Izza Shahid1, Muhammad Abdullah Nizam1, Vanita Motiani1, Ritesh G Menezes2, Unaiza Naeem3, Tariq Jamal Siddiqi4, Tehlil Rizwan3, Fahd Makhdom5, Pradhum Ram6, Muhammad Shariq Usman4. 1. Department of Medicine, Ziauddin Medical University, Karachi, Pakistan. 2. Department of Pathology, College of Medicine, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. 3. Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan. 4. Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA. 5. Department of Surgery, College of Medicine, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. 6. Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA. rampradhum@gmail.com.
Abstract
BACKGROUND AND OBJECTIVE: Previous studies and meta-analyses have assessed optimal P2Y12 inhibitors following acute coronary syndrome in overall trial cohorts. However, there are insufficient data for the elderly cohort who are prone to high bleeding and ischemic events. We aimed to assess the optimal P2Y12 inhibitor therapy for older patients. METHODS: PubMed, CENTRAL, and ClinicalTrials.gov databases were searched from inception through July 2020 to identify randomized controlled trials and propensity-matched observational studies including older patients (aged ≥ 65 years) that reported study-defined major adverse cardiovascular events (MACE) or major bleeding events. Outcomes at the mid-term follow-up were pooled to conduct a frequentist network meta-analysis. RESULTS: Fourteen studies involving 12,953 older patients were included in our analysis. No significant difference was observed with MACE when all three P2Y12 inhibitors were compared with each other. Compared with clopidogrel, ticagrelor significantly increased the risk of major bleeding (risk ratio 1.35, 95% confidence interval 1.10-1.67) while prasugrel did not (risk ratio 1.02, 95% confidence interval 0.67-1.57). A sensitivity analysis of only randomized controlled trials yielded similar results for both MACE and major bleeding. The P score displayed prasugrel (0.5871) as the best treatment for MACE, while clopidogrel (0.7701) was the best P2Y12 inhibitor to decrease the risk of major bleeding. Ticagrelor (0.0634) was ranked the lowest because of an increased bleeding risk. CONCLUSIONS: No significant difference is observed between the three P2Y12 inhibitors in study-defined MACE. Ranking by p-score suggests prasugrel as the best P2Y12 inhibitor to reduce the risk of MACE while clopidogrel is a better alternative than ticagrelor in older patients with acute coronary syndrome to decrease the risk of major bleeding. Because of a lack of individual-patient data analysis and heterogeneity amongst studies, future studies representing older patients with acute coronary syndrome are required to strengthen evidence regarding optimal antithrombotic therapy in this cohort.
BACKGROUND AND OBJECTIVE: Previous studies and meta-analyses have assessed optimal P2Y12 inhibitors following acute coronary syndrome in overall trial cohorts. However, there are insufficient data for the elderly cohort who are prone to high bleeding and ischemic events. We aimed to assess the optimal P2Y12 inhibitor therapy for older patients. METHODS: PubMed, CENTRAL, and ClinicalTrials.gov databases were searched from inception through July 2020 to identify randomized controlled trials and propensity-matched observational studies including older patients (aged ≥ 65 years) that reported study-defined major adverse cardiovascular events (MACE) or major bleeding events. Outcomes at the mid-term follow-up were pooled to conduct a frequentist network meta-analysis. RESULTS: Fourteen studies involving 12,953 older patients were included in our analysis. No significant difference was observed with MACE when all three P2Y12 inhibitors were compared with each other. Compared with clopidogrel, ticagrelor significantly increased the risk of major bleeding (risk ratio 1.35, 95% confidence interval 1.10-1.67) while prasugrel did not (risk ratio 1.02, 95% confidence interval 0.67-1.57). A sensitivity analysis of only randomized controlled trials yielded similar results for both MACE and major bleeding. The P score displayed prasugrel (0.5871) as the best treatment for MACE, while clopidogrel (0.7701) was the best P2Y12 inhibitor to decrease the risk of major bleeding. Ticagrelor (0.0634) was ranked the lowest because of an increased bleeding risk. CONCLUSIONS: No significant difference is observed between the three P2Y12 inhibitors in study-defined MACE. Ranking by p-score suggests prasugrel as the best P2Y12 inhibitor to reduce the risk of MACE while clopidogrel is a better alternative than ticagrelor in older patients with acute coronary syndrome to decrease the risk of major bleeding. Because of a lack of individual-patient data analysis and heterogeneity amongst studies, future studies representing older patients with acute coronary syndrome are required to strengthen evidence regarding optimal antithrombotic therapy in this cohort.
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