P2Y12i monotherapy reduces risk of myocardial infarction compared to aspirin monotherapy

Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: a systematic review and meta-analysis

Literature - Chiarito M, Sanz-Sánchez J, Cannata F et al., - The Lancet. 2020. doi: 10.1016/S0140-6736(20)30315-9.

Introduction and methods

Treatment with an antiplatelet agent is recommended for secondary prevention in patients with established cerebrovascular, coronary, or peripheral artery disease [1-4]. Treatment with aspirin has a proven net benefit in secondary cardiovascular prevention [5]. P2Y12 inhibitors provide an alternative to aspirin and pharmacodynamic studies have shown that P2Y12 inhibitors provide more profound platelet inhibition compared to aspirin [6,7]. In this study, a systematic review and meta-analysis were performed to evaluate the effect of P2Y12 inhibitor monotherapy vs aspirin monotherapy on clinical outcomes in patients with cerebrovascular, coronary, or peripheral artery disease.

A total of nine randomized trials were included in this study, in which 42108 patients were randomly allocated to a P2Y12 inhibitor (n=21043) or aspirin (n=21065). The co-primary endpoints were myocardial infarction (MI) and stroke. Key secondary endpoints included all-cause death and vascular death. Secondary safety endpoints were any bleeding and major bleeding.

Main results

  • Patients who received a P2Y12 inhibitor had a lower risk of MI, compared to patients who received aspirin (OR 0.81, 95%CI 0.66-0.99, I²=10.9%). The number needed to treat with P2Y12 inhibitors to prevent one MI was 244 patients.
  • There were no differences between those who received a P2Y12 inhibitor and those who received aspirin in terms of risk of stroke (OR 0.93, 95%CI 0.82-1.06, I²=24.5%), all cause death (OR 0.98, 95%CI 0.89-1.08, I²=0%), and vascular death (OR 0.97, 95%CI 0.86-1.09, I²=0%).
  • No difference between treatment with a P2Y12 inhibitor and aspirin was observed in terms of risk of any bleeding (OR 1.08, 95%CI 0.91-1.29, I²=51.3%), and major bleeding (OR 0.90, 95%CI 0.74-1.10, I²=3.9%). Patients who received a P2Y12 inhibitor had a lower risk of gastrointestinal bleeding, compared to those who received aspirin (OR 0.59, 95%CI 0.39-0.89, I²=18.2%).
  • Ischemic outcomes by type of P2Y12 inhibitor (ticlopidine, clopidogrel or ticagrelor) showed findings consistent with the primary analysis. A stratified analysis according to qualifying disease were also consistent with the primary analysis.

Conclusion

Patients who received P2Y12 inhibitor monotherapy had a lower risk of MI, compared to patients who received aspirin. No differences in risk of stroke, all cause death and vascular death were found between those who received a P2Y12 inhibitor and those who received aspirin. The clinical relevance of the benefit of P2Y12 inhibitor is debatable due to the high number needed to treat to prevent one MI and the absence of an effect on all-cause and vascular mortality.

References

1. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45: 2160–236.

2. Knuuti J, Wijns W, Saraste A, et al. 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J 2020; 41: 407–77.

3. Aboyans V, Ricco J-B, Bartelink MEL, et al. 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. Eur Heart J 2018; 39: 763–816.

4. Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: the task force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2018; 39: 213–60.

5. Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative metaanalysis of individual participant data from randomised trials. Lancet 2009; 373: 1849–60.

6. Armstrong PCJ, Dhanji A-RA, Tucker AT, Mitchell JA, Warner TD. Reduction of platelet thromboxane A2 production ex vivo and in vivo by clopidogrel therapy. J Thromb Haemost 2010; 8: 613–15.

7. Bhavaraju K, Georgakis A, Jin J, et al. Antagonism of P2Y₁₂ reduces physiological thromboxane levels. Platelets 2010; 21: 604–09.

Find this article online at The Lancet.

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