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Comparison of early clinical outcomes between dual antiplatelet therapy and triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.
Park, J, Jung, JH, Choi, EK, Lee, SW, Kwon, S, Lee, SR, Kang, J, Han, KD, Park, KW, Oh, S, et al
PloS one. 2022;(2):e0264538
Abstract
BACKGROUND AND OBJECTIVE Most Asian patients with atrial fibrillation (AF) who undergo percutaneous coronary intervention (PCI) receive only dual antiplatelet therapy (DAPT) without oral anticoagulants (vitamin K antagonists [VKA] or non-VKA oral anticoagulants [NOAC]). However, it has not been fully investigated whether the DAPT results in better clinical outcomes in the early period after PCI than the standard triple therapy with VKA or NOAC. METHODS We analyzed the claims records of 11,039 Korean AF population who had PCI between 2013 and 2018. Patients were categorized according to the post-PCI antithrombotic therapy as VKA-based triple therapy (VKA-TT), NOAC-based triple therapy (NOAC-TT), and DAPT groups. After baseline adjustment using inverse probability weighting, we compared the risks of ischemic endpoints (ischemic stroke, myocardial infarction, and all-cause mortality) and major bleeding at 3 months post-PCI. RESULTS Ischemic stroke, MI, and all-cause mortality occurred in 105, 423, and 379 patients, respectively, and 138 patients experienced major bleeding. The DAPT group was associated with a lower risk of ischemic stroke and major bleeding (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.37-0.84) compared to the VKA-TT group, despite no significant differences in the risks of MI and all-cause mortality. In contrast, the DAPT group demonstrated no significant difference in the risks for ischemic endpoints compared to the NOAC-TT group. Additionally, the DAPT group had a numerically lower risk of major bleeding than the NOAC-TT group but this was not statistically significant (HR 0.69, 95% CI 0.45-1.07). CONCLUSIONS An outcome benefit of DAPT was observed in the early period after PCI compared to the VKA-TT, but not against NOAC-TT users among the Asian AF population. Given the potential long-term benefits of NOACs, greater efforts should be made to increase compliance in clinical practice with proper combination therapy with NOAC after PCI.
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Risk Factors for Severe Bleeding Complications in Vitreoretinal Surgery and the Role of Antiplatelet or Anticoagulant Agents.
Lauermann, P, Klingelhöfer, A, Mielke, D, van Oterendorp, C, Hoerauf, H, Striebe, NA, Storch, MW, Pfeiffer, S, Koscielny, J, Sucker, C, et al
Ophthalmology. Retina. 2021;(8):e23-e29
Abstract
PURPOSE To evaluate the influences and risk factors for severe bleeding complications during vitreoretinal surgery and to investigate the role of antiplatelet and anticoagulant agents. DESIGN Prospective trial. PARTICIPANTS Patients undergoing vitreoretinal surgery. METHODS The procedures included were pars plana vitrectomy and scleral buckling. We developed a uniform classification to grade the bleeding severity. Bleeding was graded on an ordinal scale ranging from 0 to 5. Immediately after surgery and 1 day later, the incidence and the severity of bleeding events was documented on a standardized form. A grade of 3 or more was defined as severe bleeding. Furthermore, the influence of known systemic disorders before surgery, the type of anesthesia, type of surgical procedure, intraoperative blood pressure, and the use or change of antiplatelet or anticoagulant agents on intraoperative bleeding was analyzed. MAIN OUTCOME MEASURES Incidence and risk factors for severe intraoperative bleeding events. RESULTS Data from 374 eyes undergoing vitreoretinal procedures were included in our study (mean age, 67.6 ± 12.9 years). A severe intraoperative bleeding event was observed in 15 eyes (4%). We found that concomitant diseases such as diabetes mellitus and carotid artery stenosis, the presence of diabetic retinopathy, younger age, and scleral buckling combined with a transscleral puncture were associated significantly with severe bleeding events. By contrast, use of antiplatelet or anticoagulant agents, or both, had no significant influence on severe intraoperative bleeding events. CONCLUSIONS Although external manipulations during buckling surgery (e.g., drainage of subretinal fluid) and concomitant diseases such as diabetes mellitus and carotid artery stenosis influences the risk of severe intraoperative bleeding events, we did not detect an increased risk related to coexisting antiplatelet or anticoagulant medication use, or both.
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Prostacyclin analog beraprost sodium efficacy in primary glomerular disease or nephrosclerosis: Analysis of the Japanese subgroup in CASSIOPEIR study.
Kurumatani, H, Okada, K, Origasa, H, Fujita, T, Isono, M, Nakamoto, H
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2021;(5):551-564
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Abstract
We conducted a multicenter, randomized, double-blind, placebo-controlled, phase IIb/III study (CASSIOPEIR) using a renal composite endpoint (i.e., doubling of SCr or end-stage renal disease) in seven Asian countries/region. CASSIOPEIR compared TRK-100STP (120 μg and 240 μg) with placebo in patients with non-diabetic CKD patients with primary glomerular disease or nephrosclerosis (n = 892). However, the superiority of TRK-100STP over placebo was not observed. A prior phase II study on which the Phase IIb/III study design was based included only Japanese patients. We therefore evaluated TRK-100STP efficacy and safety in a subgroup of Japanese patients using the CASSIOPEIR dataset. As the timing of treatment initiation is important in CKD, we conducted additional subgroup analyses based on the baseline serum creatinine (SCr) and eGFR. ITT analysis was performed in a Japanese subgroup (n = 339) in which the primary endpoint was the first occurrence of renal composite endpoint. Significant differences were observed for TRK-100STP 240 μg vs. placebo (P = 0.0493; HR 0.69 [95% CI: 0.47, 1.00]), but no significant difference was observed between TRK-100 120 μg and placebo (P = 0.3523; HR 0.85). More prominent improvement was observed with TRK-100STP 240 μg vs. placebo for baseline SCr < 3.0 mg/dL (P = 0.0031; HR 0.43); SCr < 3.5 mg/dL (P = 0.0237, HR 0.59); and eGFR ≥ 10 mL/min/1.73 m2 (P = 0.0339, HR0.67), respectively. No significant changes in urinary albumin/creatinine ratio and blood pressure were observed. TRK-100STP was generally well tolerated and most adverse drug reactions were mild or moderate in severity. In conclusion, in the Japanese subgroup of CASSIOPEIR, TRK-100STP 240 μg/day significantly improved the renal composite endpoint compared with placebo, with greater efficacy in subjects with SCr < 3.5 or eGFR ≥ 10 mL/min/1.73 m2 .
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One-year clinical outcomes of patients with versus without acute coronary syndrome with 3-month duration of dual antiplatelet therapy after everolimus-eluting stent implantation.
Natsuaki, M, Morimoto, T, Yamamoto, E, Watanabe, H, Furukawa, Y, Abe, M, Nakao, K, Ishikawa, T, Kawai, K, Yunoki, K, et al
PloS one. 2020;(3):e0227612
Abstract
There has been no previous prospective study evaluating 3-month dual antiplatelet therapy (DAPT) after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation in patients with acute coronary syndrome (ACS). The STOPDAPT trial is a prospective multi-center single-arm study evaluating 3-month DAPT duration in all-comer population after CoCr-EES implantation. Among 1525 study patients enrolled from 58 Japanese centers, the present study compared the 1-year clinical outcomes between ACS patients (N = 487) and stable coronary artery disease (CAD) patients (N = 1038). In the ACS group, 228 patients (47%) had unstable angina and 259 patients (53%) had myocardial infarction. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, definite stent thrombosis (ST) and TIMI major/minor bleeding. Thienopyridine was discontinued within 4-month in 455 patients (94.0%) in the ACS group and 977 patients (94.3%) in the stable CAD group. Cumulative 1-year incidence of and the adjusted risk for the primary endpoint were not significantly different between the ACS and stable CAD groups (2.3% vs. 3.0%, P = 0.42, and HR 0.94, 95%CI 0.44-1.87, P = 0.87). In the 3-month landmark analysis, cumulative incidence of the primary endpoint was also not significantly different between the ACS and stable CAD groups (1.3% vs. 2.4%, P = 0.16). There was no definite/probable ST through 1-year in both groups. In the propensity matched analysis, the cumulative 1-year incidence of the primary endpoint were similar between the ACS and stable CAD groups (2.3% versus 2.1%, P = 0.82). In conclusion, stopping DAPT at 3 months after CoCr-EES implantation in patients with ACS including 47% of unstable angina was as safe as that in patients with stable CAD.
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Combination therapy with beraprost sodium and aspirin for acute ischemic stroke: a single-center retrospective study.
Cai, D, Chen, XP, Wei, DC, Zhang, Q, Chen, SQ, He, WZ
The Journal of international medical research. 2019;(7):3014-3024
Abstract
OBJECTIVES To evaluate the effectiveness and safety of the combination of beraprost sodium (BPS) and aspirin in patients with acute ischemic stroke (AIS). METHODS There were 384 patients with AIS enrolled in this single-center, retrospective study. The BPS group comprised patients who received combination therapy with BPS and aspirin, and the control group comprised those who received only aspirin. Primary measurements were glomerular filtration rate (GFR), cystatin-c (Cys-C), National Institute of Health Stroke Scale (NIHSS) score, modified activities of daily living index (MBI), modified Rankin scale (mRS), and blood coagulation indexes. Recurrence and adverse events were recorded. RESULTS There were no significant differences in patient characteristics at baseline between the two groups. GFR and Cys-C levels increased in the BPS group compared with the control group. After treatment, the NIHSS and mRS score were significantly lower in the BPS group compared with the control group, whereas the MBI scores were significantly higher in the BPS group compared with the control group. There was no significant difference in blood coagulation between the two groups. There were no serious adverse events in either group. CONCLUSIONS Combination therapy with BPS and aspirin may be a safe and effective treatment for AIS.
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Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial.
Kasner, SE, Swaminathan, B, Lavados, P, Sharma, M, Muir, K, Veltkamp, R, Ameriso, SF, Endres, M, Lutsep, H, Messé, SR, et al
The Lancet. Neurology. 2018;(12):1053-1060
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Abstract
BACKGROUND Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. METHODS NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. FINDINGS Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22-1·36), and the risk was similar for those without known PFO (1·06; 0·84-1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51-8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69-4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24-0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. INTERPRETATION Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. FUNDING Bayer and Janssen.
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Effects of Ramadan fasting on aspirin resistance in type 2 diabetic patients.
Bouida, W, Beltaief, K, Baccouche, H, Sassi, M, Dridi, Z, Trabelsi, I, Laaouiti, K, Chakroun, T, Hellara, I, Boukef, R, et al
PloS one. 2018;(3):e0192590
Abstract
AIMS: Ramadan fasting (RF) may affect aspirin resistance. We conducted this study in patients with cardiovascular risk (CVR) factors to assess the effect of RF on aspirin resistance and explore whether type 2 diabetes mellitus (DM) would influence this effect. METHODS A total of 177 stable patients with ≥2 CVR factors were recruited. All patients observed RF and were taking aspirin. Physical exam and standard biological tests including glycaemia and serum lipids data were performed before Ramadan (Pre-R), at the last week of Ramadan (R) and four weeks after the end of Ramadan (Post-R). In the same visits caloric intake was calculated and platelet reactivity to aspirin was assessed using Verify Now point-of-care assay. RESULTS In the overall population, there was no significant change in absolute aspirin reaction unit (ARU) values and in metabolic parameters. In DM patients (n = 127), ARU change from Pre-R values was+19.7 (p = 0.01) and +14.4 (p = 0.02) respectively at R and Post-R. During Ramadan, glycaemia, triglycerides, and cholesterol levels increased significantly and returned to Pre-R values thereafter. These changes were not observed in non-DM patients. CONCLUSIONS During RF aspirin resistance increased only in DM patients. This effect persisted one month after Ramadan. Simultaneous alteration of glycemic control and increase of serum lipids levels could potentially be a favorable factor. STUDY REGISTRATION The protocol was registered at clinicaltrials.gov under: NCT02720133.
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METoclopramide Administration as a Strategy to Overcome MORPHine-ticagrelOr Interaction in PatientS with Unstable Angina PectorIS-The METAMORPHOSIS Trial.
Sikora, J, Niezgoda, P, Barańska, M, Buszko, K, Skibińska, N, Sroka, W, Pstrągowski, K, Siller-Matula, J, Bernd, J, Gorog, D, et al
Thrombosis and haemostasis. 2018;(12):2126-2133
Abstract
Extensive search for methods of overcoming morphine-related delay of the absorption and onset of action of oral P2Y12 inhibitors in patients presenting with acute coronary syndrome is on-going. The aim of the trial was to investigate whether metoclopramide co-administration could reduce this delay and improve the pharmacokinetics (PKs) and pharmacodynamics (PDs) of ticagrelor and its active metabolite AR-C124900XX. Plasma concentration of both compounds and platelet reactivity were evaluated in nine pre-defined time points within 6 hours after administration of ticagrelor loading dose. The results of our study show that mean platelet activity within the first hour was noticeably higher in metoclopramide-naive patients. Moreover, ticagrelor mean plasma concentration was significantly higher within the initial four time points (15, 30, 45, 60 minutes) in patients receiving metoclopramide (p = 0.039; p = 0.009; p = 0.005; p = 0.008, respectively). To conclude, the co-administration of metoclopramide in patients presenting with unstable angina and treated with morphine, has a beneficial effect on the PK/PD profile of ticagrelor and its metabolite; however, its impact on ST-elevation myocardial infarction patients requires further investigation.
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Effectiveness, safety and costs of thromboembolic prevention in patients with non-valvular atrial fibrillation: phase I ESC-FA protocol study and baseline characteristics of a cohort from a primary care electronic database.
Giner-Soriano, M, Vedia Urgell, C, Roso-Llorach, A, Morros, R, Capellà, D, Castells, X, Ferreira-González, I, Troncoso Mariño, A, Diògene, E, Elorza, JM, et al
BMJ open. 2016;(1):e010144
Abstract
PURPOSE Atrial fibrillation is the most common arrhythmia. Its management aims to reduce symptoms and to prevent complications through rate and rhythm control, management of concomitant cardiac diseases and prevention of related complications, mainly stroke. The main objective of Effectiveness, Safety and Costs in Atrial Fibrillation (ESC-FA) study is to analyse the drugs used for the management of the disease in real-use conditions, particularly the antithrombotic agents for stroke prevention. The aim of this work is to present the study protocol of phase I of the ESC-FA study and the baseline characteristics of newly diagnosed patients with atrial fibrillation in Catalonia, Spain. PARTICIPANTS The data source is System for the Improvement of Research in Primary Care (SIDIAP) database. The population included are all patients with non-valvular atrial fibrillation diagnosis registered in the electronic health records during 2007-2012. FINDINGS TO DATE A total of 22,585 patients with non-valvular atrial fibrillation were included in the baseline description. Their mean age was 72.8 years and 51.6% were men. The most commonly prescribed antithrombotics were vitamin K antagonists (40.1% of patients) and platelet aggregation inhibitors (32.9%); 25.3% had not been prescribed antithrombotic treatment. Age, gender, comorbidities and co-medication at baseline were similar to those reported for previous studies. FUTURE PLANS The next phase in the ESC-FA study will involve assessing the effectiveness and safety of antithrombotic treatments, analysing stroke events and bleeding episodes' rates in our patients (rest of phase I), describing the current management of the disease and its costs in our setting, and assessing how the introduction of new oral anticoagulants changes the stroke prevention in non-valvular atrial fibrillation.
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Clopidogrel Improves Skin Microcirculatory Endothelial Function in Persons With Heightened Platelet Aggregation.
Salimi, S, Lewis, JP, Yerges-Armstrong, LM, Mitchell, BD, Saeed, F, O'Connell, JR, Perry, JA, Ryan, KA, Shuldiner, AR, Parsa, A
Journal of the American Heart Association. 2016;(11)
Abstract
BACKGROUND Platelet activation can lead to enhanced oxidative stress, inflammatory response, and endothelial dysfunction. To quantify the effects of platelet inhibition on endothelial function, we assessed platelet activity of healthy persons before and after clopidogrel administration and evaluated its effects on endothelial function. We hypothesized that clopidogrel, by attenuating platelet activity, would result in enhanced endothelial function. METHODS AND RESULTS Microcirculatory endothelial function was quantified by laser Doppler flowmetry (LDF) mediated by thermal hyperemia (TH) and postocclusive reactive hyperemia, respectively, in 287 and 241 relatively healthy and homogenous Old Order Amish persons. LDF and platelet aggregation measures were obtained at baseline and after 7 days of clopidogrel administration. Our primary outcome was percentage change in post- versus preclopidogrel LDF measures. Preclopidogrel TH-LDF and platelet aggregation were higher in women than in men (P<0.001). Clopidogrel administration was associated with ≈2-fold higher percentage change in TH-LDF in participants with high versus low baseline platelet aggregation (39.4±10.1% versus 17.4±5.6%, P=0.03). Clopidogrel also increased absolute TH-LDF measures in persons with high platelet aggregation (1757±766 to 2154±1055, P=0.03), with a more prominent effect in women (1909±846 to 2518±1048, P=0.001). There was no evidence that clopidogrel influenced postocclusive reactive hyperemia LDF measures. CONCLUSIONS The administration of clopidogrel in healthy persons with high baseline platelet aggregation results in improved TH-induced microcirculatory endothelial function. These data suggest that clopidogrel may have a beneficial effect on microcirculatory endothelial function, presumably through antiplatelet activity, and may confer additional vascular benefits. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT00799396.