Should Antiplatelet Therapy Be Withheld Perioperatively? The First Study Examining Outcomes in Patients Receiving Dual Antiplatelet Therapy in the Lower Extremity Free Flap Population.

BACKGROUND: Antiplatelet agents are typically withheld perioperatively because of bleeding concerns. Dual antiplatelet therapy, such as aspirin and clopidogrel, has significant morbidity and mortality benefits in patients with ischemic heart disease or peripheral vascular disease. This study aims to evaluate the impact of perioperative dual antiplatelet therapy in the lower extremity free tissue transfer population. METHODS: Lower extremity free tissue transfers performed by the senior author (K.K.E.) from 2011 to 2019 were retrospectively reviewed. Demographics, comorbidities, perioperative dual antiplatelet therapy, and free tissue transfer characteristics were recorded. Outcomes of interest included flap success, hematoma formation, blood transfusion requirements, and cardiac event occurrence. RESULTS: One hundred ninety-five free tissue transfers were included. Median age at the time of free tissue transfer was 56.5 years. Median Charlson Comorbidity Index was 3. Thirty-four patients were on clopidogrel, which was either withheld (n = 20) or continued (n = 14) on the day of free tissue transfer. Incidence of blood transfusion was significantly higher in both the withheld and continued versus nonclopidogrel groups. Flap success was statistically equivalent between groups (withheld, 90.0 percent; continued, 92.9 percent; nonclopidogrel, 95.0 percent; p = 0.346). Cardiac events occurred most often in the continued group (21.4 percent) compared to the withheld (5.0 percent) and nonclopidogrel (0.6 percent) groups. On multivariate analysis, holding clopidogrel remained significant for increased odds of postoperative transfusion. The clopidogrel group was no longer significant for intraoperative transfusion. CONCLUSIONS: Despite increases in volume of blood products transfused, free tissue transfer can be performed safely with perioperative dual antiplatelet therapy. Withholding dual antiplatelet therapy on the day of free tissue transfer was not associated with decreased intraoperative transfusion; thus, dual antiplatelet therapy can safely be continued throughout the operative course to minimize cardiovascular risk. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

A retrospective study of antithrombotic therapy use in an outpatient haemodialysis unit.

WHAT IS KNOWN AND OBJECTIVE: Patients on haemodialysis (HD) are at increased risk of both bleeding and thrombotic events, due to comorbidities and nature of dialysis treatment. However, there is a lack of research on evidence-based treatment strategies and prescribing patterns for antithrombotic therapies (ATT) in this population. To characterize ATT use and its main indications in an outpatient HD unit. METHODS: A single-centre retrospective chart review was conducted in a Toronto outpatient HD unit (n = 329). Medical histories, number of ATTs and corresponding indications were collected from adult patients prescribed at least one ATT from 1 October 2019 to 31 December 2019, inclusive. RESULTS AND DISCUSSION: Of 329 patients in the unit, a total of 135 (41%) patients were on at least one ATT. Of these 135 patients, 80% were on monotherapy (55% antiplatelet, 25.1% anticoagulant), 12.6% were on dual antiplatelet therapy (DAPT), and 7.4% were on a antiplatelet and anticoagulant combination. Primary indications for ATT in our cohort were coronary artery disease (CAD; 55%), atrial fibrillation (18.5%) and venous thromboembolism (VTE; 17%). Described ATT use was in-line with current clinical guidelines. Monotherapy was primarily used in our HD cohort, whereas few patients were on dual therapy. Low-dose aspirin was the most common antiplatelet prescribed for secondary prevention of cardiovascular events. Warfarin monotherapy was primarily indicated for VTE, and DAPT aspirin/clopidogrel was the most commonly prescribed for CAD. WHAT IS NEW AND CONCLUSION: Our characterization of ATT use in this HD cohort demonstrates that ATT is often prescribed for a number of different CVD reasons. Overlapping and confounding indications for prescribing ATTs, lack of randomized controlled trials and unclear clinical guidelines mean that individualized risk-benefit assessments for ATT use are still needed to provide care for these high-risk patients. More research to address the safety and efficacy of ATTs is warranted to develop more robust evidence-based treatment guidelines for the HD population.

Clinical Characteristics and Outcomes Associated With Oral Anticoagulant Use Among Patients Hospitalized With Intracerebral Hemorrhage.

Importance: Although the use of factor Xa (FXa) inhibitors has increased substantially over the past decade, there are limited data on characteristics and outcomes of FXa inhibitor-associated intracerebral hemorrhage (ICH). Objective: To investigate the association between prior oral anticoagulant use (FXa inhibitors, warfarin, or none) and in-hospital outcomes among patients with nontraumatic ICH. Design, Setting, and Participants: This is a cohort study of 219 701 patients with nontraumatic ICH admitted to 1870 hospitals in the Get With The Guidelines-Stroke registry between October 2013 and May 2018. Data analysis was performed in December 2019. Exposures: Anticoagulation therapy before ICH. Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes were a composite measure of in-hospital mortality or discharge to hospice, discharge home, independent ambulation, and modified Rankin Scale (mRS) score at discharge. Results: Of 219 701 patients (mean [SD] age, 68.2 [15.3] years; 104 940 women [47.8%]), 9202 (4.2%) were taking FXa inhibitors, 21 430 (9.8%) were taking warfarin, and 189 069 (86.0%) were not taking any oral anticoagulant before ICH. Patients taking FXa inhibitors or warfarin were older and had higher prevalence of cardiovascular risk factors. Compared with those not taking an oral anticoagulant (42 660 of 189 069 patients [22.6%]), the in-hospital mortality risk was higher for both FXa inhibitors (2487 of 9202 patients [27.0%]; adjusted odds ratio [aOR], 1.27; 95% CI, 1.20-1.34; P < .001) and warfarin (7032 of 21 430 patients [32.8%]; aOR, 1.67; 95% CI, 1.60-1.74; P < .001). Both FXa inhibitors (3478 of 9202 patients [37.8%]; aOR, 1.19; 95% CI, 1.13-1.26; P < .001) and warfarin (9151 of 21 430 patients [42.7%]; aOR, 1.50; 95% CI, 1.44-1.56; P < .001) were associated with higher odds of death or discharge to hospice compared with not taking oral anticoagulation (58 022 of 189 069 patients [30.7%]). Although the rates of discharge home, independent ambulation, mRS scores of 0 or 1, and mRS scores of 0 to 2 were numerically lower among patients taking FXa inhibitors, these differences were not significant compared with patients not taking oral anticoagulants. In contrast, patients taking FXa inhibitors were less likely to die (aOR, 0.76; 95% CI, 0.72-0.81; P < .001) or to experience death or discharge to hospice (aOR, 0.79; 95% CI, 0.75-0.84; P < .001), more likely to be discharged home (aOR, 1.18; 95% CI, 1.10-1.26; P < .001), and had better mRS scores at discharge (eg, mRS scores of 0-1: aOR, 1.24; 95% CI, 1.09-1.40; P < .001) than those treated with warfarin. Concomitant warfarin and antiplatelet therapy (either single or dual) was associated with worse outcomes compared with taking warfarin alone (eg, in-hospital mortality for dual-antiplatelet agents: aOR, 2.07; 95% CI, 1.72-2.50; P < .001). However, such incremental risk was not significant in patients taking FXa inhibitors. Conclusions and Relevance: In this cohort study, FXa inhibitor-associated ICH was associated with higher risk of mortality or death or discharge to hospice than not taking an oral anticoagulant, but patients taking FXa inhibitors had better outcomes than those with warfarin-related ICH.

Risk Factors for Bleeding and Clinical Ineffectiveness Associated With Clopidogrel Therapy: A Comprehensive Meta-Analysis.

Although clopidogrel is a frequently used antiplatelet medication to treat and prevent atherothrombotic disease, clinicians must balance its clinical effectiveness with the potential side effect of bleeding. However, many previous studies have evaluated beneficial and adverse factors separately. The objective of our study was to perform a comprehensive meta-analysis of studies of clopidogrel's clinical effectiveness and/or risk of bleeding in order to identify and assess all reported risk factors, thus helping clinicians to balance patient safety with drug efficacy. We analyzed randomized controlled trials (RCTs) of maintenance use in four stages: search for relevant primary articles; abstract and full article screening; quality assessment and data extraction; and synthesis and data analysis. Screening of 7,109 articles yielded 52 RCTs that met the inclusion criteria. Twenty-seven risk factors were identified. "Definite risk factors" were defined as those with aggregated odds ratios (ORs) > 1 and confidence intervals (CIs) > 1 if analyzed in more than one study. Definite risk factors for major bleeding were concomitant aspirin use (OR 2.83, 95% CI 2.04-3.94) and long duration of clopidogrel therapy (> 6 months) (OR 1.74, 95% CI 1.21-2.50). Dual antiplatelet therapy, extended clopidogrel therapy, and high maintenance dose (150 mg/day) of clopidogrel were definite risk factors for any bleeding. Reduced renal function, both mild and severe, was the only definite risk factor for clinical ineffectiveness. These findings can help clinicians predict the risks and effectiveness of clopidogrel use for their patients and be used in clinical decision support tools.

Incidence and Impact of Thrombocytopenia in Patients Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents.

Platelets are crucial in the pathophysiology of coronary artery disease and are a major target of antithrombotic agents in patients receiving percutaneous coronary intervention (PCI). We sought to evaluate the incidence and prognostic impact of thrombocytopenia on clinical outcomes in patients undergoing PCI with drug-eluting stents (DES). We evaluated consecutive patients who received PCI with DES in the IRIS-DES registry between April 2008 and December 2017. Patients were divided into 2 groups based on the presence of thrombocytopenia (platelet count <150 × 109/L) at baseline. The primary outcome was all-cause mortality, and secondary outcomes included the composite outcome of death, myocardial infarction (MI), and stroke, and major bleeding. Complete follow-up data were available for 1 to 5 years (median, 3.1). Among 26,553 eligible patients, 1,823 (6.9%) had thrombocytopenia at baseline. At 5 years, the incidences of all-cause mortality (15.6% vs 8.1%, p <0.001), composite outcome (23.2% vs 15.6%, p <0.001), and major bleeding (3.7% vs 2.2%, p <0.001) were significantly higher in patients with thrombocytopenia than in those without thrombocytopenia. In multivariable Cox proportional-hazards models, thrombocytopenia was significantly associated with increased risks of all-cause mortality (hazard ratio 1.26, 95% confidence interval 1.07 to 1.48, p = 0.01) and major bleeding (hazard ratio 1.41, 95% confidence interval 1.04 to 1.91, P=0.03). In conclusion, among who patients underwent PCI with DES, the incidence of thrombocytopenia was 6.9%. Baseline thrombocytopenia was significantly associated with increased risks of mortality and major bleeding.

Safety and Efficacy of Single Versus Dual Antiplatelet Therapy After Left Atrial Appendage Occlusion.

The optimal antiplatelet strategy after left atrial appendage (LAA) occlusion able to protect from device-related thrombosis, paying the lowest price in terms of bleeding increase, is unclear. In a real-world, observational study we performed a head-to-head comparison of single versus dual antiplatelet therapy (SAPT vs DAPT) in patients who underwent LAA occlusion. We included 610 consecutive patients, stratified according to the type of post-procedural antiplatelet therapy (280 on SAPT and 330 on DAPT). Primary outcome measure was the incidence of the net composite end point including Bleeding Academic Research Consortium classification 3-5 bleeding, major adverse cardiovascular events or device-related thrombosis at 1-year follow-up. The use of SAPT compared with DAPT was associated with similar incidence of the primary net composite end point (9.3% vs 12.7% p = 0.22), with an adjusted hazard ratio (HR) of 0.69, 95% confidence interval 0.41 to 1.15; p = 0.15) at multivariate analysis. However, SAPT significantly reduced Bleeding Academic Research Consortium classification 3-5 bleeding (2.9% vs 6.7%, p = 0.038; adjusted HR 0.37, 0.16 to 0.88; p = 0.024). The occurrence of ischemic events (major adverse cardiovascular events or device-related thrombosis) was not significantly different between the 2treatment strategies (7.8% vs 7.4%; adjusted HR 1.34, 0.70 to 2.55; p = 0.38). In patients who underwent LAA occlusion, post-procedural use of SAPT instead of DAPT was associated with reduction of bleeding complications, with no significant increase in the risk of thrombotic events. These hypothesis-generating findings should be confirmed in a specific, randomized study.

Dual Antiplatelet Therapy Duration in Medically Managed Acute Coronary Syndrome Patients: Sub-Analysis of the OPT-CAD Study.

INTRODUCTION: Optimal dual antiplatelet therapy (DAPT) duration for medically managed acute coronary syndrome (ACS) (MMACS) patients is still unknown. We explored the efficacy and safety of ≥ 12-month DAPT among MMACS patients. METHODS: In this sub-analysis of the optimal antiplatelet therapy for Chinese Patients with Coronary Artery Disease study (NCT01735305), clinical outcomes among MMACS patients were compared between the < 12-month and ≥ 12-month DAPT groups. The primary efficacy endpoint was a composite of cardiac death, myocardial infarction, and stroke. Safety endpoints included the Bleeding Academic Research Consortium (BARC) 2-5, BARC 3-5, and all bleeding events. Propensity score matching (PSM) was used to compare baseline characteristics between the < 12-month and ≥ 12-month DAPT groups. RESULTS: In this cohort of ACS patients (n = 10,016), MMACS patients (n = 2967) were less likely to use DAPT at 12 (31.64% vs. 67.47%, P < 0.0001) and 24 (13.82% vs. 18.71%, P < 0.0001) months and experienced more ischemic events at 12 (4.55% vs. 3.40%, P = 0.006) and 24 (6.88% vs. 5.08%, P = 0.0004) months than those treated with percutaneous coronary intervention (n = 7049). Among MMACS patients, the rate of primary efficacy endpoint occurring within the second year was significantly higher in the < 12-month DAPT group than in the ≥ 12-month group both before (2.88% vs. 1.60%, P = 0.040) and after (3.19% vs. 1.71%, P = 0.045) PSM. After PSM, no significant differences in all bleeding, BARC 2-5, and BARC 3-5 bleeding were found between the groups. CONCLUSION: MMACS patients with insufficient DAPT management experienced relatively more ischemic events. DAPT for at least 1 year may be beneficial to this special population without significantly increasing the bleeding risks. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01735305.

Dual antiplatelet therapy in non-ST elevation acute coronary syndromes at Veterans Affairs Hospitals.

OBJECTIVE: Current guidelines recommend that patients with non-ST elevation acute coronary syndromes (NSTEACS) receive dual antiplatelet therapy (DAPT) early in hospitalisations. However, observational studies suggest that this rarely occurs. We evaluated site-specific variation and clinical outcomes associated with early DAPT among patients undergoing angiography for NSTEACS. METHODS: In this observational analysis, we identified patients undergoing angiography for NSTEACS in Veterans Affairs hospitals from 2008 to 2016 and assessed characteristics and site variation associated with early DAPT (administration <24 hours of admission). Using propensity matching, we compared time to revascularisation, recurrent myocardial infarction (MI) and mortality between those receiving early DAPT and those not receiving early DAPT (administration ≥24 hours). RESULTS: Of 45 569 patients undergoing angiography for NSTEACS, 15 084 (33%) received early DAPT. Early DAPT was more frequent in patients with non-ST elevation MI, prior surgical revascularisation and among patients undergoing revascularisation. There was a greater than twofold difference in early DAPT across sites, independent of patient characteristics (median OR 2.43, 95% CI 2.28 to 2.55). There was no difference in time topercutaneous coronary intervention (PCI) between groups, but a significant delay to surgical revascularisation with early DAPT (median 4 vs 3 days, p<0.001) without reduction in hazard of death or MI (HR 1.08, 95% CI 1.00 to 1.16) and similar results demonstrated in the subgroup of patients undergoing revascularisation (HR 1.02, 95% CI 0.91 to 1.13). CONCLUSION: Among NSTEACS patients undergoing coronary angiography, early DAPT was not associated with improvement of outcomes but was associated with delays in surgical revascularisation.

Dual Antiplatelet Therapy Combining Aspirin and Ticagrelor for Intracranial Stenting Procedures: A Retrospective Single Center Study of 154 Consecutive Patients With Unruptured Aneurysms.

BACKGROUND: Dual antiplatelet therapy (DAPT) associating aspirin + clopidogrel is commonly utilized in neurovascular interventions despite unpredictable clopidogrel efficacy with 4% to 50% of patients considered nonresponders. Ticagrelor is an antiplatelet agent with low resistance rates but unknown efficacy and safety in neurovascular patients. OBJECTIVE: To evaluate frequency of ischemic and hemorrhagic events in patients treated with aspirin and ticagrelor when associated with perioperative heparin bolus for unruptured aneurysms treated with intracranial stents. METHODS: One hundred fifty-four consecutive patients with unruptured intracranial aneurysms treated by stent procedures (113 = flow diverter stent [FDS], 41 = stent-assisted coiling) were retrospectively analyzed. All patients received aspirin and ticagrelor without platelet function testing. Patients were separated in 2 groups following perioperative heparin dose: group I = 70 U/kg; group II = 50 U/kg. FDS versus stent-assisted coiling procedures were also separately analyzed. RESULTS: Nine patients (5.8%) presented symptomatic neurological complications poststenting (3 ischemic, 6 hemorrhagic): 8 patients received 70 U/kg of heparin (11.1%) and 1 patient received 50 U/kg (1.2%; P < .009). Four patients died (2.6%) during the 3-mo follow-up period-all deaths were correlated to intracranial hemorrhage: 3 at group I and 1 at group II (P < .251). No difference in complications or death was observed considering separately FDS and stent-assisted coiling procedures. CONCLUSION: This study did not find more neurological complications than in previous neurointerventional reports using DAPT with aspirin + ticagrelor or aspirin + clopidogrel. Overall number of neurological complications was lower when a lower dose of heparin was administered. Neurovascular studies comparing clopidogrel to ticagrelor and different doses of heparin are necessary to demonstrate which association is more efficient with lower complication rates.

Clopidogrel and Low-Dose Aspirin, Alone or Together, Reduce Risk of Colorectal Cancer.

BACKGROUND & AIMS: The antiplatelet effect of low-dose aspirin, via inhibition of cyclooxygenase-1, might contribute to its ability to reduce the risk of colorectal cancer (CRC). Antiplatelet agents with a different mechanism, such as clopidogrel, might have the same effects. We aimed to quantify the effects of low-dose aspirin and clopidogrel on the risk of CRC in a Mediterranean population. METHODS: We performed a nested case-control study using a primary care database (Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria) in Spain. We collected data, from 2001 through 2014, on 15,491 incident cases of CRC and 60,000 randomly selected individuals (controls), frequency-matched to cases by age, sex, and year. To estimate the association between exposure to different antiplatelet agents and the risk of colorectal cancer, we built multiple logistic regression models and computed the adjusted-odds ratios (AORs) and their respective 95% CIs. RESULTS: Use of low-dose aspirin was associated with a reduced risk of CRC overall (AOR, 0.83; 95% CI, 0.78-0.89) and in patients receiving treatment for more than 1 year (AOR, 0.79; 95% CI, 0.73-0.85). Use of clopidogrel was associated with a decreased risk of CRC overall (AOR, 0.8; 95% CI, 0.69-0.93) and in patients receiving treatment for more than 1 year (AOR, 0.65; 95% CI, 0.55-0.78). Dual antiplatelet therapy had the same effect as either drug taken as monotherapy. No modification by sex or age was observed. CONCLUSIONS: In a nested case-control study of a primary care database in Spain, we found clopidogrel use, alone or in combination with low-dose aspirin, to reduce the risk of CRC by 20% to 30%, a magnitude similar to that of low-dose aspirin alone. These data support the concept that inhibiting platelets is an effective strategy for prevention of CRC.