(CSPOT06) Comparative Analysis of Treatment Discontinuation Among P2Y12 receptor inhibitors Post-Acute Coronary Syndrome: A Network Meta-analysis of Randomized Controlled Trials.

Background: P2Y12 receptor inhibitors are highly effective treatment options following ACS. However, premature discontinuation compromises their effectiveness. Although extensive literature exists, the clinical assessment of their adherence remains controversial, requiring definitive investigation.

Objectives: To evaluate treatment discontinuation and non-bleeding adverse effects associated with platelet P2Y12 receptor inhibitors in individuals post-ACS through network meta-analysis.

Methods:

Design: Network meta-analysis.
Data Sources: MEDLINE, Embase, Cochrane, and clinicaltrials.gov to May 2021 and later updated to October 2022.
Study Selection: Reviewers identified RCTs that enrolled patients post-ACS taking Clopidogrel, Ticagrelor, and Prasugrel. Exclusions included non-ACS indications, anticoagulation therapy, observational studies, and crossover designs.
Main Outcome(s) and Measure(s): The primary outcomes included overall treatment discontinuation, treatment discontinuation attributed to side effects, and dyspnea. Secondary outcomes included bradycardia and atrial fibrillation.
Data Extraction and Synthesis: This network meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, employing frequentist random-effects models. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework was utilized to assess the certainty of evidence.

Results: With 139,343 participants in 32 RCTs, the overall treatment discontinuation rate was 16.57%. Ticagrelor exhibited an increased risk for discontinuation compared to Clopidogrel (RR, 1.34; 95% CI, 1.19 to 1.49; P< 0.0001), Prasugrel (RR, 1.23; 95% CI, 1.07 to 1.41; P=0.0031), and placebo (RR, 1.40; 95% CI, 1.19 to 1.65; P< 0.0001), with no significant difference between Prasugrel and Clopidogrel. Furthermore, Ticagrelor, Prasugrel, and Clopidogrel were associated with an increased risk of dyspnea compared to placebo (RR, 2.86; 95% CI, 2.57 to 3.17; P< 0.0001; RR, 1.61; 95% CI, 1.35 to 1.91; P< 0.0001; RR, 1.60; 95% CI, 1.41 to 1.82; P< 0.0001), respectively. Ticagrelor showed a higher risk of dyspnea compared to Clopidogrel (RR, 1.78; 95% CI, 1.65 to 1.92; P< 0.0001) and Prasugrel (RR, 1.78; 95% CI, 1.55 to 2.05; P< 0.0001).

Conclusions: The findings of this study suggest that Ticagrelor presents the highest risk for premature discontinuation compared to Clopidogrel and Prasugrel. Additionally, P2Y12 receptor inhibitors, in general, are notably associated with dyspnea, with Ticagrelor showing the highest risk. These results provide health professionals with valuable information for making treatment decisions in patients post-ACS.