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  • Ovid Technologies (Wolters Kluwer Health)  (22)
  • Ruff, Christian T.  (22)
  • 1
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    Effect of the Novel Thienopyridine Prasugrel Compared With Clopidogrel on Spontaneous and Procedural Myocardial Infarction in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38 : An Application of the Classification System From the Universal Definition of Myocardial Infarction
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Circulation Vol. 119, No. 21 ( 2009-06-02), p. 2758-2764
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 119, No. 21 ( 2009-06-02), p. 2758-2764
    Abstract: Background— Prasugrel is a novel thienopyridine that reduces new or recurrent myocardial infarctions (MIs) compared with clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention. This effect must be balanced against an increased bleeding risk. We aimed to characterize the effect of prasugrel with respect to the type, size, and timing of MI using the universal classification of MI. Methods and Results— We studied 13 608 patients with acute coronary syndrome undergoing percutaneous coronary intervention randomized to prasugrel or clopidogrel and treated for 6 to 15 months in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction (TRITON-TIMI 38). Each MI underwent supplemental classification as spontaneous, secondary, or sudden cardiac death (types 1, 2, and 3) or procedure related (Types 4 and 5) and examined events occurring early and after 30 days. Prasugrel significantly reduced the overall risk of MI (7.4% versus 9.7%; hazard ratio [HR] , 0.76; 95% confidence interval [CI], 0.67 to 0.85; P 〈 0.0001). This benefit was present for procedure-related MIs (4.9% versus 6.4%; HR, 0.76; 95% CI, 0.66 to 0.88; P =0.0002) and nonprocedural (type 1, 2, or 3) MIs (2.8% versus 3.7%; HR, 0.72; 95% CI, 0.59 to 0.88; P =0.0013) and consistently across MI size, including MIs with a biomarker peak ≥5 times the reference limit (HR. 0.74; 95% CI, 0.64 to 0.86; P =0.0001). In landmark analyses starting at 30 days, patients treated with prasugrel had a lower risk of any MI (2.9% versus 3.7%; HR, 0.77; P =0.014), including nonprocedural MI (2.3% versus 3.1%; HR, 0.74; 95% CI, 0.60 to 0.92; P =0.0069). Conclusion— Treatment with prasugrel compared with clopidogrel for up to 15 months in patients with acute coronary syndrome undergoing percutaneous coronary intervention significantly reduces the risk of MIs that are procedure related and spontaneous and those that are small and large, including new MIs occurring during maintenance therapy.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.108.833665
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
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  • 2
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    Clinical Application of a Novel Genetic Risk Score for Ischemic Stroke in Patients With Cardiometabolic Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 143, No. 5 ( 2021-02-02), p. 470-478
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 143, No. 5 ( 2021-02-02), p. 470-478
    Abstract: Genome-wide association studies have identified single-nucleotide polymorphisms that are associated with an increased risk of stroke. We sought to determine whether a genetic risk score (GRS) could identify subjects at higher risk for ischemic stroke after accounting for traditional clinical risk factors in 5 trials across the spectrum of cardiometabolic disease. Methods: Subjects who had consented for genetic testing and who were of European ancestry from the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation), SOLID-TIMI 52 (Stabilization of Plaques Using Darapladib), SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus), PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin), and FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) trials were included in this analysis. A set of 32 single-nucleotide polymorphisms associated with ischemic stroke was used to calculate a GRS in each patient and identify tertiles of genetic risk. A Cox model was used to calculate hazard ratios for ischemic stroke across genetic risk groups, adjusted for clinical risk factors. Results: In 51 288 subjects across the 5 trials, a total of 960 subjects had an ischemic stroke over a median follow-up period of 2.5 years. After adjusting for clinical risk factors, a higher GRS was strongly and independently associated with increased risk for ischemic stroke ( P trend=0.009). In comparison with individuals in the lowest third of the GRS, individuals in the middle and top tertiles of the GRS had adjusted hazard ratios of 1.15 (95% CI, 0.98–1.36) and 1.24 (95% CI 1.05–1.45) for ischemic stroke, respectively. Stratification into subgroups revealed that the performance of the GRS appeared stronger in the primary prevention cohort with an adjusted hazard ratio for the top versus lowest tertile of 1.27 (95% CI, 1.04–1.53), in comparison with an adjusted hazard ratio of 1.06 (95% CI, 0.81–1.41) in subjects with previous stroke. In an exploratory analysis of patients with atrial fibrillation and CHA 2 DS 2 -VASc score of 2, high genetic risk conferred a 4-fold higher risk of stroke and an absolute risk equivalent to those with CHA 2 DS 2 -VASc score of 3. Conclusions: Across a broad spectrum of subjects with cardiometabolic disease, a 32–single-nucleotide polymorphism GRS was a strong, independent predictor of ischemic stroke. In patients with atrial fibrillation but lower CHA 2 DS 2 -VASc scores, the GRS identified patients with risk comparable to those with higher CHA 2 DS 2 -VASc scores.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.120.051927
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 3
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    Stroke and Mortality Risk in Patients With Various Patterns of Atrial Fibrillation : Results From the ENGAGE AF-TIMI 48 Trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48)
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Circulation: Arrhythmia and Electrophysiology Vol. 10, No. 1 ( 2017-01)
    Details
    In: Circulation: Arrhythmia and Electrophysiology, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 1 ( 2017-01)
    Abstract: Whether the pattern of atrial fibrillation (AF) modifies the risk/benefit of anticoagulation is controversial. In ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48), the factor Xa inhibitor edoxaban was noninferior to warfarin in preventing stroke or systemic embolic events and significantly reduced bleeding and cardiovascular mortality. However, detailed analyses by AF pattern have not been reported. Methods and Results— The 21 105 patients were categorized as having paroxysmal ( 〈 7 days duration), persistent (≥7 days but 〈 1 year), or permanent (≥1 year or failed cardioversion) AF patterns at randomization. Efficacy and safety outcomes were evaluated during the 2.8 years median follow-up and compared by AF pattern. The primary end point of stroke/systemic embolic event was lower in those patients with paroxysmal AF (1.49%/year), compared with persistent (1.83%/year; P -adj =0.015) and permanent AF (1.95%/year; P -adj =0.004). Overall, all-cause mortality also was lower with paroxysmal (3.0%/year) compared with persistent (4.4%/year; P -adj 〈 0.001) and permanent AF (4.4%/year; P -adj 〈 0.001). Annualized major bleeding rates were similar across AF patterns (2.86% versus 2.65% versus 2.73%). There was no effect modification by treatment assignment. Conclusions— In ENGAGE AF-TIMI 48 trial, patients with paroxysmal AF suffered fewer thromboembolic events and deaths compared with those with persistent and permanent AF. The efficacy and safety profile of edoxaban as compared with warfarin was consistent across the 3 patterns of AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00781391.
    Type of Medium: Online Resource
    ISSN: 1941-3149 , 1941-3084
    URL: Article
    DOI: 10.1161/CIRCEP.116.004267
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
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  • 4
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    Cerebrovascular Events in 21 105 Patients With Atrial Fibrillation Randomized to Edoxaban Versus Warfarin : Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Stroke Vol. 45, No. 8 ( 2014-08), p. 2372-2378
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 8 ( 2014-08), p. 2372-2378
    Abstract: The once-daily oral factor Xa inhibitor, edoxaban, is as effective as warfarin in preventing stroke and systemic embolism while decreasing bleeding in a phase III trial of patients with atrial fibrillation at moderate–high stroke risk. Limited data regarding cerebrovascular events with edoxaban were reported previously. Methods— We analyzed the subtypes of cerebrovascular events in 21 105 patients participating in Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) comparing outcomes among patients randomized to warfarin versus 2 edoxaban regimens (high dose, low dose). The primary end point for this prespecified analysis of cerebrovascular events was all stroke (ischemic plus hemorrhagic), defined as an abrupt onset of focal neurological deficit because of infarction or bleeding with symptoms lasting ≥24 hours or fatal in 〈 24 hours. Independent stroke neurologists unaware of treatment adjudicated all cerebrovascular events. Results— Patients randomized to high-dose edoxaban had fewer strokes on-treatment (hazard ratio, 0.80; 95% confidence interval, 0.65–0.98) than warfarin (median time-in-therapeutic range, 68.4%); patients in the low-dose edoxaban group had similar rates (hazard ratio, 1.10 versus warfarin; 95% confidence interval, 0.91–1.32). Rates of ischemic stroke or transient ischemic attack were similar with high-dose edoxaban (1.76% per year) and warfarin (1.73% per year; P =0.81), but more frequent with low-dose edoxaban (2.48% per year; P 〈 0.001). Both edoxaban regimens significantly reduced hemorrhagic stroke and other subtypes of intracranial bleeds. Conclusions— In patients with atrial fibrillation, once-daily edoxaban was as effective as warfarin in preventing all strokes, with significant reductions in various subtypes of intracranial bleeding. Ischemic cerebrovascular event rates were similar with high-dose edoxaban and warfarin, whereas low-dose edoxaban was less effective than warfarin. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00781391.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.114.006025
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
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  • 5
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    Impact of Renal Function on Outcomes With Edoxaban in the ENGAGE AF-TIMI 48 Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Circulation Vol. 134, No. 1 ( 2016-07-05), p. 24-36
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 134, No. 1 ( 2016-07-05), p. 24-36
    Abstract: Edoxaban, an oral factor Xa inhibitor with 50% renal clearance, was noninferior to well-managed warfarin for stroke or systemic embolism (S/SE) prevention and reduced bleeding in patients with atrial fibrillation. We evaluated the efficacy and safety of edoxaban versus warfarin across the range of baseline creatinine clearance (CrCl) in the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction Study 48) with a focus on the higher-dose edoxaban regimen (HDER) and the upper range of CrCl. Methods: A total of 14 071 patients with atrial fibrillation at moderate to high risk for stroke were randomized to warfarin or HDER (60 mg daily or a 50% dose reduction to 30 mg daily for CrCl 30–50 mL/min, body weight of ≤60 kg, or use of a potent phosphorylated glycoprotein inhibitor). CrCl 〈 30 mL/min was exclusionary. End points of S/SE, International Society on Thrombosis and Haemostasis major bleeding, and the net clinical outcome of S/SE/major bleeding or death were evaluated by intention-to-treat analysis using the prespecified CrCl cut point of 50 mL/min and additional exploratory cut points with the Cockcroft-Gault formula. A sensitivity analysis was performed with the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula for estimating renal function. Results: The relative risk of S/SE with HDER versus warfarin in patients with CrCl 〉 50 mL/min (hazard ratio [HR], 0.87; 95% confidence interval [CI] , 0.72–1.04) was similar to that in patients with CrCl ≤50 mL/min (HR, 0.87; 95% CI, 0.65–1.18; P for interaction=0.94). Several exploratory analyses suggested lower relative efficacy for the prevention of S/SE with HDER compared with warfarin at higher levels of CrCl (CrCl ≤50 mL/min: HR, 0.87; 95% CI, 0.65–1.18; CrCl 〉 50–95 mL/min: HR, 0.78; 95% CI, 0.64–0.96; CrCl 〉 95 mL/min: HR, 1.36; 95% CI, 0.88–2.10; P for interaction=0.08). Bleeding rates were lower at all levels of CrCl with HDER ( P for interaction=0.11). Because of the preserved effect on bleeding, the net clinical outcome was more favorable with HDER across the range of CrCl ( P for interaction=0.73). Similar findings were observed in the sensitivity analysis using the CKD-EPI formula. Conclusions: Although there was an apparent decrease in relative efficacy to prevent arterial thromboembolism in the upper range of CrCl, the safety and net clinical benefit of HDER compared with warfarin are consistent across the range of renal function. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00781391.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.116.022361
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
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  • 6
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    Comparison of Events Across Bleeding Scales in the ENGAGE AF-TIMI 48 Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Circulation Vol. 140, No. 22 ( 2019-11-26), p. 1792-1801
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 140, No. 22 ( 2019-11-26), p. 1792-1801
    Abstract: Numerous scales exist for the classification of major bleeding events. Limited data compare the most commonly used bleeding scales within a single at-risk cohort of patients with atrial fibrillation. Here, we analyze bleeding outcomes according to the ISTH (International Society on Thrombosis and Hemostasis), TIMI (Thrombolysis in Myocardial Infarction), GUSTO (Global Usage of Strategies to Open Occluded Arteries), and BARC (Bleeding Academic Research Consortium) bleeding scales in the ENGAGE AF (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation)–TIMI 48 trial (NCT00781391) of edoxaban versus warfarin. Methods: A total of 21 105 patients with atrial fibrillation at risk for stroke (CHADS 2 score ≥2) were enrolled in the ENGAGE AF-TIMI 48 trial comparing warfarin with a higher- (60/30 mg daily) or lower- (30/15 mg daily) dose edoxaban regimen. Median follow-up was 2.8 years. Bleeding events occurring among on-treatment patients were examined. Annualized event rates were calculated by the ISTH, TIMI, GUSTO, and BARC scales and compared across treatment arms. Cox proportional hazards for a first bleeding event of each type were calculated for higher-dose edoxaban regimen vs warfarin and lower-dose edoxaban regimen versus warfarin. Results: A total of 10 311 bleeding events were reported. In a comparison of the most severe events in each scale, ISTH major bleeding was the most common (n=1289), followed by TIMI major (n=548), GUSTO severe/life-threatening (n=347), and BARC 3c+5 (n=276) bleeding. Lower bleeding risk with edoxaban compared with warfarin was seen regardless of bleeding scale (higher-dose edoxaban regimen range: hazard ratio [HR], 0.47 [95% CI, 0.35–0.62] for BARC 3c+5 versus HR, 0.80 [95% CI, 0.71–0.91] for ISTH major; lower-dose edoxaban regimen range: HR, 0.32 [95% CI, 0.23–0.45] for BARC 3c+5 versus HR, 0.47 [95% CI, 0.41–0.55] for ISTH major). Furthermore, a gradient of more pronounced risk reduction with edoxaban was observed with greater severity of first bleeding event (higher-dose edoxaban regimen: HR, 0.47 [95% CI, 0.35–0.62] for BARC 3c+5 bleeds versus HR, 0.86 [95% CI, 0.81–0.91] for any BARC bleed; lower-dose edoxaban regimen: HR, 0.32 [95% CI, 0.23–0.45] for BARC 3c+5 bleeds versus HR, 0.68 [95% CI, 0.63–0.72] for any BARC bleed). The direction of this trend was consistent for both gastrointestinal bleeding and nongastrointestinal bleeding. Conclusions: Among patients with atrial fibrillation at risk for stroke, there was a 〉 4-fold difference in the frequency of the most severe bleeding events across commonly used bleeding scales. Furthermore, the relative safety of edoxaban compared with warfarin tended to increase with greater severity of bleeding. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00781391.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.119.041346
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
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  • 7
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    Efficacy and Safety of Edoxaban in Patients With Active Malignancy and Atrial Fibrillation: Analysis of the ENGAGE AF‐TIMI 48 Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Journal of the American Heart Association Vol. 7, No. 16 ( 2018-08-21)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. 16 ( 2018-08-21)
    Abstract: Anticoagulation in patients with malignancy and atrial fibrillation is challenging because of enhanced risks for thrombosis and bleeding and the frequent need for invasive procedures. Data on direct oral antagonists in such patients are sparse. Methods and Results The ENGAGE AF ‐ TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction Study 48) trial randomized 21 105 patients with atrial fibrillation to edoxaban or warfarin. Patients with malignancy, defined as a postrandomization new diagnosis or recurrence of remote cancer, were followed up over a median of 2.8 years. Adjusted Cox proportional hazard models were used to evaluate the safety and efficacy of edoxaban versus warfarin. Over a median of 495 days (interquartile range, 230–771 days), 1153 patients (5.5%) were diagnosed with new or recurrent malignancy, most commonly involving the gastrointestinal tract (20.6%), prostate (13.6%), and lung (11.1%). Malignancy was associated with increased risk of death (adjusted hazard ratio [HR], 3.12; 95% confidence interval [CI] , 2.78–3.50) and major bleeding (adjusted HR, 2.45; 95% CI, 2.07–2.89), but not stroke/systemic embolism (adjusted HR, 1.08; 95% CI, 0.83–1.42). Relative outcomes with higher‐dose edoxaban versus warfarin were consistent regardless of malignancy status for stroke/systemic embolism ( HR , 0.60 [95% CI, 0.31–1.15] for malignancy versus HR , 0.89 [95% CI, 0.76–1.05] for no malignancy; interaction P =0.25) and major bleeding ( HR , 0.98 [95% CI, 0.69–1.40] for malignancy versus HR , 0.79 [95% CI, 0.69–1.05] for no malignancy; interaction P =0.31). There was, however, a significant treatment interaction for the composite ischemic end point (ischemic stroke/systemic embolism/myocardial infarction), with greater efficacy of higher‐dose edoxaban versus warfarin in patients with malignancy ( HR , 0.54; 95% CI, 0.31–0.93) compared with no malignancy ( HR , 1.02; 95% CI, 0.88–1.18; interaction P =0.026). Conclusions In patients with atrial fibrillation who develop malignancy, the efficacy and safety profile of edoxaban relative to warfarin is preserved, and it may represent a more practical alternative.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.118.008987
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
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  • 8
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    Gastrointestinal Bleeding With Edoxaban Versus Warfarin : Results From the ENGAGE AF-TIMI 48 Trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis In Myocardial Infarction)
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Circulation: Cardiovascular Quality and Outcomes Vol. 11, No. 5 ( 2018-05)
    Details
    In: Circulation: Cardiovascular Quality and Outcomes, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 5 ( 2018-05)
    Abstract: The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis In Myocardial Infarction) compared higher-dose edoxaban regimen (HD-ER) and lower-dose edoxaban regimen with well-managed warfarin in 21 105 patients with atrial fibrillation. The risk factors and clinical impact of gastrointestinal bleeding (GIB) in this trial have not been described in detail. Methods and Results: This analysis was undertaken to identify risk factors for major GIB (MGIB) and compare the severity and outcomes of GIB with edoxaban and warfarin. During 2.8 years mean follow-up, there were 579 MGIB (1.22% per year), of which 63 were life-threatening or fatal (0.13% per year). Male sex, increased age, prior GIB, concomitant aspirin, lower baseline hemoglobin, renal dysfunction, and higher HAS-BLED and CHADS 2 scores were independently associated with the risk of MGIB. Whereas the annual rate of MGIB was higher with HD-ER than with warfarin (1.53% and 1.25%, respectively; hazard ratio, 1.23; 95% confidence interval, 1.02–1.48; P =0.033), the annual rates of life-threatening or fatal GIB were similar (0.15% and 0.18%, respectively). Several indicators of more severe GIB, including hemodynamic instability, hospitalization, ≥ 4 U transfusion, and hemoglobin loss ≥5 g/dL, were similar with HD-ER and warfarin, whereas surgery required to manage bleeding was less frequent with HD-ER. Lower-dose edoxaban regimen, which achieved 50% lower trough edoxaban levels, was associated with significantly less MGIB than warfarin. Conclusions: MGIB occurred more frequently with HD-ER than warfarin. The rates of life-threatening or fatal GIB were low and similar with both HD-ER and warfarin. Clinical outcomes were generally favorable. The correlation between dose, trough edoxaban level, and the risk of GIB risk suggests GIB is exposure-related. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00781391.
    Type of Medium: Online Resource
    ISSN: 1941-7713 , 1941-7705
    URL: Article
    DOI: 10.1161/CIRCOUTCOMES.117.003998
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
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    American College of Cardiology/American Heart Association/European Society of Cardiology/World Heart Federation Universal Definition of Myocardial Infarction Classification System and the Risk of Cardiovascular Death : Observations From the TRITON-TIMI 38 Trial (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38)
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Circulation Vol. 125, No. 4 ( 2012-01-31), p. 577-583
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 125, No. 4 ( 2012-01-31), p. 577-583
    Abstract: The availability of more sensitive biomarkers of myonecrosis and a new classification system from the universal definition of myocardial infarction (MI) have led to evolution of the classification of MI. The prognostic implications of MI defined in the current era have not been well described. Methods and Results— We investigated the association between new or recurrent MI by subtype according to the European Society of Cardiology/American College of Cardiology/American Heart Association/World Health Federation Task Force for the Redefinition of MI Classification System and the risk of cardiovascular death among 13 608 patients with acute coronary syndrome in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38). The adjusted risk of cardiovascular death was evaluated by landmark analysis starting at the time of the MI through 180 days after the event. Patients who experienced an MI during follow-up had a higher risk of cardiovascular death at 6 months than patients without an MI (6.5% versus 1.3%, P 〈 0.001). This higher risk was present across all subtypes of MI, including type 4a (peri–percutaneous coronary intervention, 3.2%; P 〈 0.001) and type 4b (stent thrombosis, 15.4%; P 〈 0.001). After adjustment for important clinical covariates, the occurrence of any MI was associated with a 5-fold higher risk of death at 6 months (95% confidence interval 3.8–7.1), with similarly increased risk across subtypes. Conclusions— MI is associated with a significantly increased risk of cardiovascular death, with a consistent relationship across all types as defined by the universal classification system. These findings underscore the clinical relevance of these events and the importance of therapies aimed at preventing MI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00097591.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.111.041160
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
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    Comparison of the Efficacy and Safety Outcomes of Edoxaban in 8040 Women Versus 13 065 Men With Atrial Fibrillation in the ENGAGE AF-TIMI 48 Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 143, No. 7 ( 2021-02-16), p. 673-684
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 143, No. 7 ( 2021-02-16), p. 673-684
    Abstract: Female sex is an independent risk factor for stroke and systemic embolic events in patients with atrial fibrillation. This study aimed to examine the efficacy and safety profile of edoxaban in women versus men. Methods: The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) randomly assigned 21 105 patients (8040 women) with atrial fibrillation and CHADS 2 score ≥2 either to a higher-dose edoxaban regimen, a lower-dose edoxaban regimen, or warfarin. The primary end points of the trial were the composite of stroke or systemic embolic events (efficacy), and International Society on Thrombosis and Haemostasis–defined major bleeding (safety). Results: In comparison with men, women were older, had lower body weight, were more likely to have hypertension and renal dysfunction, but less likely to smoke, drink alcohol, or have diabetes or coronary artery disease. Pretreatment endogenous factor Xa activity was significantly higher in women than in men (92.5% versus 86.1%, P 〈 0.001). Treatment with edoxaban in women resulted in greater peak edoxaban concentration and inhibition of endogenous factor Xa in comparison with men, resulting in similar endogenous factor Xa activity between the sexes 2 to 4 hours after dose. Treatment with higher-dose edoxaban regimen (versus warfarin) resulted in similar reduction in the risk of stroke/systemic embolic events (women: hazard ratio [HR], 0.87 [0.69–1.11] , men: HR, 0.87 [0.71–1.06]; P -interaction=0.97) and major bleeding (women: HR, 0.74 [0.59–0.92], men: HR, 0.84 [0.72–0.99] ; P -interaction=0.34) in women and men. However, women assigned to higher-dose edoxaban regimen experienced greater reductions in hemorrhagic stroke (HR, 0.30 [95% CI, 0.15–0.59] versus HR, 0.70 [95% CI, 0.46–1.06] ), intracranial bleeding (HR, 0.20 [95% CI, 0.10–0.39] versus HR, 0.63 [95% CI, 0.44–0.89] ), and life-threatening or fatal bleeding (HR, 0.25 [95% CI, 0.15–0.42] versus HR, 0.72 [95% CI, 0.54–0.96] ) than men (each P -interaction 〈 0.05). Conclusions: Despite many differences in baseline characteristics between women and men and higher baseline endogenous factor Xa levels in women, the intensity of anticoagulation achieved with edoxaban between the sexes was similar. Treatment with higher-dose edoxaban regimen resulted in an even greater reduction in hemorrhagic stroke and several serious bleeding outcomes in women than in men, whereas the efficacy profile was similar between sexes.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.120.052216
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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