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1.
Artigo em Inglês | MEDLINE | ID: mdl-31713326

RESUMO

BACKGROUND: Prior randomized controlled trials (RCT) evaluating the optimal antithrombotic therapies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not been powered to evaluate ischemic outcomes. We compared double therapy with oral anticoagulation (OAC) and a P2Y12 inhibitor to triple therapy with an OAC + dual antiplatelet therapy in patients with AF requiring PCI. METHODS: Using PRISMA guidelines, we searched for RCTs including patients with AF as an indication for OAC and undergoing PCI or medical management of acute coronary syndrome. The results were pooled using fixed-effects and random-effects models to estimate the overall effect of double therapy versus triple therapy on ischemic and bleeding outcomes. RESULTS: We identified four RCTs, comprising 10,238 patients (5,498 double therapy, 4,740 triple therapy). Trial-reported major adverse cardiovascular events were similar between double therapy and triple therapy (fixed effect model OR 1.09, 95% CI 0.94-1.26). However, stent thrombosis (61/5,496 double therapy vs. 33/4738 triple therapy; fixed effect model OR 1.57, 95% CI 1.02-2.40; number needed to treat with triple therapy = 242) favored triple therapy. Bleeding outcomes were less frequent with double therapy (746/5470 vs. 950/4710; fixed effect model OR 0.59, 95% CI 0.53-0.65; number needed to harm with triple therapy = 16), but with significant heterogeneity (Q = 8.33, p = .04; I2 = 64%), as were intracranial hemorrhages (19/5470 vs. 30/4710; fixed effect model OR 0.54, 95% CI 0.31-0.96). CONCLUSIONS: Double therapy in patients with AF requiring OAC following PCI or Acute coronary syndrome has a significantly better safety profile than triple therapy but may be associated with a modest increased risk of stent thrombosis.

2.
Circ Cardiovasc Interv ; 12(11): e008160, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31707805

RESUMO

BACKGROUND: Among stented patients with atrial fibrillation, double therapy with a novel oral anticoagulant plus single antiplatelet therapy (SAPT) reduces bleeding or cardiovascular rehospitalizations compared with a vitamin K antagonist (VKA) based triple therapy regimen. A recent study demonstrated that apixaban based double therapy reduced bleeding compared with VKA based double therapy. However, it remains unknown whether rivaroxaban based double therapy is superior to a VKA based double therapy. METHODS: Patient with stented atrial fibrillation (n=2124) were randomized to 3 groups: rivaroxaban 15 mg od plus a P2Y12 inhibitor (Group 1, n=709); rivaroxaban 2.5 mg bid plus dual antiplatelet therapy (DAPT; Group 2, n=709); and warfarin plus DAPT (Group 3, n=706). Before randomization, subjects were stratified according to a prespecified duration of DAPT (1, 6, or 12 months). After the prespecified DAPT duration, subjects in Group 2 were switched to rivaroxaban 15 mg plus low dose aspirin, and those in Group 3 were switched to VKA plus low dose aspirin. The Wei, Lin, and Weissfeld time to multiple events method was used to compare the occurrence of all bleeding and cardiovascular rehospitalizations among subjects on a novel oral anticoagulant versus VKA based double therapy. RESULTS: A total of 906 subjects were prespecified to a 1 or 6 months DAPT duration and received at least one dose of study drug. Twenty subjects (3.3%) assigned to novel oral anticoagulant+SAPT, and 15 (5.1%) subjects assigned to VKA+SAPT experienced multiple rehospitalizations. In total, 124 (20.3%) events occurred among subjects on novel oral anticoagulant+SAPT compared with 87 (29.6%) among subjects on VKA+SAPT (hazard ratio=0.65 [95% CI, 0.45-0.93], P=0.008). CONCLUSIONS: Among stented patients with atrial fibrillation, rivaroxaban plus SAPT was superior to warfarin plus SAPT in lowering total bleeding and cardiovascular rehospitalization. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01830543.

3.
Thromb Haemost ; 19(10): 1553, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31564056
4.
Thromb Haemost ; 19(10): 1573-1582, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31430800

RESUMO

Primary prevention of cardiovascular events with aspirin in patients with elevated cardiovascular risk, including diabetics, is currently under intense discussion. Data from meta-analyses suggests that the efficacy of aspirin in these patients is low, whereas there is a significantly increased bleeding tendency. However, meta-analyses are based on trials that differ in many important aspects, including study selection. Fresh insights were expected from the ASCEND trial, by far the largest primary, randomized, placebo-controlled prevention trial in diabetics without known cardiovascular disease. There was a small but significant reduction in serious cardiovascular events by aspirin (8.6% vs. 9.6%) but also a significant increase in major bleeding: 4.1% versus 3.2%. Unfortunately, this trial did not meet the desired annual rate of elevated vascular risk of ≥ 2%. It was only 1.2 to 1.3%, and thus in the range of other primary prevention trials in low-risk patients. Apart from potential compliance problems, possible explanations for the small cardioprotective effect of antiplatelet treatment include a healthy lifestyle as well as improved vascular protection by comedication with vasoactive and anti-inflammatory drugs, such as statins or antihypertensive agents, as well as proton-pump inhibitors that might modify bleeding, specifically in the upper gastrointestinal tract-the most frequently affected site. Also, the introduction of new antidiabetic drugs with more favorable cardiovascular effects may in part explain the low event rate. ASCEND, similar to ARRIVE, did not study patients at elevated (as planned) but only at low vascular risk and, therefore, was largely confirmatory of earlier primary prevention trials.

5.
Eur Heart J ; 40(36): 3033-3034, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31390017
6.
Am J Med ; 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31306621

RESUMO

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes. METHODS: Adults with newly diagnosed atrial fibrillation and ≥1 investigator-defined stroke risk factor were enrolled in GARFIELD-AF between March 2010 and September 2015. The association between prior acute coronary syndromes and long-term outcomes was determined using a Cox proportional hazards model, adjusting for baseline risk factors, oral anticoagulation (OAC) ± antiplatelet (AP) therapy, and usual care. RESULTS: Of 39,679 patients, 10.5% had a history of acute coronary syndromes. At 2-year follow-up, patients with prior acute coronary syndromes had higher adjusted risks of stroke/systemic embolism (hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.08-1.78), major bleeding (HR 1.30; 95% CI, 0.95 -1.79), all-cause mortality (HR 1.34; 95% CI, 1.21 -1.49), cardiovascular mortality (HR 1.85; 95% CI, 1.51-2.26), and new acute coronary syndromes (HR 3.42; 95% CI, 2.62-4.45). Comparing antithrombotic therapy in the acute coronary syndromes vs no acute coronary syndromes groups, most patients received OAC ± AP: 60.8% vs 66.1%, but AP therapy was more likely in the acute coronary syndromes group (68.1% vs 32.9%), either alone (34.9% vs 20.8%) or with OAC (33.2% vs 12.1%). Overall, 17.8% in the acute coronary syndromes group received dual AP therapy with (5.3%) or without OAC (12.5%). Among patients with moderate/high risk for stroke/systemic embolism, fewer in the acute coronary syndromes group received OAC with or without AP therapy (Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, prior Stroke, TIA, or thromboembolism, Vascular disease, Age 65-74 years, Sex category [CHA2DS2-VASc] 2: 52.1% vs 64.6%; CHA2DS2-VASc ≥3: 62.0% vs 70.7%), and the majority with a Hypertension (uncontrolled systolic blood pressure >160 mm Hg), Abnormal renal or liver function, previous Stroke, Bleeding history or predisposition, Labile international normalized ratios, Elderly, and concomitant Drugs or alcohol excess (HAS-BLED) score ≥3 were on AP therapy (83.8% vs 65.5%). CONCLUSIONS: In GARFIELD-AF, previous acute coronary syndromes are associated with worse 2-year outcomes and a greater likelihood of under-treatment with OAC, while two-thirds of patients receive AP therapy. Major bleeding was more common with previous acute coronary syndromes, even after adjusting for all risk factors.

7.
J Am Coll Cardiol ; 74(5): 699-711, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31277840

RESUMO

For secondary prevention of coronary artery disease (CAD), oral antiplatelet therapy is essential. In case of coronary intervention, temporary dual antiplatelet therapy is mandatory as well. Recently, low-dose oral anticoagulation has entered the CAD arena. Atrial fibrillation (AF) is often seen in CAD and vice versa. In most patients stroke prevention in AF consists of oral anticoagulation. In many cases of CAD in patients with AF, anticoagulation has to be combined with antiplatelet agents (so called, dual pathway antithrombotic therapy). Excess bleeding in these conditions is a rapidly rising problem. This review addresses the antithrombotic options in CAD alone, in AF alone, and in their combination, when either an invasive or a noninvasive approach has been chosen.

8.
J Am Heart Assoc ; 8(14): e012602, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31269858

RESUMO

Background Cardiac troponin T ( cTnT ) is seen in many other conditions besides myocardial infarction, and recent studies demonstrated distinct forms of cTnT . At present, the in vivo formation of these different cTnT forms is incompletely understood. We therefore performed a study on the composition of cTnT during the course of myocardial infarction, including coronary venous system sampling, close to its site of release. Methods and Results Baseline samples were obtained from multiple coronary venous system locations, and a peripheral artery and vein in 71 non- ST -segment-elevation myocardial infarction patients. Additionally, peripheral blood was drawn at 6- and 12-hours postcatheterization. cTnT concentrations were measured using the high-sensitivity- cTnT immunoassay. The cTnT composition was determined via gel filtration chromatography and Western blotting in an early and late presenting patient. High-sensitivity - cTnT concentrations were 28% higher in the coronary venous system than peripherally (n=71, P<0.001). Coronary venous system samples demonstrated cT n T-I-C complex, free intact cTnT , and 29 kD a and 15 to 18 kD a cTnT fragments, all in higher concentrations than in simultaneously obtained peripheral samples. While cT n T-I-C complex proportionally decreased, and disappeared over time, 15 to 18 kD a cTnT fragments increased. Moreover, cT n T-I-C complex was more prominent in the early than in the late presenting patient. Conclusions This explorative study in non- ST -segment-elevation myocardial infarction shows that cTnT is released from cardiomyocytes as a combination of cT n T-I-C complex, free intact cTnT , and multiple cTnT fragments indicating intracellular cTnT degradation. Over time, the cT n T-I-C complex disappeared because of in vivo degradation. These insights might serve as a stepping stone toward a high-sensitivity- cTnT immunoassay more specific for myocardial infarction.

9.
JAMA Cardiol ; 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31215979

RESUMO

Importance: The antithrombotic treatment of patients with atrial fibrillation (AF) and coronary artery disease, in particular with acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), poses a significant treatment dilemma in clinical practice. Objective: To study the safety and efficacy of different antithrombotic regimens using a network meta-analysis of randomized controlled trials in this population. Data Sources: PubMed, EMBASE, EBSCO, and Cochrane databases were searched to identify randomized controlled trials comparing antithrombotic regimens. Study Selection: Four randomized studies were included (n = 10 026; WOEST, PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS). Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and network meta-analysis between 4 regimens using a Bayesian random-effects model. A pre hoc statistical analysis plan was written, and the review protocol was registered at PROSPERO. Data were analyzed between November 2018 and February 2019. Main Outcomes and Measures: The primary safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding; secondary safety outcomes were combined TIMI major and minor bleeding, trial-defined primary bleeding events, intracranial hemorrhage, and hospitalization. The primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE); secondary efficacy outcomes were individual components of MACE. Results: The overall prevalence of ACS varied from 28% to 61%. The mean age ranged from 70 to 72 years; 20% to 29% of the trial population were women; and most patients were at high risk for thromboembolic and bleeding events. Compared with a regimen of vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT; P2Y12 inhibitor plus aspirin), the odds ratios (ORs) for TIMI major bleeding were 0.58 (95% CI, 0.31-1.08) for VKA plus P2Y12 inhibitor, 0.49 (95% CI, 0.30-0.82) for non-VKA oral anticoagulant (NOAC) plus P2Y12 inhibitor, and 0.70 (95% CI, 0.38-1.23) for NOAC plus DAPT. Compared with VKA plus DAPT, the ORs for MACE were 0.96 (95% CI, 0.60-1.46) for VKA plus P2Y12 inhibitor, 1.02 (95% CI, 0.71-1.47) for NOAC plus P2Y12 inhibitor, and 0.94 (95% CI, 0.60-1.45) for NOAC plus DAPT. Conclusions and Relevance: A regimen of NOACs plus P2Y12 inhibitor was associated with less bleeding compared with VKAs plus DAPT. Strategies omitting aspirin caused less bleeding, including intracranial bleeding, without significant difference in MACE, compared with strategies including aspirin. Our results support the use of NOAC plus P2Y12 inhibitor as the preferred regimen post-percutaneous coronary intervention for these high-risk patients with AF. A regimen of VKA plus DAPT should generally be avoided.

11.
JAMA Cardiol ; 4(6): 526-548, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31066873

RESUMO

Importance: Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes. Objective: To assess the treatment strategies and 1-year clinical outcomes of antithrombotic and CHF therapies for patients with newly diagnosed AF with concomitant CHF stratified by etiology (ischemic cardiomyopathy [ICM] vs nonischemic cardiomyopathy [NICM]). Design, Setting, and Participants: The GARFIELD-AF registry is a prospective, noninterventional registry. A total of 52 014 patients with AF were enrolled between March 2010 and August 2016. A total of 11 738 patients 18 years and older with newly diagnosed AF (≤6 weeks' duration) and at least 1 investigator-determined stroke risk factor were included. Data were analyzed from December 2017 to September 2018. Exposures: One-year follow-up rates of death, stroke/systemic embolism, and major bleeding were assessed. Main Outcomes and Measures: Event rates per 100 person-years were estimated from the Poisson model and Cox hazard ratios (HRs) and 95% confidence intervals. Results: The median age of the population was 71.0 years, 22 987 of 52 013 were women (44.2%) and 31 958 of 52 014 were white (61.4%). Of 11 738 patients with CHF, 4717 (40.2%) had ICM and 7021 (59.8%) had NICM. Prescription of oral anticoagulant and antiplatelet drugs was not balanced between groups. Oral anticoagulants with or without antiplatelet drugs were used in 2753 patients with ICM (60.1%) and 5082 patients with NICM (73.7%). Antiplatelets were prescribed alone in 1576 patients with ICM (34.4%) and 1071 patients with NICM (15.5%). Compared with patients with NICM, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (72.6% [3439] vs 60.3% [4236]) and of ß blockers (63.3% [2988] vs 53.2% [3737]) was higher in patients with ICM. Rates of all-cause and cardiovascular death per 100 patient-years were significantly higher in the ICM group (all-cause death: ICM, 10.2; 95% CI, 9.2-11.1; NICM, 7.0; 95% CI, 6.4-7.6; cardiovascular death: ICM, 5.1; 95% CI, 4.5-5.9; NICM, 2.9; 95% CI, 2.5-3.4). Stroke/systemic embolism rates tended to be higher in ICM groups compared with NICM groups (ICM, 2.0; 95% CI, 1.6-2.5; NICM, 1.5; 95% CI, 1.3-1.9). Major bleeding rates were significantly higher in the ICM group (1.1; 95% CI, 0.8-1.4) compared with the NICM group (0.7; 95% CI, 0.5-0.9). Conclusions and Relevance: Patients with ICM received oral anticoagulants with or without antiplatelet drugs less frequently and antiplatelets alone more frequently than patients with NICM, but they received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers more often than patients with NICM. All-cause and cardiovascular death rates were higher in patients with ICM than patients with NICM. Trial Registration: ClinicalTrials.gov Identifier: NCT01090362.

12.
J Thromb Thrombolysis ; 48(1): 27-34, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30972712

RESUMO

We explored associations between INR measures and clinical outcomes in patients with AF using warfarin, and whether INR history predicted future INR measurements. We included patients in ARISTOTLE who were randomized to and received warfarin. Among patients who had events, we included those with ≥ 3 INR values in the 180 days prior to the event, with the most recent ≤ 60 days prior to the event, who were on warfarin at the time of event (n = 545). Non-event patients were included in the control group if they had ≥ 180 days of warfarin exposure with ≥ 3 INR measurements (n = 7259). The median (25th, 75th) number of INR values per patient was 29 (21, 38) over a median follow-up of 1.8 years. A total of 87% had at least one INR value < 1.5; 49% had at least one value > 4.0. The last INRs before events (median 14 [24, 7] days) were < 3.0 for at least 75% of patients with major bleeding and > 2.0 for half of patients with ischemic stroke. Historic time in therapeutic range (TTR) was weakly associated with future TTR (R2 = 0.212). Historic TTR ≥ 80% had limited predictive ability to discriminate future TTR ≥ 80% (C index 0.61). In patients with AF receiving warfarin, most bleeding events may not have been preventable despite careful INR control. Our findings suggest that INRs collected through routine management are not sufficiently predictive to provide reassurance about future time in therapeutic range or to prevent subsequent outcomes, and might be over-interpreted in clinical practice.

13.
Med Sci Sports Exerc ; 51(10): 1995-2002, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31033902

RESUMO

PURPOSE: Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate left ventricular (LV) wall thickness. Adaptations to exercise can occasionally mimic certain HCM characteristics. However, it is unclear whether physical activity affects HCM genotype expression and disease characteristics. Consequently, we compared lifelong physical activity volumes between HCM gene carriers with and without HCM phenotype, and compared disease characteristics among tertiles of physical activity in phenotypic HCM patients. METHODS: We enrolled n = 22 genotype positive/phenotype negative (G+/P-) HCM gene carriers, n = 44 genotype positive/phenotype positive (G+/P+) HCM patients, and n = 36 genotype negative/phenotype positive (G-/P+) HCM patients. Lifelong physical activity was recorded using a questionnaire and quantified as metabolic equivalent of task hours per week. RESULTS: We included 102 participants (51 ± 16 yr, 49% male). Lifelong physical activity volumes were not different between G+/P+ and G+/P- subjects (16 [10-29] vs 14 [6-26] metabolic equivalent of task-hours per week, P = 0.33). Among phenotypic HCM patients, there was no difference in LV wall thickness, mass, and late gadolinium enhancement across physical activity tertiles. Patients with the highest reported physical activity volumes were younger at the time of diagnosis (tertile 1: 52 ± 14 yr, tertile 2: 49 ± 15 yr, tertile 3: 41 ± 18 yr; P = 0.03), and more often had a history of nonsustained ventricular tachycardia (4% vs 30% vs 30%, P = 0.03). CONCLUSIONS: Lifelong physical activity volumes are not associated with genotype-to-phenotype transition in HCM gene carriers. We also found no difference in LV wall thickness across physical activity tertiles. However, the most active HCM patients were younger at the time of diagnosis and had a higher arrhythmic burden. These observations warrant further exploration of the role of exercise in HCM disease development.

14.
J Am Coll Cardiol ; 73(8): 932-934, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30819361
15.
EuroIntervention ; 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30888959

RESUMO

AIMS: To evaluate the impact of 23-month ticagrelor monotherapy following one-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) on the rates of patient-oriented composite endpoints (POCE) and net adverse clinical events (NACE). METHODS AND RESULTS: The rates of site-reported Academic Research Consortium (ARC)-2 defined POCE (all-cause death, any stroke, any myocardial infarction or any revascularization) and NACE (POCE or bleeding type 3 or 5 according to the Bleeding ARC [BARC]) were reported up to two-years by intention-to-treat principle in the randomized, multi-centre, open-label GLOBAL LEADERS study comparing two antiplatelet strategies in 15,991 patients undergoing PCI. The experimental strategy consisted of aspirin with ticagrelor for one month followed by ticagrelor monotherapy for 23 months, whereas the reference treatment consisted of 12-month DAPT followed by 12-month aspirin monotherapy. At two years, POCE occurred in 1050 (13.2%) patients in the experimental group and in 1131 (14.2%) in the reference group (HR 0.93, 95%CI 0.85-1.01, p=0.085). NACE occurred in 1145 (14.4%) patients in the experimental group and in 1237 (15.5%) patients in the reference group (HR 0.92, 95%CI 0.85-1.00, p=0.057). In prespecified subgroup analyses, no significant treatment-by-subgroup interactions were found for either POCE or NACE at two years. CONCLUSIONS: The experimental treatment strategy of one-month DAPT followed by 23 months of ticagrelor alone did not result in a significant reduction in the rates of site-reported POCE or NACE, when compared to the reference treatment.

16.
J Thromb Thrombolysis ; 47(3): 345-352, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30790160

RESUMO

Warfarin is dependent on multiple hepatic enzymes for metabolism while apixaban is a substrate for P-glycoprotein (P-gp) transport and hepatic CYP3A4 metabolism. The aim of this analysis was to assess the impact of interacting medication use on the treatment effects of apixaban versus warfarin. Outcomes were compared between apixaban and warfarin using Cox proportional hazards modeling according to the use of interacting medications at randomization in ARISTOTLE (n = 18,201). Interacting medications for apixaban were identified as combined P-gp and 3A4 inhibitors or inducers while interacting medications for warfarin were defined as those highly probable for warfarin potentiation or inhibition. At randomization, 5547 (30.5%) patients were on an interacting medication, including 2722 on apixaban and 2825 on warfarin. Patients using an interacting medication were more likely to be female, taking aspirin, and have a history of prior bleeding and were less likely to have a prior stroke or transient ischemic attack. No significant differences were observed on the treatment effect of apixaban compared with warfarin in patients on and off interacting medications for outcomes including the primary efficacy outcome of stroke or systemic embolism (P for interaction = 0.79) or the primary safety outcome of major bleeding (P for interaction = 0.75). Use of interacting medications with anticoagulants occurs often in patients with atrial fibrillation. Despite the potential for altered exposure, interacting medication use was not associated with a significant change in the efficacy or safety of apixaban compared with warfarin in the ARISTOTLE trial.Trial registration ClinicalTrials.gov, NCT00412984.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Interações de Medicamentos , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Varfarina/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Embolia/induzido quimicamente , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Resultado do Tratamento , Varfarina/efeitos adversos , Adulto Jovem
17.
J Am Heart Assoc ; 8(3): e010510, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30717616

RESUMO

Background Using data from the GARFIELD - AF (Global Anticoagulant Registry in the FIELD -Atrial Fibrillation), we evaluated the impact of chronic kidney disease ( CKD ) stage on clinical outcomes in patients with newly diagnosed atrial fibrillation ( AF ). Methods and Results GARFIELD - AF is a prospective registry of patients from 35 countries, including patients from Asia (China, India, Japan, Singapore, South Korea, and Thailand). Consecutive patients enrolled (2013-2016) were classified with no, mild, or moderate-to-severe CKD , based on the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative guidelines. Data on CKD status and outcomes were available for 33 024 of 34 854 patients (including 9491 patients from Asia); 10.9% (n=3613) had moderate-to-severe CKD , 16.9% (n=5595) mild CKD , and 72.1% (n=23 816) no CKD . The use of oral anticoagulants was influenced by stroke risk (ie, post hoc assessment of CHA 2 DS 2- VAS c score), but not by CKD stage. The quality of anticoagulant control with vitamin K antagonists did not differ with CKD stage. After adjusting for baseline characteristics and antithrombotic use, both mild and moderate-to-severe CKD were independent risk factors for all-cause mortality. Moderate-to-severe CKD was independently associated with a higher risk of stroke/systemic embolism, major bleeding, new-onset acute coronary syndrome, and new or worsening heart failure. The impact of moderate-to-severe CKD on mortality was significantly greater in patients from Asia than the rest of the world ( P=0.001). Conclusions In GARFIELD - AF , moderate-to-severe CKD was independently associated with stroke/systemic embolism, major bleeding, and mortality. The effect of moderate-to-severe CKD on mortality was even greater in patients from Asia than the rest of the world. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01090362.

18.
Circ Cardiovasc Interv ; 12(2): e007124, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30704287

RESUMO

BACKGROUND: Among atrial fibrillation patients undergoing percutaneous coronary intervention enrolled in PIONEER AF-PCI (An Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention), it is unclear if the observed reduction in bleeding events with rivaroxaban regimens is consistent across a range of the international normalized ratio (INR) among subjects administrated Vitamin K antagonist (VKA)-triple therapy. This analysis compares the occurrence of clinically significant bleeding between rivaroxaban and VKA strategies, according to INR stability of subjects administrated VKA. METHODS AND RESULTS: A total of 2124 atrial fibrillation patients undergoing percutaneous coronary intervention were randomized to 3 groups: rivaroxaban 15 mg od plus a P2Y12 inhibitor (group 1, n=709); rivaroxaban 2.5 mg bid plus dual antiplatelet therapy (group 2, n=709); and warfarin plus dual antiplatelet therapy (group 3, n=706). Subjects assigned to the VKA group were stratified according to time in therapeutic range and time spent with an INR >3. Kaplan-Meier estimates were calculated for clinically significant bleeding through 1 year and hazard ratios were derived using Cox Proportional Hazards models. Among group 3, 93.4% of the participants had a time in therapeutic range available (mean time in therapeutic range=65.0±24.8%). Both groups 1 and 2 were associated with a reduction in clinically significant bleeding compared with subjects in group 3, regardless of the time in therapeutic range (hazard ratio ranges=0.53-0.71 and 0.57-0.76; respectively, P<0.05 for all). Rivaroxaban strategies were associated with a reduction in clinically significant bleeding compared with VKA regardless of the proportion of time spent with an INR >3 (hazard ratio ranges=0.59-0.67 and 0.42-0.69; P<0.05 for all). CONCLUSIONS: Among atrial fibrillation patients undergoing percutaneous coronary intervention, rivaroxaban-based therapy was superior to warfarin plus dual antiplatelet therapy in lowering bleeding outcomes regardless of the INR stability. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01830543.

19.
Thromb Haemost ; 119(1): 14-38, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30597497

RESUMO

Non-vitamin K antagonist oral anticoagulants (NOACs) include dabigatran, which inhibits thrombin, and apixaban, betrixaban, edoxaban and rivaroxaban, which inhibit factor Xa. In large clinical trials comparing the NOACs with the vitamin K antagonist (VKA) warfarin, dabigatran, apixaban, rivaroxaban and edoxaban were at least as effective for stroke prevention in atrial fibrillation and for treatment of venous thromboembolism, but were associated with less intracranial bleeding. In addition, the NOACs are more convenient to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. Consequently, the NOACs are now replacing VKAs for these indications, and their use is increasing. Although, as a class, the NOACs have a favourable benefit-risk profile compared with VKAs, choosing among them is complicated because they have not been compared in head-to-head trials. Therefore, selection depends on the results of the individual trials, renal function, the potential for drug-drug interactions and preference for once- or twice-daily dosing. In addition, several 'special situations' were not adequately studied in the dedicated clinical trials. For these situations, knowledge of the unique pharmacological features of the various NOACs and judicious cross-trial comparison can help inform prescription choices. The purpose of this position article is therefore to help clinicians choose the right anticoagulant for the right patient at the right dose by reviewing a variety of special situations not widely studied in clinical trials.


Assuntos
Anticoagulantes/uso terapêutico , Cardiopatias/complicações , Trombina/antagonistas & inibidores , Vitamina K/antagonistas & inibidores , Administração Oral , Anticorpos Monoclonais Humanizados/uso terapêutico , Arginina/análogos & derivados , Arginina/uso terapêutico , Fibrilação Atrial/prevenção & controle , Benzamidas/uso terapêutico , Biomarcadores/metabolismo , Coagulação Sanguínea , Ensaios Clínicos como Assunto , Dabigatrana/uso terapêutico , Esquema de Medicação , Fator Xa/uso terapêutico , Cardiopatias/tratamento farmacológico , Humanos , Piperazinas/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Piridonas/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Risco , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Tiazóis/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Varfarina/uso terapêutico
20.
Am Heart J ; 208: 123-131, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30579505

RESUMO

BACKGROUND: Patients with atrial fibrillation (AF) often have multi-morbidity, defined as ≥3 comorbid conditions. Multi-morbidity is associated with polypharmacy, adverse events, and frailty potentially altering response to anticoagulation. We sought to describe the prevalence of multi-morbidity among older patients with AF and determine the association between multi-morbidity, clinical outcomes, and the efficacy and safety of apixaban compared with warfarin. METHODS: In this post-hoc subgroup analysis of the ARISTOTLE trial, we studied enrolled patients age ≥ 55 years (n = 16,800). Patients were categorized by the number of comorbid conditions at baseline: no multi-morbidity (0-2 comorbid conditions), moderate multi-morbidity (3-5 comorbid conditions), and high multi-morbidity (≥6 comorbid conditions). Association between multi-morbidity and clinical outcomes were analyzed by treatment with a median follow-up of 1.8 (1.3-2.3) years. RESULTS: Multi-morbidity was present in 64% (n = 10,713) of patients; 51% (n = 8491) had moderate multi-morbidity, 13% (n = 2222) had high multi-morbidity, and 36% (n = 6087) had no multi-morbidity. Compared with the no multi-morbidity group, the high multi-morbidity group was older (74 vs 69 years), took twice as many medications (10 vs 5), and had higher CHA2DS2-VASc scores (4.9 vs 2.7) (all P < .001). Adjusted rates per 100 patient-years for stroke/systemic embolism, death, and major bleeding increased with multi-morbidity (Reference no multi-morbidity; moderate multi-morbidity 1.42 [1.24-1.64] and high multi-morbidity 1.92 [1.59-2.31]), with no interaction in relation to efficacy or safety of apixaban. CONCLUSIONS: Multi-morbidity is prevalent among the population with AF; efficacy and safety of apixaban is preserved in this subgroup supporting extension of trial results to the most complex AF patients.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/epidemiologia , Embolia/epidemiologia , Inibidores do Fator Xa/uso terapêutico , Hemorragia/epidemiologia , Multimorbidade , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Acidente Vascular Cerebral/epidemiologia , Varfarina/uso terapêutico , Fibrilação Atrial/complicações , Método Duplo-Cego , Embolia/etiologia , Embolia/prevenção & controle , Feminino , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Polimedicação , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle
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