-
1.
Non-vitamin K antagonist oral anticoagulants with amiodarone, P-glycoprotein inhibitors, or polypharmacy in patients with atrial fibrillation: Systematic review and meta-analysis.
Kim, IS, Kim, HJ, Yu, HT, Kim, TH, Uhm, JS, Kim, JY, Joung, B, Lee, MH, Pak, HN
Journal of cardiology. 2019;(6):515-521
Abstract
BACKGROUND Amiodarone, which inhibits CYP2C9 and P-glycoprotein, is commonly prescribed with non-vitamin K antagonist oral anticoagulants (NOACs) and polypharmacy in high-risk atrial fibrillation (AF) patients. We studied efficacy and safety of NOACs in AF patients receiving amiodarone, P-glycoprotein inhibitor, or polypharmacy. METHODS After a systematic database search (Medline, EMBASE, CENTRAL, SCOPUS, and Web of Science), four phase-III randomized trials comparing NOACs and warfarin in "with/without amiodarone," "with/without P-glycoprotein inhibitors," or "with/without multiple (≥5, polypharmacy) concomitant drugs" subgroups were included. The outcomes were pooled using a random-effects model to determine the relative risks (RRs) for stroke/systemic thromboembolism (SSTE), major bleeding (MB), intracranial hemorrhage (ICH), and all-cause mortality. RESULTS Among patients taking amiodarone, superiority of NOACs over warfarin in non-amiodarone users disappeared in terms of SSTE (p=0.11), MB (p=0.95), ICH (p=0.26), and mortality (p=0.32). No safety benefit (MB) of NOACs compared to warfarin was shown in patients taking P-glycoprotein inhibitors (p=0.47), but SSTE prevention was still superior with NOACs compared to warfarin in the same patient group [RR=0.78 (0.61-0.99), p=0.04, I2=11%]. In AF patients with polypharmacy, NOACs showed a lower risk of SSTE [RR=0.82 (0.71-0.96), p=0.01, I2=0%] and mortality [RR=0.91 (0.83-0.99), p=0.04, I2=0%], but not MB (p=0.81) compared to warfarin. CONCLUSIONS NOACs were equivalent to warfarin among AF patients with concomitant amiodarone use in terms of efficacy, safety, and mortality. There was no safety benefit of NOACs over warfarin in patients using polypharmacy or P-glycoprotein inhibitors. SYSTEMATIC REVIEW REGISTRATION The protocol of this meta-analysis was registered on PROSPERO under CRD42018104808 (https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42018104808).
-
2.
Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention.
Paciaroni, M, Agnelli, G, Caso, V, Silvestrelli, G, Seiffge, DJ, Engelter, S, De Marchis, GM, Polymeris, A, Zedde, ML, Yaghi, S, et al
Stroke. 2019;(8):2168-2174
Abstract
Background and Purpose- Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non-vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods- Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results- Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95-5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63-9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83-3.16), and CHA2DS2-VASc score (OR, 1.72 for each point increase; 95% CI, 1.58-1.88) were associated with ischemic events. Among the CHA2DS2-VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33-0.61). Conclusions- In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA2DS2-VASc score were associated with increased risk of cerebrovascular events.
-
3.
Safety and Efficacy of Triple Antithrombotic Therapy with Dabigatran versus Vitamin K Antagonist in Atrial Fibrillation Patients: A Pilot Study.
Russo, V, Rago, A, Proietti, R, Attena, E, Rainone, C, Crisci, M, Papa, AA, Calabrò, P, D'Onofrio, A, Golino, P, et al
BioMed research international. 2019;:5473240
Abstract
BACKGROUND Combination of dual antiplatelet (DAPT) and oral anticoagulation therapy is required to decrease cardioembolic stroke and stent thrombosis risk in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS). We compared the safety and efficacy of dabigatran etexilate with vitamin K antagonist (VKA), in combination with DAPT (aspirin plus clopidogrel) treatment in AF patients who underwent percutaneous coronary intervention (PCI) with stenting for ACS. METHODS Consecutive nonvalvular AF patients who received twice-daily dabigatran 110 mg (n = 389) or VKA (n = 510) and DAPT were included. Primary endpoints were major bleeding (safety) and the composite of ischemic stroke, systemic embolism, and myocardial infarction (efficacy). The secondary efficacy endpoint was hospitalization for cardiovascular disease. RESULTS After propensity score matching, comparative treatment groups comprised 175 dabigatran recipients and 175 VKA recipients. The cumulative incidence of major bleeding was lower in the dabigatran group (2.3%) compared with the VKA group (10.3%) with a hazard ratio (HR) of 4.81 [95% confidence interval (CI) 1.6-14.2, p < 0.005]. The cumulative incidence of thromboembolic events with dabigatran was slightly higher (8.0%) than with VKA (6.85%), but not statistically significantly so (0.8, 0.39-1.8; p = 0.6). Cumulative incidence of hospitalization for cardiovascular disease was lower with dabigatran (10.3%) compared with VKA (20.6%) treatment (2.2, 1.25-3.8; p < 0.006). CONCLUSION Dabigatran at the dose used for stroke prevention appears safer than VKA and maintains a similar efficacy profile, when used with DAPT, in AF patients who have undergone PCI with stenting for ACS.
-
4.
Non-vitamin K antagonist oral anticoagulants in elderly patients with atrial fibrillation: A systematic review with meta-analysis and trial sequential analysis.
Caldeira, D, Nunes-Ferreira, A, Rodrigues, R, Vicente, E, Pinto, FJ, Ferreira, JJ
Archives of gerontology and geriatrics. 2019;:209-214
Abstract
BACKGROUND Elderly population is known to be associated with polymedication, comorbidities and altered drug pharmacokinetics. However, the most adequate oral anticoagulant, attending to its relative efficacy and safety, remains unclear. METHODS We searched for phase III randomized controlled trials (MEDLINE, Cochrane Library, SciELO collection and Web of Science) comparing novel non-vitamin K antagonist oral anticoagulants (NOACs) with Vitamin K antagonists (VKA) in the elderly population (≥75 years-old) in atrial fibrillation (AF). Risk ratios (RR) were calculated using a random effects model. Trial sequential analysis (TSA) was performed in statistically significant results to evaluate whether cumulative sample size was powered. RESULTS Four trials rendered data about elderly (≥75 years-old) and younger patients (<75 years-old) with AF. NOACs demonstrated a 30% significant risk reduction (RR 0.70, 95% CI: 0.61 to 0.80) in elderly patients compared to VKA, without heterogeneity across studies (I2 = 0%). The TSA showed that cumulative evidence of this subgroup exceeded the minimum information size required for the risk reduction. In younger patients, VKA and NOACs shared a similar risk of stroke and systemic embolism (RR 0.97, 95% CI: 0.79 to 1.18). Regarding major bleeding risk in the elderly, the overall comparative risk of NOACs was not different from VKA (RR 0.91, 95% CI: 0.72 to 1.16; I2 = 86%). CONCLUSIONS NOACs reduce significantly the risk of stroke and systemic embolism in elderly patients without increasing major bleeding events. The dimension of stroke risk reduction was significantly higher in the elderly than in younger adults.
-
5.
Clinical Outcomes of Antithrombotic Strategies for Patients with Atrial Fibrillation After Percutaneous Coronary Intervention.
Gao, X, Ge, Z, Kong, X, Wang, Z, Zuo, G, Wang, F, Chen, S, Zhang, J
International heart journal. 2019;(3):546-553
Abstract
Antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remain challenging. This study aims to explore the best antithrombotic strategy for AF patients after PCI based on a network meta-analysis. This study was registered in PROSPERO (CRD42018093928). The PubMed, Cochrane, and EMBASE databases were searched to identify clinical trials concerning antithrombotic therapy for AF patients with PCI from inception to April 2018. Pairwise and network meta-analysis were conducted to compare clinical outcomes of different antithrombotic therapy. The primary endpoint was major bleeding. Fifteen studies including 16,382 patients were identified with follow-up ranging from 3 to 12 months. Non-vitamin K oral anticoagulants (NOAC) plus P2Y12 inhibitor ranked first with a reduced risk of major bleeding compared with vitamin K antagonist (VKA) plus dual antiplatelet therapy (OR: 0.57, 95% CI: 0.43-0.75) but with no significant difference compared with VKA plus single platelet therapy (OR: 0.85, 95% CI: 0.62-1.16). Similar thrombotic events were evident among these groups. Subgroup analysis showed that VKA plus aspirin exhibited a similar risk of major bleeding compared with VKA plus clopidogrel (OR: 0.94, 95% CI: 0.73-1.23) but was associated with increased risks of ischaemic stroke (OR: 2.10, 95% CI: 1.33-3.32) and all-cause death (OR: 1.77, 95% CI: 1.15-2.74) versus VKA plus clopidogrel. In AF patients undergoing PCI, NOAC plus P2Y12 inhibitor and VKA plus clopidogrel, but not VKA plus aspirin, were associated with reduced risk of major bleeding compared with the recommended VKA-based triple therapy, while thrombotic events were similar among these treatments.
-
6.
Security profile of direct anticoagulants. Preferred use in atrial fibrillation.
Roldán Rabadán, I, Alonso de Leciñana, M, Barba Martín, R, Páramo Fernández, JA, ,
Clinica e investigacion en arteriosclerosis : publicacion oficial de la Sociedad Espanola de Arteriosclerosis. 2019;(6):263-270
Abstract
A multidisciplinary panel of cardiologists, neurologists, internal medicine and specialists in hemostasis and thrombosis has elaborated this document showing recent scientific evidences supporting a better profile of direct oral anticoagulants (DOACs) versus vitaminK antagonists (VKA), as well as the indications of specific antidotes and hemostatic agents to reverse the anticoagulant effects of DOACs. The analysis reinforces the best profile of DOACs and its special benefit in patients with basal high hemorrhagic risk.
-
7.
Antithrombotic treatment in patients with atrial fibrillation and acute coronary syndromes: results of the European Heart Rhythm Association survey.
Lane, DA, Dagres, N, Dan, GA, García Seara, J, Iliodromitis, K, Lenarczyk, R, Lip, GYH, Mansourati, J, Marín, F, Scherr, D, et al
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 2019;(7):1116-1125
Abstract
The management of an acute coronary syndrome (ACS) in a patient with existing atrial fibrillation (AF) often presents a management dilemma both in the acute phase and post-ACS, since the majority of AF patients will already be receiving oral anticoagulation (OAC) for stroke prevention and will require further antithrombotic treatment to reduce the risk of in-stent thrombosis or recurrent cardiac events. Current practice recommendations are based largely on consensus option as there is limited evidence from randomized controlled trials. Prior to the launch of the new European Heart Rhythm Association (EHRA) consensus document, a survey was undertaken to examine current clinical management of these patients across centres in Europe. Forty-seven centres submitted valid responses, with the majority (70.2%) being university hospitals. This EHRA survey demonstrated overall the management of ACS in AF patients is consistent with the available guidance. Most centres would use triple therapy for a short duration (4 weeks) and predominantly utilize a strategy of OAC (vitamin K antagonist, VKA or non-vitamin K antagonist oral anticoagulant, NOAC) plus aspirin and clopidogrel, followed by dual therapy [(N)OAC plus clopidogrel] until 12 months post-percutaneous coronary intervention, followed by (N)OAC monotherapy indefinitely. Where NOAC was used in combination with antiplatelet(s), the lower dose of the respective NOAC was preferred, in accordance with current recommendations.
-
8.
Novel Oral Anticoagulants for the Prevention of Stroke in Patients with Atrial Fibrillation and Hypertension: A Meta-Analysis.
Zheng, Y, Liu, Y, Bi, J, Lai, W, Lin, C, Zhu, J, Yao, W, Chen, Q
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2019;(5):477-485
Abstract
INTRODUCTION Hypertension is associated with increased risk of stroke and bleeding in patients with atrial fibrillation (AF). In the present study, we aimed to investigate the influence of hypertension status in patients with AF receiving treatment with non-vitamin K antagonist oral anticoagulants (NOACs). METHODS PubMed, Embase, and Cochrane Library were searched from the inception of each database to November 2017. Randomized controlled trials (RCTs) that evaluated NOACs versus warfarin in patients with AF and hypertension were identified. A meta-analysis was performed using random- or fixed-effects models according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS Five trials (72,967 patients, including 51,378 patients with hypertension) were enrolled. NOACs significantly reduced the risk of stroke and systemic embolism (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.81-0.94, n = 51,378 patients), hemorrhagic stroke (HR 0.55, 95% CI 0.41-0.74, n = 28,818 patients), death from any cause (HR 0.91, 95% CI 0.85-0.97, n = 43,101 patients), major bleeding (HR 0.78, 95% CI 0.74-0.83, n = 51,378 patients) and intracranial bleeding (HR 0.50, 95% CI 0.38-0.67, n = 27,185 patients). The benefits of NOACs in comparison with warfarin were consistent in AF patients with or without hypertension (Pinteraction for all outcomes > 0.05). CONCLUSIONS Our findings suggest that NOACs can be recommended for the prevention of stroke or systemic embolism in patients with AF and hypertension.
-
9.
Association of Antihyperglycemic Therapy with Risk of Atrial Fibrillation and Stroke in Diabetic Patients.
Lăcătușu, CM, Grigorescu, ED, Stătescu, C, Sascău, RA, Onofriescu, A, Mihai, BM
Medicina (Kaunas, Lithuania). 2019;(9)
Abstract
Type 2 diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Atrial fibrillation (AF) and stroke are both forms of CVD that have major consequences in terms of disabilities and death among patients with diabetes; however, they are less present in the preoccupations of scientific researchers as a primary endpoint of clinical trials. Several publications have found DM to be associated with a higher risk for both AF and stroke; some of the main drugs used for glycemic control have been found to carry either increased, or decreased risks for AF or for stroke in DM patients. Given the risk for thromboembolic cerebrovascular events seen in AF patients, the question arises as to whether stroke and AF occurring with modified incidences in diabetic individuals under therapy with various classes of antihyperglycemic medications are interrelated and should be considered as a whole. At present, the medical literature lacks studies specifically designed to investigate a cause-effect relationship between the incidences of AF and stroke driven by different antidiabetic agents. In default of such proof, we reviewed the existing evidence correlating the major classes of glucose-controlling drugs with their associated risks for AF and stroke; however, supplementary proof is needed to explore a hypothetically causal relationship between these two, both of which display peculiar features in the setting of specific drug therapies for glycemic control.
-
10.
The efficacy and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation and coronary artery disease: A meta-analysis of randomized trials.
Zelniker, TA, Ruff, CT, Antman, EM, Giugliano, RP
European heart journal. Acute cardiovascular care. 2019;(6):554-561
Abstract
BACKGROUND Patients with atrial fibrillation and concomitant coronary artery disease (CAD) are at higher risk for myocardial infarction or cardiovascular death, often require antiplatelet therapy and are therefore exposed to an increased risk of bleeding. This meta-analysis aimed to compare the efficacy and safety profile of non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin in patients with atrial fibrillation and concomitant CAD. MATERIALS AND METHODS We performed a trial-level meta-analysis of CAD subgroups from four trials of NOAC versus warfarin in patients with atrial fibrillation, comparing the primary trial endpoints (efficacy: stroke or systemic embolic event; safety: International Society on Thrombosis and Haemostasis major bleeding) in patients with versus those without CAD, and used interaction testing to assess for treatment effect modification. RESULTS In total, 58,606 patients with established CAD were included in this meta-analysis. NOACs reduced the risk of stroke/systemic embolic event irrespective of presence of CAD (CAD: 0.76 (0.56-1.04); no CAD: hazard ratio 0.77 (0.56-1.06); p-INT 0.93). Similarly, there was no effect modification by presence of CAD for major bleeding (CAD: hazard ratio 0.92 (0.65-1.32), no CAD: 0.83 (0.61-1.12); p-INT 0.46) or myocardial infarction (CAD: hazard ratio 0.95 (0.62-1.44); no CAD: hazard ratio 0.95 (0.60-1.50); p-INT = 0.98). While NOACs reduced all-cause mortality in patients without CAD compared with warfarin (hazard ratio 0.85 (0.71-1.02)), there was no difference in mortality between NOACs and warfarin in the CAD group (hazard ratio 0.99 (0.82-1.20); p-INT 0.01). CONCLUSION The present meta-analysis of four trials supports that NOACs are safe and at least as effective as warfarin in patients with atrial fibrillation and established CAD.