FDA Approves Ticagrelor for High-Risk Coronary Artery Disease Patients

The FDA has granted approval for ticagrelor (Brilinta, AstraZeneca) for the reduction of risk of first heart attack or stroke in high-risk patients with coronary artery disease (CAD).

A press release from AstraZeneca noted that the approval was based primarily on positive results from the THEMIS trial, which showed a statistically significant reduction in its primary endpoint of MACE at 36 months using aspirin plus 60 mg ticagrelor compared with aspirin alone. The more than 19,000 patients in THEMIS had CAD and about one-third of them had type 2 diabetes mellitus, and were considered high-risk for a first heart attack and for stroke.

According to the THEMIS results, researchers reported a 10% relative risk reduction of the composite endpoint of heart attack, stroke, or cardiovascular death using aspiring plus ticagrelor compared with aspirin alone in the high-risk patients who also had no history of heart attack or stroke (7.7% vs. 8.5%; HR=0.90; 95% CI, 0.81 to 0.99; P=0.04). An increase in bleeding events was also reported, which the press release noted “was consistent with the known profile of the medicine.”

“Coronary artery disease is a potentially life-threatening condition that causes significant morbidity in many people,” Deepak L. Bhatt, MD, MPH, co-chair of the THEMIS trial and executive director of interventional Cardiovascular Programs at Brigham and Women’s Hospital, said in the news release. “The addition of ticagrelor to aspirin offers a new therapeutic option to decrease the likelihood of both heart attack and stroke, a significant advance in our ability to treat these high-risk patients.”

The original results of the THEMIS study were published in The Lancet and the New England Journal of Medicine.

@US_FDA expands ticagrelor indication for primary prev pts w/ DM2 + stable CAD(noPCI)w/o prior MI or CVA based on THEMIS data https://t.co/5CgxyLlrpf showing reduction in composite endpt CVdeath,MI,&CVA 🙈 risk of TIMI major🩸 >than 2x and #ICH rates⬆️ ticagrelor group vs placebo

— Dr. Sheila Sahni (@DrSheilaSahni) June 3, 2020

New FDA label for ticagrelor in "high-risk CAD patients", following THEMIS. But:
1) THEMIS was in CAD and DM: what does "high risk" mean? And where is DM?
2) NNT and NNH in THEMIS were 125 and 83, with more ICH.

A bit surprised by the broad indication.https://t.co/6JyyWpbu6Y

— Davide Capodanno (@DFCapodanno) June 1, 2020

And here's the trial that led to the approval

Patient population:

a) >=50
b) type 2 diabetes

*AND*

c) stable CAD = history of CABG, PCI, non-obstructive CAD on angio

Ticagrelor in Patients with Stable Coronary Disease and Diabetes | NEJM https://t.co/jUmQyYVuyG

— Sek Kathiresan MD (@skathire) June 1, 2020

https://twitter.com/ATRIUMRx/status/1267558338658816003