Aspirin and P2Y12 inhibitors in treating COVID-19
Ontology highlight
ABSTRACT:
SUBMITTER: Khalaji A
PROVIDER: S-EPMC9682055 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
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Project description:Objective Antithrombotic drugs are being used increasingly frequently to prevent cardiovascular diseases. Few studies have evaluated small bowel mucosal injury induced by dual antiplatelet therapy (DAPT). The aim of the present study was to evaluate small bowel mucosal injury induced by DAPT compared with other antithrombotics using video capsule endoscopy (VCE). Methods The study included chronic users of antithrombotics who underwent VCE for obscure gastrointestinal bleeding between January 2007 and July 2018. We evaluated the instances of small bowel injury classified into erosions and ulcers. Results Overall, 183 patients (114 men and 69 women; mean age, 73.6 years old) were enrolled, and the study groups comprised 49 patients taking low-dose aspirin (LDA) only, 50 taking anticoagulants only, 37 being treated with DAPT, 33 on combined LDA and anticoagulants, and 14 taking P2Y12 inhibitors. Small bowel erosions and ulcers were most frequently observed in the DAPT group, with frequencies of 78.4% and 37.8%, respectively. Exacerbating factors of small bowel ulcers were DAPT [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.2-7.7] and age over 80 years old (OR 2.4, 95% CI 1.1-5.4). Conclusion P2Y12 inhibitors seem to exacerbate LDA-induced small bowel injury. Preventive strategies for small bowel injury induced by LDA, especially DAPT, are urgently required.
| S-EPMC8666225 | biostudies-literature
Project description:Background The ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high- versus low-dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. Methods and Results Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness end point was a composite of death, myocardial infarction, or stroke; and the primary safety end point was major bleeding requiring blood transfusions. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Of 13 815 (91.6%) participants with available data, 3051 (22.1%) were receiving clopidogrel (2849 [93.4%]) or prasugrel (203 [6.7%]) at baseline. P2Y12 inhibitor use was associated with higher risk of the primary effectiveness end point (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22-1.62]) but was not associated with bleeding (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91-2.22]). We found no interaction in the relative effectiveness and safety of high- versus low-dose aspirin by P2Y12 inhibitor use. Overall, dose switching or discontinuation was more common in the high-dose compared with low-dose aspirin group, but the pattern was not modified by P2Y12 inhibitor use. Conclusions In this prespecified analysis of ADAPTABLE, we found that the relative effectiveness and safety of high- versus low-dose aspirin was not modified by baseline P2Y12 inhibitor use. Registration https://www.clinical.trials.gov. Unique identifier: NCT02697916.
| S-EPMC10757508 | biostudies-literature
Project description:COVID-19 is a highly infectious disease caused by SARS-CoV-2. First reported in December 2019, it rapidly escalated into a global pandemic, resulting in over 6.3 million fatalities by July 4, 2022. The first oral coronavirus main protease inhibitor, nirmatrelvir, was granted Emergency Use Authorization by the U.S. FDA in December 2021. It is a tripeptide incorporated with a C-terminal nitrile designed to bind and form a covalent attachment to the SARS-CoV-2 main protease. Shortly after nirmatrelvir's approval, Enanta Pharmaceuticals' peptidomimetic SARS-CoV-2 main protease inhibitor entered clinical trials in February 2022. This patent highlight reports key structures of di- and tripeptide inhibitors described in Enanta Pharmaceuticals' patent WO 2022/020242 A1.
| S-EPMC9465979 | biostudies-literature
Project description:The current COVID-19 global pandemic caused by SARS-CoV-2 has claimed more than 6 million lives since its emergence in December 2019. The first oral coronavirus main protease inhibitor, nirmatrelvir, was granted Emergency Use Authorization by the U.S. FDA in December 2021, with a twice-daily dosing regimen in combination with ritonavir. In March 2022, Shionogi & Co. announced their single-agent, once-daily oral SARS-CoV-2 main protease inhibitor, ensitrelvir, was granted approval for global phase 3 clinical trials. Unlike nirmatrelvir, ensitrelvir is a nonpeptidic, noncovalent, small molecule. This Patent Highlight describes key structures and their inhibitory activities in Shionogi & Co.'s and Hokkaido University's patent WO 2022/138987 A1.
| S-EPMC9465980 | biostudies-literature
Project description:BackgroundThe coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the health workforce and societies worldwide. Favipiravir was suggested by some experts to be effective and safe to use in COVID-19. Although this drug has been evaluated in randomized controlled trials (RCTs), it is still unclear if it has a definite role in the treatment of COVID-19.ObjectivesTo assess the effects of favipiravir compared to no treatment, supportive treatment, or other experimental antiviral treatment in people with acute COVID-19.Search methodsWe searched the Cochrane COVID-19 Study Register, MEDLINE, Embase, the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease, and three other databases, up to 18 July 2023.Selection criteriaWe searched for RCTs evaluating the efficacy of favipiravir in treating people with COVID-19.Data collection and analysisWe used standard Cochrane methodological procedures for data collection and analysis. We used the GRADE approach to assess the certainty of evidence for each outcome.Main resultsWe included 25 trials that randomized 5750 adults (most under 60 years of age). The trials were conducted in Bahrain, Brazil, China, India, Iran, Kuwait, Malaysia, Mexico, Russia, Saudi Arabia, Thailand, the UK, and the USA. Most participants were hospitalized with mild to moderate disease (89%). Twenty-two of the 25 trials investigated the role of favipiravir compared to placebo or standard of care, whilst lopinavir/ritonavir was the comparator in two trials, and umifenovir in one trial. Most trials (24 of 25) initiated favipiravir at 1600 mg or 1800 mg twice daily for the first day, followed by 600 mg to 800 mg twice a day. The duration of treatment varied from five to 14 days. We do not know whether favipiravir reduces all-cause mortality at 28 to 30 days, or in-hospital (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.49 to 1.46; 11 trials, 3459 participants; very low-certainty evidence). We do not know if favipiravir reduces the progression to invasive mechanical ventilation (RR 0.86, 95% CI 0.68 to 1.09; 8 trials, 1383 participants; very low-certainty evidence). Favipiravir may make little to no difference in the need for admission to hospital (if ambulatory) (RR 1.04, 95% CI 0.44 to 2.46; 4 trials, 670 participants; low-certainty evidence). We do not know if favipiravir reduces the time to clinical improvement (defined as time to a 2-point reduction in patients' admission status on the WHO's ordinal scale) (hazard ratio (HR) 1.13, 95% CI 0.69 to 1.83; 4 trials, 721 participants; very low-certainty evidence). Favipiravir may make little to no difference to the progression to oxygen therapy (RR 1.20, 95% CI 0.83 to 1.75; 2 trials, 543 participants; low-certainty evidence). Favipiravir may lead to an overall increased incidence of adverse events (RR 1.27, 95% CI 1.05 to 1.54; 18 trials, 4699 participants; low-certainty evidence), but may result in little to no difference inserious adverse eventsattributable to the drug (RR 1.04, 95% CI 0.76 to 1.42; 12 trials, 3317 participants; low-certainty evidence).Authors' conclusionsThe low- to very low-certainty evidence means that we do not know whether favipiravir is efficacious in people with COVID-19 illness, irrespective of severity or admission status. Treatment with favipiravir may result in an overall increase in the incidence of adverse events but may not result in serious adverse events.
| S-EPMC10840071 | biostudies-literature
Project description: Not available
| S-EPMC7232130 | biostudies-literature
Project description:ImportancePlatelet activation is a potential therapeutic target in patients with COVID-19.ObjectiveTo evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19.Design, setting, and participantsThis international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients.InterventionParticipants were randomly assigned to receive a P2Y12 inhibitor or no P2Y12 inhibitor (usual care) for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor.Main outcomes and measuresThe primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death and, for participants who survived to hospital discharge, the number of days free of cardiovascular or respiratory organ support up to day 21 of the index hospitalization. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Hemostasis.ResultsAt the time of trial termination, 949 participants (median [IQR] age, 56 [46-65] years; 603 male [63.5%]) had been randomly assigned, 479 to the P2Y12 inhibitor group and 470 to usual care. In the P2Y12 inhibitor group, ticagrelor was used in 372 participants (78.8%) and clopidogrel in 100 participants (21.2%). The estimated adjusted odds ratio (AOR) for the effect of P2Y12 inhibitor on organ support-free days was 1.07 (95% credible interval, 0.85-1.33). The posterior probability of superiority (defined as an OR > 1.0) was 72.9%. Overall, 354 participants (74.5%) in the P2Y12 inhibitor group and 339 participants (72.4%) in the usual care group survived to hospital discharge (median AOR, 1.15; 95% credible interval, 0.84-1.55; posterior probability of superiority, 80.8%). Major bleeding occurred in 13 participants (2.7%) in the P2Y12 inhibitor group and 13 (2.8%) in the usual care group. The estimated mortality rate at 90 days for the P2Y12 inhibitor group was 25.5% and for the usual care group was 27.0% (adjusted hazard ratio, 0.96; 95% CI, 0.76-1.23; P = .77).Conclusions and relevanceIn this randomized clinical trial of critically ill participants hospitalized for COVID-19, treatment with a P2Y12 inhibitor did not improve the number of days alive and free of cardiovascular or respiratory organ support. The use of the P2Y12 inhibitor did not increase major bleeding compared with usual care. These data do not support routine use of a P2Y12 inhibitor in critically ill patients hospitalized for COVID-19.Trial registrationClinicalTrials.gov Identifier: NCT04505774.
| S-EPMC10214036 | biostudies-literature
Project description:The unprecedented pandemic of coronavirus disease 2019 (COVID-19) demands effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The infection of SARS-CoV-2 critically depends on diverse viral or host proteases, which mediate viral entry, viral protein maturation, as well as the pathogenesis of the viral infection. Endogenous and exogenous agents targeting for proteases have been proved to be effective toward a variety of viral infections ranging from HIV to influenza virus, suggesting protease inhibitors as a promising antiviral treatment for COVID-19. In this Review, we discuss how host and viral proteases participated in the pathogenesis of COVID-19 as well as the prospects and ongoing clinical trials of protease inhibitors as treatments.
| S-EPMC7640965 | biostudies-literature
Project description: Not available
| S-BSST563 | biostudies-other
Project description:BackgroundA modified antiplatelet therapy approach after percutaneous coronary intervention (PCI), specifically reducing dual antiplatelet therapy (DAPT) duration and transitioning to P2Y12 inhibitor monotherapy, may offer advantages in terms of bleeding risk reduction. However, the impact of initiating aspirin-free P2Y12 inhibitor monotherapy immediately after PCI is not yet fully understood.MethodsWe systematically searched the PubMed and Embase databases until January 2024 for studies that examined the use of P2Y12 inhibitor monotherapy as a treatment approach without initial DAPT following PCI.ResultsFour single-arm pilot prospective studies and 1 randomized controlled trial were included. In acute coronary syndrome patients with P2Y12 monotherapy following aspirin withdrawal immediately after PCI, the occurrence rates of the primary ischemic and bleeding endpoint were 2.91 % (8 out of 275 patients) and 1.09 % (3 out of 275 patients) respectively, whereas both the incidence rates of the primary ischemic and bleeding endpoints were 0.25 % (1 out of 407 patients) in individuals with stable coronary artery disease. In the STOPDAPT-3 trial comparing the effect of aspirin-free prasugrel monotherapy with standard DAPT after PCI, no differences were found in the primary ischemic or bleeding endpoints and most secondary outcomes (death, stroke, and myocardial infarction). However, there was an increased risk of coronary revascularization and stent thrombosis in the no-aspirin group.ConclusionsSingle-arm studies suggest the safety and feasibility of aspirin-free P2Y12 inhibitor monotherapy without initial DAPT after PCI in selected patients with acute coronary syndrome or stable coronary artery disease. However, the safety and efficacy of this aspirin-free approach compared with standard DAPT strategies following PCI still require further investigation.
| S-EPMC11336810 | biostudies-literature