| 31. |
- Povsic, Thomas J., et al.
(författare)
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P2Y12 Inhibitor Switching in Response to Routine Notification of CYP2C19 Clopidogrel Metabolizer Status Following Acute Coronary Syndromes
- 2019
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Ingår i: JAMA cardiology. - : AMER MEDICAL ASSOC. - 2380-6583 .- 2380-6591. ; 4:7, s. 680-684
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Tidskriftsartikel (refereegranskat)abstract
- Importance Physician behavior in response to knowledge of a patient’s CYP2C19 clopidogrel metabolizer status is unknown.Objective To investigate the association of mandatory reporting of CYP2C19 pharmacogenomic testing, provided to investigators with no direct recommendations on how to use these results, with changes in P2Y12 inhibitor use, particularly clopidogrel, in the Randomized Trial to Compare the Safety of Rivaroxaban vs Aspirin in Addition to Either Clopidogrel or Ticagrelor in Acute Coronary Syndrome (GEMINI-ACS-1) clinical trial.Design, Setting, and Participants The GEMINI-ACS-1 trial compared rivaroxaban, 2.5 mg twice daily, with aspirin, 100 mg daily, plus open-label clopidogrel or ticagrelor (provided), in patients with recent acute coronary syndromes (ACS). The trial included 371 clinical centers in 21 countries and 3037 patients with ACS. Data were analyzed between May 2017 and February 2019.Interventions Investigators were required to prestipulate their planned response to CYP2C19 metabolizer status. In response to a regulatory mandate, results for all patients were reported to investigators approximately 1 week after randomization.Main Outcomes and Measures Reasons for switching P2Y12 inhibitors and occurrence of bleeding and ischemic events were collected.Results Of 3037 patients enrolled (mean [SD] age, 62.8 [9.0] years; 2275 men [74.9%], and 2824 white race/ethnicity [93.0%]), investigators initially treated 1704 (56.1%) with ticagrelor and 1333 (43.9%) with clopidogrel. Investigators prestipulated that they would use CYP2C19 metabolizer status to change P2Y12 inhibitor in 48.5% of genotyped clopidogrel-treated patients (n = 642 of 1324) and 5.5% of genotyped ticagrelor-treated patients (n = 93 of 1692). P2Y12 inhibitor switching for any reason occurred in 197 patients and was more common in patients treated with ticagrelor (146 of 1704 [8.6%]) compared with clopidogrel (51 of 1333 [3.8%]). Of patients initially treated with ticagrelor, only 1 (0.1% overall; 0.7% of all who switched) was switched based on CYP2C19 status. Of patients initially treated with clopidogrel, 23 (1.7% overall,;45.1% of all who switched) were switched owing to metabolizer status. Of 48 patients (3.6%) with reduced metabolizer status treated initially with clopidogrel, 15 (31.3%) were switched based on metabolizer status, including 48.1% (13 of 27) in which switching was prestipulated.Conclusions and Relevance Physicians were evenly split on how to respond to knowledge of CYP2C19 metabolizer status in clopidogrel-treated patients. Mandatory provision of this information rarely prompted P2Y12 inhibitor switching overall, including a minority of patients with reduced metabolizer status. These findings highlight the clinical equipoise among physicians regarding use of this information and the reluctance to use information from routine genotyping in the absence of definitive clinical trial data demonstrating the efficacy of this approach.
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| 32. |
- Redfors, Björn, et al.
(författare)
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Ambient temperature and infarct size, microvascular obstruction, left ventricular function and clinical outcomes after ST-segment elevation myocardial infarction.
- 2022
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Ingår i: Coronary artery disease. - 1473-5830. ; 33:2, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- Incidence and prognosis of ST-segment elevation myocardial infarction (STEMI) vary according to ambient temperature and season. We sought to assess whether season and temperature on the day of STEMI are associated with infarct size, microvascular obstruction (MVO), left ventricular ejection fraction (LVEF) and clinical outcomes after primary percutaneous coronary intervention (PCI).Individual patient data from 1598 patients undergoing primary PCI in six randomized clinical trials were pooled. Infarct size was evaluated by cardiac magnetic resonance within 30 days in all trials. Patients were categorized either by whether they presented on a day of temperature extremes (minimum temperature <0 °C or maximum temperature >25 °C) or according to season.A total of 558/1598 (34.9%) patients presented with STEMI on a day of temperature extremes, and 395 (24.7%), 374 (23.4%), 481 (30.1%) and 348 (21.8%) presented in the spring, summer, fall and winter. After multivariable adjustment, temperature extremes were independently associated with larger infarct size (adjusted difference 2.8%; 95% CI, 1.3-4.3; P < 0.001) and smaller LVEF (adjusted difference -2.3%; 95% CI, -3.5 to -1.1; P = 0.0002) but not with MVO (adjusted P = 0.12). In contrast, infarct size, MVO and LVEF were unrelated to season (adjusted P = 0.67; P = 0.36 and P = 0.95, respectively). Neither temperature extremes nor season were independently associated with 1-year risk of death or heart failure hospitalization (adjusted P = 0.79 and P = 0.90, respectively).STEMI presentation during temperature extremes was independently associated with larger infarct size and lower LVEF but not with MVO after primary PCI, whereas season was unrelated to infarct severity.
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| 33. |
- Roe, Matthew T., et al.
(författare)
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Regional Patterns of Use of a Medical Management Strategy for Patients With Non-ST-Segment Elevation Acute Coronary Syndromes : Insights From the EARLY ACS Trial
- 2012
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Ingår i: Circulation. Cardiovascular Quality and Outcomes. - 1941-7713 .- 1941-7705. ; 5:2, s. 205-213
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Tidskriftsartikel (refereegranskat)abstract
- Background: Regional differences in the profile and prognosis of non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients treated with medical management after angiography remain uncertain.Methods and Results: Using data from the Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndromes (EARLY ACS) trial, we examined regional variations in the use of an in-hospital medical management strategy in NSTE ACS patients who had significant coronary artery disease (CAD) identified during angiography, factors associated with the use of a medical management strategy, and 1-year mortality rates. Of 9406 patients, 8387 (89%) underwent angiography and had significant CAD; thereafter, 1766 (21%) were treated solely with a medical management strategy (range: 18% to 23% across 4 major geographic regions). Factors most strongly associated with a medical management strategy were negative baseline troponin values, prior coronary artery bypass grafting, lower baseline hemoglobin values, and greater number of diseased vessels; region was not a significant factor. One-year mortality was higher among patients treated with a medical management strategy compared with those who underwent revascularization (7.8% versus 3.6%; adjusted hazard ratio, 1.46; 95% CI, 1.21-1.76), with no significant interaction by region (interaction probability value=0.42).Conclusions: Approximately 20% of NSTE ACS patients with significant CAD in an international trial were treated solely with an in-hospital medical management strategy after early angiography, with no regional differences in factors associated with medical management or the risk of 1-year mortality. These findings have important implications for the conduct of future clinical trials, and highlight global similarities in the profile and prognosis of medically managed NSTE ACS patients.
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| 34. |
- Sigmundsson, Thorir S., et al.
(författare)
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Comparison between capnodynamic and thermodilution method for cardiac output monitoring during major abdominal surgery An observational study
- 2021
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Ingår i: European Journal of Anaesthesiology. - : Wolters Kluwer. - 0265-0215 .- 1365-2346. ; 38:12, s. 1242-1252
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Cardiac output (CO) monitoring is the basis of goal-directed treatment for major abdominal surgery. A capnodynamic method estimating cardiac output (COEPBF) by continuously calculating nonshunted pulmonary blood flow has previously shown good agreement and trending ability when evaluated in mechanically ventilated pigs. OBJECTIVES To compare the performance of the capnodynamic method of CO monitoring with transpulmonary thermodilution (COTPTD) in patients undergoing major abdominal surgery. DESIGN Prospective, observational, method comparison study. Simultaneous measurements of COEPBF and COTPTD were performed before incision at baseline and before and after increased (+10 cmH(2)O) positive end-expiratory pressure (PEEP), activation of epidural anaesthesia and intra-operative events of hypovolemia and low CO. The first 25 patients were ventilated with PEEP5 cmH(2)O (PEEN, while in the last 10 patients, lung recruitment followed by individual PEEP adjustment (PEEPadi) was performed before protocol start. SETTING Karolinska University Hospital, Stockholm, Sweden. PATIENTS In total, 35 patients (>18 years) scheduled for major abdominal surgery with advanced hemodynamic monitoring were included in the study. MAIN OUTCOME MEASURES AND ANALYSIS Agreement and trending ability between COEPBF and COTPTD at different clinical moments were analysed with Bland-Altman and four quadrant plots. RESULTS In total, 322 paired values, 227 in PEEP5 and 95 in PEEPadj were analysed. Respectively, the mean COEPBF and COTPTD were 4.5 +/- 1.0 and 4.8 +/- 1.1 in the PEEP5 group and 4.9 +/- 1.2 and 5.0 +/- 1.0 l min(-1) in the PEEPadj group. Mean bias (levels of agreement) and percentage error (PE) were -0.2 (-2.2 to 1.7) l min(-1) and 41% for the PEEP5 group and -0.1 (-1.7 to 1.5) l min(-1) and 31% in the PEEP(adj )group. Concordance rates during changes in COEPBF and COTPTD were 92% in the PEEP5 group and 90% in the PEEPadj group. CONCLUSION COEPBF provides continuous noninvasive CO estimation with acceptable performance, which improved after lung recruitment and PEEP adjustment, although not interchangeable with COTPTD. This method may become a tool for continuous intra-operative CO monitoring during general anaesthesia in the future.
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| 35. |
- 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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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Wallentin, Lars, et al.
(författare)
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How can we optimize the processes of care for acute coronary syndromes to improve outcomes?
- 2014
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 168:5, s. 622-631
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Tidskriftsartikel (refereegranskat)abstract
- Acute coronary syndromes (ACS), either ST-elevation myocardial infarction or non ST-elevation ACS, are still one of the most common cardiac emergencies with substantial morbidity and mortality. The availability of evidence-based treatments, such as early and intense platelet inhibition and anticoagulation, and timely reperfusion and revascularization, has substantially improved outcomes in patients with ACS. The implementation of streamlined processes of care for patients with ST-elevation myocardial infarction and non ST-elevation ACS over the last decade including both appropriate tools, especially cardiac troponin, for rapid diagnosis and risk stratification and for decision support, and the widespread availability of modern antithrombotic and interventional treatments, have reduced morbidity and mortality to unprecedented low levels. These changes in the process of care require a synchronized approach, and research using a team-based strategy and effective regional networks has allowed healthcare systems to provide modern treatments for most patients with ACS. There are still areas needing improvement, such as the delivery of care to people in rural areas or with delayed time to treatment.
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| 40. |
- Weisz, Giora, et al.
(författare)
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Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI) : a multicentre, randomised, double-blind, placebo-controlled trial
- 2016
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 387:10014, s. 136-145
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Incomplete revascularisation is common after percutaneous coronary intervention and is associated with increased mortality and adverse cardiovascular events. We aimed to assess whether adjunctive anti-ischaemic pharmacotherapy with ranolazine would improve the prognosis of patients with incomplete revascularisation after percutaneous coronary intervention.METHODS: We performed this multicentre, randomised, parallel-group, double-blind, placebo-controlled, event-driven trial at 245 centres in 15 countries in Europe, Israel, Russia, and the USA. Patients (aged ≥18 years) with a history of chronic angina with incomplete revascularisation after percutaneous coronary intervention (defined as one or more lesions with ≥50% diameter stenosis in a coronary artery ≥2 mm diameter) were randomly assigned (1:1), via an interactive web-based block randomisation system (block sizes of ten), to receive either twice-daily oral ranolazine 1000 mg or matching placebo. Randomisation was stratified by diabetes history (presence vs absence) and acute coronary syndrome presentation (acute coronary syndrome vs non-acute coronary syndrome). Study investigators, including all research teams, and patients were masked to treatment allocation. The primary endpoint was time to first occurrence of ischaemia-driven revascularisation or ischaemia-driven hospitalisation without revascularisation. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT01442038.FINDINGS: Between Nov 3, 2011, and May 27, 2013, we randomly assigned 2651 patients to receive ranolazine (n=1332) or placebo (n=1319); 2604 (98%) patients comprised the full analysis set. After a median follow-up of 643 days (IQR 575-758), the composite primary endpoint occurred in 345 (26%) patients assigned to ranolazine and 364 (28%) patients assigned to placebo (hazard ratio 0·95, 95% CI 0·82-1·10; p=0·48). Incidence of ischaemia-driven revascularisation and ischaemia-driven hospitalisation did not differ significantly between groups. 189 (14%) patients in the ranolazine group and 137 (11%) patients in the placebo group discontinued study drug because of an adverse event (p=0·04).INTERPRETATION: Ranolazine did not reduce the composite rate of ischaemia-driven revascularisation or hospitalisation without revascularisation in patients with a history of chronic angina who had incomplete revascularisation after percutaneous coronary intervention. Further studies are warranted to establish whether other treatment could be effective in improving the prognosis of high-risk patients in this population.FUNDING: Gilead Sciences, Menarini.
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