Key result
Ticagrelor linked to ~59% more premature discontinuations due to adverse events versus control.
Why the study?
Premature ticagrelor discontinuation due to adverse effects like bleeding and dyspnea may limit its advantages over clopidogrel, prompting a meta-analysis to precisely quantify the incidence and causes of discontinuation.
Does ticagrelor increase the risk of premature discontinuation due to adverse events compared to comparators in patients with atherosclerotic CVD?
Meta-Analysis (n=66,870)
Does ticagrelor increase the risk of premature discontinuation due to adverse events compared to comparators in patients with atherosclerotic CVD?
Relative Risk: 1.59
Ticagrelor is associated with a high rate of premature discontinuation (25%), primarily driven by significantly increased risks of bleeding and dyspnea compared to control therapies.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“There's a lot of focus these days on trying to get patients to adhere to the things that we prescribe because if the pill never makes it from the bottle to the mouth of the patient, or from the pharmacy into the hand of the patient, it's not going to do a lot of good. We prescribe agents like ticagrelor because we think it's very beneficial for preventing some pretty serious events, so I think that understanding all the issues that can lead to noncompliance or nonadherence is important.”
“The biggest issues in practice are that there are these side effects, but they usually are quite manageable and can be handled by just reassuring the patients and following up and making sure that [they're] not developing intolerable symptoms. And then the cost is something that we need to be more aware of and willing to have frank discussions with our patients about.”
Ticagrelor users warrant proactive dyspnea and bleeding management to boost adherence; extends RCT evidence on key tolerability barriers.
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.
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Arora et al. (2019) conducted a meta-analysis in Acute coronary syndrome and after percutaneous coronary intervention (n=66,870). Ticagrelor vs. Comparators (e.g., clopidogrel) was evaluated on Premature ticagrelor discontinuation (RR 1.59). Ticagrelor was associated with a 25% rate of premature discontinuation and a 59% higher relative risk of discontinuation due to any adverse event compared to control.
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