Platelet inhibition by low-dose aspirin is not influenced by body mass or weight

Heffron, Sean; Windheim, Joseph; Barrett, Tessa; Voora, Deepak; Berger, Jeffrey S.

doi:10.1080/09537104.2022.2087868

Cited by 2 publications

(2 citation statements)

References 37 publications

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“…15,16 Accordingly, we recently showed that in individuals without diabetes, neither body weight nor mass influenced platelet inhibition by either 81 mg or 325 mg of aspirin. 17 These observations together suggest that aspirin formulation may be responsible for the observed reductions in platelet inhibition, but that this mechanism is not wholly responsible for the observed differences in rates of MACE. Thus, to thoroughly dissect the robust findings of the meta-analysis, other mechanisms beyond aspirin-mediated COX-1 inhibition must be investigated.…”

Section: Introductionmentioning

confidence: 94%

A randomized, placebo-controlled crossover trial to assess the influence of body weight on aspirin-triggered specialized pro-resolving mediators: protocol for the discover study

McGowan,

Zhong,

Trasande

et al. 2024

Int J Clin Trials

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Background: Low-dose aspirin is ineffective for primary prevention of cardiovascular events in people with body weight greater than 70kg. While the prevalent explanation for this is reduced platelet cyclooxygenase-1 (COX-1) inhibition at higher body weights, supporting data are limited, thereby demanding further investigation of the reason(s) underlying this observation. We propose that aspirin-mediated cyclooxygenase-2 (COX-2) acetylation and the resulting synthesis of 15-epi-lipoxin A4, a specialized pro-resolving mediator, is suboptimal in higher weight individuals, which may contribute to the clinical trial findings. Methods: To test this hypothesis, we are conducting a double-blind, placebo-controlled, randomized, mechanistic crossover trial. Healthy men and women exhibiting a wide range of body weights take 81mg aspirin and 325mg aspirin for 3 weeks each, following 3-week placebo run-in and wash-out phases. Our target sample size is 90 subjects, with a minimum of 72 completing all visits estimated to be necessary to achieve power adequate to test our primary hypothesis. Our primary endpoint is the difference in change in plasma 15-epi-lipoxin A4 occurring with each dose of aspirin. Secondary endpoints include lipid mediator profiles, serum bioactive lipid profiles, and other endpoints involved in the resolution of vascular inflammation. Conclusions: Study enrollment began in November 2021 and is ongoing. The results of this study will improve our understanding of the mechanisms underlying aspirin’s role(s) in the prevention of adverse cardiovascular outcomes. They may also lead to additional studies with the potential to inform dosing strategies for patients based on body weight. Trial registration: This trial is registered with ClinicalTrials.gov identifier NCT04697719.

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Section: Introductionmentioning

confidence: 94%

A randomized, placebo-controlled crossover trial to assess the influence of body weight on aspirin-triggered specialized pro-resolving mediators: protocol for the discover study

McGowan,

Zhong,

Trasande

et al. 2024

Int J Clin Trials

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“…Results of aspirin trials are further confounded by evidence that the dose required for optimal CV prevention may be influenced by weight, body mass, and the drug formulation. 20,21 A meta-analysis of 10 aspirin primary prevention trials 20 found the effect of low-dose aspirin (75-100 mg) to reduce CV events attenuated with increasing weight. In contrast, higher doses (≥325 mg) of aspirin showed a reverse interaction with weight, reducing CV events only at larger body size and increased weights.…”

Section: • the Recent United States Preventive Services Taskmentioning

confidence: 99%

Aspirin for the Primary Prevention of Cardiovascular Disease: Time for a Platelet-Guided Approach

Cofer

Barrett

2022

ATVB

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Aspirin protects against atherothrombosis while increasing the risk of major bleeding. Although it is widely used to prevent cardiovascular disease (CVD), its benefit does not outweigh its risk for primary CVD prevention in large population settings. The recent United States Preventive Services Task Force guidelines on aspirin use to prevent CVD reflect this clinical tradeoff as well as the persistent struggle to define a population that would benefit from prophylactic aspirin therapy. Past clinical trials of primary CVD prevention with aspirin have not included consideration of a biomarker relevant to aspirin’s mechanism of action, platelet inhibition. This approach is at odds with the paradigm used in other key areas of pharmacological CVD prevention, including antihypertensive and statin therapy, which combine cardiovascular risk assessment with the measurement of mechanistic biomarkers (eg, blood pressure and LDL [low-density lipoprotein]-cholesterol). Reliable methods for quantifying platelet activity, including light transmission aggregometry and platelet transcriptomics, exist and should be considered to identify individuals at elevated cardiovascular risk due to a hyperreactive platelet phenotype. Therefore, we propose a new, platelet-guided approach to the study of prophylactic aspirin therapy. We think that this new approach will reveal a population with hyperreactive platelets who will benefit most from primary CVD prevention with aspirin and usher in a new era of precision-guided antiplatelet therapy.

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Platelet inhibition by low-dose aspirin is not influenced by body mass or weight

Cited by 2 publications

References 37 publications

A randomized, placebo-controlled crossover trial to assess the influence of body weight on aspirin-triggered specialized pro-resolving mediators: protocol for the discover study

A randomized, placebo-controlled crossover trial to assess the influence of body weight on aspirin-triggered specialized pro-resolving mediators: protocol for the discover study

Aspirin for the Primary Prevention of Cardiovascular Disease: Time for a Platelet-Guided Approach

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