P2Y12 Inhibitors in Acute Coronary Syndromes: A Real-World, Community-Based Comparison of Ischemic and Bleeding
Amit Sachdeva1, Ratnabhushan Mutyala2, Neha Mantri3
1Division of Cardiology, Kaiser Permanente Northern California, Walnut Creek, California, USA.
Insights
In patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), ticagrelor showed a lower risk of all-cause mortality compared to clopidogrel. No significant differences were observed for other endpoints between ticagrelor and clopidogrel, or between prasugrel and clopidogrel.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Research
Background:
- Randomized trials suggest novel P2Y12 inhibitors are superior to clopidogrel in acute coronary syndrome (ACS) patients.
- Clinical benefit of these agents in real-world, community settings remains debated.
- This study compares clopidogrel, ticagrelor, and prasugrel in ACS patients undergoing percutaneous coronary intervention (PCI).
Purpose of the Study:
- To compare the safety and efficacy of clopidogrel versus ticagrelor and prasugrel.
- To evaluate outcomes in a real-world population of ACS patients treated with P2Y12 inhibitors.
- To assess associations with all-cause mortality, myocardial infarction, stroke, and bleeding events.
Main Methods:
- Retrospective cohort study of 15,476 ACS patients undergoing PCI from 2012-2018.
- Patients were discharged on clopidogrel, ticagrelor, or prasugrel.
- Cox proportional hazard models with propensity-score matching were used to analyze outcomes.
Main Results:
- Ticagrelor use was associated with a lower risk of all-cause mortality compared to clopidogrel (HR 0.43 [0.20-0.92]).
- No significant differences in myocardial infarction, stroke, or bleeding events were found between ticagrelor and clopidogrel.
- No differences in any primary endpoints were observed between prasugrel and clopidogrel.
Conclusions:
- Ticagrelor demonstrated a reduced risk of all-cause mortality versus clopidogrel in ACS patients post-PCI.
- No significant differences in other clinical endpoints were noted between ticagrelor and clopidogrel, or between prasugrel and clopidogrel.
- Further research is needed to determine optimal P2Y12 inhibitor selection in real-world ACS populations.
Background:
Randomized trials have shown superiority of the novel P2Y12 inhibitors over clopidogrel in patients with acute coronary syndrome (ACS), but clinical benefit in the community remains controversial. Our objective was to compare the safety and efficacy of clopidogrel to ticagrelor and prasugrel in patients with ACS undergoing percutaneous coronary intervention (PCI) in a real-world population.
Methods:
We conducted a retrospective cohort study of patients with ACS who underwent PCI and were discharged with clopidogrel, ticagrelor, or prasugrel from 2012 to 2018 within Kaiser Permanente Northern California. We used Cox proportional hazard models with propensity-score matching to evaluate the association of the P2Y12 agent with the primary outcomes of all-cause mortality, myocardial infarction (MI), stroke, and bleeding events.
Results:
The study included 15,476 patients (93.1% on clopidogrel, 3.6% on ticagrelor and 3.2% on prasugrel). Compared to the clopidogrel group, ticagrelorand prasugrel patients were younger with less comorbidities. In multivariable models with propensity-score matching, we found a lower risk of all-cause mortality in the ticagrelor vs the clopidogrel group (HR (95% CI) 0.43 (0.20-0.92)), but no differences in the other endpoints, and no difference between prasugrel and clopidogrel among any endpoints. A larger proportion of patients on ticagrelor or prasugrel switched to an alternative P2Y12 agent vs. clopidogrel (p < 0.01), and a higher level of persistence was seen among patients on clopidogrel vs. ticagrelor (p = 0.03) or prasugrel (p < 0.01).
Conclusion:
Among patients with ACS who underwent PCI, we observed a lower risk of all-cause mortality in patients treated with ticagrelor vs clopidogrel, but no difference in other clinical endpoints nor any differences in endpoints between prasugrel vs. clopidogrel users. These results suggest that further study is needed to identify an optimal P2Y12 inhibitor in a real-world population.
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