Aspirin Cohort Research Articles

The efficacy of aspirin versus low-molecular-weight heparin for venous thromboembolism prophylaxis after knee and hip arthroplasty: A systematic review and meta-analysis of randomized controlled trials.

The purpose of this study was to assess the efficacy of aspirin versus low-molecular-weight heparin (LMWH) in preventing venous thromboembolism (VTE) following hip and knee arthroplasty. PubMed/Medline, Embase, Cochrane Library and Google Scholar databases were searched from inception till June 2024 for original trials investigating the outcomes of aspirin versus LMWH in hip and knee arthroplasty. The primary outcome was VTE. Secondary outcomes included minor and major bleeding events, and postoperative mortality within 90 days. This review was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 7 randomized controlled trials with 12,134 participants were included. The mean ages for the aspirin and LMWH cohorts were 66.6 (57.6-69.0) years and 66.8 (57.9-68.9) years, respectively. There was no statistically significant difference in the overall risk of VTE between the aspirin and the LMWH cohorts (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.48-1.89; p: 0.877). A subanalysis based on the specific VTE entity (pulmonary embolism [PE] or deep venous thrombosis) showed a significantly higher PE risk for patients receiving aspirin than the LMWH cohort (OR: 1.79; 95% CI: 1.11-2.89; p: 0.017). There was no difference in minor (OR: 0.64; 95% CI: 0.40-1.04; p: 0.072) and major bleeding (OR: 0.77; 95% CI: 0.40-1.47; p: 0.424) episodes across both groups. Furthermore, subanalysis among the total knee arthroplasty group showed that the aspirin cohort was significantly more likely to suffer VTEs than their LMWH counterparts (OR: 1.55; 95% CI: 1.21-1.98; p < 0.001). This study demonstrated a significantly higher risk of PE among patients receiving aspirin compared to LMWH following hip or knee arthroplasty for osteoarthritis. Aspirin was associated with a significantly higher overall VTE risk among patients undergoing knee arthroplasty, in particular. This might suggest the inferiority of aspirin compared to LMWH in preventing VTE following such procedures. Level I.

Evaluating Aspirin's Efficacy for Primary Prevention in Cardiovascular and Cerebrovascular Disease: Insights from a Nationwide Cohort Study.

The effectiveness of aspirin for the primary prevention of cerebro-cardiovascular diseases in Koreans remains unclear. Therefore, we evaluated the preventive effects of low-dose aspirin (equal or less than 100 mg) on cerebro-cardiovascular events. We conducted a retrospective cohort study using the National Sample Cohort dataset. From the 1,106,580 individuals eligible in 2004, we selected 200 individuals (47% male and 22.5% aged 65 or older) who consistently received low-dose aspirin from 2004 to 2013 for inclusion in the aspirin cohort. Participants for the control cohort, who did not use aspirin, were selected through propensity score matching based on variables. We compared the incidences of endpoints (acute myocardial infarction, cerebral infarction, gastrointestinal hemorrhage, and cerebral hemorrhage) between the aspirin group and the non-aspirin group over the 9-year follow-up period. There was no significant difference in the incidence rates of acute myocardial infarction, cerebral infarction, gastrointestinal hemorrhage, or cerebral hemorrhage between the aspirin and non-aspirin groups. Low-dose aspirin for primary prevention in Koreans did not reduce myocardial or cerebral infarctions and did not increase the risk of gastrointestinal or cerebral hemorrhage. Therefore, we suggest that aspirin for primary prevention should be used cautiously and tailored to the individual's baseline cardiovascular risk.

Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Male and Female Patients

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in the US. Although aspirin is recommended for secondary prevention of ASCVD, there was no difference in safety and effectiveness of aspirin dosed daily at 81 mg or 325 mg in the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) randomized clinical trial. However, it is unknown whether differences by sex exist in the safety and effectiveness of the different aspirin doses. To evaluate sex-specific differences in the safety and effectiveness of 2 aspirin doses in the ADAPTAPLE trial. The ADAPTABLE study was an open-label, pragmatic, randomized clinical trial that randomly assigned participants with chronic, stable ASCVD to 81 mg vs 325 mg of aspirin daily. Using Cox proportional-hazard models, male and female participants were compared for outcomes. In addition, it was assessed whether sex was an effect modifier in the association between aspirin dose and outcomes. The ADAPTABLE trial was conducted at 40 medical centers and 1 health plan. Eligible patients were 18 years and older and had established ASCVD. Study data were analyzed from December 2021 to March 2024. Patients received 81 mg or 325 mg of aspirin daily for the secondary prevention of ASCVD. The primary effectiveness outcomes included all-cause death and hospitalization for myocardial infarction (MI) or stroke. The primary safety outcome was hospitalization for major bleeding requiring transfusion. A total of 15 076 patients (median [IQR] age, 67.6 [60.7-73.6] years; 10 352 male [68.7%]) were followed up for a median (IQR) of 26.2 (19.0-34.9) months. Overall, 4724 (31.3%) were female, and 2307 of the female participants (48.8%) received aspirin 81 mg. Compared with males, female participants were younger (median [IQR] age, 66.3 [59.4-72.6] years vs 68.2 (61.4-73.9) years, less likely to self-report White race (3426 [72.5%] vs 8564 [82.7%]), more likely to smoke (564 [12.9%] vs 818 [8.4%]), and more likely to have a history of peripheral arterial disease (1179 [25.7%] vs 2314 [23.0%]). The primary effectiveness outcome of all-cause death and hospitalization for MI or stroke occurred in 379 female participants (8.1%) and 780 male participants (7.1%). There was no significant interaction by sex for the primary effectiveness end point between the 2 aspirin doses (female adjusted hazard ratio [aHR], 1.01; 95% CI, 0.82-1.26 and male aHR, 1.06; 95% CI, 0.91-1.23; P interaction term for sex = .74). During the trial, female participants had fewer revascularization procedures (237 [5.0%] vs 680 [6.6%]; aHR, 0.79; 95% CI, 0.68-0.92; P = .002) but had a higher risk of hospitalization for stroke (aHR, 1.72; 95% CI, 1.27-2.33; P < .001). Among female participants, there was a slightly higher rate of bleeding in the 81-mg aspirin cohort compared with the 325-mg cohort (20 [0.83%] vs 13 [0.52%]; aHR, 2.21; 95% CI, 1.04-4.70; P interaction term for sex = .07). There were no significant differences between female and male participants regarding aspirin dose adherence. In this secondary analysis of the ADAPTABLE trial, there were no significant sex-specific differences in the effectiveness and safety of 2 aspirin doses for secondary prevention of ASCVD events. ClinicalTrials.gov Identifier: NCT02697916.

The Impact of Sex on Antiplatelet and Anticoagulant Thromboprophylaxis in Patients With Peripheral Artery Disease Post-revascularization.

The aim of this prospective study was to (1) objectively quantify the impact of sex on platelet function in patients with peripheral artery disease (PAD) taking antiplatelet and anticoagulant medications and (2) to develop and test a personalized, iterative algorithm that personalizes thromboprophylaxis that incorporates platelet function testing. Women with PAD have worse outcomes as compared with their male counterparts despite having lower risk factors. This health disparity may be mitigated by personalizing thromboprophylaxis regimens. Patients undergoing revascularization were enrolled. Serial thromboelastography (TEG) and TEG with platelet mapping (TEG-PM) were performed up to 6 months postoperatively to determine objective coagulation profiles. In a subset of patients, the Antiplatelet Coagulation Exactness (ACE) algorithm was implemented, where patients were iteratively evaluated with TEG and given antiplatelet medications to maintain platelet inhibition at >29%. Statistical analysis was performed using unpaired t test, analysis of variance, and Fisher exact test. One hundred eighty-one patients met the study criteria. Fifty-eight (32%) patients were females and 123 (68%) were males. In the Aspirin cohort, females showed significantly greater clot strength as maximum amplitude - arachidonic acid (MA AA ) and significantly lower platelet inhibition than males: (37.26 vs 32.38, P <0.01) and (52.95% vs 61.65%, P <0.05), respectively. In the Clopidogrel cohort, females showed higher Maximum Amplitude - Adenosine Diphosphate (MA ADP ) (42.58 vs 40.35, P = not significant [NS]) compared with males. Females on dual antiplatelet therapy had higher MA ADP (39.74 vs 35.07, P =NS) and lower platelet inhibition (45.25% vs 54.99%, P= NS) than males. The incidence of thrombosis of the revascularized segment, defined as thrombotic event, was objectively identified on an arterial duplex. Women showed significantly higher thrombotic events than men (22.95% vs 10.57%, P< 0.05) on the same medication. In our pilot study, implementation of the ACE algorithm led to a significant decrease in the thrombosis rate (3%), including nonthrombotic events for females, versus the historic thrombotic rate (22%) from our institution. Women with PAD exhibited higher platelet reactivity, clot strength, and reduced platelet inhibition in response to antiplatelet therapy. The use of the ACE algorithm to tailor antiplatelet medication in patients with PAD post-revascularization, resulted in a significant decrease in thrombotic event rates. This may serve as an opportune way to mitigate outcome sex-specific disparities caused by inadequate thromboprophylaxis in women.

Reduced risk of gastrointestinal bleeding associated with eupatilin in aspirin plus acid suppressant users: nationwide population-based study.

Mucoprotective agents, such as eupatilin, are often prescribed to prevent gastrointestinal (GI) bleeding in addition to an acid suppressant despite the absence of a large-scale study. We evaluated the additional effect of eupatilin on the prevention of GI bleeding in both the upper and lower GI tract in concomitant aspirin and acid suppressant users using the nationwide database of national claims data from the Korean National Health Insurance Service (NHIS). An aspirin cohort was constructed using the NHIS claims data from 2013 to 2020. Patients who manifested with hematemesis, melena, or hematochezia were considered to have GI bleeding. A Cox proportional hazards regression model was used to determine the risk factors for GI bleeding associated with the concomitant use of GI drugs and other covariates among aspirin users. Overall, a total of 432,208 aspirin users were included. The concurrent use of an acid suppressant and eupatilin (hazard ratio [HR] = 0.85, p = 0.016, vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Moreover, a more than 3-month duration (HR = 0.88, p = 0.030) of acid suppressant and eupatilin prescription (vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Eupatilin administration for ≥ 3 months showed additional preventive effect on GI bleeding in concomitant aspirin and acid suppressant users. Thus, cotreatment with eupatilin with a duration of 3 months or longer is recommended for reducing GI bleeding among aspirin plus acid suppressant users.

Differential Effect of Non-Steroidal Anti-Inflammatory Drugs Aspirin and Naproxen against TMPRSS2-ERG (Fusion)-Driven and Non-Fusion-Driven Prostate Cancer.

The consumption of the non-steroidal anti-inflammatory drug (NSAID) aspirin is associated with a significant reduction in the risk of developing TMPRSS2-ERG (fusion)-positive prostate cancer (PCa) compared to fusion-negative PCa in population-based case-control studies; however, no extensive preclinical studies have been conducted to investigate and confirm these protective benefits. Thus, the focus of this study was to determine the potential usefulness of aspirin and another NSAID, naproxen, in PCa prevention, employing preclinical models of both TMPRSS2-ERG (fusion)-driven (with conditional deletion of Pten) and non-TMPRSS2-ERG-driven (Hi-Myc+/- mice) PCa. Male mice (n = 25 mice/group) were fed aspirin- (700 and 1400 ppm) and naproxen- (200 and 400 ppm) supplemented diets from (a) 6 weeks until 32 weeks of Hi-Myc+/- mice age; and (b) 1 week until 20 weeks post-Cre induction in the fusion model. In all NSAID-fed groups, compared to no-drug controls, there was a significant decrease in higher-grade adenocarcinoma incidence in the TMPRSS2-ERG (fusion)-driven PCa model. Notably, there were no moderately differentiated (MD) adenocarcinomas in the dorsolateral prostate of naproxen groups, and its incidence also decreased by ~79-91% in the aspirin cohorts. In contrast, NSAIDs showed little protective effect against prostate tumorigenesis in Hi-Myc+/- mice, suggesting that NSAIDs exert a specific protective effect against TMPRSS2-ERG (fusion)-driven PCa.

Association between non-steroidal anti-inflammatory drug use and development of age-related macular degeneration—A 10-year retrospective cohort study

To analyze the associations between development of age-related macular degeneration (AMD) and regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs). We retrospectively recruited individuals who received ≥28-day prescriptions of aspirin or NA-NSAIDs exclusively between 2008 and 2017 in one tertiary center as regular users. Non-regular users were free from regular use of any anti-inflammatory drugs and were matched to regular users in terms of age, sex, and visit date at a ratio of 1-4:1. The aspirin cohort included 36,771 regular users and 110,808 matched non-regular users, while the NA-NSAID cohort included 59,569 regular users and 179,732 matched non-regular users. Stratified multivariate Cox regression analyses with adjustment for systemic confounding factors were performed for the development of AMD and neovascular AMD. In the aspirin cohort, the adjusted hazard ratios of aspirin use for AMD in the whole cohort, individuals without cardiovascular diseases (CVDs), and those with CVDs were 0.664, 0.618, and 0.702, respectively (P<0.0001 for all), while those of aspirin use for neovascular AMD were 0.486, 0.313, and 0.584 (P<0.05 for all), respectively. In the NA-NSAID cohort, regular use of NA-NSAIDs was associated with a decreased risk of AMD (hazard ratio=0.823, P<0.0001) and neovascular AMD (hazard ratio=0.720, P=0.040) only in people without arthritis. Regular use of aspirin or NA-NSAIDs had protective effects on AMD and neovascular AMD. The effect of aspirin was observed in all patients, while the effect of NA-NSAIDs was observed only in people without arthritis.

Effectiveness and Safety of Enteric-Coated vs Uncoated Aspirin in Patients With Cardiovascular Disease

Clinicians recommend enteric-coated aspirin to decrease gastrointestinal bleeding in secondary prevention of coronary artery disease even though studies suggest platelet inhibition is decreased with enteric-coated vs uncoated aspirin formulations. To assess whether receipt of enteric-coated vs uncoated aspirin is associated with effectiveness or safety outcomes. This is a post hoc secondary analysis of ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness), a pragmatic study of 15 076 patients with atherosclerotic cardiovascular disease having data in the National Patient-Centered Clinical Research Network. Patients were enrolled from April 19, 2016, through June 30, 2020, and randomly assigned to receive high (325 mg) vs low (81 mg) doses of daily aspirin. The present analysis assessed the effectiveness and safety of enteric-coated vs uncoated aspirin among those participants who reported aspirin formulation at baseline. Data were analyzed from November 11, 2019, to July 3, 2023. ADAPTABLE participants were regrouped according to aspirin formulation self-reported at baseline, with a median (IQR) follow-up of 26.2 (19.8-35.4) months. The primary effectiveness end point was the cumulative incidence of the composite of myocardial infarction, stroke, or death from any cause, and the primary safety end point was major bleeding events (hospitalization for a bleeding event with use of a blood product or intracranial hemorrhage). Cumulative incidence at median follow-up for primary effectiveness and primary safety end points was compared between participants taking enteric-coated or uncoated aspirin using unadjusted and multivariable Cox proportional hazards models. All analyses were conducted for the intention-to-treat population. Baseline aspirin formulation used in ADAPTABLE was self-reported for 10 678 participants (median [IQR] age, 68.0 [61.3-73.7] years; 7285 men [68.2%]), of whom 7366 (69.0%) took enteric-coated aspirin and 3312 (31.0%) took uncoated aspirin. No significant difference in effectiveness (adjusted hazard ratio [AHR], 0.94; 95% CI, 0.80-1.09; P = .40) or safety (AHR, 0.82; 95% CI, 0.49-1.37; P = .46) outcomes between the enteric-coated aspirin and uncoated aspirin cohorts was found. Within enteric-coated aspirin and uncoated aspirin, aspirin dose had no association with effectiveness (enteric-coated aspirin AHR, 1.13; 95% CI, 0.88-1.45 and uncoated aspirin AHR, 0.99; 95% CI, 0.83-1.18; interaction P = .41) or safety (enteric-coated aspirin AHR, 2.37; 95% CI, 1.02-5.50 and uncoated aspirin AHR, 0.89; 95% CI, 0.49-1.64; interaction P = .07). In this post hoc secondary analysis of the ADAPTABLE randomized clinical trial, enteric-coated aspirin was not associated with significantly higher risk of myocardial infarction, stroke, or death or with lower bleeding risk compared with uncoated aspirin, regardless of dose, although a reduction in bleeding with enteric-coated aspirin cannot be excluded. More research is needed to confirm whether enteric-coated aspirin formulations or newer formulations will improve outcomes in this population. ClinicalTrials.gov Identifier: NCT02697916.

Aspirin for Venous Thromboembolic Prophylaxis Following Total Hip and Total Knee Arthroplasty: An Analysis of Safety and Efficacy Accounting for Surgeon Selection Bias

BackgroundAspirin may be effective at preventing venous thromboembolism following total knee arthroplasty (TKA) or total hip arthroplasty (THA). Current evidence is limited by bias as many surgeons who use aspirin prescribe for high-risk patients alternative chemoprophylactic agents. Therefore, this study aimed to evaluate the risk of pulmonary embolism (PE) and deep vein thrombosis (DVT) in patients who received aspirin and warfarin while accounting for surgeon selection bias. MethodsA national database was queried for patients undergoing primary elective TKA or THA from 2015 to 2020. Patients whose surgeon used aspirin in >90% of their patients were compared to patients whose surgeon used warfarin in >90% of cases. Instrumental variable analyses were performed to assess for PE, DVT, and transfusion while accounting for selection bias. Among TKA patients, 26,657 (18.8%) were in the warfarin cohort and 115,005 (81.2%) were in the aspirin cohort. Among THA patients, 13,035 (17.7%) were in the warfarin cohort and 60,726 (82.3%) were in the aspirin cohort. ResultsAnalyses were unable to identify a difference in the risk of PE (TKA: adjusted odds ratio [aOR]: 0.98, P = .659; THA: aOR = 0.93, P = .310) and DVT (TKA: aOR = 1.05, P = .188; THA: aOR = 0.96, P = .493) between the aspirin and warfarin cohorts. However, the aspirin cohort was associated with a lower risk of transfusion (TKA: aOR = 0.58, P < .001, THA: 0.84, P < .001). DiscussionAfter accounting for surgeon selection bias, aspirin was as effective as warfarin at preventing PE and DVT following TKA and THA. Furthermore, aspirin was associated with a lower risk of transfusion compared to warfarin.

Effect of Antiplatelet and Anticoagulant Agents on Outcomes Following Emergent Surgery for Traumatic Brain Injuries.

Traumatic brain injury (TBI) is the largest cause of death from injury in the United States. This study utilized the Michigan Trauma Quality Improvement Program (MTQIP) database to determine the effect that antiplatelets and anticoagulants (AP/AC) have on outcomes following emergent surgery for TBI patients. Patients were included with age ≥18years, maximum head/neck abbreviated injury score (AIS) ≥2, and underwent a neurosurgical procedure within 24hours. Patients were excluded if they had an AIS ≥3 in other body region or no signs of life at initial evaluation. Within the 1,932 patients analyzed, 139 (8.74%) were in the warfarin with or without (+/-) aspirin cohort, 101 (6.35%) in the direct oral anticoagulants (DOAC) +/- aspirin cohort, 169 (10.62%) in the clopidogrel +/- aspirin cohort, and 1,182 (74.29%) in the no AP/AC cohort (control group). After controlling for demographic and clinical characteristics, no significant difference in mortality rates was observed in the treatment groups (P > 0.05). However, our subgroup analysis did reveal a significantly higher mortality rate within the warfarin and aspirin subgroup when compared to the control group (odds ratio [OR], 2.368; confidence interval [CI], 1.306-4.294, P = 0.005). With regards to hospital complications, there was a significant increase in this outcome within the DOAC +/- aspirin (OR, 1.825; CI, 1.143-2.915, P = 0.012) and clopidogrel +/- aspirin (OR, 1.82; CI, 1.244-2.663, P=0.002) groups. Patients on AP/AC who experience a TBI requiring an emergent operation do not have an increased risk of mortality compared to patients not on AP/AC.

1303: IMPACT OF ANTIPLATELET AND ANTICOAGULANT AGENTS ON EMERGENT SURGERY FOR ORTHOPEDIC TRAUMAS

Introduction: Traumatic injuries bring about an increasing and significant challenge to healthcare systems worldwide. Most traumatic injuries are orthopedic in nature commonly caused by falls and road traffic accidents. A large concern relates to older patients taking anticoagulants and/or antiplatelets (AP/AC) prior to an injury due to the increased risk of hemorrhagic complications. This study utilized the Michigan Trauma Quality Improvement Program (MTQIP) database to determine the effect that AP/AC have on outcomes following emergent surgery for orthopedic traumas. Methods: Patients were included with age >18 years, Maximum Extremity or Pelvic Girdle severity value of abbreviated injury score (AIS) >2, injury severity score (ISS) >5, underwent extremity-related operation (based on the MTQIP Hospital Procedures ICD-10 codes), and underwent a procedure within 24 hours of ED admission. Patients were excluded if they had an AIS >3 in other body region, or no signs of life at initial evaluation. Results: Within the 4,030 patients analyzed, 97 were in the warfarin with or without (+/-) aspirin cohort, 146 in the direct oral anticoagulants (DOAC) +/- aspirin cohort, 140 in the clopidogrel +/- aspirin cohort, and 2,981 in the no AP/AC cohort (control group). After controlling for demographic, comorbid, and clinical characteristics, no significant difference in mortality rates was observed in the treatment groups (p>0.05). However, our subgroup analysis did reveal a significantly higher mortality rate within the warfarin and aspirin subgroup as compared to the control group (odds ratio [OR], 5.849; confidence interval [CI], 1.557-21.975, p=0.009). With regards to hospital complications, there was a significant increase in this outcome within all treatment groups, DOAC +/- aspirin (OR, 1.898; CI, 1.252-2.879, p=0.003), warfarin +/- aspirin (OR, 3.06; CI, 1924-4.868, p< 0.001), clopidogrel +/- aspirin (OR, 2.345; CI, 1.56-3.526, p< 0.001) groups. Conclusions: Patients on AP/AC who experience an orthopedic trauma requiring an emergent operation do not have an increased risk of mortality compared to patients not on AP/AC except for patients on warfarin and aspirin prior to admission.

Weight-Based Aspirin Dosing May Further Reduce the Incidence of Venous Thromboembolism Following Primary Total Joint Arthroplasty

Obesity poses a challenge to thromboembolic prophylaxis following total joint arthroplasty (TJA). The purpose of this study is to evaluate a weight-based aspirin dosing regimen for prevention of venous thromboembolism (VTE) following TJA.This is a retrospective observational study of 2403 patients who underwent primary total hip or knee arthroplasty at one institution. A weight-based aspirin dosing regimen for VTE prophylaxis was administered to 1247 patients: patients weighing ≥120 kg received 325 mg aspirin twice daily (BID) and those weighing <120 kg received 81 mg aspirin BID for 4 weeks. In total, 1156 patients in the comparison cohort received 81 mg aspirin BID. VTE and gastrointestinal bleeding events were identified through chart review at 42 days and 6 months postoperatively. A multivariable logistic regression was performed to adjust for covariates.The weight-based aspirin cohort had a significantly lesser incidence of VTE at 42 days (P = .03, relative risk [RR] 0.31, 95% confidence interval 0.12-0.82) and 6 months (P = .03, RR 0.38, 95% confidence interval 0.18-0.80). There was no difference in VTE incidence between total hip arthroplasty and total knee arthroplasty cases (P = .8). There was no difference in gastrointestinal bleeding events between the cohorts at 42 days (P = .69) or 6 months (P = .92). Subanalysis of patients weighing ≥120 kg demonstrated a significant difference between the cohorts with a VTE incidence of 3.48% and 0% in the 81 mg and weight-based cohorts, respectively (P = .02).Patients prescribed a weight-based aspirin regimen had significantly fewer VTEs after TJA compared to historical controls with an RR reduction of 69% at 6 weeks and 62% at 6 months postoperatively. This suggests the need to factor patient weight when determining postoperative VTE prophylaxis with aspirin.

ANTIHYPERTENSIVE TREATMENTS AND RISKS OF LUNG CANCER: A LONG-TERM RETROSPECTIVE COHORT STUDY IN HONG KONG

Objective: There remains a lack of strong evidence to identify the association between antihypertensive treatments (AHTs) and the risk of lung cancer. We studied the relationship between AHTs and the risk of lung cancer for further investigation. Design and method: The Aspirin Cohort was conducted from 2000 to 2013. The adjusted hazard ratio (HR) with 95% confidence intervals (95% CIs) was assessed for lung cancer risk through Cox proportional hazards models with inverse probability weighting. The cumulative duration of usage was also considered. Results: Among all the participants, 8,618 used aspirin only, 238,663 used AHT only, and 182,747 used both aspirin and antihypertensive, with lung cancer incidence rates of 2.5%, 2.8%, 2.4%, and 3.7% respectively. The mean age was 67.5 (SD = 12.0) years old. Among the classes of AHT, the lung cancer incidence rates for ACEi/ARB, CCB, alpha-blocker, and beta-blocker were 1.6%, 2.5%, 3.9%, and 2.2% respectively. Compared to the patients from the control group, the overall lung cancer risk decreased significantly (HR: 0.63, 95% CI: 0.60–0.66) for the patients who accepted AHT. For specific classes of AHTs, there were significant association between ACEi/ARB (HR: 0.45, 95% CI: 0.32–0.62), alpha-blocker (HR: 0.64, 95% CI: 0.54–0.76), and beta-blocker (HR: 0.79, 95% CI: 0.65–0.96) usage and decreased lung cancer risk. When aspirin and alpha-blocker were used simultaneously, it reduced the risk of lung cancer significantly (HR: 0.53, 95% CI: 0.34–0.84). Moreover, as the follow-up period went on, the use of AHTs was still associated with a decreased risk of lung cancer after 5-year (HR: 0.60, 95% CI: 0.57–0.63) and 7-year (HR: 0.63, 95% CI: 0.60–0.66) of usage. Similar effects were also identified for the combination usage of aspirin and ATHs. Specifically, analyses by the different duration of follow-ups for ACEi/ARB and alpha-blocker treatment also revealed significantly decreased lung cancer risk consistently. Conclusions: Long-term AHTs among the Chinese population might lower the risk of lung cancer. This study should offer further reassurance to patients using AHTs, but more evidence is warranted to address the effects of these drugs on the risk of lung cancer.

Aspirin Is Associated with Decreased Allogeneic Transfusions and Resource Utilization following Hip Fracture Care

AbstractThe purpose of our study is to assess the relationship and compare the impact of aspirin, enoxaparin, and warfarin use on postoperative anemia, allogenic transfusions, and resource utilization following hip fracture fixation. This is a retrospective study at a Level 1 trauma center with 450 geriatric hip fracture patients who underwent hip fracture surgery and chemoprophylaxis. Hip fracture patients were separated into three cohorts depending on the type of chemoprophylaxis administered aspirin, enoxaparin, or warfarin. Initially, all three cohorts were assessed for baseline characteristics, postoperative anemia, transfusion rates, and resource utilization. Next, aspirin and enoxaparin were comparatively evaluated for the same variables. Four hundred and fifty patients met inclusion criteria for the first portion of this study. No baseline variance was evident among the three cohorts except for body mass index (p = 0.007) and diagnosis of congestive heart failure (p = 0.001). Outcomes were insignificant for in-hospital mortality (p = 0.19), postoperative anemia (p = 0.43), hemoglobin levels (p = 0.91), and ∆hemoglobin (p = 0.99), length-of-stay (p = 0.12), disposition (p = 0.13), and 30-day readmission (p =0.09). The transfusion rate (p &lt; 0.001) and hospital cost (p = 0.01) varied significantly among the prophylactic cohorts. Three hundred and eighty nine patients met inclusion criteria for the aspirin and enoxaparin comparison. Baseline characteristics between the cohorts only revealed a significant variance for age (p = 0.03). Outcomes did not vary significantly among aspirin and enoxaparin cohorts; however, hospital cost was 12.3% greater in patients receiving enoxaparin (p = 0.01). Our study compares administration of aspirin, warfarin, and enoxaparin as means of chemoprophylaxis following hip fracture repair. Analyses of outcomes demonstrated patients receiving warfarin were more likely to require transfusions. Additionally, when compared with aspirin, resource utilization was 16.9 and 12.3% greater with warfarin and enoxaparin, respectively. Thus, our study suggests that aspirin is a safe and cost-effective option for chemoprophylaxis following hip fracture fixation.

1051 Preeclampsia prevention with 81mg versus 162mg of aspirin prophylaxis based upon timing of initiation

Though an aspirin dose of 81mg is recommended for preeclampsia prevention, evidence suggests that doses higher than 100mg and/or initiation prior to 16 weeks confers improved prophylaxis and benefit. The goal of this study is to determine how aspirin dose alongside timing of initiation affects preeclampsia rates. This is a retrospective cohort analysis of pregnancies treated with prophylactic aspirin initiated prior to 20 weeks of gestation between July 2016 and December 2019. All patients who met ACOG risk classifications for aspirin prophylaxis were started either on 81 or 162 mg of aspirin. Outcomes reviewed included preeclampsia rates among pregnancies using 81 versus 162mg of aspirin, initiated prior to 14 weeks ( first trimester) versus 14-20 weeks of gestation (second trimester). Variables were examined using logistic regression. A total of 163 pregnancies were examined. In Figure 1, with 81 mg aspirin dose, timing of initiation did not significantly affect preeclampsia rates (34.2% first trimester initiation vs 22.7% second trimester initiation). However, with higher dosing, preeclampsia rates with first trimester initiation was lower in comparison to second trimester initiation (17.9% vs 24.6%). Logistic regression analysis shows significant (p<0.001) risk reduction with earlier initiation in only the 162mg aspirin cohort, with an average 1.6% decrease of preeclampsia risk with each week of aspirin use prior to 20 weeks of gestation. Analogous significant results were not found in the 81mg aspirin cohort. This study suggests first trimester initiation of a higher dose of aspirin confers improved preeclampsia prophylaxis among high risk mothers; future studies should seek strategies to improve the prophylactic potential of aspirin through exploration of optimal dosing and gestational age for initiation.

Admission Rothman Index, Aspirin, and Intermediate Dose Anticoagulation Effects on Outcomes in COVID-19: A Multi-Site Propensity Matched Analysis

Introduction: Venous thromboembolism and in-situ small vessel thrombosis are increased in hospitalized patients with COVID-19 in several patient cohorts. Endotheliopathy and activation of both platelets and coagulation predict critical illness and death. For these reasons the use of anti-platelet agents and increased-intensity anticoagulation in the care of hospitalized patients with COVID-19 is under intense study in several clinical trials. We sought to examine the impact of aspirin and anticoagulation on hospitalization outcomes.Methods: We examined outcomes in a large multi-site cohort of consecutive, hospitalized, COVID-19 laboratory confirmed patients under a risk-stratified treatment algorithm from March 13 through June 18, with a focus on efficacy of aspirin and/or increased-intensity anticoagulation. Out of 4150 identified hospitalized patients with COVID-19, we created 3 study cohorts. The overall cohort (2785 patients) excluded pediatric patients, those with incomplete electronic data, and those with multiple admissions. The aspirin (1956 patients) and anticoagulation (1623 patients) cohorts were nested within the overall cohort; the former excluded patients on any home anti-platelet therapy or those who received non-aspirin anti-platelet therapy in the hospital, while the latter excluded patients who did not receive prophylactic or intermediate dose anticoagulation in the hospital. The primary outcome was in-hospital death. Secondary outcomes were time-to-death with a competing risk (time-to-hospital-discharge), escalation to ICU, length-of-stay and use of mechanical ventilation. Variables examined included age, gender, BMI, race, Rothman Index (RI), D-dimer (DD) and patient co-morbidities including cardiovascular disease, chronic kidney disease, and prior VTE. The aspirin and anticoagulation cohorts underwent propensity score (PS) matching utilizing variables found to be significant in multivariable regression modeling in the overall cohort with 638 and 386 patients, respectively.Results: Univariate followed by multivariable regression modeling in the 2785 patient overall cohort established a novel role for RI, and independent roles for age, BMI, and maximum DD, in predicting severity of illness. In all cohorts the 50th and lower percentile of admission RI was predictive of mortality in multivariable modeling (i.e. aspirin: 3rd and 4th admission RI quartiles with HR = 0.18 for both, p<0.001 for both). In PS matched patients, aspirin was associated with a significant decrease in mortality (OR 0.65 [0.42, 0.98], p=0.044) and a significant increase in mechanical ventilation (OR 1.49 [1.03, 2.18], p=0.037) and ICU status (OR = 1.45 [1.06, 1.98], p=0.021). In PS matched patients in the anticoagulation cohort, intermediate versus prophylactic dose anticoagulation was associated with a marginal decrease in mortality (OR 0.60, p=0.053). In the aspirin cohort examining in-hospital death and discharge as competing risks, the use of aspirin was associated with decreased mortality (p=0.042) and had no effect on discharge (p=0.31). In the anticoagulation cohort a similar competing risk model showed the use of intermediate rather than prophylactic anticoagulation decreased mortality (p=0.046) and had no effect on discharge (p = 0.21).Conclusion: We show in a large cohort of consecutively hospitalized patients with COVID-19 treated under a risk-stratified algorithm the prognostic utility of the admission RI in assessing outcomes in hospitalized patients with COVID-19 and a potential benefit of aspirin therapy on in-hospital death from COVID-19. A potential albeit marginal benefit of intermediate dose anticoagulation over prophylactic dose anticoagulation merits further study with results of clinical trials awaited.FigureDisclosuresNeuberg:Pharmacyclics: Research Funding; Madrigak Pharmaceuticals: Current equity holder in publicly-traded company; Celgene: Research Funding.

Clopidogrel increases risk of pneumonia compared with aspirin in acute ischemic minor stroke patients.

Antiplatelet agents may increase the risk of infections via suppressing platelet-mediated immune response. Here we assessed the contribution of clopidogrel versus aspirin to the development of pneumonia during an acute ischemic stroke admission. A retrospective cohort study was conducted of acute ischemic stroke patients who were admitted to our hospital from 2015 to 2018. Included patients received uninterrupted clopidogrel or aspirin therapy and did not take other antiplatelet agents throughout their stay. The interest outcome was development of pneumonia after stroke. Conditional logistic regression model after propensity score matching and adjusted logistic regression model were used to assess the impact of clopidogrel versus aspirin on post-stroke pneumonia. Among 1470 included patients, 1135 received aspirin and 335 received clopidogrel. Total 149 patients (10.1%) experienced pneumonia during the stroke hospitalization period. No difference was observed between clopidogrel cohort and aspirin cohort in the incidence of post-stroke pneumonia after propensity score matching (relative risk, 1.04; 95% confidence interval (CI) 0.65-1.65; P = 0.875). However, we found that clopidogrel was associated with increased risk of pneumonia compared with aspirin in minor stroke patients (adjusted odds ratio, 2.21; 95% CI 1.12-4.34; P = 0.021), and a statistically insignificant increase of pneumonia in diabetics (adjusted odds ratio, 1.94; 95% CI 0.96-3.94; P = 0.065). Compared with aspirin, clopidogrel is associated with increased pneumonia in minor stroke patients among who the interference of stroke-induced immunosuppression is minimized. Hence, aspirin may be a better choice for minor stroke patients in acute phase of ischemic stroke when pneumonia most frequently occurs.

Effects of Dual Antiplatelet Therapy on Graft Patency After Lower Extremity Bypass

The objective of this study was to explore prescribing patterns of single vs dual antiplatelet therapy (DAPT) after lower extremity bypass surgery and to investigate the effects of antiplatelet therapy on bypass graft patency. A retrospective review of nonemergent infrainguinal lower extremity bypass operations entered in the national Vascular Quality Initiative (2003-2018) was performed. Patients discharged on aspirin monotherapy or DAPT were identified. Multivariable Cox regression investigated predictors of primary, primary assisted, and secondary patency. Of the 13,020 patients investigated, 52.2% were discharged on aspirin monotherapy and 47.8% on DAPT. The proportion of patients discharged on DAPT increased from 10.6% in 2003 to 60.6% in 2018 (P < .001). The DAPT cohort was younger, had higher rates of medical (hypertension, diabetes, congestive heart failure, chronic obstructive pulmonary disease) and atherosclerotic (coronary artery disease, prior coronary artery bypass graft, prior lower extremity intervention) comorbidities, and had higher risk bypass procedures (more distal targets, prior inflow bypass procedure, prosthetic conduit use). Multivariable Cox regression analysis did not show any difference between the DAPT and aspirin cohorts in primary patency (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.88-1.10; P = .78), primary assisted patency (HR, 0.93; 95% CI, 0.80-1.07; P = .30), or secondary patency (HR, 0.88; 95% CI, 0.74-1.06; P = .18). On subgroup analysis delineated by bypass conduit, DAPT was found to have a protective effect on patency only in the prosthetic bypass cohort: primary patency (HR, 0.81; 95% CI, 0.66-1.00; P = .05), primary assisted patency (HR, 0.74; 95% CI, 0.58-0.94; P = .01), and secondary patency (HR, 0.60; 95% CI, 0.44-0.82; P < .001). No patency differences were observed on adjusted subgroup analysis for the other conduits (Fig). A significant and increasing proportion of patients are discharged on DAPT after lower extremity bypass revascularization. These patients represent a higher risk cohort with more medical comorbidities and higher risk bypass features. After controlling for these differences, DAPT therapy had no beneficial effect on overall bypass graft patency or major adverse limb events. However, on subgroup analysis, DAPT was associated with improved bypass graft patency in patients receiving prosthetic bypass conduits.

Effects of dual antiplatelet therapy on graft patency after lower extremity bypass

ObjectiveCurrent guidelines recommend single-agent antiplatelet therapy for patients with symptomatic peripheral artery disease and consideration of dual antiplatelet therapy (DAPT) after surgical revascularization. The objective of this study was both to explore prescribing patterns of single antiplatelet therapy vs DAPT after lower extremity bypass surgery and to investigate the effects of antiplatelet therapy on bypass graft patency. MethodsA retrospective analysis of prospectively collected nonemergent infrainguinal lower extremity bypass operations entered in the national Vascular Quality Initiative (2003-2018) with captured long-term follow-up was performed. Patients discharged on aspirin monotherapy or DAPT were identified. Linear regression investigated temporal trends in antiplatelet use. Multivariable Cox regression investigated predictors of primary, primary assisted, and secondary patency. ResultsOf the 13,020 patients investigated, 52.2% were discharged on aspirin monotherapy and 47.8% on DAPT. The proportion of patients discharged on DAPT increased from 10.6% in 2003 to 60.6% in 2018 (P < .001). The DAPT cohort was younger, had higher rates of medical (hypertension, diabetes, congestive heart failure, chronic obstructive pulmonary disease) and atherosclerotic (coronary artery disease, prior coronary artery bypass graft or percutaneous coronary intervention, prior lower extremity intervention) comorbidities, and had higher risk bypass procedures (more distal targets, prior inflow bypass procedure, prosthetic conduit use). Multivariable Cox regression analysis did not show any difference between the DAPT and aspirin cohorts in primary patency (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.88-1.10; P = .78), primary assisted patency (HR, 0.93; 95% CI, 0.80-1.07; P = .30), or secondary patency (HR, 0.88; 95% CI, 0.74-1.06; P = .18). On subgroup analysis based on bypass conduit, DAPT was found to have a protective effect on patency only in the prosthetic bypass cohort (primary patency: HR, 0.81 [95% CI, 0.66-1.00; P = .05]; primary assisted patency: HR, 0.74 [95% CI, 0.58-0.94; P = .01]; and secondary patency: HR, 0.60 [95% CI, 0.44-0.82; P < .001]). No patency differences were observed on adjusted subgroup analysis for the other bypass conduits. ConclusionsA significant and increasing proportion of patients are discharged on DAPT after lower extremity bypass revascularization. These patients represent a higher risk cohort with more medical comorbidities and higher risk bypass features. After controlling for these differences, DAPT therapy had no beneficial effect on overall bypass graft patency or major adverse limb events. However, on subgroup analysis, DAPT was associated with improved bypass graft patency in patients receiving prosthetic bypass conduits. Further study is warranted to investigate optimal duration of DAPT therapy and its possible bleeding complications in prosthetic bypass patients.

P1931Effect of de-escalated switching dual antiplatelet therapy after acute myocardial infarction in patients undergoing percutaneous coronary intervention: real-world data from a nationwide cohort study

Abstract Background Recently, both unguided (platelet function testing independent) and guided (platelet function testing dependent) DAPT de-escalation strategies have been investigated in different clinical studies but the data is still limited and conflicting. The aim of this study was to examine the effect of switching dual antiplatelet therapy (DAPT) on the major vascular risk after acute myocardial infarction (AMI) in patients undergoing percutaneous coronary intervention (PCI) by using Taiwan National Health Insurance Research Database. Methods In total, 1,903 and 4,059 patients defined as switched to aspirin and clopidogrel (switched DAPT) and continuation of aspirin and ticagrelor (unswitched DAPT) cohort, respectively who had received PCI during AMI hospitalization, on aspirin and ticagrelor initially and without occurring adverse events at 3 months were evaluated between 2013 and 2015. An inverse probability treatment of weighted approach was adopted to balance the baseline differences between two groups and Cox proportional hazard regression and competing risk regression were used to evaluated the effect of switching DAPT on death, AMI readmission, major bleeding and non-major clinically relevant bleeding. Results The incidence rates (per 100 person-year) of death and AMI readmission were 3.97 (95% confidence interval [CI] = 3.19–4.84) and 3.84 (95% CI = 3.09–4.73) in switched cohort and 1.83 (95% CI = 1.47–2.24) and 2.23 (95% CI = 1.82–2.68) in unswitched cohort, respectively. After adjustment for patients' clinical variables, switched cohort had higher risk of death (adjusted hazard ratio = 2.18, 95% CI = 1.62–2.93, P&lt;0.001), and AMI readmission (adjusted sub-distribution ratio = 1.72, 95% CI = 1.27–2.34, P&lt;0.001) compared to these in unswitched cohort; however, there was no difference in the risk of bleeding. Subgroup analysis showed a similar findings in many specific groups, except the patients who were younger age and had lower comorbidity score. Conclusion Switching DAPT might increase the risk of death and AMI readmission among patients with AMI undergoing PCI.