P2Y12 Inhibitor or Aspirin Monotherapy for Atherosclerosis Prevention

May 20, 2020
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Authors:
Chiarito M, Sanz-Sánchez J, Cannata F, et al.
Citation:
Monotherapy With a P2Y12 Inhibitor or Aspirin for Secondary Prevention in Patients With Established Atherosclerosis: A Systematic Review and Meta-Analysis. Lancet 2020;395:1487-1495.
Summary By:
Debabrata Mukherjee, MD, FACC

Quick Takes

  • The risk of all-cause death, vascular death, and stroke does not differ between patients receiving a P2Y12 inhibitor and those receiving aspirin monotherapy.
  • The risk of MI is marginally lower in patients receiving a P2Y12 inhibitor compared with aspirin, with a number needed to treat (NNT) of 244 patients to prevent one MI.
  • Overall, the benefit favoring P2Y12 inhibitor monotherapy appears to be of questionable clinical relevance in view of the high NNT to prevent one MI and the absence of any effect on all-cause and vascular death and higher cost of novel P2Y12 inhibitors.

Study Questions:

What is the efficacy of a P2Y12 inhibitor monotherapy strategy compared with aspirin monotherapy for secondary prevention in patients with established atherosclerosis?

Methods:

The investigators conducted a systematic review and meta-analysis, and evaluated for inclusion all randomized trials comparing P2Y12 inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease. They searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, the authors reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients’ features including the baseline condition determining study inclusion (i.e., cerebrovascular, coronary, or peripheral artery disease), P2Y12 inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected.

Odds ratios (ORs) and 95% confidence intervals (CIs) were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction (MI) and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I2 index. ORs and 95% CIs were calculated using the DerSimonian and Laird random-effects model, with the estimate of heterogeneity being taken from the Mantel-Haenszel method. This study is registered with PROSPERO (CRD42018115037).

Results:

Nine randomized trials were identified and included in this study, and 42,108 patients randomly allocated to a P2Y12 inhibitor (n = 21,043) or aspirin (n = 21,065) were included in the analyses. Patients who received a P2Y12 inhibitor had a borderline reduction for the risk of MI compared with those who received aspirin (OR, 0.81; 95% CI, 0.66-0.99; I2 = 10.9%). Risks of stroke (OR, 0.93; 0.82-1.06; I2 = 34.5%), all-cause death (OR, 0.98; 0.89-1.08; I2 = 0%), and vascular death (OR, 0.97; 0.86-1.09; I2 = 0%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR, 0.90; 0.74-1.10; I2 = 3.9%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. The number needed to treat (NNT) to prevent one MI with P2Y12 inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y12 inhibitor used.

Conclusions:

The authors concluded that compared with aspirin monotherapy, P2Y12 inhibitor monotherapy is associated with a risk reduction for MI and a comparable risk of stroke in the setting of secondary prevention.

Perspective:

This study reports that the risk of all-cause death, vascular death, and stroke does not differ between patients receiving a P2Y12 inhibitor and those receiving aspirin. The risk of MI is marginally lower in patients receiving a P2Y12 inhibitor compared with aspirin, with a NNT of 244 patients to prevent one MI. Furthermore, these findings are consistent irrespective of the type of P2Y12 inhibitor used. Overall, the benefit favoring P2Y12 inhibitor monotherapy appears to be of debatable clinical relevance in view of the high NNT to prevent one MI and the absence of any effect on all-cause and vascular death. The marginal risk reduction of MI and high accompanying NNT, combined with the higher costs of novel P2Y12 inhibitors compared with aspirin, emphasize the need for a thorough evaluation of cost-effectiveness before implementing changes of antiplatelet therapy strategies in clinical practice.

Clinical Topics: Cardiovascular Care Team, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD)

Keywords: Aspirin, Atherosclerosis, Cerebrovascular Disorders, Coronary Disease, Cost-Benefit Analysis, Hemorrhage, Myocardial Infarction, Myocardial Ischemia, Peripheral Arterial Disease, Platelet Aggregation Inhibitors, Risk, Secondary Prevention, Stroke, Vascular Diseases


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