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J Am Coll Cardiol. 2019 May 21;73(19):2454-2464. doi: 10.1016/j.jacc.2019.03.470.

Premature Ticagrelor Discontinuation in Secondary Prevention of Atherosclerotic CVD: JACC Review Topic of the Week.

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Division of Cardiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Division of Cardiology, University of Texas Southwestern School of Medicine, Dallas, Texas.
Heart & Vascular Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota.
Health Sciences Digital Library and Learning Center, University of Texas Southwestern School of Medicine, Dallas, Texas.
Department of Medicine, Florida Atlantic University, Boca Raton, Florida.
Department of Medicine, Florida Atlantic University, Boca Raton, Florida. Electronic address:


Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor.


acute coronary syndrome; adherence; myocardial infarction; secondary prevention; ticagrelor


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