Author + information
- Received February 19, 2019
- Accepted March 3, 2019
- Published online May 13, 2019.
- Sameer Arora, MDa,∗,
- Kamal Shemisa, MDb,∗,
- Muthiah Vaduganathan, MD, MPHc,
- Arman Qamar, MDc,
- Ankur Gupta, MD, PhDb,
- Sushil K. Garg, MDd,
- Dharam J. Kumbhani, MD, SMb,
- Helen Mayo, MLSe,
- Houman Khalili, MDf,
- Ambarish Pandey, MD, MSCSb and
- Sandeep R. Das, MD, MPH, MBAf,∗ (, )@sandeepdasmd@UTSWNews
- aDivision of Cardiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
- bDivision of Cardiology, University of Texas Southwestern School of Medicine, Dallas, Texas
- cHeart & Vascular Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- dDivision of Gastroenterology, Mayo Clinic, Rochester, Minnesota
- eHealth Sciences Digital Library and Learning Center, University of Texas Southwestern School of Medicine, Dallas, Texas
- fDepartment of Medicine, Florida Atlantic University, Boca Raton, Florida
- ↵∗Address for correspondence:
Dr. Sandeep Das, University of Texas Southwestern Medical Center, Cardiology Division, 5323 Harry Hines Boulevard, MC 8830, Dallas, Texas 73590-8830.
• Ticagrelor is a cornerstone of antithrombotic therapy after ACS, but its effectiveness is limited by nonadherence.
• Premature ticagrelor discontinuation occurs in 25% of patients and is related to adverse events.
• The most frequent adverse events of ticagrelor are bleeding and dyspnea.
• Appropriate patient selection, early follow-up, patient education, and appropriate bleeding prophylaxis can mitigate ticagrelor nonadherence.
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.
↵∗ Drs. Arora and Shemisa contributed equally to this work.
Dr. Shemisa has served on the Speakers Bureau for Boehringer Ingelheim. Dr. Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (National Institutes of Health/National Center for Advancing Translational Sciences Award UL 1TR002541); has served on advisory boards for Amgen, AstraZeneca, Bayer AG, and Baxter Healthcare; and has participated in clinical endpoint committees for studies sponsored by Novartis and the National Institutes of Health. Dr. Qamar is supported by the NHLBI T32 postdoctoral training grant (T32HL007604) and the American Heart Association Strategically Focused Research Network in Vascular Disease grant (18SFRN3390085 & 18SFRN33960262); has received grant support through Brigham and Women’s Hospital from Daiichi-Sankyo; and has received fees for educational activities from the American College of Cardiology, Society for Cardiovascular Angiography and Interventions, Pfizer, Medscape, and Clinical Exercise Physiology Association. Dr. Kumbhani has received honoraria from the American College of Cardiology. Dr. Pandey is funded by the Texas Health Resources Clinical Scholarship. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received February 19, 2019.
- Accepted March 3, 2019.
- 2019 American College of Cardiology Foundation
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