 60 kg) had high rates of bleeding prasugrel-based DAPT despite taking a reduced dose, 5 mg, of prasugrel. “Therefore, corresponding label prescriptions of 5 mg for high-bleeding-risk patients have to be questioned,” Jeger said.

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Long-term DAPT mortality analysis

Laura Mauri, MD, from Brigham and Women’s Hospital, presented a mortality analysis of patients from the DAPT trial, which evaluated 1-year DAPT vs. 30-month DAPT in patients after stenting.

Mauri and colleagues observed a trend toward increased mortality in the 30-month DAPT group (during treatment: 1.9% vs. 1.5%; P = .07; across treatment and discontinuation phases, 2.2% vs. 1.8%; P = .05).

Laura Mauri

However, they found that deaths from bleeding were low and most of the difference was accounted for by cancer-related deaths.

“Whether cancer-related deaths are truly related to treatment is uncertain, and could be a chance finding,” she said, noting that there is not enough evidence to recommend against extended DAPT in this population because of cancer-related death.

Restarting ticagrelor

In a substudy of the PEGASUS–TIMI 54 population of ticagrelor (Brilinta, AstraZeneca) often combined with aspirin in patients at least 1 year beyond MI, researchers determined that re-initiating ticagrelor in patients who were stable for at least 1 year on aspirin alone did not confer a thrombosis-related benefit and appeared to increase bleeding.

Marc P. Bonaca

“Patients who recently stopped P2Y12 inhibition are at higher risk for ischemic events than those who have been stable off therapy for an extended time,” said Marc P. Bonaca, MD, MPH, from Brigham and Women’s Hospital. “The early hazard may be due to unmasking of thrombotic potential.”

He noted, however, that there was a robust ischemic benefit (27% RR ratio; number needed to treat = 46) for those who continued on ticagrelor or restarted it after an interruption of less than 30 days. – by Erik Swain

References:

Bonaca P, et al.

Helft G. Hot Line III: Diabetes Mellitus/Pharmacology.

Jeger RV, et al.

Mauri L, et al.

Udell JA, et al. Clinical Trial Update II – Antiplatelet therapy.

All presented at: European Society of Cardiology Congress; Aug. 29-Sept. 2, 2015; London.

Disclosures: Bonaca reports consulting for AstraZeneca, Bayer, Merck and Roche and receiving grant support via the TIMI Study Group from AstraZeneca and Merck. Helft reports receiving grants from the French Ministry of Health, the Fédération Française de Cardiologie, Biotronik, Boston Scientific, Cordis, Medtronic and Terumo, and personal fees from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim and Pfizer. Mauri reports receiving research grants from Abbott, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cordis, Daiichi Sankyo, Eli Lilly, Medtronic Vascular and Sanofi Aventis, consulting for Biotronik, Boehringer Ingelheim, Eli Lilly, Medtronic Vascular, Recor and St. Jude Medical, and receiving honoraria from AstraZeneca and Sanofi Aventis. Udell reports serving on advisory boards for Merck, Novartis and Sanofi Pasteur and receiving honoraria from Elsevier. Jeger reports no relevant financial disclosures.