Combined Antiplatelet Therapy Research Articles

Long-term combined antiplatelet therapy for secondary prevention of noncardioembolic stroke

Introduction. The high risk of recurrent ischemic events after non-cardioembolic ischemic stroke(IS), the prevalence of which is 25% of all strokes in the Russian Federation, determines the need to search for effective and safe secondary prevention strategies.Аim. The study was to evaluate the efficacy and safety of a combination of ADP receptor inhibitors (dipyridamole) with acetylsalicylic acid in patients with ischemic stroke (IS) in the secondary prevention of noncardioembolic stroke.Materials and methods. 229 patients in the early recovery period of noncardioembolic IS (139 women, 90 men), with an average age of 59.0 ± 5.7 years were included in the study. The duration of IS was 54.4 ± 6.1 days. All patients received a multimodal medical rehabilitation (MMR) program. Long-term double antiplatelet therapy with acetylsalicylic acid (ASA) 75 mg per day and dipyridamole at a daily dose of 225 mg divided into 3 doses were prescribed to all the patients. The neurological and neuropsychological status of the patient, quality of life and hemorheological parameters were assessed initially (T0), after MMR (T1, 6 weeks) and 12 months after IS(T2).Results. Motor and coordination indicators of patients as well as the cognitive and emotional parameters were significantly (p < 0,05) improved due to MMR technology. These were confirmed by the dynamics of the corresponding scales. The prescribed double antiplatelet therapy did not cause significant adverse events and worsening of the patients’ well-being both during the MMR process and during the observation period. The combination of ASA with dipyridamole was well tolerated. At the end of the study, recurrent IS, myocardial infarctions, and fatal bleeding were not recorded. In 5.2% patients with severe risks of cardiovascular complications there was occurred TIA. The effectiveness of the dual antiplatelet therapy was confirmed by a decrease in the level of platelet aggregation (p < 0,05).Conclusions. The high effectiveness of secondary prevention of IS with a combination of ASA and dipyridamole with good tolerability and safety in patients after IS has been shown.

Safety and efficacy of combined dual antiplatelet therapy and factor VIII prophylaxis in patients with haemophilia A after acute coronary syndrome.

The increased life expectancy of patients with haemophilia A (HA) has led to a growing prevalence of cardiovascular risk factors and events. There is still scarce evidence on the safety and appropriate duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) in HA patients. We describe our experience on the clinical management of Italian HA patients after ACS. Nine patients with congenital HA treated with DAPT after a revascularization procedure performed for ACS have been enrolled and followed at the Angelo Bianchi Bonomi Haemophilia and Thrombosis Center in Milan between 2005 and September 2022. The safety and efficacy of DAPT with or without FVIII prophylaxis were assessed. Ten ACS events occurred in the nine HA patients (four mild and five severe). All events were treated with percutaneous transluminal coronary angioplasty with deployment of 1 to 3 drug-eluting stents followed by DAPT for 1-12 months. All patients except one were treated with FVIII prophylaxis during DAPT aimed at achieving FVIII trough levels ≥20-30IU/dL. DAPT was effective in all cases in preventing early ACS recurrence, with only a late recurrence. We observed two clinically relevant non-major bleeds (one in a patient without FVIII prophylaxis) and three minor bleeds. No venous thrombosis occurred. The long-term secondary antithrombotic prevention consisting of DAPT and FVIII prophylaxis achieving a trough level of 20-30IU/dL can be effective and safe in HA patients.

Efficacy of antiplatelet drugs combined with Argatroban in treating acute ischemic stroke and its impact on patients’ coagulation function and neurological function: a preliminary trial

This retrospective study analyzed the efficacy of combined antiplatelet therapy with Argatroban in treating acute ischemic stroke (AIS) and its impact on patients’ coagulation and neurological functions. Clinical data of 113 AIS patients admitted between January 2021 and January 2023 were retrospectively analyzed. Patients were divided into control (n = 56) and observation (n = 57) groups based on treatment interventions. The control group patients were treated with antiplatelet drugs, while the observation group patients received combination therapy with apatinib on the basis of the control group treatment. Compared to the control group, the observation group demonstrated higher clinical efficacy, improved coagulation parameters, reduced stroke severity (measured by NIHSS), enhanced daily living abilities (BI scores), and lowered inflammatory and neural injury markers post-treatment. Adverse reaction incidence was similar between groups. Combining Argatroban with antiplatelet drugs in AIS management showed superior efficacy without increasing adverse effects, suggesting its potential for clinical application.

Do We Still Need Aspirin in Coronary Artery Disease?

Aspirin has for some time been used as a first-line treatment for acute coronary syndromes, including ST-elevation myocardial infarction, for secondary prevention of established coronary disease, and for primary prevention in patients at risk of coronary artery disease. Although aspirin has been in use for decades, the available evidence for its efficacy largely predates the introduction of other drugs, such as statins and P2Y12 inhibitors. Based on recent trials, the recommendation for aspirin use as primary prevention has been downgraded. In addition, P2Y12 inhibitors given as a single antiplatelet therapy have been associated with a lower incidence of bleeding than dual antiplatelet therapy in combination with aspirin in patients with stable and unstable coronary artery disease. The aim of this review is to discuss the role of aspirin considering the available evidence for primary prevention, secondary prevention for stable coronary artery disease or acute coronary syndromes, and after percutaneous coronary intervention or coronary artery bypass revascularization.

Prevalence, adequacy and adherence of anticoagulation for stroke thromboprophylaxis in minority patients with atrial fib referred for transthyretin cardiac amyloidosis screening: The SCAN-MP Study

Abstract Introduction/Background Atrial fibrillation (AF) is the most common arrhythmia in adults, confers a 5-fold increase in risk of stroke, and is present in up to 50% of patients with transthyretin cardiac amyloidosis (ATTR-CA). 1,2 When present in ATTR-CA, AF is associated with a significant risk of stroke and systemic thromboembolism, even independent of CHA2DS2VASc score. 2-4. Current guidelines advocate the use of oral anticoagulant therapy in all patients with ATTR-CA and AF, without a contraindication for such treatment. Up to 50% of patients with an escalated risk for systemic thromboembolism may not be receiving appropriate anticoagulation, but less is known about patterns and adequacy of anticoagulation in minority patients, specifically Black/Hispanic patients with suspected amyloidosis and AF. 5,6. Methods We conducted a retrospective study of patients in SCAN-MP (Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations) who were ≥60 years of age with heart failure, Black or Hispanic, with an EF >30% and increased left ventricular wall thickness, (n=431) from 4 large urban hospitals who had documented AF in their medical records. We assessed the prescription of anticoagulation in participants stratified by the CHA2DS2VASc score and whether they received an appropriate dose (versus inappropriately low or high dose, when adjusted for renal function for dabigatran, edoxaban, and rivaroxaban; for renal function, age, and weight for apixaban). Results 122 subjects (28.3%) had a history of atrial fibrillation and of that number, 25.4% (n=31) were either not receiving any treatment (n=14) or only received a single anti-platelet therapy (n=17) for stroke thromboprophylaxis. Among participants with AF, patients with a CHA2DS2VASc of 6-9 (n=27), 21 patients (77.8%) were receiving an oral anticoagulant (either VKA or DOAC) either alone or in combination with antiplatelet therapy (Table 1). Among patients with CHA2DS2VASc of 2-5 (n=95), 70 patients (73.7%) were receiving such therapy. Among patients receiving a DOAC (n=74), dosing was incorrect in 20.3% (n=15). There were a significant proportion of patients receiving antiplatelet therapy in combination with oral anticoagulant (n=30, 24.5%). Among these patients receiving both therapies, only about half (n=16, 53.3%) had some form of vascular disease, coronary artery disease and/or peripheral arterial disease (Table 2). Conclusions These data suggest that thromboprophylaxis in Black and Hispanic patients with AF and suspected amyloidosis with heart failure is better than the often ≤50% historically reported in the literature. 6 Nearly ¼ of patients were receiving both antiplatelet and anticoagulant therapy, even though only half had documentation of vascular disease. Factors underlying this observation requires additional study, but the indication for such dual anti-thrombotic therapy is limited, may be associated with harm 7, and is an opportunity for improvement.Anti-thrombotic regimens in patientsTable 2:Frequency of vascular disease

Incorporating Anticoagulant and Antiplatelet Dual Functional Groups into Thermosetting Polymer Chain for Enhancing Antithrombogenicity.

In clinical practice, high-effective antithrombosis remains a challenge for blood-contacting medical devices. Inspired by the enhanced antithrombogenicity of anticoagulant and antiplatelet combination therapy, a strategy is proposed to synthesize dual-pathway antithrombotic polymers by incorporating anticoagulant and antiplatelet dual functional groups into a single thermosetting polymer chain. The synthesized polymer shows increased antithrombogenicity in vitro, with prolonged activated partial thromboplastin time (APTT) and decreased platelet adhesion. Additionally, it downregulates the expression of coagulation- and inflammation-related factors in rabbit plasma after ex vivo arteriovenous shunt assay and maintains patency of small vascular grafts for at least 6 months without thrombosis on the luminal surface after invivoreplacement of rabbit carotid artery. Thiswork provides a new approach to producing novel antithrombotic polymers for blood-contacting medical devices.

Is It Really Safe to Discontinue Antiplatelet Therapy 12 Months After Percutaneous Coronary Intervention in Patients with Atrial Fibrillation?

The prevalence of AF in patients with coronary artery disease is high. The guidelines from many professional groups, including the European Society of Cardiology, American College of Cardiology/American Heart Association and Heart Rhythm Society, recommend a maximum duration of 12 months of combination single antiplatelet and anticoagulation therapy in patients who undergo percutaneous coronary intervention and who have concurrent AF, followed by anticoagulation alone beyond 1 year. However, the evidence that anticoagulation alone without antiplatelet therapy adequately reduces the well-documented attritional risk of stent thrombosis after coronary stent implantation is relatively sparse, particularly given that very late stent thrombosis (>1 year from stent implantation) is the commonest type. By contrast, the elevated risk of bleeding from combined anticoagulation and antiplatelet therapy is clinically important. The aim of this review is to assess the evidence for long-term anticoagulation alone without antiplatelet therapy 1 year post-percutaneous coronary intervention in patients with AF.

Inappropriate Combined Antiplatelet and Anticoagulant Therapy in Older Patients with Atrial Fibrillation: Trend over Time (2009-18).

Antiplatelet therapy, when prescribed in combination with anticoagulant therapy to older patients with atrial fibrillation and no recent cardiovascular event, is inappropriate and a reversible risk factor of major bleeding. We aimed to assess the trend over time of the prevalence of inappropriate combined antiplatelet and anticoagulant therapy and to determine its associated factors during the direct oral anticoagulant era. This was a study of consecutive older patients (age ≥75 years) with atrial fibrillation, receiving anticoagulant therapy upon admission, and undergoing a comprehensive geriatric assessment during their first admission in a Belgian teaching hospital between 2009 and 2018. Antiplatelet therapy was considered inappropriate in the absence of a recent cardiovascular event. We studied the prevalence of inappropriate combined antiplatelet and anticoagulant therapy by 2-year periods and assessed its associated factors since the year 2013. Inappropriate combined antiplatelet and anticoagulant therapy was identified in 21% of the 654 patients (median age 84 years, 51% women), with a prevalence decreasing (p ≤ 0.01) from 25% (2009-10) to 14.8% (2017-18). Among the 469 patients recruited during the direct oral anticoagulant era, inappropriate combined antiplatelet and anticoagulant therapy (19%) was associated in a multivariable analysis with a history of stroke/transient ischemic attack (odds ratio 2.13, p = 0.007), anticoagulation with low-molecular-weight heparin (odds ratio 3.44, p = 0.015), and a history of vascular disease (odds ratio 5.68, p < 0.001). While inappropriate combined antiplatelet and anticoagulant therapy has declined over the last decade, there is still room for improvement. Antiplatelet deprescribing should be considered in all patients with inappropriate combined antiplatelet and anticoagulant therapy, including those with vascular disease and no recent cardiovascular event.

Applicability of the European Society of Cardiology Guidelines on the management of acute coronary syndromes to older people with haemophilia A - A modified Delphi consensus by the ADVANCE Working Group.

As people with haemophilia (PWH) receive better treatment and live longer they are more likely to encounter cardiovascular disease (CVD) and other comorbidities. ESC guidelines for the acute management of patients presenting with acute coronary syndrome (ACS) are based on the non-haemophilia population. To review the guidelines and propose relevant adaptations for PWHA without inhibitors who are treated with prophylaxis and present with ACS. As part of the ADVANCE Group, 20 European haemophilia experts used a modified Delphi approach to develop and gain consensus on proposed adaptations of the ESC guidelines for PWHA without inhibitors. Of the 32 Class I recommendations across both guidelines, adaptions were considered necessary and proposed for 15. The adaptions highlight the need to provide sufficient FVIII trough levels at the time of antithrombotic treatment in people with haemophilia A (HA) without inhibitors. Patients receiving emicizumab prophylaxis and requiring oral anticoagulation therapy or combined single antiplatelet plus oral anticoagulation therapy will require additional FVIII replacement therapy. In the absence of high-quality clinical evidence, the combined expert opinion used to develop these adaptions to the current ESC guidelines may help to guide clinicians in their treatment decisions when a PWHA presents with ACS.

Outcomes of dual antiplatelet therapy in combination with direct oral anticoagulants in patients with acute coronary syndrome: a meta-analysis

Abstract Background Recent data showed that the use of direct oral anticoagulants (DOAC) in addition to dual antiplatelet therapy (DAPT) is associated with reduced risk of adverse cardiovascular (CV) outcomes in patients with acute coronary syndrome (ACS) with or without percutaneous coronary intervention (PCI), but It has also been associated with increased risk of bleeding. The data differs among different studies, thus, the CV outcomes associated with use of DOAC therapy plus DAPT are not fully understood. We conducted a meta-analysis to explore the CV and bleeding outcomes of DOAC therapy plus DAPT vs DAPT with or without placebo in patients with ACS Methods We conducted a literature search of studies exploring the use of DAPT plus DOAC therapy with focusing on bleeding and CV outcomes including myocardial infarction (MI), stroke, stent thrombosis, limb thrombosis and VTE using Ovid, Scopus, PubMed, Medline, and EBSCO databases from January 2010 to March 2020. We used the following terms for the literature search: (Aspirin AND Clopidogrel OR Prasugrel OR Ticagrelor) AND (Apixaban OR Rivaroxaban OR Edoxaban OR Dabigatran OR Betrixaban). The efficacy outcome was a composite of CV death, MI and stroke, and the safety outcome was major bleeding. Results 4857 articles were included. Only RCTs and RCTs post-hoc analysis, were included (N=3). We found no significant heterogeneity and lower odds of the efficacy outcome in DOAC plus DAPT (experimental arm) compared to DAPT plus placebo (Control arm), which were unchanged in both the fixed and random effect models (Odds Ratio [OR] 0.87, 95% Confidence Interval [CI]: 0.78–0.97, I2=0%). We found no significant heterogeneity and higher odds of the safety outcome in DOAC plus DAPT (experimental arm) compared to DAPT plus placebo (Control arm) (OR fixed model 3.27, 95% CI: 2.28–4.70; OR random model 3.18, 95% CI: 2.21–4.57; I2=0%). Conclusion DOAC therapy plus DAPT in patients with ACS with or without PCI was associated with a lower rate of CV death, MI and stroke when compared to DAPT alone or with placebo and also associated with significant increase in major bleeding Funding Acknowledgement Type of funding sources: None.

LIFE-THREATENING HEMOPTYSIS AS A COMPLICATION OF ENDOBRONCHIAL ULTRASOUND-GUIDED NEEDLE ASPIRATION IN A 55-YEAR-OLD MAN WITH END-STAGE RENAL DISEASE

LIFE-THREATENING HEMOPTYSIS AS A COMPLICATION OF ENDOBRONCHIAL ULTRASOUND-GUIDED NEEDLE ASPIRATION IN A 55-YEAR-OLD MAN WITH END-STAGE RENAL DISEASE

Combined Antiplatelet And Novel Oral Anticoagulant Therapy Is Increasingly Utilized But Associated With Worse Limb Outcomes And Equivalent Survival Compared To Antiplatelet And Warfarin And Antiplatelet Therapy Alone After Suprainguinal Bypass For Peripheral Artery Disease

Recent trials have reported that combined antiplatelet and novel oral anticoagulant (NOAC) therapy reduces limb and cardiovascular events compared to antiplatelet therapy alone after infrainguinal surgical revascularization. The goal of this study is to compare long-term limb outcomes and survival in patients treated with antiplatelet + NOAC, antiplatelet + warfarin, and antiplatelet therapy alone after suprainguinal bypass.

Editors' Note: Early Neurologic Deterioration in Lacunar Stroke: Clinical and Imaging Predictors and Association With Long-term Outcome

Early neurologic deterioration (END) is a frequent complication of acute ischemic stroke and is often due to progressive tissue infarction. In their single-center analysis of acute lacunar stroke identified on magnetic resonance imaging (n = 365), Dr. Vynckier and colleagues report 16.7% of patients experienced a worsening of 2 or more points in the NIH Stroke Scale within 24 hours of arrival and were classified as having END. It is important that milder stroke severity, ventral pontine injury, capsular warning syndrome, and hypoperfusion on baseline imaging were predictive of END. Dr. Alpert comments that early mobilization—while important for expediting rehabilitation and discharge—may increase the risk of END. Dr. Zini and colleagues also highlight the putative relationship between END and branch atheromatous disease, which may be targeted with combination antiplatelet therapy. Indeed, the study by Vynckier et al. found that acute dual antiplatelet therapy was associated with a 90% lower chance of END (adjusted odds ratio 0.10, 95% CI 0.01–0.89). Dual antiplatelet therapy may be useful for preventing progressive tissue infarction in lacunar disease; however, this can only be confirmed in a randomized clinical trial. Early neurologic deterioration (END) is a frequent complication of acute ischemic stroke and is often due to progressive tissue infarction. In their single-center analysis of acute lacunar stroke identified on magnetic resonance imaging (n = 365), Dr. Vynckier and colleagues report 16.7% of patients experienced a worsening of 2 or more points in the NIH Stroke Scale within 24 hours of arrival and were classified as having END. It is important that milder stroke severity, ventral pontine injury, capsular warning syndrome, and hypoperfusion on baseline imaging were predictive of END. Dr. Alpert comments that early mobilization—while important for expediting rehabilitation and discharge—may increase the risk of END. Dr. Zini and colleagues also highlight the putative relationship between END and branch atheromatous disease, which may be targeted with combination antiplatelet therapy. Indeed, the study by Vynckier et al. found that acute dual antiplatelet therapy was associated with a 90% lower chance of END (adjusted odds ratio 0.10, 95% CI 0.01–0.89). Dual antiplatelet therapy may be useful for preventing progressive tissue infarction in lacunar disease; however, this can only be confirmed in a randomized clinical trial.

Predictive Value of HAS-BLED Score Regarding Bleeding Events and Graft Survival following Renal Transplantation.

Objective: Due to the high prevalence and incidence of cardio- and cerebrovascular diseases among dialysis-dependent patients with end-stage renal disease (ERSD) scheduled for kidney transplantation (KT), the use of antiplatelet therapy (APT) and/or anticoagulant drugs in this patient population is common. However, these patients share a high risk of complications, either due to thromboembolic or bleeding events, which makes adequate peri- and post-transplant anticoagulation management challenging. Predictive clinical models, such as the HAS-BLED score developed for predicting major bleeding events in patients under anticoagulation therapy, could be helpful tools for the optimization of antithrombotic management and could reduce peri- and postoperative morbidity and mortality. Methods: Data from 204 patients undergoing kidney transplantation (KT) between 2011 and 2018 at the University Hospital Leipzig were retrospectively analyzed. Patients were stratified and categorized postoperatively into the prophylaxis group (group A)—patients without pretransplant anticoagulation/antiplatelet therapy and receiving postoperative heparin in prophylactic doses—and into the (sub)therapeutic group (group B)—patients with postoperative continued use of pretransplant antithrombotic medication used (sub)therapeutically. The primary outcome was the incidence of postoperative bleeding events, which was evaluated for a possible association with the use of antithrombotic therapy. Secondary analyses were conducted for the associations of other potential risk factors, specifically the HAS-BLED score, with allograft outcome. Univariate and multivariate logistic regression as well as a Cox proportional hazard model were used to identify risk factors for long-term allograft function, outcome and survival. The calibration and prognostic accuracy of the risk models were evaluated using the Hosmer–Lemshow test (HLT) and the area under the receiver operating characteristic curve (AUC) model. Results: In total, 94 of 204 (47%) patients received (sub)therapeutic antithrombotic therapy after transplantation and 108 (53%) patients received prophylactic antithrombotic therapy. A total of 61 (29%) patients showed signs of postoperative bleeding. The incidence (p < 0.01) and timepoint of bleeding (p < 0.01) varied significantly between the different antithrombotic treatment groups. After applying multivariate analyses, pre-existing cardiovascular disease (CVD) (OR 2.89 (95% CI: 1.02–8.21); p = 0.04), procedure-specific complications (blood loss (OR 1.03 (95% CI: 1.0–1.05); p = 0.014), Clavien–Dindo classification > grade II (OR 1.03 (95% CI: 1.0–1.05); p = 0.018)), HAS-BLED score (OR 1.49 (95% CI: 1.08–2.07); p = 0.018), vit K antagonists (VKA) (OR 5.89 (95% CI: 1.10–31.28); p = 0.037), the combination of APT and therapeutic heparin (OR 5.44 (95% CI: 1.33–22.31); p = 0.018) as well as postoperative therapeutic heparin (OR 3.37 (95% CI: 1.37–8.26); p < 0.01) were independently associated with an increased risk for bleeding. The intraoperative use of heparin, prior antiplatelet therapy and APT in combination with prophylactic heparin was not associated with increased bleeding risk. Higher recipient body mass index (BMI) (OR 0.32 per 10 kg/m2 increase in BMI (95% CI: 0.12–0.91); p = 0.023) as well as living donor KT (OR 0.43 (95% CI: 0.18–0.94); p = 0.036) were associated with a decreased risk for bleeding. Regarding bleeding events and graft failure, the HAS-BLED risk model demonstrated good calibration (bleeding and graft failure: HLT: chi-square: 4.572, p = 0.802, versus chi-square: 6.52, p = 0.18, respectively) and moderate predictive performance (bleeding AUC: 0.72 (0.63–0.79); graft failure: AUC: 0.7 (0.6–0.78)). Conclusions: In our current study, we could demonstrate the HAS-BLED risk score as a helpful tool with acceptable predictive accuracy regarding bleeding events and graft failure following KT. The intensified monitoring and precise stratification/assessment of bleeding risk factors may be helpful in identifying patients at higher risks of bleeding, improved individualized anticoagulation decisions and choices of antithrombotic therapy in order to optimize outcome after kidney transplantation.

Rivaroxaban Monotherapy vs Combination Therapy With Antiplatelets on Total Thrombotic and Bleeding Events in Atrial Fibrillation With Stable Coronary Artery Disease

Appropriate regimens of antithrombotic therapy for patients with atrial fibrillation (AF) and coronary artery disease (CAD) have not yet been established. To compare the total number of thrombotic and/or bleeding events between rivaroxaban monotherapy and combined rivaroxaban and antiplatelet therapy in such patients. This was a post hoc secondary analysis of the Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease (AFIRE) open-label, randomized clinical trial. This multicenter analysis was conducted from February 23, 2015, to July 31, 2018. Patients with AF and stable CAD who had undergone percutaneous coronary intervention or coronary artery bypass grafting 1 or more years earlier or who had angiographically confirmed CAD not requiring revascularization were enrolled. Data were analyzed from September 1, 2020, to March 26, 2021. Rivaroxaban monotherapy or combined rivaroxaban and antiplatelet therapy. The total incidence of thrombotic, bleeding, and fatal events was compared between the groups. Cox regression analyses were used to estimate the risk of subsequent events in the 2 groups, with the status of thrombotic or bleeding events that had occurred by the time of death used as a time-dependent variable. A total of 2215 patients (mean [SD] age, 74 [8.2] years; 1751 men [79.1%]) were included in the modified intention-to-treat analysis. The total event rates for the rivaroxaban monotherapy group (1107 [50.0%]) and the combination-therapy group (1108 [50.0%]) were 12.2% (135 of 1107) and 19.2% (213 of 1108), respectively, during a median follow-up of 24.1 (IQR, 17.3-31.5) months. The mortality rate was 3.7% (41 of 1107) in the monotherapy group and 6.6% (73 of 1108) in the combination-therapy group. Rivaroxaban monotherapy was associated with a lower risk of total events compared with combination therapy (hazard ratio, 0.62; 95% CI, 0.48-0.80; P < .001). Monotherapy was an independent factor associated with a lower risk of subsequent events compared with combination therapy. The mortality risk after a bleeding event (monotherapy, 75% [6 of 8]; combination therapy, 62.1% [18 of 29]) was higher than that after a thrombotic event (monotherapy, 25% [2 of 8]; combination therapy, 37.9% [11 of 29]). Rivaroxaban monotherapy was associated with lower risks of total thrombotic and/or bleeding events than combination therapy in patients with AF and stable CAD. Tapered antithrombotic therapy with a sole anticoagulant should be considered in these patients. ClinicalTrials.gov Identifier: NCT02642419.

Micelle-Incorporated Liquid Chromatography in the Light of Green Chemistry: An Application for the Quality Control Analysis of Anti-Platelet Fixed-Dose Combinations.

Oral anti-platelet agents are the cornerstone of the treatment of multiple cardiovascular diseases and in the long-term prevention of their recurrence. In the present work, we report a method based on micellar liquid chromatography coupled with ultraviolet detection (MLC/UV), for the simultaneous quantification of combined anti-platelet therapy namely, clopidogrel bisulfate (CPS), aspirin (ASP), together with salicylic acid (SA), in their pharmaceutical dosage form. The incorporation of 0.1M polyoxyethylene 23 lauryl ether (Brij-35) as a surfactant into the mobile phase improved solute-mobile phase interaction allowing for minimal organic solvent utilization, enhanced resolution, and rapid analysis (7 min). Furthermore, we performed a comprehensive evaluation of the environmental impact caused by our procedures versus previously reported analytical procedures applied in the determination of CPS and ASP. The evaluation was made using the Eco-scale tool. The results of the developed method indicated the superiority of our procedures in terms of greenness without compromising the quality of performance characteristics. The method was linear in the range of 1-100 µg/mL with limits of detection of 0.28, 0.32, and 0.29 µg/mL for CPS, ASP, and SA, respectively. The developed method can also be utilized to test the purity and the stability of ASP in pharmaceutical formulations through monitoring SA as its main degradation product. The MLC/UV method was successfully applied to the quantitative analysis of CPS, ASP together with SA-as a main degradation product of ASP-in their pharmaceutical dosage form. The developed method was successfully applied for the determination of clopidogrel bisulfate (CPS), aspirin (ASP), together with salicylic acid (SA), in their pharmaceutical dosage form.

Persistent Lung Injury and Prothrombotic State in Long COVID.

Lung injury may persist during the recovery period of COVID-19 as shown through imaging, six-minute walk, and lung function tests. The pathophysiological mechanisms leading to long COVID have not been adequately explained. Our aim is to investigate the basis of pulmonary susceptibility during sequelae and the possibility that prothrombotic states may influence long-term pulmonary symptoms of COVID-19. The patient’s lungs remain vulnerable during the recovery stage due to persistent shedding of the virus, the inflammatory environment, the prothrombotic state, and injury and subsequent repair of the blood-air barrier. The transformation of inflammation to proliferation and fibrosis, hypoxia-involved vascular remodeling, vascular endothelial cell damage, phosphatidylserine-involved hypercoagulability, and continuous changes in serological markers all contribute to post-discharge lung injury. Considering the important role of microthrombus and arteriovenous thrombus in the process of pulmonary functional lesions to organic lesions, we further study the possibility that prothrombotic states, including pulmonary vascular endothelial cell activation and hypercoagulability, may affect long-term pulmonary symptoms in long COVID. Early use of combined anticoagulant and antiplatelet therapy is a promising approach to reduce the incidence of pulmonary sequelae. Essentially, early treatment can block the occurrence of thrombotic events. Because impeded pulmonary circulation causes large pressure imbalances over the alveolar membrane leading to the infiltration of plasma into the alveolar cavity, inhibition of thrombotic events can prevent pulmonary hypertension, formation of lung hyaline membranes, and lung consolidation.

Antithrombotic therapy in patients with atrial fibrillation after percutaneous coronary interventions

Highlights. The article analyzes the current evidence base for anticoagulant and antiplatelet therapy in patients with atrial fibrillation undergoing percutaneous coronary interventions, and future perspectives of such therapy.Abstract. A number of patients undergoing percutaneous coronary intervention may require intensification of antithrombotic therapy. These include patients with atrial fibrillation. The difficulty of treatment of this group of patients consists in the achievement of a certain level of hypocoagulation, which will be sufficient for the prevention of acute ischemic events, mainly associated with the implanted coronary stent, but will not lead to the clinically relevant bleeding. Achieving this balance requires a careful and personalized approach to prescribing a variety of combination (antiplatelet and anticoagulant) therapy regimens. The article provides an overview of modern antithrombotic therapy regimens in this group of patients, their evidence base and promising directions for improving such therapy.

The WOEST2registry : Aprospective registry on antithrombotic therapy in atrial fibrillation patients undergoing percutaneous coronary intervention.

BackgroundPatients on oral anticoagulants (OACs) undergoing percutaneous coronary intervention (PCI) also require aspirin and a P2Y12 inhibitor (triple therapy). However, triple therapy increases bleeding. The use of non-vitamin K antagonist oral anticoagulants (NOACs) and stronger P2Y12 inhibitors has increased. The aim of our study was to gain insight into antithrombotic management over time.MethodsA prospective cohort study of patients on OACs for atrial fibrillation or a mechanical heart valve undergoing PCI was performed. Thrombotic outcomes were myocardial infarction, stroke, target-vessel revascularisation and all-cause mortality. Bleeding outcome was any bleeding. We report the 30-day outcome.ResultsThe mean age of the 758 patients was 73.5 ± 8.2 years. The CHA2DS2-VASc score was ≥ 3 in 82% and the HAS-BLED score ≥ 3 in 44%. At discharge, 47% were on vitamin K antagonists (VKAs), 52% on NOACs, 43% on triple therapy and 54% on dual therapy. Treatment with a NOAC plus clopidogrel increased from 14% in 2014 to 67% in 2019. The rate of thrombotic (4.5% vs 2.0%, p = 0.06) and bleeding (17% vs. 14%, p = 0.42) events was not significantly different in patients on VKAs versus NOACs. Also, the rate of thrombotic (2.9% vs 3.4%, p = 0.83) and bleeding (18% vs 14%, p = 0.26) events did not differ significantly between patients on triple versus dual therapy.ConclusionsPatients on combined oral anticoagulation and antiplatelet therapy undergoing PCI are elderly and have both a high bleeding and ischaemic risk. Over time, a NOAC plus clopidogrel became the preferred treatment. The rate of thrombotic and bleeding events was not significantly different between patients on triple or dual therapy or between those on VKAs versus NOACs.Supplementary InformationThe online version of this article (10.1007/s12471-022-01664-0) contains supplementary material, which is available to authorized users.

Brainstem stroke in a Nigerian male with prosthetic heart valves—A case report

Stroke following cardiac surgery particularly valvular implantation is an anticipated complication. This is due to the prosthetic valve as well as possible associated comorbid conditions. There is dearth of published data on stroke post valve replacement surgery in Nigeria. There is no general consensus on the role of antiplatelet agents in combination with anticoagulant therapy in at-risk patients. Our paper documents the case of a 46-year-old male hypertensive, who in 2016 had mitral and aortic valve replacement surgery in a Tertiary Teaching Hospital and presented in May 2020 with sudden onset abnormal tongue sensation and double vision. A left internuclear ophthalmoplegia with bilateral torsional nystagmus was evident. Brain magnetic resonance imaging confirmed pontine lacunar infarction. There were no intracardiac clots on echocardiography. He had full resolution of deficits following treatment with anticoagulants. This case report demonstrates that ischemic stroke can occur in people with prosthetic heart valve and that other comorbid risk factors may be contributory. Anticoagulation therapy is important, though there is no consensus on time of starting therapy and the role of adjunctive antiplatelet combination therapy in such patients. Individualized therapy should be based on the type of implant, numbers, and location of valve replaced, comorbid clinical conditions, and the risk of hemorrhagic transformation.