Is There a Need for Precision Medicine? Aspirin

The pharmacogenomics of aspirin non-response are poorly elucidated and appear to be of relatively minimal concern compared to other, non-genetic factors. Enteric aspirin has reduced bioavailability and does not have sufficient evidence to support its use in ASCVD; thus, it should be avoided in the cardiac patient, although guidelines do not always explicitly make this point [123]. With respect to personalization, the most useful application appears to be that of dosing according to bodyweight and/or BMI. The common low-dose aspirin strategy is aimed at achieving the minimum protective dose such that the risk of bleeding is lessened. However, this leaves minimal “buffer,” putting many non-average patients at risk of failing to reach the threshold concentration required to achieve benefit, which can be due to any number of factors, including body size and composition [124]. Moreover, the studies from which this approach is derived are decades old and took place when the prevalence of obesity was much lower. Recent evidence suggests that only patients of lower bodyweight benefit from the cardioprotective effects of low-dose aspirin. In contrast to patients on warfarin who receive functional testing to verify the adequate response, aspirin response is not routinely tested for and is simply presumed to be conferring a benefit. Considering the pervasiveness of ASCVD and the widespread use of aspirin in its treatment, this represents a considerable issue that could potentially be remedied through standardized dosing strategies. Furthermore, non-adherence appears to be especially relevant to aspirin, which may be a consequence of the patient belief that aspirin is less important than other medications, given its routine household use for minor indications and the ability to acquire it without a prescription. Whatever the reason, non-adherence is likely a sizeable contributor to treatment failure, necessitating appropriate intervention. Inflammation is another important consideration; common afflictions, including obesity and ASCVD, constitute chronic inflammatory states and have all been associated with increased platelet reactivity [125, 126]. Thus, many patients, including those receiving aspirin for secondary prevention, may be predisposed to HTPR, and yet continue to be prescribed the same low-dose regimens as those without preexisting disease. All these factors can impact the holistic efficacy of DAPT and should not be overlooked. However, with evidence that short DAPT followed by P2Y12 inhibitor monotherapy is as effective as conventional DAPT but with less bleeding, there may be a move away from using aspirin post-PCI [127] Finally, the avoidance of aspirin in the primary prevention of ASCVD is likely a missed opportunity for clinicians. RCTs of aspirin in primary prevention have demonstrated an excess risk of bleeding, negating any potential benefit; however, inappropriate patient selection in these studies might underpin the disappointing results. Increased personalization with PFTs, such as LTA, might be better able to identify high-risk patients who are more likely to achieve a net clinical benefit from primary prophylactic aspirin