| 1. |
- Lopes, Renato D., et al.
(författare)
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Highlights from the III International Symposium of Thrombosis and Anticoagulation (ISTA), October 14-16, 2010, Sao Paulo, Brazil
- 2011
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 32:2, s. 242-266
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Tidskriftsartikel (refereegranskat)abstract
- To discuss and share knowledge around advances in the care of patients with thrombotic disorders, the Third International Symposium of Thrombosis and Anticoagulation was held in So Paulo, Brazil, from October 14-16, 2010. This scientific program was developed by clinicians for clinicians, and was promoted by four major clinical research institutes: the Brazilian Clinical Research Institute, the Duke Clinical Research Institute of the Duke University School of Medicine, the Canadian VIGOUR Centre, and the Uppsala Clinical Research Center. Comprising 3 days of academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.
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| 2. |
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| 3. |
- Alexander, John H., et al.
(författare)
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Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome : results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial
- 2009
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 119:22, s. 2877-2885
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: After an acute coronary syndrome, patients remain at risk of recurrent events. Apixaban, an oral direct factor Xa inhibitor, is a novel anticoagulant that may reduce these events but also poses a risk of bleeding. METHODS AND RESULTS: Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) was a phase 2, double-blind, placebo-controlled, dose-ranging study. Patients (n=1715) with recent ST-elevation or non-ST-elevation acute coronary syndrome were randomized to 6 months of placebo (n=611) or 1 of 4 doses of apixaban: 2.5 mg twice daily (n=317), 10 mg once daily (n=318), 10 mg twice daily (n=248), or 20 mg once daily (n=221). Nearly all patients received aspirin; 76% received clopidogrel. The primary outcome was International Society of Thrombosis and Hemostasis major or clinically relevant nonmajor bleeding. A secondary outcome was cardiovascular death, myocardial infarction, severe recurrent ischemia, or ischemic stroke. At the recommendation of the Data Monitoring Committee, the 2 higher-dose apixaban arms were discontinued because of excess total bleeding. Compared with placebo, apixaban 2.5 mg twice daily (hazard ratio, 1.78; 95% confidence interval, 0.91 to 3.48; P=0.09) and 10 mg once daily (hazard ratio, 2.45; 95% confidence interval, 1.31 to 4.61; P=0.005) resulted in a dose-dependent increase in major or clinically relevant nonmajor bleeding. Apixaban 2.5 mg twice daily (hazard ratio, 0.73; 95% confidence interval, 0.44 to 1.19; P=0.21) and 10 mg once daily (hazard ratio, 0.61; 95% confidence interval, 0.35 to 1.04; P=0.07) resulted in lower rates of ischemic events compared with placebo. The increase in bleeding was more pronounced and the reduction in ischemic events was less evident in patients taking aspirin plus clopidogrel than in those taking aspirin alone. CONCLUSIONS: We observed a dose-related increase in bleeding and a trend toward a reduction in ischemic events with the addition of apixaban to antiplatelet therapy in patients with recent acute coronary syndrome. The safety and efficacy of apixaban may vary depending on background antiplatelet therapy. Further testing of apixaban in patients at risk of recurrent ischemic events is warranted.
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| 4. |
- Carnicelli, Anthony P, et al.
(författare)
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Individual Patient Data from the Pivotal Randomized Controlled Trials of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation (COMBINE AF) : Design and Rationale
- 2021
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; Mar:233, s. 48-58
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are the preferred class of medications for prevention of stroke and systemic embolism in patients with atrial fibrillation unless contraindications exist. Five large, international, randomized, controlled trials of NOACs versus either warfarin or aspirin have been completed to date.DESIGN: COMBINE AF incorporates de-identified individual patient data from 77,282 patients with atrial fibrillation at risk for stroke randomized to NOAC, warfarin, or aspirin from 5 pivotal randomized controlled trials. All patients randomized in the constituent trials are included. Variables common to ≥3 of the constituent trials are included in the master database. Individual trial data sets from the 4 coordinating centers were combined at the Duke Clinical Research Institute. The final database will be securely shared with the 4 academic coordinating centers. The combined master database will be used to perform statistical analyses aimed at better understanding underlying risk factors and outcomes in patients with atrial fibrillation treated with oral anticoagulants, with a special focus on patient subgroups and uncommon outcomes. The initial analysis from COMBINE AF will be a network meta-analysis investigating the relative efficacy and safety of pooled higher-dose NOACs versus pooled lower-dose NOACs versus warfarin with respect to multiple time-to-event efficacy and safety outcomes. COMBINE AF is registered with PROSPERO (CRD42020178771).CONCLUSIONS: In conclusion, COMBINE AF provides a rich and robust database consisting of individual patient data and will offer opportunities to investigate oral anticoagulants across many patient subgroups. Data sharing and collaboration across academic institutions and investigators will serve as overarching themes.
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| 5. |
- Fanaroff, Alexander C., et al.
(författare)
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Frequency, Regional Variation, and Predictors of Undetermined Cause of Death in Cardiometabolic Clinical Trials : A Pooled Analysis of 9259 Deaths in 9 Trials
- 2019
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 139:7, s. 863-873
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Modern cardiometabolic clinical trials often include cardiovascular death as a component of a composite primary outcome, requiring central adjudication by a clinical events committee to classify cause of death. However, sometimes the cause of death cannot be determined from available data. The US Food and Drug Administration has indicated that this circumstance should occur only rarely, but its prevalence has not been formally assessed. METHODS: Data from 9 global clinical trials (2009-2017) with long-term follow-up and blinded, centrally adjudicated cause of death were used to calculate the proportion of deaths attributed to cardiovascular, noncardiovascular, or undetermined causes by therapeutic area (diabetes mellitus/pre-diabetes mellitus, stable atherosclerosis, atrial fibrillation, and acute coronary syndrome), region of patient enrollment, and year of trial manuscript publication. Patient-and trial-level variables associated with undetermined cause of death were identified using a logistic model. RESULTS: Across 127 049 enrolled participants from 9 trials, there were 9259 centrally adjudicated deaths: 5012 (54.1%) attributable to cardiovascular causes, 2800 (30.2%) attributable to noncardiovascular causes, and 1447 (15.6%) attributable to undetermined causes. There was variability in the proportion of deaths ascribed to undetermined causes by trial therapeutic area, region of enrollment, and year of trial manuscript publication. On multivariable analysis, acute coronary syndrome or atrial fibrillation trial (versus atherosclerotic vascular disease or diabetes mellitus/pre-diabetes mellitus), longer time from enrollment to death, more recent trial manuscript publication year, enrollment in North America (versus Western Europe), female sex, and older age were associated with greater likelihood of death of undetermined cause. CONCLUSIONS: In 9 cardiometabolic clinical trials with long-term followup, approximately 16% of deaths had undetermined causes. This provides a baseline for quality assessment of clinical trials and informs operational efforts to potentially reduce the frequency of undetermined deaths in future clinical research.
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| 6. |
- Guimarães, Patrícia O, et al.
(författare)
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Effect of Apixaban on All-Cause Death in Patients with Atrial Fibrillation : a Meta-Analysis Based on Imputed Placebo Effect
- 2017
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Ingår i: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 31:3, s. 295-301
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Vitamin K antagonists (VKAs) are the standard of care for stroke prevention in patients with atrial fibrillation (AF); therefore, there is not equipoise when comparing newer oral anticoagulants with placebo in this setting.METHODS: To explore the effect of apixaban on mortality in patients with AF, we performed a meta-analysis of apixaban versus placebo using a putative placebo analysis based on randomized controlled clinical trials that compared warfarin, aspirin, and no antithrombotic control. We used data from two prospective randomized controlled trials for our comparison of apixaban versus warfarin (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) and apixaban versus aspirin (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment). Using meta-analysis approaches, we indirectly compared apixaban with an imputed placebo with respect to the risk of death in patients with AF. We used results from meta-analyses of randomized trials as our reference for the comparison between warfarin and placebo/no treatment, and aspirin and placebo/no treatment.RESULTS: In these meta-analyses, a lower rate of death was seen both with warfarin (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.57-0.97) and aspirin (OR 0.86, 95% CI 0.69-1.07) versus placebo/no treatment. Using data from ARISTOTLE and AVERROES, apixaban reduced the risk of death by 34% (95% CI 12-50%; p = 0.004) and 33% (95% CI 6-52%; p = 0.02), respectively, when compared with an imputed placebo. The pooled reduction in all-cause death with apixaban compared with an imputed placebo was 34% (95% CI 18-47%; p = 0.0002).CONCLUSIONS: In patients with AF, indirect comparisons suggest that apixaban reduces all-cause death by approximately one third compared with an imputed placebo.
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| 7. |
- Sherwood, Matthew W, et al.
(författare)
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Apixaban following acute coronary syndromes in patients with prior stroke : Insights from the APPRAISE-2 trial
- 2018
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 197, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Patients with prior stroke are at greater risk for recurrent cardiovascular events post-acute coronary syndromes (ACS) and may have a different risk/benefit profile with antithrombotic therapy than patients without prior stroke.METHODS: We studied 7391 patients with ACS from APPRAISE-2, stratified by the presence or absence of prior stroke. Baseline characteristics and outcomes of cardiovascular death, myocardial infarction (MI), or stroke were compared between groups. Interactions between prior stroke, treatment assignment (apixaban vs placebo), and outcomes were tested before and after multivariable adjustment with Cox proportional hazards models.RESULTS: A total of 902 patients (12%) had prior stroke. Those with prior stroke were older (69 vs 67 years), had more hypertension (91% vs 77%), peripheral vascular disease (22% vs18%), and impaired renal function (38% vs 30%) but less diabetes (44% vs 48%) than those without prior stroke. Patients with prior stroke vs no prior stroke had higher unadjusted rates of cardiovascular death (4.8% vs 4.0%), MI (11.2% vs 7.1%), and ischemic stroke (3.2% vs 0.9%). Patients with prior stroke assigned to apixaban had similar rates of the composite of cardiovascular death, MI, or stroke compared with those assigned to placebo (HR 1.39; 95% CI 0.92-2.08). Patients without prior stroke assigned to apixaban had similar rates of cardiovascular death, MI, or ischemic stroke compared with those assigned to placebo (HR 0.87; 95% CI 0.73-1.04; P-interaction=.041). Median follow-up was 240 days.CONCLUSIONS: Patients with prior stroke are at higher risk for recurrent cardiovascular events post-ACS and had a differential risk/benefit profile with oral anticoagulation.
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| 8. |
- Vinereanu, Dragos, et al.
(författare)
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Heart rate and death and hospitalization for heart failure in patients with persistent or permanent atrial fibrillation : Insights from the ARISTOTLE trial
- 2023
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 265, s. 132-136
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Tidskriftsartikel (refereegranskat)abstract
- Rate control is fundamental in the treatment of patients with atrial fibrillation (AF). The independent association of heart rate with outcomes and range of heart rate associated with best outcomes remains uncertain. We assessed the relationship between heart rate and clinical outcomes in patients with persistent or permanent AF enrolled in the randomized, double-blind ARISTOTLE trial. In patients with persistent or permanent AF, a faster heart rate is associated with a modest, but statistically significant increase in death and heart failure hospitalizations.
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