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Ticagrelor as compared to conventional antiplatelet agents in coronary artery disease: A comprehensive meta-analysis
Monica Verdoia1, Stefano Savonitto2, Dariusz Dudek3
1Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
Insights
Ticagrelor did not reduce mortality in coronary artery disease patients but significantly lowered recurrent myocardial infarction. However, it increased major bleeding risks, particularly intracranial hemorrhage, compared to traditional antiplatelet agents.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Ticagrelor shows potential benefits in acute coronary syndromes and long-term cardiovascular prevention.
- Real-world data and meta-analyses suggest ticagrelor's anti-ischemic benefits may be lower than anticipated, with a potential increase in bleeding risks.
- Existing research necessitates a comprehensive evaluation of ticagrelor's comparative effectiveness and safety.
Purpose of the Study:
- To evaluate the prognostic impact of ticagrelor versus conventional antiplatelet agents (aspirin and clopidogrel).
- To compare ticagrelor's efficacy in reducing mortality and ischemic events against standard therapies.
- To assess the safety profile of ticagrelor, focusing on major bleeding complications in patients with coronary artery disease (CAD).
Main Methods:
- A meta-analysis of 15 randomized clinical trials involving 73,402 patients with coronary artery disease (CAD).
- Studies compared ticagrelor-based regimens against alternative antiplatelet agents.
- Primary endpoints included all-cause mortality and major bleeding events; secondary endpoints covered cardiovascular mortality, myocardial infarction, stroke, and intracranial hemorrhage (ICH).
Main Results:
- Ticagrelor did not significantly reduce overall mortality compared to traditional therapy (OR 0.88 [0.70, 1.09]).
- A significant reduction in recurrent myocardial infarction was observed with ticagrelor (OR 0.84 [0.78, 0.90]).
- Major bleeding events, including intracranial hemorrhage, were significantly increased with ticagrelor (OR 1.40 [1.06, 1.84] for major bleeding; OR 1.45 [1.13, 1.84] for ICH).
Conclusions:
- Ticagrelor therapy in CAD patients is associated with a significant increase in major bleeding complications, particularly ICH, compared to conventional antiplatelet agents.
- While ticagrelor showed a neutral effect on overall survival, it significantly reduced recurrent myocardial infarction.
- The findings suggest a need to carefully weigh the benefits of reduced myocardial infarction against the increased bleeding risks associated with ticagrelor.
Background:
Ticagrelor has been shown to offer potential outcome benefits in acute coronary syndromes and for the long-term cardiovascular prevention, reducing mortality and the recurrence of ischemic events. However, data from real-world and recent meta-analyses have suggested that the anti-ischemic benefits of ticagrelor could be lower than expected, potentially outweighed by an increased risk of bleeding complications. Therefore, the aim of the present meta-analysis was to evaluate the prognostic impact of ticagrelor as compared to the conventional antiplatelet agents (ASA and clopidogrel) in patients with coronary artery disease (CAD), enclosing patients with acute coronary syndromes and stable CAD.
Methods:
Literature and main scientific session abstracts were searched for studies comparing a ticagrelor-based antiplatelet regimen vs different antiplatelet agents in patients with CAD. The primary efficacy endpoint was mortality, and the primary safety endpoint was the occurrence of major bleedings. Secondary endpoints were cardiovascular mortality, myocardial infarction, stroke and intracranial hemorrhage (ICH).
Results:
We included 15 randomized clinical trials, with a total population of 73,402 patients (55% randomized to ticagrelor). At a mean follow-up of 15 ± 11.3 months, the ticagrelor based strategy did not significantly reduce mortality as compared to the traditional therapy (OR[95%CI] = 0.88[0.70,1.09], p = 0.24; phet<0.00001), with comparable results and no interaction according to patients' presentation (p interaction = 0.80). A similar result was achieved for cardiovascular mortality, whereas the reduction of recurrent myocardial infarction was significant (OR[95%CI] = 0.84[0.78,0.90], p < 0.00001; phet = 0.76). As for the risk of stroke, the largest reduction was observed in stable patients, while a neutral effect was observed in the ACS subgroup (p int = 0.35). Major bleeding events were increased in ticagrelor-treated patients (OR [95%CI] = 1.40 [1.06, 1.84], p = 0.02; phet<0.00001), especially ICH (OR [95% CI] = 1.45[1.13,1.84], p = 0.003; phet = 0.93), and mainly among non-ACS patient. No interaction for any outcome endpoint was observed according to patients' age.
Conclusions:
Based on the current meta-analysis, a ticagrelor-based strategy for the treatment of patients with coronary artery disease is associated to a significant increase in major bleeding complications and especially for intracranial hemorrhage, as compared to a strategy based on conventional antiplatelet agents, while resulting in a neutral effect on survival. However, a significant reduction of recurrent myocardial infarction was observed with ticagrelor.
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