Dataset Information

Personalized Dual Antiplatelet Therapy in Acute Coronary Syndromes: Striking a Balance Between Bleeding and Thrombosis.

ABSTRACT:

Purpose of review

Dual antiplatelet therapy (DAPT)-aspirin in conjunction with a P2Y₁₂ inhibitor-is the cornerstone of managing patients with acute coronary syndromes post-revascularization, but the clinical response is highly variable, with potentially devastating consequences. Herein, we review the mechanisms underpinning said variability and explore emerging approaches to normalizing therapeutic benefit.

Recent findings

The potent P2Y₁₂ inhibitors, prasugrel and ticagrelor, exhibit minimal inter-individual variability, replacing clopidogrel in DAPT and achieving greater rates of therapeutic response. However, these benefits decline in later phases when bleeding risk begins to supersede that of ischemia. Guided de-escalation of P2Y₁₂ inhibition as well as shortening DAPT duration have emerged as strategies that retain antithrombotic efficacy while reducing bleeding risk. Aspirin is the other component of DAPT but is also used in isolation for secondary prevention of thrombotic disease. In contrast to the P2Y₁₂ inhibitors, genetic influences on aspirin non-response appear to be outweighed by a triad of clinical factors: non-adherence, enteric aspirin use, and inappropriate dosing according to bodyweight and BMI. Multiple de-escalation strategies for DAPT have been shown to mitigate bleeding risk, but it remains unclear which approach is ideal, necessitating head-to-head investigations to determine which exhibits the most favorable cost-to-benefit ratio. However, there is likely a role for more than one approach in clinical practice, depending on patient risk profile. Our approach to aspirin use is also in need of reassessment: strategies to improve adherence, avoidance of enteric aspirin in cardiac patients, and dose adjustment according to bodyweight and/or BMI are all likely to improve rates of therapeutic response. Moreover, platelet function testing may have a role in identifying patients expected to benefit from primary prophylactic aspirin.

SUBMITTER: Shpigelman J

PROVIDER: S-EPMC10307718 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Personalized Dual Antiplatelet Therapy in Acute Coronary Syndromes: Striking a Balance Between Bleeding and Thrombosis.

Shpigelman Jonathan J Proshkina Anastasia A Daly Michael J MJ Cox Dermot D

Current cardiology reports 20230601 7

<h4>Purpose of review</h4>Dual antiplatelet therapy (DAPT)-aspirin in conjunction with a P2Y<sub>12</sub> inhibitor-is the cornerstone of managing patients with acute coronary syndromes post-revascularization, but the clinical response is highly variable, with potentially devastating consequences. Herein, we review the mechanisms underpinning said variability and explore emerging approaches to normalizing therapeutic benefit.<h4>Recent findings</h4>The potent P2Y<sub>12</sub> inhibitors, prasugr ...[more]

PMID: 37261665

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Project description:BackgroundThe relationship between "on-treatment" low platelet reactivity and longitudinal risks of major bleeding dual antiplatelet therapy following acute coronary syndromes remains uncertain, especially for patients who do not undergo percutaneous coronary intervention.Methods and resultsWe analyzed 2428 medically managed acute coronary syndromes patients from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial who had serial platelet reactivity measurements (P2Y12 reaction units; PRUs) and were randomized to aspirin+prasugrel versus aspirin+clopidogrel for up to 30 months. Contal's method was used to determine whether a cut point for steady-state PRU values could distinguish high versus low bleeding risk using 2-level composites: Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe/life-threatening or moderate bleeding unrelated to coronary artery bypass grafting (CABG) and non-CABG Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding. Exploratory analyses used 3-level composites that incorporated mild and minimal GUSTO and TIMI events. Continuous measures of PRUs (per 10-unit decrease) were not independently associated with the 2-level GUSTO (adjusted hazard ratio [HR], 1.01; 95% CI, 0.96-1.06) or TIMI composites (1.02; 0.98-1.07). Furthermore, no PRU cut point could significantly distinguish bleeding risk using the 2-level composites. However, the PRU cut point of 75 differentiated bleeding risk with the 3-level composites of GUSTO (26.5% vs 12.6%; adjusted HR, 2.28; 95% CI, 1.77-2.94; P<0.001) and TIMI bleeding events (25.9% vs 12.2%; adjusted HR, 2.30; 95% CI, 1.78-2.97; P<0.001).ConclusionsAmong medically managed non-ST-segment elevation acute coronary syndromes patients receiving prolonged dual antiplatelet therapy, PRU values were not significantly associated with the long-term risk of major bleeding events, suggesting that low on-treatment platelet reactivity does not independently predict serious bleeding risk.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00699998.

Dataset Information

Personalized Dual Antiplatelet Therapy in Acute Coronary Syndromes: Striking a Balance Between Bleeding and Thrombosis.

Purpose of review

Recent findings

Publications

Personalized Dual Antiplatelet Therapy in Acute Coronary Syndromes: Striking a Balance Between Bleeding and Thrombosis.

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