Reviewer: Dr. Fatih Aksoy

Name of the Study: PANTHER - P2Y12 inhibitor versus aspirin monotherapy in patients with coronary artery disease

Published Congress: ESC 2022

Link : https://www.escardio.org/The-ESC/Press-Office/Press-releases/Patients-with-coronary-artery-disease-should-receive-P2Y12-inhibitor-instead-of-aspirin

Background:

Long-term antiplatelet therapy with aspirin is the cornerstone of secondary prevention in patients with atherosclerosis. In patients with acute coronary syndrome or percutaneous coronary intervention, life-long aspirin is the standard of care after the first course of dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor and aspirin. The CAPRIE randomized trial demonstrated a significant but slight reduction in cardiovascular events with clopidogrel monotherapy compared to aspirin monotherapy in patients with coronary, cerebrovascular, and/or peripheral atherosclerosis. Different results were obtained in studies comparing P2Y12 inhibitor monotherapy with clopidogrel or ticagrelor versus aspirin monotherapy.

Objective:

The PANTHER trial aimed to address this uncertainty by evaluating data from randomized controlled trials evaluating the effect of monotherapy with oral P2Y12 inhibitors (clopidogrel, prasugrel, or ticagrelor) versus currently recommended aspirin on ischemic and bleeding outcomes among identified major cardiac events, by meta-analyzing data.

Methods:

The analysis included 24,325 patients from seven randomized controlled trials. Of these patients, 12,178 were assigned to P2Y12 inhibitor monotherapy (7,545 to clopidogrel, 4,633 [38,0%) to ticagrelor) and 12,147 to aspirin monotherapy.

Results:

The median treatment duration of the patients included in the analysis was 557 days, the mean age of the participants was 64.3%, and 21.7% were women. The risk of the primary outcome, assessing cardiovascular death, myocardial infarction, and stroke, was lower with P2Y12 inhibitor monotherapy compared to aspirin monotherapy (6.3% versus 5.5%; hazard ratio [HR] 0.88; 95% confidence interval [CI]) 0.79–0.97; p=0.014). The number that needs to be treated to prevent an adverse outcome is 123 patients. P2Y12 inhibitor monotherapy was associated with a lower risk of myocardial infarction than aspirin monotherapy (2.3 vs. 3.0%; HR 0.77; 95% CI 0.66-0.90; p<0.001). There was no significant difference between the groups for stroke (HR 0.85; 95% CI 0.70-1.02) or CV death (HR 1.02; 95% CI 0.86-1.20).

Considering secondary outcomes, the risk of major bleeding was similar between patients using P2Y12 inhibitor and aspirin (1.2% vs. 1.4%; HR 0.87; 95% CI 0.70-1.09; p=0. 23). The net risk of adverse clinical events, defined as the combination of the primary efficacy endpoint and major bleeding, was reduced with P2Y12 inhibitor monotherapy compared to aspirin monotherapy (6.4% vs. 7.2%; HR 0.89; 95% CI 0.81-0, 98; p =0.020). Some secondary results also supported P2Y12 inhibitor therapy. Hemorrhagic stroke (HR 0.32; 95% CI: 0.14-0.75), definite stent thrombosis (HR 0.42; 95% CI: 0.19-0.97), definite/probable stent thrombosis (HR 0.46; 95% CI: 0.23-0.92)), gastrointestinal bleeding (HR 0.75; 95% CI 0.57-0.97). There was evidence supporting a significant reduction in myocardial infarction with P2Y12 inhibitor monotherapy versus high-dose aspirin versus low-dose aspirin (HR 0.59; 95% CI 0.43-0.79) (HR 0.85; 95% CI 0.71- 1.01; p=0.040 for interaction).

Conclusion:

Based on findings from the PANTHER study, P2Y12 inhibitor monotherapy was associated with lower risks of cardiovascular death, myocardial infarction (MI), and stroke compared to aspirin monotherapy in patients with coronary artery disease.

Interpretations:

An additional alternative has been presented in individuals with coronary artery disease. Based on available randomized evidence, long-term P2Y12 inhibitor monotherapy may be considered instead of long-term aspirin monotherapy for secondary prevention in patients with coronary artery disease. However, the existing meta-analysis needs to be supported by additional studies.