Antiplatelet Agent Therapy Research Articles

Optimising Medications in Older Vascular Surgery Patients Through Geriatric Co-management.

Prescribing of potentially inappropriate medications and under-prescribing of guideline-recommended medications for cardiovascular risk modification have both been associated with negative outcomes in older adults. Hospitalisation represents an important opportunity to optimise medication use and may be achieved through geriatrician-led interventions. We aimed to evaluate whether implementation of a novel model of care called Geriatric Comanagement of older Vascular (GeriCO-V) surgery patients is associated with improvements in medication prescribing. We used a prospective pre-post study design. The intervention was a geriatric co-management model, where a geriatrician delivered comprehensive geriatric assessment-based interventions including a routine medication review. We included consecutively admitted patients to the vascular surgery unit at a tertiary academic centre aged ≥65 years with an expected length of stay of ≥2 days and who were discharged from hospital. Outcomes of interest were the prevalence of at least one potentially inappropriate medication as defined by the Beers Criteria at admission and discharge, and rates of cessation of at least one potentially inappropriate medication present on admission. In the subgroup of patients with peripheral arterial disease, the prevalence of guideline-recommended medications on discharge was determined. There were 137 patients in the pre-intervention group (median [interquartile range] age: 80.0 [74.0-85.0] years, 83 [60.6%] with peripheral arterial disease) and 132 patients in the post-intervention group (median [interquartile range] age: 79.0 (73.0-84.0) years, 75 [56.8%] with peripheral arterial disease). There was no change in the prevalence of potentially inappropriate medication use from admission to discharge in either group (pre-intervention: 74.5% on admission vs 75.2% on discharge; post-intervention: 72.0% vs 72.7%, p = 0.65). Forty-five percent of pre-intervention group patients had at least one potentially inappropriate medication present on admission ceased, compared with 36% of post-intervention group patients (p = 0.11). A higher number of patients with peripheral arterial disease in the post-intervention group were discharged on antiplatelet agent therapy (63 [84.0%] vs 53 [63.9%], p = 0.004) and lipid-lowering therapy (58 [77.3%] vs 55 [66.3%], p = 0.12). Geriatric co-management was associated with an improvement in guideline-recommended antiplatelet agent prescribing aimed at cardiovascular risk modification for older vascular surgery patients. The prevalence of potentially inappropriate medications was high in this population, and was not reduced with geriatric co-management.

Transarterial Embolization for Spontaneous Soft-Tissue Hematomas: Predictive Factors for Early Death.

The aim of this retrospective monocentric study was to assess the safety and efficacy of spontaneous soft-tissue hematoma transarterial embolization (TAE) and to evaluate predictive factors for early mortality (≤30 days) after TAE for spontaneous soft-tissue hematoma (SSTH). Between January 2010 and March 2022, all patients referred to our hospital for spontaneous soft-tissue hematoma and treated by emergency TAE were reviewed. Inclusion criteria were patients: ≥18-year-old, with active bleeding shown on preoperative multidetector row computed tomography, with spontaneous soft-tissue hematoma, and treated by TAE. Exclusion criteria were patients with soft-tissue hematomas of traumatic, iatrogenic, or tumoral origin. Clinical, biological, and imaging records were reviewed. Imaging data included delimitation of hematoma volume and presence of fluid level. Univariate and multivariate analyses were performed to check for associations with early mortality. Fifty-six patients were included. Median age was 75.5 [9-83] ([Q1-Q3] years and 23 (41.1%) were males. Fifty-one patients (91.1%) received antiplatelet agent and/or anticoagulant therapy. All 56 patients had active bleeding shown on a preoperative CT scan. Thirty-seven (66.0%) hematomas involved the retroperitoneum. Median hemoglobin level was 7.6 [4.4-8.2] g/dL. Gelatine sponge was used in 32/56 (57.1%) procedures. Clinical success was obtained in 48/56 (85.7%) patients and early mortality occurred in 15/56 (26.8%) patients. In univariate and multivariate analysis, retroperitoneal location and volume of hematoma were associated with early mortality. Retroperitoneal location and volume of hematoma seem to be risk factors for early death in the context of TAE for spontaneous soft-tissue hematoma. Larger multicenter studies are necessary to identify others predictive factors for early mortality and to anticipate which patients may benefit from an interventional strategy with TAE.

The Safety of Long-Term Proton Pump Inhibitor Use on Cardiovascular Health: A Meta-Analysis.

Introduction: Proton pump inhibitors (PPIs) are one of the most prescribed classes of drugs worldwide as a first-line treatment of acid-related disorders. Although adverse effects are rare and rapidly reversible after a short exposure, concerns have been recently raised about a greater toxicity on cardiovascular health after a longer exposure, especially when combined with clopidogrel. We aimed to evaluate the safety of long-term PPI use on cardiovascular health in patients with known atheromatous cardiovascular disease. Methods: A literature search was conducted in the PubMed, Embase, and Cochrane Library databases and grey literature in April 2022. Articles published between 2014 and 2022 were considered relevant if they were designed as randomized controlled trials (RCTs) that included post hoc analyses or prospective observational studies and if they investigated clinical cardiovascular outcomes associated with PPI use for 6 months or more in patients suffering from cardiovascular disease requiring antiplatelet agent therapy and/or coronary angioplasty. Statistical analyses were performed using RevMan 5.4 software (Computer program, the Cochrane Collaboration, 2020, London, UK). The risk of bias was assessed using the Cochrane risk-of-bias tool for the RCTs and the Newcastle–Ottawa scale for the observational studies. Results: A total of 10 full-text articles involving 53,302 patients were included. Substantial heterogeneity was found among the 10 included studies. The primary analysis showed no significant differences between the PPI group and the control group for the risks of major adverse cardiovascular events (MACEs), all-cause death (ACD), or target vessel revascularization (TVR) using a random-effects model (OR 1.15, 95% CI 0.98–1.35, p = 0.08, I2 = 73%; OR 1.24, 95% CI 0.94–1.65, p = 0.13, I2 = 63%; and OR 1.19, 95% CI 0.76–1.87, p = 0.45, I2 = 61%, respectively). The primary analysis yielded similar results for the risks of myocardial infarction (MI), stroke, and cardiovascular death (CVD) using a fixed-effects model (OR 0.98, 95% CI 0.88–1.09, p = 0.66, I2 = 0%; OR 1.02, 95% CI 0.90–1.17, p = 0.73, I2 = 0%; and OR 1.04, 95% CI 0.94–1.16, p = 0.44, I2 = 35%, respectively). Likewise, a subgroup analysis based on eight randomized controlled trials failed to identify any association between PPI use and the risks of MACEs, MI, stroke, TVR, ACD, or CVD using a fixed-effects model (overall pooled OR 1.01, 95% CI 0.96–1.06; p = 0.66; I2 = 0%). The pulled data from the two included observational studies (OS) demonstrated a significantly increased risk of MACEs in the PPI group (OR 1.42, 95% CI [1.29–1.57], p <0.001; I2 = 0%). In another subgroup analysis, no evidence of an increased risk of adverse cardiovascular events in the co-therapy PPI/clopidogrel versus clopidogrel alone groups was found with the exception of the risk of ACD (OR 1.50, 95% CI 1.23–1.82, p = 0.001, I2 = 0%). Nevertheless, after performing a sensitivity analysis reaching heterogeneity I2 = 0%, the co-prescription of PPIs and clopidogrel was at increased risk of MACEs (p < 0.001), CVD (p = 0.008), and TVR (p < 0.001) but remained statistically non-significant for the risk of MI (p = 0.11). Conclusions: The overall results of this meta-analysis showed that long-term PPI use was not associated with an increased risk of adverse cardiovascular events. However, inconsistent results were found for combined PPI/clopidogrel therapy. These results should be considered with caution in light of the significant heterogeneity, the limited number of included studies, and the lack of adjustment for potential confounders.

Spinal Cord Ischemia Secondary to Atrial Fibrillation: A Case Report

Spinal cord ischemia is exceptionally uncommon, accounting for 0.3–1% of all strokes. Here, we reported the case of a 64-year-old patient with spinal cord ischemia secondary to atrial fibrillation. Spinal magnetic resonance imaging showed increased intramedullary signal intensity at the T9 level in T2-weighted. An electrocardiogram showed atrial fibrillation. The patient was given corticosteroids and antiplatelet agent therapy. After 8 weeks of rehabilitation, the patient was able to walk with the support of a medical walker.

Impact of dual antiplatelet therapy after lower extremity revascularization for chronic limb-threatening ischemia

ObjectiveThe optimal antiplatelet regimen after lower extremity revascularization in patients with chronic limb-threatening ischemia (CLTI) is unknown because current recommendations are based on extrapolation of data from trials in coronary artery disease and stroke. MethodsWe identified all patients undergoing an elective lower extremity revascularization for CLTI in the Vascular Quality Initiative registry discharged on a mono antiplatelet agent (MAPT) or dual antiplatelet therapy (DAPT). ResultsFrom 2003 to 2018, 50,890 patients underwent revascularization procedures for CLTI, and were discharged on MAPT or DAPT. Of these, 33,781 patients underwent endovascular therapy (EVT), and 17,109 patients underwent open surgery (OS) procedures. The rate of major amputation at 30 days in the target limb in the EVT group was 0.3% and 0.4% in the OS group (P = .22). On Kaplan-Meier analyses, patients on MAPT at discharge had a higher risk of 1-year major amputation compared with DAPT after EVT but not after OS procedures. Patients on MAPT had lower overall survival and amputation-free survival at 30 days and 1 year compared with DAPT after both EVT and OS. At 1 year, the MAPT group was at higher risk for target lesion reintervention after EVT compared with the DAPT group (15.9% vs 13%; P = .0012). There was no significant difference in thrombosis at 1 year between the MAPT and DAPT groups either after EVT (3.9% vs 3.7%; P = .3048) or OS (3.1% vs 3.2%; P = .2893). On Cox regression analysis, DAPT was associated with improved survival but not major amputation after both EVT and OS. ConclusionsIn patients with CLTI, DAPT at the time of discharge has a positive impact on amputation-free survival and overall survival after both EVT and OS as well as target lesion reintervention after EVT. DAPT was not associated with a positive impact on major amputation after either EVT or OS.

Anticoagulation with or without antiplatelet therapy after transcatheter aortic valve replacement, when less is more: a meta-analysis

Abstract Background About 40% of patients undergoing transcatheter aortic valve replacement (TAVR) have a history of atrial fibrillation (AF) and an additional 10% develop AF after TAVR. However, there is paucity of data regarding the optimal antithrombotic regimen following TAVR in patients with a clinical indication for oral anticoagulants (OAC). Purpose To compare the prognostic impact of OAC plus at least one antiplatelet agent (APT) versus OAC therapy alone in patients undergoing TAVR. Methods We systematically searched the literature for studies evaluating the comparative efficacy and safety of OAC + APT versus OAC alone in TAVR. Random-effect meta-analysis was performed comparing clinical outcomes between the two groups. All-cause mortality and cardiovascular mortality were the efficacy outcomes. Stroke and major bleeding, defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety outcome. Results Overall, 398 titles and abstracts were identified through database searching. Four observational studies were selected, for a total of 1929 patients. After a median follow-up of 18.5 months (IQR 11.3–29.3), OAC + APT increased major bleeding events compared to OAC alone (OR=1.79; 95% CI 1.21–2.66; P=0.004) with no difference in stroke (OR 01.02; 95% CI 0.52–2.01; P=0.95), all-cause mortality (OR=1.07; 95% CI 0.78–1.47; P=0.66) and cardiovascular mortality (OR=1.08; 95% CI 0.79–1.47; P=0.62). Conclusion A combination strategy of OAC + APT provides increased risk of bleeding compared to OAC therapy alone in patients undergoing TAVR with similar outcomes in terms of stroke, all-cause mortality and cardiovascular mortality; therefore, when feasible, it should be advised not to add APT on top of OAC therapy in patients without other clinical indications for APT treatment. Funding Acknowledgement Type of funding source: None

Multiple versus fewer antiplatelet agents for preventing early recurrence after ischaemic stroke or transient ischaemic attack.

Stroke is a leading cause of morbidity and mortality worldwide. Antiplatelet agents are considered to be the cornerstone for secondary prevention of stroke, but the role of using multiple antiplatelet agents early after stroke or transient ischaemic attack (TIA) to improve outcomes has not been established. To determine the effectiveness and safety of initiating, within 72 hours after an ischaemic stroke or TIA, multiple antiplatelet agents versus fewer antiplatelet agents to prevent stroke recurrence. The analysis explores the evidence for different drug combinations. We searched the Cochrane Stroke Group Trials Register (last searched 6 July 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 7 of 12, 2020) (last searched 6 July 2020), MEDLINE Ovid (from 1946 to 6 July 2020), Embase (1980 to 6 July 2020), ClinicalTrials.gov, and the WHO ICTRP. We also searched the reference lists of identified studies and reviews and used the Science Citation Index Cited Reference search for forward tracking of included studies. We selected all randomised controlled trials (RCTs) that compared the use of multiple versus fewer antiplatelet agents initiated within 72 hours after stroke or TIA. We extracted data from eligible studies for the primary outcomes of stroke recurrence and vascular death, and secondary outcomes of myocardial infarction; composite outcome of stroke, myocardial infarction, and vascular death; intracranial haemorrhage; extracranial haemorrhage; ischaemic stroke; death from all causes; and haemorrhagic stroke. We computed an estimate of treatment effect and performed a test for heterogeneity between trials. We analysed data on an intention-to-treat basis and assessed bias for all studies. We rated the certainty of the evidence using the GRADE approach. We included 15 RCTs with a total of 17,091 participants. Compared with fewer antiplatelet agents, multiple antiplatelet agents were associated with a significantly lower risk of stroke recurrence (5.78% versus 7.84%, risk ratio (RR) 0.73, 95% confidence interval (CI) 0.66 to 0.82; P < 0.001; moderate-certainty evidence) with no significant difference in vascular death (0.60% versus 0.66%, RR 0.98, 95% CI 0.66 to 1.45; P = 0.94; moderate-certainty evidence). There was a higher risk of intracranial haemorrhage (0.42% versus 0.21%, RR 1.92, 95% CI 1.05 to 3.50; P = 0.03; low-certainty evidence) and extracranial haemorrhage (6.38% versus 2.81%, RR 2.25, 95% CI 1.88 to 2.70; P < 0.001; high-certainty evidence) with multiple antiplatelet agents. On secondary analysis of dual versus single antiplatelet agent therapy, benefit for stroke recurrence (5.73% versus 8.06%, RR 0.71, 95% CI 0.62 to 0.80; P < 0.001; moderate-certainty evidence) was maintained as well as risk of extracranial haemorrhage (1.24% versus 0.40%, RR 3.08, 95% CI 1.74 to 5.46; P < 0.001; high-certainty evidence). The composite outcome of stroke, myocardial infarction, and vascular death (6.37% versus 8.77%, RR 0.72, 95% CI 0.64 to 0.82; P < 0.001; moderate-certainty evidence) and ischaemic stroke (6.30% versus 8.94%, RR 0.70, 95% CI 0.61 to 0.81; P < 0.001; high-certainty evidence) were significantly in favour of dual antiplatelet therapy, whilst the risk of intracranial haemorrhage became less significant (0.34% versus 0.21%, RR 1.53, 95% CI 0.76 to 3.06; P = 0.23; low-certainty evidence). Multiple antiplatelet agents are more effective in reducing stroke recurrence but increase the risk of haemorrhage compared to one antiplatelet agent. The benefit in reduction of stroke recurrence seems to outweigh the harm for dual antiplatelet agents initiated in the acute setting and continued for one month. There is lack of evidence regarding multiple versus multiple antiplatelet agents. Further studies are required in different populations to establish comprehensive safety profiles and long-term outcomes to establish duration of therapy.

Intracranial haemorrhages vs. stent thromboses with direct oral anticoagulant plus single antiplatelet agent or triple antithrombotic therapy: a meta-analysis of randomized trials in atrial fibrillation and percutaneous coronary intervention/acute coronary syndrome patients.

To assess the efficacy-safety profile of dual antithrombotic therapy (DAT) including direct oral anticoagulant (DOAC) vs. triple antithrombotic therapy (TAT) in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Randomized trials of AF patients with ACS/PCI, comparing DAT using DOACs against TAT, were selected. Overall, 11161 studies were screened, 458 trials assessed, and four included, comprising 10234 patients followed for a mean of 11 months. DAT compared to TAT resulted in significant reductions of trial-defined primary safety outcome [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.50-0.79, number needed to treat (NNT) 17] and of thrombolysis in myocardial infarction (TIMI) major bleeding (OR 0.54, 95% CI 0.41-0.70, NNT 76) and in a numerical reduction of intracranial haemorrhage (OR 0.50, 95% CI 0.21-1.19, NNT 314), which became significant after exclusion of DOACs from TAT and vitamin K antagonist from DAT arms (OR 0.31, 95% CI 0.15-0.64). There were no significant differences in the risks of cardiovascular or any deaths or stroke, but with DAT, there was a numerical increase in myocardial infarctions (MIs) (OR 1.23, 95% CI 0.99-1.54, estimated NNT for an additional harmful outcome (NNTH) 151), which became significant in the ACS/PCI subgroup (OR 1.43, 95% CI 1.02-2.00), and a 60% significant increase in stent thrombosis risk (OR 1.60, 95% CI 1.02-2.52; NNTH 274). Dual antithrombotic therapy, compared to TAT, conferred a significantly reduced risk of overall bleeding but with a significant increase of stent thrombosis risk in the overall population and a significant 43% increase of MI in the ACS/PCI subgroup.

Effects of Guidelines for Gastroenterological Endoscopy in Patients Undergoing Antithrombotic Treatment on Postoperative Bleeding after Endoscopic Submucosal Dissection for Early Gastric Cancer: A Propensity Score-Matching Analysis

Background: Management of antithrombotic agents during endoscopic treatment changed after the publishing of ­Japan Gastroenterological Endoscopy Society guidelines for gastroenterological endoscopy in antithrombotic drug users (GL-2012). Objectives: We aimed to evaluate the effect of implementing antithrombotic agent management guidelines (GL-2012) on postoperative bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and on the prevention of thromboembolic events. Methods: A total of 1,264 patients who underwent ESD for EGC at Kyoto Prefectural University Hospital between June 2002 and March 2017 were enrolled and divided into 2 groups: 621 patients before the publication of GL-2012 (Pre-GL group) and 643 patients after (Post-GL group). Relationships between postoperative bleeding and various clinicopathological factors in each group were investigated through propensity score-matching analysis. Results: In the Pre-GL group, antihypertensive agent use (p < 0.01) and upper third of the stomach (p < 0.01) were significantly related to postoperative bleeding in univariate analysis. Antihypertensive agent use (OR 4.6, 95% CI 1.6–12.8) and upper third of the stomach (OR 4.9, 95% CI 1.8–13.4) were significantly related to postoperative bleeding in multivariate analysis. In the Post-GL group, antihypertensive agent use (p < 0.01), dual antiplatelet agents use (p < 0.01), anticoagulant agents use (p < 0.01), and heparin replacement therapy (p < 0.01) were significantly related to postoperative bleeding in univariate analysis. Antihypertensive agent use (OR 3.4, 95% CI 1.1–9.6), dual antiplatelet agents (OR 12.3, 95% CI 2.4–63.0), and heparin replacement therapy (OR 10.2, 95% CI 2.5–41.5) were significantly related to postoperative bleeding in multivariate analysis. Conclusions: The adherence to GL-2012 might reduce risk of thromboembolic events. On the other hand, dual antiplatelet agents therapy and heparin replacement therapy were the new independent risk factors for ESD postoperative bleeding in EGC after GL-2012. Especially as for heparin replacement therapy, uninterrupted warfarin or a temporary short interruption of direct oral anticoagulants without heparin replacement therapy might be recommended rather than heparin replacement therapy.

Suboptimal Secondary Prevention Post Acute Coronary Syndromes: Insights from the SMART-REHAB Trial

Introduction: International guidelines clearly state optimal secondary prevention with targets for blood pressure, cholesterol and diabetes as well as optimal medical therapy and smoking cessation. It is uncertain how many of these targets are met post acute coronary syndromes (ACS). Methods: SMART-REHAB was a randomised controlled trial assessing the impact of a smartphone-based cardiac rehabilitation programme post ACS. Patients were recruited from 6 major tertiary hospitals in Victoria. We assessed the proportion of patients receiving optimal medical therapy (dual antiplatelet therapy, statin, beta-blocker, ACE inhibition) and those not achieving target BP (<130/80 mmHg), cholesterol (total cholesterol <4 mmol/L and LDL-C <1.8 mmol/L) or diabetic control (HbA1c < 7%) as well as those continuing to smoke at 8-week post ACS. Results: 168 patients were included (mean age 56 ± 10 years, 57% STEMI). At 8-weeks, the majority of patients were receiving aspirin (99%), a second anti-platelet agent (99%) and statin therapy (98%). The rate of beta-blocker (82%) and ACE/ARB (83%) use was lower. Suboptimal secondary prevention was evident, as seen below, but was not improved with smartphone technology.Tabled 1SmartphoneUsual Carep-valueTC >1.8mmol/L24%21%0.42LDL-C >1.8mmol/L38%45%0.42BP >130/80mmHg24%74%0.93HbA1C > 7%8%6%0.52Current Smokers15%15%0.76 Open table in a new tab Conclusion: A significant proportion of patients are not meeting secondary prevention targets, particularly for blood pressure, cholesterol and smoking, despite the use of smartphone technology. An updated approach with the use artificial intelligence and mhealth can be used to up-titrate medication to meet secondary prevention targets.

The use of antiplatelet agents after an acute coronary syndrome in a large community Italian setting of more than 12 million subjects.

Antiplatelet agents are the cornerstone of medical treatment in acute coronary syndromes. The aim of this study was to evaluate the clinical epidemiology of patients after an acute coronary syndrome treated with different antiplatelet agent regimens in a large real community setting. The ARCO database, including more than 12 million inhabitants, was evaluated. Antiplatelet agent prescriptions were analysed as follows: aspirin, clopidogrel, other antiplatelet agents used alone; the free and fixed combination of clopidogrel and aspirin; the free combination of aspirin with other antiplatelet agents. Healthcare costs included drug prescriptions (prices reimbursed by the Italian National Health System), outpatient specialist services and hospitalisations (Italian national tariffs). From 1 January to 31 December 2014, 26,834 patients were discharged after an acute coronary syndrome. Of these, 19,333 (77%) were prescribed with an antiplatelet agent. Among patients undergoing a revascularisation procedure either percutaneous or surgical (47% of the total population), antiplatelet agents were prescribed in 90% of cases. Dual antiplatelet agent therapy was prescribed in 49.6% of the total population and in 68.5% of those treated invasively. Prescription continuity was observed in just 75% of patients. The highest adherence was observed for the fixed combination of aspirin/clopidogrel (81.5%). Throughout one year of follow-up re-hospitalisation occurred in 47.9% of the patients and the direct cost per patient treated with an antiplatelet agent was €13,297 versus €16,647 in patients not treated with antiplatelet agents. This study highlights that antiplatelet agent prescriptions, specifically dual antiplatelet agent therapy, are at least suboptimal as well as in prescription continuity. Hospitalisations were frequent and were the main driver of the costs, accounting for 84% of the total costs for the Italian National Health System.

Network meta-analysis of patent foramen ovale management strategies in cryptogenic stroke

To compare the outcomes of patent foramen ovale (PFO) closure vs antiplatelet agent (APA) vs oral anticoagulation therapy (OAT) for secondary prevention of stroke in patients with cryptogenic stroke, using direct and indirect evidence from existing randomized data. Relevant randomized controlled trials were identified by a systematic review. The efficacy outcome was stroke recurrence, and safety outcomes were atrial fibrillation and bleeding complications at the end of follow-up. Bayesian network meta-analysis was performed to calculate risk estimates and the rank probabilities using APA therapy as the reference. In a network meta-analysis of 6 randomized controlled trials consisting of 3,497 patients (1,732 PFO closure, 1,252 APA, 513 OAT), PFO closure and OAT were associated with lower rates of recurrent stroke (odds ratio [OR] 0.30, 95% credibility interval [CrI] 0.17-0.49 and OR 0.42, 95% CrI 0.22-0.78, respectively) with equal efficacy of OR 0.70 (95% CrI 0.37-1.49). PFO closure had the highest top rank probability of atrial fibrillation and OAT had the highest risk of bleeding complications. These findings suggest that closure and OAT may be equally effective in recurrent stroke prevention in patients with PFO. There is an increased risk of atrial fibrillation and bleeding with closure and OAT therapy, respectively. A randomized trial is needed to identify patients who would benefit most from each strategy.

Antiplatelet and anticoagulant agents for secondary prevention of stroke and other thromboembolic events in people with antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ-5D-5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains.The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low-quality evidence). Investigators reported similar rates of clinically relevant non-major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate-quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ-5D-5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low-quality evidence) but not measured as health utility (MD 0.04, 95% CI -0.02 to 0.10 [on a scale from 0 to 1]).Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low-quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high-intensity warfarin treatment compared to the standard-intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low-quality evidence).In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high-intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high-intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future.

Outcome of traumatic brain injury in patients on antiplatelet agents: a retrospective 20-year observational study in a single neurosurgery unit

ABSTRACTObjective: To evaluate the outcomes after Traumatic Brain Injury (TBI) in patients taking Antiplatelet Agents (APAs).Methods: We reviewed the clinical records of 934 patients with TBI between 1995 and 2014. Multivariate analysis was performed to correlate patient outcome with various factors, including pre-injury APA intake. Cause of death was compared among groups stratified according to APA dose.Results: Increasing doses of APAs were positively associated with mortality rates, however, differences were primarily due to non-traumatic causes. APA therapy before injury was independent of both overall and non-traumatic mortality. In multivariate analysis, mortality was significantly correlated with the Charlson Comorbidity Index (CCI), pupillary abnormalities, age, Glasgow Coma Scale (GCS), head Abbreviated Injury Scale (AIS) and additional AIS >2. Conversely, non-traumatic mortality was associated with age, GCS, additional AIS >2 and CCI, though only CCI was correlated with increasing APA dose. Furthermore, no significant difference was observed when comparing mortalities according to CCI score among APA groups. Thus, mortalities were associated with the severity of pre-existing conditions rather than APA dose.Conclusions: The outcome of patients with TBI, who were on APAs may be determined by the severity of pre-existing conditions. Aggressive TBI treatment should be implemented when tolerable, regardless of pre-existing APA treatment status.

Anti-platelet drugs in patients with femoral neck fractures undergoing cemented hip hemiarthroplasty surgery. A study of complications and mortality

ObjectiveTo assess complications and factors predicting one-year mortality in patients on anti-platelet agents presenting with femoral neck fractures undergoing hip hemiarthroplasty surgery. Material and methodsA review was made on 50 patients on preoperative anti-platelet agents and 83 patients without preoperative anti-platelet agents. Patients in both groups were treated with cemented hip hemiarthroplasty. A statistical comparison was performed using epidemiological data, comorbidities, mental state, complications and mortality. There was no lost to follow-up. ResultsThe one-year mortality was 20.3%. In patients without preoperative anti-platelet agents it was 14.4% and in patients with preoperative anti-platelet agents was 30%. Age, ASA grade, number of comorbidities and anti-platelet agent therapy were predictors of one-year mortality.The one-year mortality of patients on clopidogrel was 46.1%, versus 24.3% in patients on acetylsalicylic acid. ConclusionPatients with preoperative anti-platelet therapy were older and had greater number of comorbidities, ASA grade, delayed surgery, and a longer length of stay than patients without anti-platelet therapy. The one-year mortality was higher in patients with preoperative anti-platelet therapy.

Death after discharge: predictors of mortality in older brain-injured patients.

Older patients with traumatic brain injury (TBI) may be at high risk of death after hospitalization. The purpose of this study was to characterize long-term mortality of older TBI patients who survived to discharge. We hypothesized that predictors of postdischarge mortality differed from those of inpatient mortality. A retrospective cohort study was performed on TBI patients older than 55 years admitted to our Level I trauma center between July 1, 2006, and December 31, 2011. Postdischarge deaths were identified by matching patient data with local vital records up to December 31, 2011, when data collection was terminated (censoring). Patients were categorized by age, comorbidities, history of preinjury anticoagulant/prescription antiplatelet agent therapy, injury severity indices, initial TBI type, prehospital living status, discharge location, and discharge condition. The effect of risk factors on postdischarge mortality was evaluated by Cox proportional hazards modeling. Of 353 patients, 322 (91.2%) survived to discharge. Postdischarge mortality was 19.8% (n = 63) for the study period. Of the postdischarge deaths, 54.0% died within 6 months of discharge, and 68.3% died within 1 year. Median days to death after discharge or censoring were 149 and 410, respectively. Factors associated with death after discharge included age, preinjury anticoagulant use, higher number of Charlson comorbidities, discharge to a long-term care facility, and severe disability. Factors related to injury severity (i.e., Injury Severity Score [ISS], initial Glasgow Coma Scale [GCS] score) and preinjury prescription antiplatelet agent use, previously found to predict inpatient death, did not predict postdischarge mortality. Older TBI patients who survive to discharge have a significant risk of death within 1 year. Predictors of postdischarge mortality and inpatient death differ. Death after discharge is largely a function of overall health status. Monitoring health status and continued aggressive management of comorbidities after discharge may be essential in determining long-term outcomes. Epidemiologic study, level III.

Precision and reliability of 5 platelet function tests in healthy volunteers and donors on daily antiplatelet agent therapy.

Anticoagulation protocols used during mechanical circulatory support call for titration of antiplatelet agents. We compared the precision and reliability of 5 platelet function tests in healthy volunteers and donors on daily antiplatelet therapy to distinguish their efficacy for titrating antiplatelet therapy. We assessed arachidonic acid-induced platelet function by light transmission aggregometry (LTA), Multiplate impedance aggregometry, VerifyNow, and platelet mapping by thromboelastography (TEG PM). We assessed ADP-induced platelet function by the same methods and flow cytometry. Forty healthy volunteers and 10-13 volunteers on daily aspirin and/or clopidogrel therapy were evaluated. We compared tests for intraassay precision, interassay precision (samples from 2 separate blood draws), and reliability coefficient. For arachidonic acid-induced platelet aggregation in healthy volunteers, intra- and interassay CVs were ≤ 10% for all methods. Intra- and interassay precision among donors on daily aspirin was ≤ 30% for all methods except LTA (38% interassay CV) and TEG PM (95% intraassay and 104% interassay CV). For ADP-induced platelet function, intra- and interassay precision was ≤ 10% and ≤ 30% for all methods. Only Multiplate demonstrated moderate or greater (R > 0.40) reliability coefficients for arachidonic acid-induced platelet function among all subjects. All methods of ADP-induced platelet function, except TEG PM, demonstrated substantial or greater (R > 0.60) reliability among all subjects. TEG PM is least suited to monitor effects of antiplatelet agents. Multiplate impedance aggregometry was the only method to demonstrate an acceptable reliability coefficient among healthy volunteers and donors on both aspirin and clopidogrel therapy.

Antiagregación en pacientes con fractura subcapital desplazada de fémur tratados con prótesis parcial cementada. Estudio de complicaciones y mortalidad

ObjectiveTo assess complications and factors predicting one-year mortality in patients on antiplatelet agents presenting with femoral neck fractures undergoing hip hemiarthroplasty surgery. Material and methodsA review was made on 50 patients on preoperative antiplatelet agents and 83 patients without preoperative antiplatelet agents. Patients in both groups were treated with cemented hip hemiarthroplasty. A statistical comparison was performed using epidemiological data, comorbidities, mental state, complications and mortality. There was no lost to follow-up. ResultsThe one-year mortality was 20.3%. In patients without preoperative antiplatelet agents it was 14.4% and in patients with preoperative antiplatelet agents was 30%. Age, ASA grade, number of comorbidities and antiplatelet agent therapy were predictors of one-year mortality.The one-year mortality of patients on clopidogrel was 46.1%, versus 24.3% in patients on acetylsalicylic acid. ConclusionPatients with preoperative antiplatelet therapy were older and had greater number of comorbidities, ASA grade, delayed surgery, and a longer length of stay than patients without antiplatelet therapy. The one-year mortality was higher in patients with preoperative antiplatelet therapy.

Retrospective analysis of correlative factors between digestive system injury and anticoagulant or antiplatelet-agents

To explore the correlative factors and clinical characteristics of digestive system injury during the treatment of anticoagulant and (or) antiplatelet-agents. A total of 1 443 hospitalized patients on anticoagulant and (or) antiplatelet-agents from January 2010 to December 2013 at Renmin Hospital of Wuhan University were analyzed retrospectively. Their length of hospital stay was from 5 to 27 days. Most of them were elderly males (n = 880, 61.0%) with an average age of (62 ± 6) years. 1 138 patients (78.9%) were farmers, workers or someone without a specific occupation. During the treatment of anticoagulant/antiplatelet-agents, statistical difference existed (P = 0.01) between positively and negatively previous digestive disease groups for actively newly occurring digestive system injury (16.0% (41/256) vs 15.9% (189/1 187)). After the dosing of anticoagulant and (or) antiplatelet-agents, 57 (66.3%, 57/86) patients were complicated by hemorrhage of digestive tract, taking 62.9% (61/97) of all positive result patients for Helicobacter pylori test. Comparing preventive PPI group with no PPI group, there was no marked statistical differences (P = 2.67) for digestive system complication (including hemorrhage of digestive tract) while receiving anticoagulant and (or) antiplatelet-agents (13.9% (74/533) vs 17.1% (156/910)). During anticoagulant and/or antiplatelet-agent therapy, 185 patients (12.8%) were complicated by peptic ulcer or peptic ulcer with bleeding, 40 patients (2.8%) had erosive gastritis and 5 (0.3%) developed acute gastric mucosal lesions. And 42 of 76 patients complicated by hemorrhage of digestive tract underwent endoscopic hemostasis while 2 patients were operated. Ninety-seven patients (6.7%) died, including 61 (62.9%, 61/97) from hemorrhage of digestive tract. The remainder became cured, improved and discharged. Moreover, no significant statistical differences existed (P = 2.29) among three combination group (aspirin, clopidogrel, warfarin), two combination group (aspirin, clopidogrel), exclusive aspirin group and exclusive warfarin group in short-term (<27 d) mortality. It is necessary to clearly dictate the details of medication to the patients not highly educated. Elder, male, history of digestive system disease and Helicobacter pylori infection are possibly highly risk correlative factors for digestive system complications during anticoagulant/antiplatelet-agent therapy. The short-term protective effect of routine dose of PPI is inconspicuous. No significant correlation exists between short-term mortality and the dosage (or type) of anticoagulant/antiplatelet-agents.

Totally implantable venous access port: A prospective long-term study of early and late complications in adult patients with cancer.

e20635 Background: The main complications caused by Totally Implantable Venous Access Port (TIVAP) for chemotherapy are infections and thromboembolic events. However, only a limited amount of data is available on the overall safety and tolerance of TIVAP. We conducted a prospective study of early and long term adverse events in order to better appreciate the overall tolerance and to research and pinpoint risk factors in a chemotherapy-treated population. Methods: A prospective single-center observational study was conducted in Clinique Victor Hugo, Le Mans (France). All adult patients with cancer who had a TIVAP implanted between January 1st and December 31st 2006 were registered. Early and late complications were recorded until removal of the device, patient's death or until December 31st 2013. Cancer type and staging, any thrombotic history, antiplatelet agent or anticoagulant therapy, surgeon experience, site of insertion, and type of chemotherapy were recorded. Results: TIVAPs were implanted for 467 p...