Comparison of effectiveness and safety of treatment with apixaban vs. other oral anticoagulants among elderly nonvalvular atrial fibrillation patients

Objective: To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) of elderly (≥65 years of age) nonvalvular atrial fibrillation (NVAF) patients initiating apixaban vs. rivaroxaban, dabigatran, or warfarin.

Methods: NVAF patients with Medicare Advantage coverage in the US initiating oral anticoagulants (OACs, index event) were identified from the Humana database (1 January 2013–30 September 2015) and grouped into cohorts depending on OAC initiated. Propensity score matching (PSM), 1:1, was conducted among patients treated with apixaban vs. each other OAC, separately. Rates of S/SE and MB were evaluated in the follow-up. Cox regressions were used to compare the risk of S/SE and MB between apixaban and each of the other OACs during the follow-up.

Results: The matched pairs of apixaban vs. rivaroxaban (n?=?13,620), apixaban vs. dabigatran (n?=?4654), and apixaban vs. warfarin (n?=?14,214) were well balanced for key patient characteristics. Adjusted risks for S/SE (hazard ratio [HR] vs. rivaroxaban: 0.72, p?=?.003; vs. warfarin: 0.65, p?p?p?p?=?.27) and MB (HR: 0.82, p?=?.23) of NVAF patients treated with apixaban vs. dabigatran trended to be lower, but did not reach statistical significance.

Conclusions: In the real-world setting after controlling for differences in patient characteristics, apixaban is associated with significantly lower risk of S/SE and MB than rivaroxaban and warfarin, and a trend towards better outcomes vs. dabigatran among elderly NVAF patients in the US.     

Continuation with apixaban treatment is associated with lower risk for hospitalization and medical costs among elderly patients

Objective: To compare the risk of hospitalization and costs associated with major bleeding (MB) or stroke/systemic embolism (SE) among elderly patients with nonvalvular atrial fibrillation (NVAF) who initiated apixaban then switched to another oral anticoagulant (OAC) vs. those who continued with apixaban treatment.

Methods: NVAF patients (≥65?years) initiating apixaban were identified from the Humana database (1 January 2013–30 September 2017) and grouped into switcher and continuer cohorts. For switchers, the earliest switch from apixaban to another OAC was defined as the index event/date. A random date during apixaban treatment was selected as the index date for continuers. Patients were followed from index date to health plan disenrollment or 31 December 2017, whichever was earlier. Multivariable regression analyses were used to examine the association of switchers vs. continuers with risk of MB-related or stroke/SE-related hospitalization and healthcare costs during follow-up.

Results: Of 7858 elderly NVAF patients included in the study, 14% (N?=?1110; mean age: 78?years) were switchers; 86% (N?=?6748; mean age: 79?years) were continuers. Apixaban switchers vs. continuers had significantly greater risk of MB-related hospitalization (hazard ratio [HR]: 2.00; 95% CI: 1.52–2.64; p?<?.001) during follow-up; risk of stroke/SE hospitalization did not differ significantly (HR: 1.36, 95% CI: 0.89–2.06, p?=?.154). MB- and stroke/SE-related medical costs were higher for switchers vs. continuers, although total all-cause healthcare costs were similar.

Conclusion: Elderly patients with NVAF in the US who continued with apixaban treatment had a lower risk of MB-related hospitalization and lower MB- and stroke/SE-related medical costs compared to patients who switched to another OAC.     

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.     

Impact of renal function on ischemic stroke and major bleeding rates in nonvalvular atrial fibrillation patients treated with warfarin or rivaroxaban: a retrospective cohort study using real-world evidence

Objectives: Renal dysfunction is associated with increased risk of cardiovascular disease and is an independent predictor of stroke and systemic embolism. Nonvalvular atrial fibrillation (NVAF) patients with renal dysfunction may face a particularly high risk of thromboembolism and bleeding. The current retrospective cohort study was designed to assess the impact of renal function on ischemic stroke and major bleeding rates in NVAF patients in the real-world setting (outside a clinical trial).

Methods: Medical claims and Electronic Health Records were retrieved retrospectively from Optum’s Integrated Claims–Clinical de-identified dataset from May 2011 to August 2014. Patients with NVAF treated with warfarin (2468) or rivaroxaban (1290) were selected. Each treatment cohort was stratified by baseline estimated creatinine clearance (eCrCl) levels. Confounding adjustments were made using inverse probability of treatment weights (IPTWs). Incidence rates and hazard ratios of ischemic stroke and major bleeding events were calculated for both cohorts.

Results: Overall, patients treated with rivaroxaban had an ischemic stroke incidence rate of 1.9 per 100 person-years (PY) while patients treated with warfarin had a rate of 4.2 per 100 PY (HR?=?0.41 [0.21–0.80], p?=?.009). Rivaroxaban patients with an eCrCl below 50?mL/min (N?=?229) had an ischemic stroke rate of 0.8 per 100 PY, while the rate for the warfarin cohort (N?=?647) was 6.0 per 100 PY (HR?=?0.09 [0.01–0.72], p?=?.02). For the other renal function levels (i.e. eCrCl 50–80 and ≥80?mL/min) HRs indicated no statistically significant differences in ischemic stroke risks. Bleeding events did not differ significantly between cohorts stratified by renal function.

Conclusions: Ischemic stroke rates were significantly lower in the overall NVAF population for rivaroxaban vs. warfarin users, including patients with eCrCl below 50?mL/min. For all renal function groups, major bleeding risks were not statistically different between treatment groups.     

Safety,effectiveness, and health care cost comparisons among elderly patients with venous thromboembolism prescribed warfarin or apixaban in the United States Medicare population

Abstract

Objective: To compare safety, effectiveness, and healthcare costs of major bleeding (MB), clinically relevant non-major (CRNM) bleeding, recurrent venous thromboembolism (VTE), and all-cause hospitalization among elderly Medicare VTE patients prescribed warfarin vs apixaban.

Methods: Using 100% Medicare data, elderly patients prescribed apixaban or warfarin within 30 days after a VTE encounter were identified. Patients had continuous health plan enrollment and no parenteral or oral anticoagulant use ≤6 months preceding the VTE encounter. Cohorts were balanced using 1:1 propensity score matching (PSM). Cox proportional hazard models were used to assess the risk of MB, CRNM bleeding, recurrent VTE, and all-cause hospitalization. Generalized linear and two-part models were used to estimate MB-, recurrent VTE-, and all-cause related costs (per patient per month [PPPM]).

Results: In the pre-matched cohort, 25,284 (66.9%) patients were prescribed warfarin and 12,515 (33.1%) apixaban. After 1:1 PSM, 11,363 matched pairs of apixaban-warfarin patients were included for a mean follow-up of 4.0 and 4.4 months, respectively. Matched cohorts had a mean age of 78 years and mean Charlson Comorbidity Index score of 2.9. Warfarin was associated with a higher risk of MB (hazard ratio [HR]?=?1.31; 95% confidence interval [CI]?=?1.10–1.57) and CRNM bleeding (HR?=?1.31; 95% CI?=?1.19–1.43) vs apixaban. The risks of recurrent VTE (HR?=?0.96; 95% CI?=?0.70–1.33) and all-cause hospitalization (HR?=?1.05; 95% CI?=?0.99–1.12) were similar among warfarin and apixaban patients. Warfarin patients had higher MB-related ($147 vs $75; p?=?.003) and all-cause costs PPPM ($3,267 vs $3,033; p?<?.001), but similar recurrent VTE-related medical costs PPPM ($30 vs $36; p?=?.516) vs apixaban patients.

Conclusions: Warfarin was associated with significantly higher risk of MB and CRNM bleeding as well as higher MB-related and all-cause costs vs apixaban patients. Recurrent VTE risk and costs were similar among warfarin and apixaban patients.     

Patient-reported treatment satisfaction with rivaroxaban in Japanese non-valvular atrial fibrillation patients: an observational study

Objectives: Rivaroxaban has previously been shown to be as efficacious and safe as warfarin for the prevention of stroke in non-valvular atrial fibrillation (NVAF). Therefore, treatment satisfaction becomes an important consideration. Here we examine treatment satisfaction in Japanese NVAF patients who were switched from warfarin to rivaroxaban.

Methods: Patient-reported outcome (PRO) data were collected as part of a prospective, multi-center, post-marketing surveillance (PMS) of a direct oral-anticoagulant, rivaroxaban, in Japan. The Anti-Clot Treatment Scale (ACTS) and the Treatment Satisfaction Questionnaire for Medication version II (TSQM-II) were collected at baseline, month 3, and month 6. Change in scores from baseline to month 3 and month 6 were assessed. Exploratory analyses included change in scores by patient characteristics. Safety and effectiveness of rivaroxaban were also assessed.

Results: ACTS Burdens scores significantly improved at month 3 (54.6?±?6.3) and month 6 (54.5?±?6.5) compared to baseline (51.0?±?7.6) (p?<?.001). ACTS Benefits score remained stable over time (baseline?=?10.1?±?2.8, month 3?=?10.2?±?3.1, month 6?=?10.1?±?3.1). Mean TSQM-II sub-scale scores significantly improved at month 3 and month 6 compared to baseline for all four domains (all p?<?.001).

Conclusions: Findings suggest treatment satisfaction may improve in Japanese NVAF patients after a switch from warfarin to rivaroxaban. Higher treatment satisfaction may translate into improved treatment adherence, which is critical for the long-term prevention of stroke.     

An early evaluation of bleeding-related hospital readmissions among hospitalized patients with nonvalvular atrial fibrillation treated with direct oral anticoagulants

Objective:

Clinical trials have demonstrated that direct oral anticoagulants (DOACs) are efficacious in reducing stroke risk among patients with nonvalvular atrial fibrillation (NVAF) with differences in the reduction of bleeding risks vs. warfarin. The objective of this study was to assess bleeding-related hospital readmissions among hospitalized NVAF patients treated with dabigatran, rivaroxaban, and apixaban in the US.

Research design and methods:

Patients (≥18 years) with a discharge diagnosis of NVAF who received apixaban, dabigatran, or rivaroxaban during hospitalization were identified from the Premier Hospital database (1 January 2012–31 March 2014) and the Cerner Health Facts hospital database (1 January 2012–31 August 2014). Patients identified from each database were analyzed separately and grouped into three cohorts depending on which DOAC was received. Patient characteristics, hospital resource use and costs, and frequency of readmissions within 1 month were evaluated.

Results:

Among study populations identified from the Premier database (N?=?74,730) and the Cerner database (N?=?14,201), patients who received apixaban were older, had greater comorbidity, and had higher stroke and bleeding risks. After controlling for patient characteristics, including comorbidity and stroke and bleeding risks, compared with patients who received apixaban during their index hospitalizations, the odds of bleeding-related hospital readmissions were significantly greater by 1.4-fold (p?<?0.01) for patients who received rivaroxaban and 1.2-fold (p?=?0.16) numerically greater for patients who received dabigatran among patients identified from the Premier Hospital database. Among patients in the Cerner Health Facts hospital database, bleeding-related hospital readmissions were significantly greater by 1.6-fold (p?=?0.04) for patients who received rivaroxaban and 1.3-fold (p?=?0.30) numerically greater for patients who received dabigatran compared to patients who received apixaban.

Limitations:

No causal relationship between treatment and outcomes can be concluded.

Conclusions:

NVAF patients using different DOACs had different characteristics, including stroke and bleeding risks. Use of rivaroxaban, compared to apixaban was associated with significantly greater risk of bleeding-related readmissions across two database claims analyses.     

Modeling the impact of real-world adherence to once-daily (QD) versus twice-daily (BID) non-vitamin K antagonist oral anticoagulants on stroke and major bleeding events among non-valvular atrial fibrillation patients

Objectives: To estimate the real-world (RW) impact of adherence to once-daily (QD: rivaroxaban and edoxaban) and twice-daily (BID: apixaban and dabigatran) non-vitamin K antagonist (NOACs) on the risk of stroke and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients.

Methods: First, claims from the Optum Clinformatics Data Mart database (July 2012–December 2016) were analyzed. Adult NVAF patients with ≥2 NOAC dispensings (index date) were included. The relationship between NOAC adherence (proportion of days covered ≥80%) and stroke/MB 1-year post-index was evaluated using adjusted Cox proportional hazards models. Second, the natural logarithm of hazard ratios (HRs) was multiplied to a literature-derived mean adherence difference between QD and BID NOACs yielding stroke and MB rates. Third, these rates were multiplied by 1-year Kaplan-Meier rates of stroke and MB which yielded the number of strokes prevented and MBs caused. Annual cost savings were evaluated using literature-based stroke ($81,414/patient) and MB ($63,905/patient) cost estimates.

Results: In total, 54,280 patients were included. HRs for adherent vs non-adherent patients were 0.67 (p?<?.001) for stroke and 1.09 (p?=?.179) for MB. The claims-derived 1-year Kaplan-Meier rates were 3.0% and 3.4% for strokes and MBs, respectively. For 100,000?AF patients, 64 strokes were prevented (p?<?.001), and a non-significant number of MBs (n?=?15, p?<?.191) were caused by QD vs BID NOACs annually, which leads to cost savings estimated at $58 million for QD NOACs.

Conclusion: QD NOACs prevented a significant number of strokes and caused no significant increase in MBs compared to BID NOACs, which leads to significant net cost savings for NVAF patients in the US.     

Warfarin therapy in Chinese patients with atrial fibrillation treated with percutaneous coronary intervention: a 5 year follow-up retrospective cohort study

Objective: To evaluate warfarin use in Chinese patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) by investigating the stroke and major adverse cardiac and cerebral events (MACCEs) and bleeding events.

Methods: Retrospective cohort study of the 5?year follow-up of 1134 patients with AF who underwent PCI. The patients were grouped according to whether they received warfarin or not. Baseline characteristics and the occurrence of MACCEs and bleeding events were compared between the two groups using the CHA2DS2-VASc and HAS-BLED scoring. Cox regression analysis was used to identify factors related to the occurrence of MACCEs and bleeding.

Results: Overall MACCE (p?=?.008) and mortality (p?=?.004) rates were significantly lower in the warfarin group compared with the non-warfarin group. Major bleeding, minor bleeding and overall bleeding were comparable in the two groups. Recurrent myocardial infarction (HR?=?10.129, 95% CI?=?4.737–21.655; p?<?.001) and a baseline CHA2DS2-VASc score >4 (HR?=?2.035, 95% CI?=?1.121–3.692; p?=?.019) were independent predictors of MACCEs in the warfarin group. A baseline HAS-BLED score ≥3 (HR?=?5.498, 95% CI?=?3.773–8.013; p?<?.001) and previous bleeding (HR?=?3.058, 95% CI?=?1.319–7.088; p?=?.009) were independent predictors of bleeding.

Conclusions: Warfarin reduces the incidence of MACCEs but does not increase bleeding events in Chinese patients with AF who underwent PCI. For patients taking warfarin, recurrent myocardial infarction and a baseline CHA2DS2-VASc score >4 were related to MACCE occurrence.     

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.     

Effectiveness and safety of rivaroxaban in nonvalvular atrial fibrillation: data from a contemporary Spanish registry

Objective: To ascertain the clinical profile, management and rates of thromboembolic and bleeding complications in a contemporary cohort of patients with nonvalvular atrial fibrillation (NVAF) on rivaroxaban treatment, with a particular focus on some subgroups of patients.

Methods: Retrospective study that included all NVAF patients who started treatment with rivaroxaban for the prevention of stroke or systemic embolism between December 2012 and December 2015. Rates of outcomes (stroke, nonfatal myocardial infarction, major bleeding, intracranial bleeding and death) during follow-up were calculated.

Results: A total of 732 patients (mean age 76.4?±?9.2?years; 54.5% women) were included. Comorbidities were common (hypertension 87.5%; diabetes 26.5%; renal insufficiency 24.6%; prior stroke/transient ischemic attack 16.8%). Mean CHA₂DS₂-VASc was 3.9?±?1.5 and HAS-BLED 2.3?±?0.9; 61.9% of patients were rivaroxaban naïve users. After a mean treatment period of 22.7?±?7.4?months, rates of stroke, nonfatal myocardial infarction, major bleeding, intracranial bleeding and death were 1.8, 1.0, 3.2, 0.4 and 5.5 events per 100 patient-years, respectively. Rates of stroke and death were higher in patients >75?years (vs. ≤75?years) and in patients with prior stroke/transient ischemic attack or renal insufficiency. Rates of major bleeding were higher among patients >75?years and in patients with prior stroke/transient ischemic attack.

Conclusions: In this contemporary Spanish cohort of NVAF patients on rivaroxaban, patients had many comorbidities, a high thromboembolic risk and a moderate bleeding risk. Overall, rates of stroke and bleeding complications were low and similar to other previous studies. These data suggest that rivaroxaban is effective and safe in routine practice.     

Real-life behaviour of direct oral anticoagulants in a Spanish cohort with non-valvular atrial fibrillation: Refase Registry

Abstract

Aim: To analyse the effectiveness and safety of DOAC (direct oral anticoagulants) in non-valvular atrial fibrillation (NVAF) patients attending clinical practice.

Methods: Retrospective study of AF patients who started treatment with DOAC from January 1, 2013 to December 31, 2016 in three Spanish hospitals. Mean follow-up was 1.6?years. The primary outcomes were rates of all-cause death, ischaemic stroke, and bleeding. These outcomes were also studied depending on correct dosage adjustment and standard/adjusted dose.

Results: The study included 2494 patients (age = 76.0?±?9.5?years, CHA₂DS₂-VASc = 4.0?±?1.6). The most prescribed DOAC was rivaroxaban (41.1%). Patients taking dabigatran were the youngest (mean age = 73.1?±?10.3 years), with better kidney function (mean CrCl = 80.6?±?35.8?ml/min) and lower CHA₂DS₂-VASc (3.7?±?1.4) and HAS-BLED (2.1?±?0.9) scores. Patients taking apixaban were the oldest, and had the highest CHA2DS2-VASc and HAS-BLED scores (4.3?±?1.6 and 2.6?±?0.9, respectively). Rates of stroke/major bleeding/intracranial bleeding were 1.8/3.0/0.3 events per 100 patient-years, respectively, with no differences among DOAC. Based on dose adjustment according to technical data, it was observed that 517 patients (23.5%) received DOAC doses inconsistent with labelling (p?<?.001) and, within this group, under-dosed patients had a higher death rate although it did not reach a significant result after multivariate adjustment.

Conclusions: The results of safety and efficacy are very similar to those of other previously published national registries. There were no differences among the different types of DOAC regarding outcomes. However, it was found that people taking the adjusted dose of the drug seemed to have a higher risk of death. A non-negligible proportion of patients received DOAC doses inconsistent with labelling (mostly underdose).     

Uric acid and incident chronic kidney disease in dyslipidemic individuals

Background: Elevated uric acid (UA) is a recognized risk factor for chronic kidney disease (CKD). This study aimed to investigate whether this association exists in dyslipidemic patients receiving multifactorial treatment.

Methods: An observational study conducted in Greece including 1,269 dyslipidemic individuals followed-up in a lipid clinic for ≥3 years. Estimated glomerular filtration rate (eGFR) was calculated by CKD-EPI equation and CKD was defined as ≤60?mL/min/1.73 m². The correlation was assessed between UA levels and the CKD risk after adjusting for potential confounding factors, after defining the following UA quartiles: Q1: ?6?mg/dL.

Results: After excluding patients with baseline eGFR <60?mL/min/1.73 m², gout and those taking UA-lowering drugs, 1,095 individuals were eligible; of those, 91% and 69% were treated with statins and anti-hypertensive drugs, respectively. During their follow-up (6 years; IQR?=?4–10), 11.9% of the subjects developed CKD, whereas the median annual eGFR decline was 0.69?mL/min/1.73 m² (IQR?=?0.45–2.33). Multivariate analysis showed that baseline UA levels (HR?=?1.26; 95% CI?=?1.09–1.45, p?=?.001), female gender (HR?=?1.74; 95% CI?=?1.14–2.65, p?=?.01), age (HR?=?1.10; 95% CI?=?1.07–1.12, p?p?=?.03), cardiovascular disease (HR?=?1.62; 95% CI?=?1.02–2.58, p?=?.04), decreased baseline renal function (eGFR <90?mL/min/1.73 m²) (HR?=?2.38; 95% CI?=?1.14–4.81, p?=?.02), and low-density lipoprotein cholesterol reduction (HR?=?0.995; 95% CI?=?0.991–0.998, p?=?.01) were associated with incident CKD. Additionally, patients with UA ≥6?mg/dL exhibited a higher risk of incident CKD compared with those in the lowest UA quartile (HR?=?2.01; 95% CI?=?1.11–3.65, p?=?.02).

Conclusion: Higher UA levels are correlated with a higher risk of incident CKD in dyslipidemic individuals taking multifactorial treatment.     

Efficacy of neodymium-doped yttrium aluminum garnet laser iridotomies in primary angle-closure diseases: superior peripheral iridotomy versus inferior peripheral iridotomy

Purpose: To evaluate the efficacy and safety of superior peripheral iridotomy versus inferior peripheral iridotomy in the treatment of primary angle-closure glaucoma (PACG) in phakic patients.

Methods: In this randomized, prospective, paired-eye comparative study, patients with primary angle closure or primary angle-closure suspects were recruited and randomized to receive neodymium-doped yttrium aluminum garnet (Nd:YAG) laser peripheral iridotomy (LPI) superiorly in one eye and inferiorly in the other eye. Patients were masked to the location of treatment in each eye. The main outcome measures were patency of iridotomy, intraocular pressure (IOP), complications and visual symptoms at each postoperative visit during a 1 year follow-up.

Results: A total of 164 patients were recruited, of whom 150 (91.46%) completed the study. The mean age was 58.85?±?6.4 years. Average IOP measurements before LPI was 22.85?±?7.53 and 23.62?±?8.32 in superior LPI and inferior LPI eyes respectively. After LPI, average IOP was 25.14?±?2.73 and 20.97?±?2.72 in superior LPI and inferior LPI eyes respectively. Inferior LPIs required less use of mean total laser energy to perforate the tissue (p?=?.05) and resulted in a significantly lower incidence of iris bleeding at the time of treatment (p?=?.004), lower IOP elevation following treatment (p?=?.002), lower incidence of focal corneal damage (p?=?.002) and a lower post-laser iritis (p?=?.04). All the 300 iridotomies were patent at 12 month follow up.

Conclusion: The inferior LPI appeared to be an efficient method of preventing pupil block with fewer complications. Visual symptoms following inferior LPI are similar to superior LPI.     

Safety and efficacy of non-vitamin K oral anticoagulants in non-valvular atrial fibrillation: a Bayesian meta-analysis approach

Introduction: Choosing between different non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF) is difficult due to the absence of head to head comparative studies. We performed a Bayesian meta-analysis to explore similarities and differences between different NOACs and to rank treatments overall for safety and efficacy outcomes.

Areas covered: Through a systematic literature search we identified randomized controlled Phase III trials of dabigatran, rivaroxaban, apixaban, and edoxaban versus adjusted-dose warfarin in patients with NVAF.

Expert opinion: Warfarin ranked worst for all-cause mortality and intracranial bleedings and had a nil probability of ranking first for any outcome. The risk of major bleeding versus warfarin was lower with apixaban, dabigatran 110 mg, and both doses of edoxaban. All agents reduced the risk of intracranial bleeding versus warfarin. Edoxaban 30 mg was the best among the treatments being compared for major and gastrointestinal bleeding. Dabigatran 150 mg was the best for stroke and systemic embolism. This study suggests that NOACs are generally preferable to warfarin in patients with NVAF. However, safety and efficacy differences do exist among NOACs, which might drive their use in specific subsets of AF patients, allowing prescribers to tailor treatment to distinct patient profiles.     

Warfarin time in therapeutic range and its impact on healthcare resource utilization and costs among patients with nonvalvular atrial fibrillation

Background:

Warfarin is efficacious for reducing stroke risk among patients with nonvalvular atrial fibrillation (NVAF). However, the efficacy and safety of warfarin are influenced by its time in therapeutic range (TTR).

Objective:

To assess differences in healthcare resource utilization and costs among NVAF patients with low (<60%) and high (≥60%) warfarin TTRs in an integrated delivery network (IDN) setting.

Methods:

Patients with NVAF were identified from an electronic medical record database. Patients were required to have ≥6 international normalized prothrombin time ratio (INR) tests. NVAF patients were grouped into two cohorts: those with warfarin TTR <60% (low TTR) and those with warfarin TTR ≥60% (high TTR). Healthcare resource utilization and costs were evaluated during a 12 month follow-up period. Multivariable regressions were used to assess the impact of different warfarin TTRs on healthcare costs.

Results:

Among the study population, greater than half (54%, n?=?1595) had a low TTR, and 46% (n?=?1356) had a high TTR. Total all-cause healthcare resource utilization was higher among patients in the low TTR cohort vs. the high TTR cohort (number of encounters: 70.2 vs. 56.1, p?<?0.001). After adjusting for patient characteristics, total all-cause healthcare costs and stroke-related healthcare costs were $2398 (p?<?0.001) and $687 (p?=?0.02) higher, respectively, for patients in the low TTR cohort vs. the high TTR cohort.

Limitations:

In this retrospective study, we were only able to evaluate the association and not the causality between healthcare resource utilization and costs with the different warfarin TTRs.

Conclusion:

Many warfarin-treated NVAF patients have a low warfarin TTR. NVAF patients with low vs. patients with high warfarin TTR used healthcare resources to a greater extent, which was reflected in higher healthcare costs.     

More light at the end of the tunnel – apixaban in atrial fibrillation

Introduction: Subjects with atrial fibrillation are at risk of thromboembolic events. The vitamin K antagonists (e.g., warfarin) are useful at preventing coagulation in atrial fibrillation, but are difficult to use. One of the FXa inhibitors, oral apixaban, has been tested as an anticoagulant in atrial fibrillation.

Areas covered: In ARISTOTLE (Apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation) apixaban was compared to warfarin in subjects with atrial fibrillation, and shown to cause a lower rate of stroke or systemic embolism and of major bleeding, than warfarin. In the AVERROES (Apixaban versus acetylsalicylic acid [ASA] to prevent stroke in atrial fibrillations patients who have failed or are unsuitable for vitamin K antagonist treatment) trial, stroke or systemic embolism occurred less often with apixaban than aspirin, whereas the occurrence of major bleeding was similar in the groups.

Expert opinion: Apixaban is much easier for subjects with atrial fibrillation to use than warfarin, as it does not require regular monitoring by a health professional, with dosage adjustment. In addition to replacing warfarin in subjects with atrial fibrillation who are unable or not prepared to use warfarin, apixaban has the potential to replace warfarin more widely in the prevention of thromboembolism in subjects with atrial fibrillation.     

Influence of andrographolide on the pharmacokinetics of warfarin in rats

Context: Andrographolide and warfarin are often used together in clinics in China. However, the herb-drug interaction between andrographolide and warfarin is still unknown.

Objective: This study investigates the herb-drug interaction between andrographolide and warfarin in vivo and in vitro.

Materials and methods: A sensitive and reliable LC-MS/MS method was developed for the determination of warfarin in male Sprague-Dawley rats plasma, and then the pharmacokinetics of orally administered warfarin (0.5?mg/kg) with or without andrographolide (30?mg/kg/day for 7?days) pretreatment was investigated. In addition, Sprague-Dawley rat liver microsomes incubation systems were used to support the in vivo pharmacokinetic data and investigate its potential mechanism.

Results: The method validation results showed that a sensitive and reliable LC-MS/MS method was developed for the determination of warfarin in rat plasma samples. The pharmacokinetic results indicated that co-administration of andrographolide could increase the systemic exposure of warfarin significantly, including area under the curve (118.92?±?18.08 vs. 60.58?±?9.46?μg?×?h/mL), maximum plasma concentration (3.32?±?0.41 vs. 2.35?±?0.25?μg/mL) and t_1/2 (22.73?±?3.28 vs. 14.27?±?2.67?h). Additionally, the metabolic stability of warfarin increased from 23.5?±?4.7 to 38.7?±?6.1?min with the pretreatment of andrographolide, and the difference was significant (p?Discussion and conclusion: In conclusion, andrographolide could increase the systemic exposure of warfarin in rats when andrographolide and warfarin were co-administered, and possibly by slowing down the metabolism of warfarin in rat liver by inhibiting the activity of CYP3A4 or CYP2C9.