NSAIDs, corticosteroids and atrial fibrillation?

Evidence that a number of drugs can cause atrial fibrillation has been accumulating since the 2000s. A case-control analysis of a UK general medicine database showed statistically significant increases in the risk of chronic atrial fibrillation in patients taking NSAIDs, after as little as one month of treatment. When NSAID treatment lasted more than 30 days, the incidence was 9.4%, versus 4.7% in the control group, corresponding to a relative risk (RR) of 1.57 (95% confidence interval (95% CI): 1.15 to 2.15). Similar results were found in patients with no history of heart failure. A Danish case-control study yielded similar results. In the UK case-control study, a statistically significant increase in the risk of chronic atrial fibrillation was found in patients taking corticosteroids (5% versus 1.4% in the control group, RR=2.5, 95% CI: 1.6 to 4). The risk increased with the dose. Another Danish case-control study showed that hospitalisation for atrial fibrillation or flutter was twice as frequent among patients exposed to corticosteroids. In contrast, trials in which corticosteroids were given shortly after cardiac surgery, a highly specific setting, showed a decreased risk of atrial fibrillation. In practice, the risk of atrial fibrillation should be taken into account before deciding whether or not to prescribe a corticosteroid or an NSAID, especially to a patient with known risk factors for atrial fibrillation. The heart rate of treated patients should be closely monitored.     

Treatment patterns and real-world effectiveness of warfarin in nonvalvular atrial fibrillation within a managed care system

ABSTRACT

Objective: To examine warfarin utilization and clinical effectiveness among patients with nonvalvular atrial fibrillation within usual clinical care in a managed care system.

Research design and methods: A retrospective analysis of health care claims for an approximately four million member managed care organization was performed. Health plan members with a diagnosis of nonvalvular atrial fibrillation in calendar year 2000 were identified and stratified into two cohorts: Warfarin Therapy (newly initiating warfarin) or Warfarin Candidates (eligible for warfarin therapy according to the ACC/AHA/ESC Guidelines for the Management of Patients with Atrial Fibrillation, but did not receive warfarin).

Measurements: The occurrence of thromboembolism, ischemic stroke, and hemorrhage during a maximum 720‐day follow-up were compared between cohorts, adjusting for age, gender, and other risk factors, using Cox regression.

Results: Among 12?539 subjects (mean age 78.0 ± 8.8 years) with nonvalvular atrial fibrillation, 4895 (39.0%) initiated Warfarin Therapy and 7644 (61.0%) were Warfarin Candidates. Event occurrences among Warfarin Therapy vs. Warfarin Candidates were: ischemic stroke, 3.7% vs. 4.5%; any thromboembolism, 7.8% vs. 10.8%; and hemorrhage, 4.4% vs. 4.9%, respectively. Warfarin therapy was not associated with an increased risk for hemorrhage (hazard ratio [HR] = 0.97, 95% confidence interval [CI] = 0.82–1.15), while risks for ischemic stroke and any thromboembolism were significantly reduced, by 22% (HR = 0.78, 95% CI = 0.65–0.93) and 34% (HR = 0.66, 95% CI = 0.59–0.75), respectively.

Conclusions: Within usual clinical care for the managed care population examined, warfarin remains underused despite current guidelines recommending its use in nearly all patients with nonvalvular atrial fibrillation. Although utilization of anticoagulation clinics and INR values attained were unknown in this study, the observed risk reductions for ischemic stroke and thromboembolism were lower than those achieved in clinical trials, while no increased risk for hemorrhage was observed. These findings suggest that warfarin is used conservatively, and dosed cautiously, diminishing the full potential benefit of anticoagulant therapy in patients with nonvalvular atrial fibrillation.     

The efficacy and safety of novel oral anticoagulants for the preventive treatment in atrial fibrillation patients: a systematic review and meta-analysis

Abstract

Background: Novel oral anticoagulants, including direct factor Xa inhibitors and direct factor IIa inhibitors, have been used to prevent stroke in patients with atrial fibrillation (AF) for a decade. In this study, the efficacy and safety of the novel oral anticoagulants were assessed in AF patients.

Methods: No language restrictions were applied. Study selection and data extraction were carried out by searching PubMed, EMBASE, OVID, the BIOSIS, the Web of Science, Clinical Trials Registers, Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. Each database was searched from its inception date to June 2013. Using odds ratio (OR) as an indicator, we systematically evaluated the primary efficacy endpoints and safety endpoints, as well as 10 secondary endpoints.

Result: Compared to the control drugs, the novel oral anticoagulants showed an OR decreased by 26% (OR: 0.74, 95% confidence interval (CI): 0.62–0.88) for stroke or systemic embolism, decreased by 24% (OR: 0.76, 95% CI: 0.64–0.90) for major bleeding, decreased by 10% (OR: 0.90, 95% CI: 0.84–0.95) for death from any cause, decreased by 27% for disabling or fatal stroke (OR: 0.73, 95% CI: 0.54–0.97), decreased by 31% (OR: 0.69, 95% CI: 0.60–0.8) for fatal bleeding, and decreased by 8% (OR: 0.92, 95% CI: 0.88–0.95) for serious adverse events. However, there was no significant difference in acute myocardial infarction, systemic embolism, major bleeding or clinically relevant non-major, all bleeding events, all adverse events and liver function disorder, between the novel oral anticoagulants and control drugs (p?>?0.05).

Conclusions: Compared to the control drugs, the novel oral anticoagulants showed higher efficiency and safety in patients with AF, as evidenced by their superior performance not only in reducing the risk of stroke or systemic embolism with a lower risk of major bleeding but also in decreasing the incidence of death from any cause, disabling or fatal stroke, serious adverse events and fatal bleeding.     

Use of salmeterol with and without concurrent use of inhaled corticosteroids and the risk of asthma-related hospitalization among patients with asthma

ABSTRACT

Rationale: Studies evaluating the safety of salmeterol are inconclusive, which might be the result from not taking into account the impact of concomitant inhaled corti­costeroids (ICS).

Objective: To study whether salmeterol use with and without concomitant ICS, respectively, was associated with an increased risk of asthma-related hospitalizations among patients with asthma.

Methods: A case-control study nested within a cohort of patients with asthma, identified in the year 2000, over a 2-year period was conducted. Cases were subjects who had a first-time hospitalization for asthma in the year 2001, and were matched with up to five controls by age (± 5 years), sex, and number of asthma-related outpatient visits.

Measurements: Hospitalizations and medication use were extracted from the MEDSTAT's MarketScan database.

Main results: There were 333 cases of asthma-related hospitalizations and 1607 matched control subjects. Any use of salmeterol with concomitant ICS use during the prior year was associated with a 32% risk reduction for being hospitalized due to asthma (OR = 0.68; 95% CI = 0.48, 0.96). In the presence of concomitant ICS use, patients who either used salmeterol currently or used seven or more canisters of salmeterol during the prior year had 46% (OR = 0.54, 95% CI = 0.32, 0.92), and 59% (OR = 0.41, 95% CI = 0.21, 0.79) reductions in the risk of hospital admissions for asthma, respectively.

Limitations: Though indirect measure of asthma severity was adjusted during the analyses, the lack of information on lung function might result in a selection bias. Additionally, only a small sample size of patients was found to use salmeterol without concomitant ICS use, and this introduced the issue of lack of power.

Conclusions: Use of salmeterol in conjunction with ICS is associated with a decreased risk of hospital admission for asthma.     

Stroke risk reduction outweighed bleeding risk increase from vitamin K antagonist treatment among nonvalvular atrial fibrillation patients with high stroke risk and low bleeding risk

Objective: Warfarin is widely used for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). We compared the rates of stroke and major bleeding in NVAF patients with a high stroke risk and low bleeding risk profile during warfarin treated (W+) and warfarin untreated (W?) periods.

Method: Insurance claims from six commercial, Medicaid or Medicare databases were analyzed from 2000 to 2014. NVAF patients treated with warfarin, with a CHADS₂/CHA₂DS₂-VASc score ≥2, and an ATRIA score ≤3 at baseline were identified. Incidence rate ratios (IRRs) of stroke and major bleeding were calculated for W?+?versus W? episodes of person-time, as well as for first 30 days versus beyond 30 days of W?+?episodes.

Results: Among 316,145 patients, anticoagulant prophylaxis with warfarin significantly reduced stroke risk, with IRRs ranging from 0.48 (95% CI: 0.46–0.51) to 0.80 (95% CI: 0.70–0.91), and increased major bleeding risk, with IRRs ranging from 1.13 (95% CI: 1.10–1.15) to 1.95 (95% CI: 1.10–3.45). Stroke and major bleeding rates were higher during the first 30 days of W?+?than beyond.

Conclusion: In NVAF patients at high risk for stroke and low risk for bleeding, our data confirm the effectiveness of anticoagulation for stroke prevention. The decrease in stroke risk of anticoagulation may outweigh the risk of major bleeding events, particularly among elderly patients. Potential risks of warfarin during initiation warrant attention, especially among patients who stop and start therapy repeatedly.     

Risk of stroke/systemic embolism,major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban,dabigatran or rivaroxaban compared with warfarin in the United States Medicare population

Objective: To compare the risk and cost of stroke/systemic embolism (SE) and major bleeding between each direct oral anticoagulant (DOAC) and warfarin among non-valvular atrial fibrillation (NVAF) patients.

Methods: Patients (≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Medicare database from 1 January 2013 to 31 December 2014. Patients initiating each DOAC were matched 1:1 to warfarin patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major-bleeding-related medical costs between matched cohorts.

Results: Of the 186,132 eligible patients, 20,803 apixaban–warfarin pairs, 52,476 rivaroxaban–warfarin pairs, and 16,731 dabigatran–warfarin pairs were matched. Apixaban (hazard ratio [HR]?=?0.40; 95% confidence interval [CI] 0.31, 0.53) and rivaroxaban (HR?=?0.72; 95% CI 0.63, 0.83) were significantly associated with lower risk of stroke/SE compared to warfarin. Apixaban (HR?=?0.51; 95% CI 0.44, 0.58) and dabigatran (HR?=?0.79; 95% CI 0.69, 0.91) were significantly associated with lower risk of major bleeding; rivaroxaban (HR?=?1.17; 95% CI 1.10, 1.26) was significantly associated with higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban ($63 vs. $131) and rivaroxaban ($93 vs. $139) had significantly lower stroke/SE-related medical costs; apixaban ($292 vs. $529) and dabigatran ($369 vs. $450) had significantly lower major bleeding-related medical costs.

Conclusions: Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.     

Treating arrhythmias: an expert opinion

Introduction: Significant progress has recently been made in the pharmacological treatment of arrhythmias. This concerns mainly atrial fibrillation, which affects millions of patients.

Areas covered: This review covers recent, clinically relevant developments in arrhythmia treatment, especially with regard to novel agents for the management of atrial fibrillation: dronedarone for rhythm control, vernakalant for pharmacological conversion, and advances in antithrombotic treatment. The field of pharmacological treatment of ventricular arrhythmias is also briefly discussed. Relevant papers were identified by an extensive Pubmed search using appropriate keywords.

Expert opinion: Dronedarone has been proposed as one of the first-choice antiarrhythmic drugs for almost all categories of patients with atrial fibrillation. However, its effectiveness in prevention of arrhythmia recurrences is less than that of amiodarone. Administration to patients with severe heart failure is associated with increased mortality and should be avoided. There are also very recent reports over rare but severe cases of hepatic injury in patients treated with dronedarone, including two cases of acute liver failure leading to liver transplant. Intravenous vernakalant is effective for the rapid pharmacological conversion of atrial fibrillation. Dabigatran, an oral direct thrombin inhibitor, has been shown to be effective in stroke reduction without increase in bleeding rates; additionally, no monitoring of antithrombotic effectiveness is needed. Rivaroxaban, an oral direct factor Xa inhibitor, has also shown promising results. These developments in the pharmacological treatment of arrhythmia will presumably affect clinical decision making.     

Amiodarone prophylaxis for atrial fibrillation after cardiac surgery: meta-analysis of dose response and timing of initiation

STUDY OBJECTIVE: To investigate a possible dose-response relationship between amiodarone and reduction in incidence of postoperative atrial fibrillation, and to determine whether pre- or postoperative initiation of amiodarone is superior. DESIGN: Meta-analysis of randomized controlled trials. DATA SOURCE: MEDLINE and EMBASE databases and the Cochrane Central Register of Controlled Trials for English-language reports published between 1966 and December 2005. MEASUREMENTS AND MAIN RESULTS: Of 23 identified randomized controlled trials of amiodarone prophylaxis of postoperative atrial fibrillation, 14 were included in the final analysis. These studies enrolled a total of 2864 patients. For each study, the total administered amiodarone dose--categorized as low (< 3000 mg), medium (3000-5000 mg), or high (> 5000 mg)--and preoperative versus postoperative initiation were aggregated by using meta-analytic techniques. The incidence of postoperative atrial fibrillation was significantly reduced by amiodarone compared with placebo (p<0.001). Although the odds of developing atrial fibrillation appeared to be somewhat higher in the low-dose group, no significant differences were noted in the odds ratios (ORs) of developing atrial fibrillation among the low-, medium-, and high-dose groups: OR 0.58, 95% confidence interval (CI) 0.44-0.77; OR 0.45, 95% CI 0.30-0.69; and OR 0.44, 95% CI 0.33-0.58; respectively (p=0.238). In addition, the ORs for atrial fibrillation development associated with preoperative and postoperative initiation of amiodarone were not significantly different (OR 0.50, 95% CI 0.39-0.63; and OR 0.48, 95% CI 0.37-0.63; respectively, p=0.862). CONCLUSION: Total amiodarone doses of 3000 mg or higher may be more effective than lower doses in reducing the rate of postoperative atrial fibrillation after cardiac surgery. Preoperative initiation of amiodarone appears to be unnecessary. These findings require confirmation in prospective, randomized trials.     

All-cause hospitalization and associated costs in patients with schizophrenia or bipolar disorder initiating long-acting injectable antipsychotics

Objective: To compare all-cause hospitalization and associated costs among patients with schizophrenia or bipolar disorder (BD) treated with long-acting injectable antipsychotics (LAIs).

Methods: The Truven MarketScan Medicaid claims database was used to identify patients with schizophrenia; MarketScan Medicaid and commercial claims databases were used to identify BD. Adult patients with ≥1 LAI claim from January 1, 2013–June 30, 2014 (ID period) were identified. The first day of LAI initiation was the index date; patients were followed for ≥1 year. Logistic and general linear regression models were used to estimate the risk of hospitalization and associated costs.

Results: Adjusted analyses showed that, in the schizophrenia cohort, risks of hospitalization were statistically significantly higher in the haloperidol [OR (95% CI)?=?1.51 (1.05–2.16); HR (95% CI)?=?1.35 (1.05–1.73)] and risperidone [OR (95% CI)?=?1.58 (1.07–2.33); HR (95% CI)?=?1.33 (1.01–1.74)] cohorts than in the aripiprazole once monthly extended release (AOM 400) cohort. Similarly, in patients with BD, risks of hospitalization were significantly higher in haloperidol [OR (95% CI)?=?1.49 (1.01–2.19); HR (95% CI)?=?1.33 (1.03–1.73)] and risperidone [OR (95% CI)?=?1.78 (1.19–2.66); HR (95% CI)?=?1.33 (1.01–1.75)] than in AOM400. No statistically significant differences in hospitalization costs were observed in either disease group.

Conclusions: Although the study results may be subject to confounding variables that are not contained in claims databases, such as disease severity, it appears that AOM400 may be more effective than haloperidol and risperidone LAIs among patients with schizophrenia or BD.     

Non-vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation and Liver Disease: A Meta-Analysis and Systematic Review

Background

The effect of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and liver disease remains largely unresolved. Therefore, we performed a meta-analysis to compare the efficacy and safety of NOACs with warfarin in this population.

Methods

We systematically searched the Cochrane Library, PubMed, and Embase databases for studies reporting the comparisons of NOACs with warfarin in patients with AF and liver disease. A random-effects model was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs).

Results

A total of six studies with 41,954 participants were included in this meta-analysis. In AF patients with liver disease, compared with warfarin use, the use of NOACs was associated with reduced risks of all-cause death (RR 0.78, 95% CI 0.66–0.93), major bleeding (RR 0.68, 95% CI 0.53–0.88), and intracranial hemorrhage (RR 0.49, 95% CI 0.41–0.59), but had comparable risks of stroke or system embolism (RR 0.80, 95% CI 0.57–1.12) and gastrointestinal bleeding (RR 0.90, 95% CI 0.61–1.34). In AF patients with cirrhosis, NOACs significantly reduced the risks of major bleeding (RR 0.53, 95% CI 0.37–0.76), gastrointestinal bleeding (RR 0.57, 95% CI 0.38–0.84), and intracranial hemorrhage (RR 0.55, 95% CI 0.31–0.97) compared with warfarin.

Conclusions

Based on current publications, the use of NOACs is at least non-inferior to warfarin in patients with AF and liver disease.

     

Incidence of postoperative residual neuromuscular blockade after general anesthesia: a prospective,multicenter, anesthetist-blind,observational study

Objective:

Evidences demonstrate that postoperative residual neuromuscular blockade (rNMB) is a primary and frequent anesthetic risk factor for postoperative complications. This study was designed to mitigate the paucity of data regarding the occurrence and degree of rNMB in a real-life setting.

Methods:

This prospective, multicenter, anesthetist-blind, observational study enrolled 1571 Chinese adults undergoing elective open or laparoscopic abdominal surgery lasting ≤4 hours from 32 hospitals across China. The patients received anesthesia in accordance with routine practice at the study site. Neuromuscular blockade (NMB) was monitored using acceleromyography, with rNMB defined as a train-of-four (TOF) ratio <0.9.

Results:

The patients’ mean age was 46 years and 71% were female. The procedures included laparoscopic (67%), open abdominal (31%), and laparoscopic to open abdominal (2%). NMB was reversed with neostigmine in 78% of patients. The overall incidence of rNMB at extubation was 57.8%, and the proportions of participant with TOF ratios <0.6, 0.6–0.7, 0.7–0.8, 0.8–0.9 were 22.9%, 6.9%, 11.1% and 16.9%, respectively, immediately prior to endotracheal extubation. Age <45 years (OR?=?0.630, 95% CI?=?0.496–0.801, p?=?0.002), use of one neuromuscular blocking agent (NMBA) (OR?=?0.387, 95% CI?=?0.243–0.618, p?<?0.0001), time from neostigmine administration to endotracheal extubation ≥10?min (OR?=?0.513, 95% CI?=?0.400–0.658, p?<?0.0001) and time from last NMBA administration to endotracheal extubation ≥60?min (OR?=?0.902, 95% CI?=?0.801–0.989, p?=?0411) were correlated with non-rNMB at the time of extubation.

Conclusions:

This observational study demonstrated that the overall incidence of rNMB at the time of endotracheal extubation was high in Chinese patients undergoing abdominal procedures, which necessitates appropriate management in current real-life practice.

Clinical trial registry number:

NCT01871064.     

Anticoagulation in patients with non-valvular atrial fibrillation: an evaluation of stability and early factors that predict longer-term stability on warfarin in a large UK population

ABSTRACT

Objective: To determine the proportion of patients with non-valvular atrial fibrillation (NVAF) treated with warfarin that achieved a 6‐month period within the target INR range (stability). To then evaluate any associations between stability and outcome and to determine whether stability can be predicted by clinical factors at an early stage in warfarin treatment.

Methods: This study was a record linkage study in 1513 patients with NVAF treated with warfarin for a minimum of 6‐months, carried out in a large UK population. The main outcome measures were stability (defined as six months within the target INR range [2.0–3.0]), thromboembolic and bleeding event rates and mortality. Secondary outcome measures were the predictive value of baseline characteristics and other treatment variables.

Results: Stability was achieved in 52% of the study group. Standardised mean survival was significantly higher in the group who achieved stability (? = 16.91 months, p < 0.001) with a hazard ratio of 4.36 (?p < 0.001). The stable group had a lower rate of both thromboembolic events (0.8% vs. 2.3% per patient year) and bleeds recorded on inpatient diagnoses (0.4% vs. 1.2% per patient year). Failure to achieve stable control was associated with age (Odds Ratio [OR] 1.011 (95% Confidence Interval [CI] 1.001–1.021)) and morbidity at baseline (OR 1.015; 95% CI 1.007–1.022). An increase in mean time between visits (OR 0.939; 95% CI 0.926–0.952) and the percentage time in range (OR 0.889; 95% CI 0.879–0.900) was associated with a decrease in the chance of instability. Greater variability in INR was also associated with a failure to achieve stability (OR 1.518; 95% CI 1.427–1.615). Receiver Operator Characteristic (ROC) analysis using data from the first three months of treatment demonstrated good discrimination of stability using age and morbidity at baseline and percentage time in range and frequency of visits during the first three months of treatment (area under curve [AUC] 0.780; standard error [SE] 0.012; 95% CI 0.757–0.803).

Conclusions: Many patients never achieved a period of 6‐months stability and were at increased risk of thromboembolic events and bleeds. Age, morbidity at baseline and variability of INR control in the first three months could be used to predict instability using warfarin. This study infers that patients should be treated more intensively in the early stages of warfarinisation in order to improve outcome.     

Dronedarone as a new treatment option for atrial fibrillation patients: pharmacokinetics,pharmacodynamics and clinical practice

Importance of the field: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting 1 – 2% of the population. Despite several developments in antithrombotic, antiatherosclerotic and device-based cardiac therapies, few noteworthy antiarrhythmic drugs have been developed.

Areas covered in this review: Dronedarone, a modified analogue of amiodarone, has the pharmacological ability of blocking multiple ion channels. This overview summarizes the pharmacokinetic and pharmacodynamic properties of dronedarone, evaluates its potential application to daily clinical cardiology practice according to the evidence provided by clinical trials, and provides a future clinical perspective for the use of this drug.

What the reader will gain: The readers will gain an understanding of the findings of recent trials performed with dronedarone, which will provide important information for this relatively new antiarrhythmic drug, used for the treatment of atrial fibrillation.

Take home message: Dronedarone provides a reasonable efficacy and safety profile. Recent clinical trials indicate that dronedarone may support maintenance of sinus rhythm, decrease hospitalizations and reduce healthcare costs even in AF patients with structural heart disease but without severe or unstable cardiac failure.     

The relationship between statin use and atrial fibrillation*

ABSTRACT

Objective: To investigate the relationship between statin therapy and the development of new-onset, recurrent, and postoperative atrial fibrillation (AF).

Research design and methods: A systematic literature search was conducted through September 2006. Included studies were either randomized, controlled trials or observational studies with adjusted analyses using multivariate regression or covariate matching, compared patients receiving or not receiving a statin, and reported data on the incidence of AF. Weighted averages were reported as odds ratios with 95% confidence intervals (CIs) using a random-effects model.

Main outcome measures: The primary outcome measured was a combined endpoint of any AF type. Secondary outcomes included new-onset, recurrent, and postoperative AF.

Results: Fourteen trials reporting the results of 15 unique analyses (n = 7402) were included. There was a 20% incidence rate for any AF with varying rates depending on AF type (new-onset [11%], recurrent [56%], recurrent after cardioversion [54%], postoperative [22%]). The use of a statin reduced the odds of developing any AF by 45% (odds ratio [OR] 0.55; 95% CI 0.43–0.70); Q statistic p = 0.001). Statins reduced the odds of developing new-onset AF by 32% (OR 0.68; 95% CI 0.51–0.90), recurrent AF by 57% (OR 0.43; 95% CI 0.24–0.79), recurrent AF after cardioversion by 42% (OR 0.58; 95% CI 0.32–1.05) and postoperative AF by 58% (OR 0.42; 95% CI 0.27–0.65).

Limitations: We considered studies that were observ­ational in nature or only available in abstract form. Publication bias could not be ruled out.

Conclusions: Statin therapy was associated with a reduced odds of developing AF, thus providing evidence of the benefit of statins beyond the lipid-lowering activity.     

Serum uric acid and incident atrial fibrillation: A systematic review and dose–response meta-analysis

The exposure-effect association between serum uric acid and atrial fibrillationis not well known. We conduct a meta-analysis to quantitatively examine the exposure-effect relationship between serum uric acid and atrial fibrillation. Prospective studies (including cohort or nested case-control) that reported the serum uric acid and atrial fibrillation were identified through electronic searches using EMBASE, PubMed, and the Cochrane Library database. The exposure-effect analysis was performed using a stage robust error meta-regression. Eleven studies were included, with a total of 6831 cases of atrial fibrillation among 527 908 individuals. Both the highest (risk ratio (RR), 1.9; 95% confidence interval (CI), 1.64–2.23; I² = 0%) and intermediate (RR, 1.36; 95% CI, 1.16–1.59; I² = 36%) level of serum uric acid were associated with increased risks of atrial fibrillation compared to the patients with the lowest level of serum uric acid. In the exposure-effect analysis, for each 1 mg/dL increase in serum uric acid level, the incidence of atrial fibrillation increased by 21% (RR, 1.21; 95% CI, 1.12–1.32; I² = 78%). Furthermore, a significant positive linear relationship between serum uric acid and the risk of atrial fibrillation, P_nonlinearity = 0.47 was found. The exposure-effect analysis demonstrated that serum uric acid over 5.0 mg/dL significantly increased the risk of atrial fibrillation. There was a positive linear association between serum uric acid and risk of atrial fibrillation, both in subjects with noruricaemia and hyperuricaemia. More studies are needed to explore the impact of serum uric acid reduction on the incidence of atrial fibrillation.     

Changes in risk behaviours during and following treatment for hepatitis C virus infection among people who inject drugs: The ACTIVATE study

BackgroundThe risk of hepatitis C virus (HCV) reinfection due to continued injecting risk behaviours might remain a barrier to HCV treatment among people who inject drugs. We aimed to evaluate changes in risk behaviours during and following HCV treatment among people with ongoing injecting drug use or receiving opioid substitution treatment (OST).MethodsACTIVATE was an international multicentre clinical trial conducted between 2012 and 2014. Participants with HCV genotypes 2/3 infection were treated with peg-interferon/ribavirin for 12 or 24 weeks and completed a self-administered behavioural questionnaire at each study visit. The impact of time in treatment and follow-up on longitudinally measured recent (past month) behavioural outcomes was evaluated using generalized estimating equations.ResultsAmong 93 enrolled participants (83% male, median age 41 years), 55 (59%) had injected in the past month. Any injecting drug use decreased during HCV treatment and follow-up (OR 0.89 per incremental study visit; 95% CI 0.83–0.95). No significant changes were found in ≥daily injecting (OR 0.98; 95% CI 0.89–1.07), use of non-sterile needles (OR 0.94; 95% CI 0.79–1.12), sharing of injecting paraphernalia (OR 0.87; 95% CI 0.70–1.07) or non-injecting drug use (OR 1.01; 95% CI 0.92–1.10). Hazardous alcohol use decreased throughout (OR 0.56; 95% CI 0.40–0.77) and OST increased between enrolment and end of treatment (OR 1.48; 95% CI 1.07–2.04).ConclusionsRecent injecting drug use and hazardous alcohol use decreased, while OST increased during and following HCV treatment among participants with ongoing injecting drug use. These findings support further expansion of HCV care among PWID.     

Adverse clinical events in Japanese atrial fibrillation patients with and without coronary artery disease—findings from the SAKURA AF Registry

Abstract

Background: Although atrial fibrillation (AF) and coronary artery disease (CAD) are increasing in prevalence in Japan, real-world data regarding clinical outcomes in Japanese AF patients with CAD are limited.

Methods: The SAKURA AF Registry is a prospective multi-center registry created to investigate outcomes of oral anticoagulant (OAC) use in Japanese AF patients. A study was conducted involving 3237 enrollees from 63 Tokyo-area institutions who were followed up for a median of 39.3?months. Clinical adverse events were compared between the patients accompanied with (n?=?312) and without CAD (n?=?2925).

Results: The incidence of cardiovascular events and all-cause mortality rates were significantly higher among patients with CAD than among those without CAD (5.98 vs 2.52 events per 100 patient-years, respectively, p?<?0.001; 3.27 vs 1.94 deaths per 100 patient-years, respectively, p?=?0.012), but there was no difference in strokes/transient ischemic attacks or systemic embolisms (1.70 vs 1.34). After a multivariate adjustment, CAD remained a risk factor for cardiovascular events (hazard ratio [HR]?=?1.57, 95% confidence interval [CI]?=?1.08–2.25, p?=?0.018). Among CAD patients, the propensity score-adjusted risk for major bleeding was significantly decreased among direct oral anticoagulant (DOAC) users in comparison to that among warfarin users (HR?=?0.29, 95% CI?=?0.07–0.94, p?=?0.04), but other adverse clinical events did not differ significantly between these two groups.

Conclusions: CAD did not appear to be a major determinant of strokes/TIAs, major bleeding, or all-cause mortality, but appeared to increase the risk of cardiovascular events in Japanese AF patients. The risk of major bleeding in CAD patients appeared to decrease when a DOAC rather than warfarin was administered. The data suggested that patients with AF and concomitant CAD require careful management and follow-up to reduce cardiovascular risks, and DOACs may be a better choice over warfarin when considering the risk of major bleeding.