Superior Overall Survival in Patients with Colorectal Cancer, Regular Aspirin Use, and Combined Wild-Type PIK3CA and KRAS-Mutated Tumors

The impact of aspirin use after the diagnosis of colorectal cancer is unknown. Among others, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) mutational status was proposed as a molecular biomarker for the response to adjuvant aspirin therapy. However, prognostic data on aspirin use after a colorectal cancer diagnosis in relation to KRAS mutational status is limited. In a single-center retrospective study, we obtained KRAS and PIK3CA mutational status in a cohort of 153 patients with a first diagnosis of colorectal cancer receiving tumor surgery with curative intent. PIK3CA mutational status was determined by pyrosequencing, and KRAS mutational status was determined by next-generation sequencing. Clinicopathological data and survival data were assessed using patient records and reporting registers. We observed a significant 10-year overall survival benefit in patients with aspirin use and combined wild-type PIK3CA and mutated-KRAS tumors (HR = 0.38; 95% CI = 0.17–0.87; p = 0.02), but not in patients without aspirin use. Our data indicate a benefit of aspirin usage particularly for patients with combined wild-type PIK3CA and mutated-KRAS tumor characteristics.

Associations of aspirin and non-aspirin non-steroidal anti-inflammatory drugs with colorectal cancer mortality after diagnosis

Background Aspirin-use reduces colorectal cancer (CRC) incidence, but there is limited evidence regarding associations of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) with CRC-specific survival. Methods This prospective analysis includes women and men from the Cancer Prevention Study-II Nutrition Cohort who were cancer-free at baseline (1992 or 1993) and diagnosed with CRC during incidence follow-up through 2015. Detailed information on aspirin and non-aspirin NSAID-use was self-reported on questionnaires at baseline, in 1997, and every 2 years thereafter. Pre- and post-diagnosis data were available for 2,686 and 1,931 participants without distant-metastases, respectively, among whom 512 and 251 died from CRC during mortality follow-up through 2016. Secondary analyses examined associations between pre-diagnosis aspirin-use and stage at diagnosis (distant-metastatic versus localized or regional). All statistical tests were two-sided. Results Long-term regular use of aspirin (>15 times per month) before diagnosis was associated with lower CRC-specific mortality (multivariable-adjusted hazard ratio (HR)= 0.69; 95% CI = 0.52–0.92). Post-diagnosis regular aspirin use was not statistically significantly associated with risk of CRC-specific mortality overall (HR = 0.82; 95% CI = 0.62–1.09), although participants who began regular aspirin use only after their diagnosis were at lower risk than participants who did not use aspirin at both the pre-and post-diagnosis periods (HR = 0.60; 95% CI = 0.36–0.98). Long-term aspirin use before diagnosis was also associated with lower odds of diagnosis with distant metastases (multivariable-adjusted odds ratio = 0.73; 95% CI = 0.53–0.99). Conclusions Our results suggest that long-term aspirin use before a diagnosis of non-metastatic colorectal cancer may be associated with lower CRC-specific mortality after diagnosis, consistent with possible inhibition of micro-metastases before diagnosis.

Association between renal function and platelet reactivity during aspirin therapy in elderly patients with atherosclerotic cardiovascular disease

Background Aspirin is the key treatment in the secondary prevention of atherosclerotic cardiovascular disease. High on-treatment platelet reactivity (HTPR) to aspirin has been reported to partially account for the enhanced risk of thrombotic events. In particular, HTPR has been described more frequently among elderly patients. The aim of this study was to identify the clinical and biological factors associated with HTPR in a real-life elderly population. Methods In this retrospective study, elderly patients with atherosclerotic cardiovascular disease on regular aspirin treatment were enrolled. Cardiovascular risk factors, routine biological parameters, comorbidities, and concomitant medications were recorded. The upper quartile of the platelet aggregation rate, determined by light transmission aggregometry with arachidonic acid, was defined as the HTPR group. Results A total of 304 patients were included (mean age 77 ± 8 years, 76% men). Patients in the HTPR group were older than the patients in the non-HTPR group (mean age: 79 ± 7 vs. 76 ± 8 years, p = 0.008). Patients with moderately decreased estimated glomerular filtration rate (eGFR) had a higher frequency of HTPR than patients with slightly decreased eGFR or normal eGFR (35.8, 22.5, 12.2%, respectively, p < 0.05). In multivariate analysis, an independent risk factor for HTPR was the eGFR (OR: 0.984, 95% CI: 0.980–0.988, p < 0.001). Conclusions Advanced age and decreased eGFR are correlated with poor pharmacodynamic response to aspirin.

Association between renal function and platelet reactivity during aspirin therapy in elderly patients with atherosclerotic cardiovascular disease

Background: Aspirin is the key treatment in the secondary prevention of atherosclerotic cardiovascular disease. High on-treatment platelet reactivity (HTPR) to aspirin has been reported to partially account for the enhanced risk of thrombotic events. In particular, HTPR has been described more frequently among elderly patients. The aim of this study was to identify the clinical and biological factors associated with HTPR in a real-life elderly population.Methods: In this retrospective study, elderly patients with atherosclerotic cardiovascular disease on regular aspirin treatment were enrolled. Cardiovascular risk factors, routine biological parameters, comorbidities, and concomitant medications were recorded. The upper quartile of the platelet aggregation rate, determined by light transmission aggregometry with arachidonic acid, was defined as the HTPR group.Results: A total of 304 patients were included (mean age 77 ± 8 years, 76% men). Patients in the HTPR group were older than the patients in the non-HTPR group (mean age: 79 ± 7 vs. 76 ± 8 years, p = 0.008). Patients with moderately decreased estimated glomerular filtration rate (eGFR) had a higher frequency of HTPR than patients with slightly decreased eGFR or normal eGFR (35.8%, 22.5%, 12.2%, respectively, p < 0.05). In multivariate analysis, an independent risk factor for HTPR was the eGFR (OR: 0.984, 95% CI: 0.980-0.988, p < 0.001).Conclusions: Advanced age and decreased eGFR are correlated with poor pharmacodynamic response to aspirin.

Association between renal function and platelet reactivity during aspirin therapy in elderly patients with atherosclerotic cardiovascular disease

Background: Aspirin is the key treatment in the secondary prevention of atherosclerotic cardiovascular disease. High on-treatment platelet reactivity (HTPR) to aspirin has been reported to partially account for the enhanced risk of thrombotic events. In particular, HTPR has been described more frequently among elderly patients. The aim of this study was to identify the clinical and biological factors associated with HTPR in a real-life elderly population.Methods: In this retrospective study, elderly patients with atherosclerotic cardiovascular disease on regular aspirin treatment were enrolled. Cardiovascular risk factors, routine biological parameters, comorbidities, and concomitant medications were recorded. The upper quartile of the platelet aggregation rate, determined by light transmission aggregometry with arachidonic acid, was defined as the HTPR group.Results: A total of 304 patients were included (mean age 77 ± 8 years, 76% men). Patients in the HTPR group were older than the patients in the non-HTPR group (mean age: 79 ± 7 vs. 76 ± 8 years, p = 0.008). Patients with moderately decreased estimated glomerular filtration rate (eGFR) had a higher frequency of HTPR than patients with slightly decreased eGFR or normal eGFR (35.8%, 22.5%, 12.2%, respectively, p < 0.05). In multivariate analysis, an independent risk factor for HTPR was the eGFR (OR: 0.984, 95% CI: 0.980-0.988, p < 0.001).Conclusions: Advanced age and decreased eGFR are correlated with poor pharmacodynamic response to aspirin.

Association between renal function and platelet reactivity during aspirin therapy in elderly patients with atherosclerotic cardiovascular disease

Background: Aspirin is the key treatment in the secondary prevention of atherosclerotic cardiovascular disease. High on-treatment platelet reactivity (HTPR) to aspirin has been reported to partially account for the enhanced risk of thrombotic events. In particular, HTPR has been described more frequently among elderly patients. The aim of this study was to identify the clinical and biological factors associated with HTPR in a real-life elderly population.Methods: In this retrospective study, elderly patients with atherosclerotic cardiovascular disease on regular aspirin treatment were enrolled. Cardiovascular risk factors, routine biological parameters, comorbidities, and concomitant medications were recorded. The upper quartile of the platelet aggregation rate, determined by light transmission aggregometry with arachidonic acid, was defined as the HTPR group.Results: A total of 304 patients were included (mean age 77 ± 8 years, 76% men). Patients in the HTPR group were older than the patients in the non-HTPR group (mean age: 79 ± 7 vs. 76 ± 8 years, p = 0.008). Patients with moderately decreased estimated glomerular filtration rate (eGFR) had a higher frequency of HTPR than patients with slightly decreased eGFR or normal eGFR (35.8%, 22.5%, 12.2%, respectively, p < 0.05). In multivariate analysis, an independent risk factor for HTPR was the eGFR (OR: 0.984, 95% CI: 0.980-0.988, p < 0.001).Conclusions: Advanced age and decreased eGFR are correlated with poor pharmacodynamic response to aspirin. Antiplatelet strategy in elderly patients with atherosclerotic cardiovascular disease should be driven by an individualized approach, especially in patients with impaired renal function.

Association Between Long-Term Aspirin Use and Frailty in Men: The Physicians’ Health Study

Background Chronic inflammation may lead to frailty, however the potential for anti-inflammatory medications such as aspirin to prevent frailty is unknown. We sought to examine the association between long-term aspirin use and prevalent frailty. Methods We included 12 101 men ≥60 years who participated in the Physicians’ Health Study I, a completed aspirin randomized controlled trial (1982–1989). Annual questionnaires collected self-reported data on daily aspirin use, lifestyle, and clinical variables. Average aspirin use was summed into 2 categories: ≤60 days/year and &gt;60 days/year. Frailty was assessed using a 33-item index 11 years after trial completion. A score of ≥0.21 was considered frail. Propensity score inverse probability of treatment weighting was used for statistical control of confounding. Logistic regression models estimated odds of frailty as a function of categories of average aspirin use. Results Mean age was 70.5 years (range 60–101). Following an average of 11 ± 0.6 years of follow-up, aspirin use was reported as ≤60 days/year for 15%; 2413 participants (20%) were frail. Frequency of aspirin use was associated with smoking, alcohol consumption, hypertension, and cardiovascular disease, but negatively associated with bleeding and Coumadin use. The odds ratio (95% confidence intervals) for frailty was 0.85 (0.76–0.96) for average aspirin use &gt;60 days/year versus aspirin use ≤60 days/year. Results were similar using an alternate definition of frailty. Conclusions Long-term regular aspirin use is inversely associated with frailty among older men, even after consideration of multimorbidity and health behaviors. Work is needed to understand the role of medications with anti-inflammatory properties on aging.