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

Figures

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  Figure 1.. The clinical benefit and risk of aspirin therapy by baseline cardiovascular risk. Past primary cardiovascular disease prevention trials of low-dose aspirin have attempted to characterize the clinical benefit (blue line) and risk (red dashed lines) of aspirin therapy by the baseline cardiovascular risks of enrolled populations. However, the clinical risk-benefit threshold, that is, the baseline cardiovascular risk at which the benefit of aspirin therapy exceeds the risk, remains unknown and is dependent upon bleeding risk. CV indicates cardiovascular.

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  Figure 2.. Approaches to pharmacological primary cardiovascular disease prevention. Primary preventive antihypertensive and statin therapy are prescribed after a cardiovascular risk assessment and the measurement of a biomarker related to the drug class’s primary mechanism of action. In contrast, primary preventive aspirin therapy is prescribed after cardiovascular risk assessment alone and is not guided by any related biomarker. CV indicates cardiovascular; and LDL-C, low-density lipoprotein cholesterol.

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  Figure 3.. Characteristics of light transmission aggregometry (LTA). A, Introduction of an agonist into platelet-rich plasma induces platelet aggregation, increasing light transmission through the suspension. Aggregation extent can be quantified using a calibrated light detection system. B, LTA with high-dose agonists is used clinically to diagnose hematologic disorders of platelet dysfunction (eg, minimal aggregation despite stimulation with a high-dose agonist). C, LTA with submaximal-dose agonists can be used to identify individuals with a hyperreactive platelet phenotype, a subgroup that may receive net value from low-dose aspirin therapy.

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  Figure 4.. Aspirin primary prevention trials: past and future. Historical and proposed designs of trials evaluating low-dose aspirin for primary cardiovascular disease prevention. CV indicates cardiovascular; and LTA, light transmission aggregometry.

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  Figure 5.. Platelet-guided aspirin therapy. The traditional approach to aspirin therapy involves suppressing platelet activity in a nontargeted manner, which likely unnecessarily increases bleeding risk without conferring vascular benefit in individuals with an optimal or hyporeactive platelet phenotype at baseline. We propose a new, targeted approach to aspirin therapy in which use is limited to individuals with a hyperreactive platelet phenotype who are most likely to receive maximum vascular benefit and minimal bleeding risk from platelet inhibition.