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- Sun, Michelle T., et al.
(författare)
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Meta-Analysis of Intraocular Bleeding With Dual Antiplatelet Therapy Using P2Y12 Inhibitors Prasugrel or Ticagrelor
- 2020
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Ingår i: American Journal of Cardiology. - : EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. - 0002-9149 .- 1879-1913. ; 125:8, s. 1280-1283
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Forskningsöversikt (refereegranskat)abstract
- Intraocular bleeding is a devastating clinical event due to its potentially blinding nature. It is not known if determine if dual antiplatelet therapy using aspirin and potent P2Y12 inhibitors increases this risk. We searched MEDLINE and ClinicalTrials.gov for randomized controlled trials that were phase III, randomly assigned patients to dual antiplatelet therapy with either aspirin and a potent P2Y12 inhibitor or aspirin and clopidogrel, had follow-up of 6 months, and at least 200 patients. Corresponding authors were contacted for intraocular bleeding data. Inverse-variance, weighted, fixed-effects meta-analysis was undertaken, with random-effects meta-analysis performed as a sensitivity analysis. Four trials enrolling 42,850 patients were included. The median follow-up ranged from 12 to 14 months. There was overall low risk of bias. Pooled analysis demonstrated no statistically significant increase in the risk of intraocular bleeding with dual antiplatelet therapy using potent P2Y12 inhibitors compared with clopidogrel (risk ratio 0.89, 95% confidence interval 0.58 to 136). There was no significant heterogeneity observed across trials (I-2 statistic 0%, p = 0.98). The use of random-effects meta-analysis did not change the effect estimate or confidence intervals, and the results appeared similar when stratified by potent P2Y12 inhibitor (p = 0.97). In conclusion, this collaborative meta-analysis of dual antiplatelet trials does not suggest that the risk of intraocular bleeding is increased with the use of potent P2Y12 inhibitors compared with clopidogrel. Our results suggest that these potent P2Y12 inhibitors may continue to be used cautiously where indicated as part of dual antiplatelet therapy, even in those at high risk of spontaneous intraocular bleeding. Crown Copyright (C) 2020 Published by Elsevier Inc. All rights reserved.
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| 2. |
- Alfredsson, Joakim, et al.
(författare)
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Risks and Benefits of Triple Oral Anti-Thrombotic Therapies After Acute Coronary Syndromes and Percutaneous Coronary Intervention
- 2015
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Ingår i: Drug Safety. - : Adis / Springer Verlag (Germany). - 0114-5916 .- 1179-1942. ; 38:5, s. 481-491
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Forskningsöversikt (refereegranskat)abstract
- The key pathophysiological process underlying symptomatic coronary artery disease, including acute coronary syndromes (ACS), is usually a rupture or an erosion of an atherosclerotic plaque, followed by platelet activation and subsequent thrombus formation. Early clinical trials showed benefit with long-term aspirin treatment, and later-based on large clinical trials-dual anti-platelet therapy (DAPT), initially with clopidogrel, and more recently with prasugrel or ticagrelor, has become the established treatment in the post-ACS setting and after percutaneous coronary intervention (PCI). Treatment with DAPT is recommended for both ST-elevation myocardial infarction and non-ST-elevation ACS, as well as after PCI with stenting, in American and European clinical guidelines. Notwithstanding the benefits observed with DAPT, including third-generation P2Y(12) receptor inhibitors plus aspirin, ACS patients remain at high risk for a recurrent cardiovascular event, suggesting that other treatment strategies, including the addition of a third oral anti-platelet agent or a novel oral anticoagulant (NOAC) to standard DAPT regimens, may provide additional benefit for post-ACS patients and for patients undergoing PCI. Adding a third anti-thrombotic agent to DAPT after an ACS event or a PCI procedure has been shown to have modest benefit in terms of ischemic event reduction, but has consistently been associated with increased bleeding complications. Therefore, the quest to optimize anti-thrombotic therapies post-ACS and post-PCI continues unabated but is tempered by the historical experiences to date that indicate that careful patient and dose selection will be critical features of future randomized trials.
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| 3. |
- Gurbel, Paul A., et al.
(författare)
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Translational platelet research in patients with coronary artery disease: hat are the rnalor knowledge gaps?
- 2012
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 108:1, s. 12-20
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Forskningsöversikt (refereegranskat)abstract
- Translational platelet function investigations performed in the percutaneous coronary intervention (PCI)-treated population receiving clopidogrel have identified high platelet reactivity to ADP (HPR) as a major risk factor for both acute as well as long-term ischaemic event occurrence, including stent thrombosis. Recent studies have highlighted the relation of single nucleotide polymorphisms of genes involved in clopidogrel absorption and metabolism to reduced pharmacokinetic and pharmacodynamic responses to clopidogrel. CYP2C19 loss-of-function (LoF) allele carriage has been associated with increased thrombotic risk in the PCI population. However, there is no information regarding the utility of platelet function testing to predict outcomes in patients with stable coronary artery disease and in medically managed patients with acute coronary syndromes. Additionally, few studies have included longitudinal assessment of platelet function to assess a potential time-dependent relation to ischaemic event occurrence and no phase-III antiplatelet-therapy trial has included a large enough platelet function sub-study to examine the relation between on-treatment platelet reactivity, bleeding, and ischaemic event occurrence. Therefore, futher studies are needed to delineate the role of platelet function testing across the spectrum of symptomatic coronary artery disease.
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| 4. |
- Khan, Muhammad Shahzeb, et al.
(författare)
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Leveraging electronic health records to streamline the conduct of cardiovascular clinical trials
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1890-1909
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Forskningsöversikt (refereegranskat)abstract
- Conventional randomized controlled trials (RCTs) can be expensive, time intensive, and complex to conduct. Trial recruitment, participation, and data collection can burden participants and research personnel. In the past two decades, there have been rapid technological advances and an exponential growth in digitized healthcare data. Embedding RCTs, including cardiovascular outcome trials, into electronic health record systems or registries may streamline screening, consent, randomization, follow-up visits, and outcome adjudication. Moreover, wearable sensors (i.e. health and fitness trackers) provide an opportunity to collect data on cardiovascular health and risk factors in unprecedented detail and scale, while growing internet connectivity supports the collection of patient-reported outcomes. There is a pressing need to develop robust mechanisms that facilitate data capture from diverse databases and guidance to standardize data definitions. Importantly, the data collection infrastructure should be reusable to support multiple cardiovascular RCTs over time. Systems, processes, and policies will need to have sufficient flexibility to allow interoperability between different sources of data acquisition. Clinical research guidelines, ethics oversight, and regulatory requirements also need to evolve. This review highlights recent progress towards the use of routinely generated data to conduct RCTs and discusses potential solutions for ongoing barriers. There is a particular focus on methods to utilize routinely generated data for trials while complying with regional data protection laws. The discussion is supported with examples of cardiovascular outcome trials that have successfully leveraged the electronic health record, web-enabled devices or administrative databases to conduct randomized trials.
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