Dataset Information

Optimal P2Y₁₂ inhibitor durations in older men and older women following an acute myocardial infarction: A nationwide cohort study using Medicare data.

ABSTRACT:

Study objective

Identify optimal P2Y₁₂ inhibitor durations balancing ischemic-benefit and bleeding-risk outcomes after acute myocardial infarction (AMI) in older men and women.

Design

Observational retrospective cohort with 2 years of follow-up, using clone-censor-weight marginal structural models to emulate randomization.

Setting

20 % sample of US Medicare administrative claims data.

Participants

P2Y₁₂ inhibitor new users ≥66 years old following 2008-2013 AMI hospitalization.

Exposures

12- to 24-month P2Y₁₂ inhibitor durations in 1-month intervals.

Main outcome measures

Effectiveness outcome (composite of all-cause mortality, recurrent AMI, ischemic stroke), safety outcome (hospitalized bleed), and negative control outcome (heart failure hospitalization).

Results

Of 28,488 P2Y₁₂ inhibitor new users, 51 % were female, 50 % were > 75 years old, 88 % were White/non-Hispanic, and 93 % initiated clopidogrel. Negative control outcome results for 16- through 24-month durations appeared most likely to meet assumptions of no unmeasured confounding. Compared to men taking 24-month therapy, men taking 16-month therapy had higher 2-year risks of the composite effectiveness outcome (relative risk [RR] = 1.08; 95 % confidence interval [95%CI]:1.00-1.15) with similar bleeding risks (RR = 0.98; 95%CI:0.85-1.13). Compared to women taking 24-month therapy, women taking 16-month therapy had similar 2-year risks of the composite effectiveness outcome (RR = 0.98; 95%CI:0.92-1.04) and lower bleeding risks (RR = 0.88; 95%CI:0.80-0.96).

Conclusions

Older men taking 24-month P2Y₁₂ inhibitor therapy had the lowest composite effectiveness outcome risk with no increased bleeding risk compared to shorter durations. Women taking 16-month versus 24-month P2Y₁₂ inhibitor therapy had similar composite effectiveness outcome risks but a substantially lower hospitalized bleeding risk, suggesting durations beyond 15-17 months lacked benefit while increasing bleeding risk.

SUBMITTER: Hickson RP

PROVIDER: S-EPMC10939016 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Optimal P2Y<sub>12</sub> inhibitor durations in older men and older women following an acute myocardial infarction: A nationwide cohort study using Medicare data.

Hickson Ryan P RP Kucharska-Newton Anna M AM Rodgers Jo E JE Sleath Betsy L BL Fang Gang G

American heart journal plus : cardiology research and practice 20231031

<h4>Study objective</h4>Identify optimal P2Y<sub>12</sub> inhibitor durations balancing ischemic-benefit and bleeding-risk outcomes after acute myocardial infarction (AMI) in older men and women.<h4>Design</h4>Observational retrospective cohort with 2 years of follow-up, using clone-censor-weight marginal structural models to emulate randomization.<h4>Setting</h4>20 % sample of US Medicare administrative claims data.<h4>Participants</h4>P2Y<sub>12</sub> inhibitor new users ≥66 years old followin ...[more]

PMID: 38487715

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Project description:Selatogrel is a potent and reversible P2Y12 receptor antagonist developed for subcutaneous self-administration by patients with suspected acute myocardial infarction. After single-dose emergency treatment with selatogrel, patients are switched to long-term treatment with oral P2Y12 receptor antagonists. Selatogrel shows rapid onset and offset of inhibition of platelet aggregation (IPA) to overcome the critical initial time after acute myocardial infarction. Long-term benefit is provided by oral P2Y12 receptor antagonists such as clopidogrel, prasugrel, and ticagrelor. A population pharmacokinetic (PK)/pharmacodynamic (PD) model based on data from 545 subjects in 4 phase I and 2 phase II studies well described the effect of selatogrel on IPA alone and in combination with clopidogrel, prasugrel, and ticagrelor. The PK of selatogrel were described by a three-compartment model. The PD model included a receptor-pool compartment to which all drugs can bind concurrently, reversibly or irreversibly, depending on their mode of action. Furthermore, ticagrelor and its active metabolite can bind to the selatogrel-receptor complex allosterically, releasing selatogrel from the binding site. The model provided a framework for predicting the effect on IPA of selatogrel followed by reversibly and irreversibly binding oral P2Y12 receptor antagonists for sustained effects. Determining the timepoint for switching from emergency to maintenance treatment is critical to achieve sufficient IPA at all times. Simulations based on the interaction model showed that loading doses of clopidogrel and prasugrel administered 15 h and 4.5 h after selatogrel, respectively, provide sustained IPA with clinically negligible drug interaction. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Selatogrel is a potent reversible P2Y12 receptor antagonist developed for subcutaneous self-administration by patients in case of suspected acute myocardial infarction. Transition to oral P2Y12 receptor antagonists without drug interaction and sufficient inhibition of platelet aggregation must be assured at all times. WHAT QUESTION DID THIS STUDY ADDRESS? The pharmacokinetic/pharmacodynamic model semimechanistically describes the effect of selatogrel on platelet inhibition alone and in combination with the oral P2Y12 receptor antagonists clopidogrel, prasugrel, and ticagrelor. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Model-based simulations showed that loading doses of clopidogrel and prasugrel can be administered from 15 h and 4.5 h after selatogrel, respectively. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? These results support guiding the clinical transition from selatogrel emergency treatment to oral maintenance therapy in a safe and efficacious way.

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Dataset Information

Optimal P2Y₁₂ inhibitor durations in older men and older women following an acute myocardial infarction: A nationwide cohort study using Medicare data.

Study objective

Design

Setting

Participants

Exposures

Main outcome measures

Results

Conclusions

Publications

Optimal P2Y<sub>12</sub> inhibitor durations in older men and older women following an acute myocardial infarction: A nationwide cohort study using Medicare data.

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Optimal P2Y12 inhibitor durations in older men and older women following an acute myocardial infarction: A nationwide cohort study using Medicare data.

Study objective

Design

Setting

Participants

Exposures

Main outcome measures

Results

Conclusions

Publications

Optimal P2Y&lt;sub&gt;12&lt;/sub&gt; inhibitor durations in older men and older women following an acute myocardial infarction: A nationwide cohort study using Medicare data.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Optimal P2Y₁₂ inhibitor durations in older men and older women following an acute myocardial infarction: A nationwide cohort study using Medicare data.

Optimal P2Y<sub>12</sub> inhibitor durations in older men and older women following an acute myocardial infarction: A nationwide cohort study using Medicare data.