Dataset Information

Indirect comparison of novel Oral anticoagulants among Asians with non-Valvular atrial fibrillation in the real world setting: a network meta-analysis.

ABSTRACT:

Background

The development of novel oral anticoagulants (NOACs) has changed the landscape of non-valvular atrial fibrillation (NVAF) management. In this study, the effectiveness and the safety of several NOACs were evaluated in a real-world setting among Asian patients with NVAF.

Methods

The literature search was conducted crossing different databases including Embase, MEDLINE, and the Cochrane Library from inception through March 1, 2019, for studies which included real-world perspectives comparing the individual NOACs with each other or with warfarin among Asians with NVAF. The primary outcomes were defined as stroke or systemic embolism (SSE) and major bleeding; ischemic stroke, all-cause death as well as intracranial bleeding were classified as the secondary outcomes.

Results

From sixteen real-world studies, a total of 312,827 Asian patients were included in this analysis. In comparison with warfarin, the utilization of apixaban, dabigatran, and rivaroxaban significantly lowered the risk of major bleeding (apixaban: HR 0.47, 95%CI 0.35-0.63; dabigatran: HR 0.59, 95%CI 0.47-0.73; rivaroxaban: HR 0.66, 95%CI 0.52-0.83) and lessened the all-cause death rate (apixaban: HR 0.29, 95%CI 0.16-0.52; dabigatran: HR 0.40, 95%CI 0.27-0.60; rivaroxaban: HR 0.42, 95%CI 0.28-0.65). Apixaban (HR 0.59; 95%CI 0.40-0.85) reduced the possibility of ischemic stroke when compared against dabigatran. Rivaroxaban showed a higher chance of causing an ischemic stroke (HR 1.61; 95%CI 1.08-2.41) and major bleeding (HR 1.39; 95%CI 1.02-1.90) than Apixaban.

Conclusions

Apixaban, dabigatran and rivaroxaban were more effective than warfarin on reducing the risks of stroke and haemorrhage; meanwhile, apixaban was likely to lower the risk of major bleeding comparing to rivaroxaban.

Trial registration

PROSPERO registry number: CRD42018086914 .

SUBMITTER: Zhang J

PROVIDER: S-EPMC6670242 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Indirect comparison of novel Oral anticoagulants among Asians with non-Valvular atrial fibrillation in the real world setting: a network meta-analysis.

Zhang Jianchao J Tang Junnan J Cui Xiaolin X Wang Bo B Bu Mengsen M Bai Yan Y Wang Kai K Guo Jiacheng J Shen Deliang D Zhang Jinying J

BMC cardiovascular disorders 20190731 1

<h4>Background</h4>The development of novel oral anticoagulants (NOACs) has changed the landscape of non-valvular atrial fibrillation (NVAF) management. In this study, the effectiveness and the safety of several NOACs were evaluated in a real-world setting among Asian patients with NVAF.<h4>Methods</h4>The literature search was conducted crossing different databases including Embase, MEDLINE, and the Cochrane Library from inception through March 1, 2019, for studies which included real-world per ...[more]

PMID: 31366374

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Project description:OBJECTIVES:To examine the characteristics and persistence in patients newly initiated with oral anticoagulants (OACs) for stroke prevention in non-valvular atrial fibrillation (NVAF). DESIGN:Cohort study in Clinical Practice Research Datalink. SETTING:UK primary care. PARTICIPANTS:15?242 patients with NVAF newly prescribed apixaban, rivaroxaban, dabigatran or vitamin K antagonists (VKAs) between 1 December 2012 and 31 October 2014. 13?089 patients were OAC naïve. OUTCOME MEASURES:Patient characteristics and risk of non-persistence compared to apixaban using Cox regression models over the entire follow-up and using a time-partitioned approach to handle non-proportional hazards. RESULTS:Among the OAC naïve patients, VKAs were most common (78.1%, n=10?218), followed by rivaroxaban (12.1%, n=1589), dabigatran (5.7%, n=741) and apixaban (4.1%, n=541). High baseline stroke risk (CHA2DS2VASc ?2) ranged from 80.2% (dabigatran) to 88.4% (apixaban and rivaroxaban). History of stroke and bleeding was the highest among apixaban (23.7% and 31.6%) and lowest among VKA patients (15.9% and 27.5%). Across the entire follow-up period, adjusting for differences in characteristics, there was no evidence of a difference in non-persistence between VKA and apixaban (HR 0.92 (95% CI 0.68 to 1.23)). Non-persistence was higher with dabigatran (HR 1.67 (1.20 to 2.32)) and rivaroxaban (HR 1.41 (1.02 to 1.93)) than apixaban. Using the partitioned approach, non-persistence was lower with VKA (HR 0.33 (0.22 to 0.48)), and higher with dabigatran (HR 1.65 (1.08 to 2.52)) compared to apixaban in the first 2?months of follow-up. After 2?months, non-persistence was higher with VKA (HR 1.70 (1.08 to 2.66)) and dabigatran (HR 2.10 (1.30 to 3.41)). Pooling OAC naïve and experienced patients, non-persistence was also higher with rivaroxaban compared to apixaban after 2?months of follow-up (HR 1.69 (1.19 to 2.39)). CONCLUSIONS:Observed differential prescribing of OACs can result in channelling bias in comparative effectiveness research. Persistence patterns changed over follow-up time, but there are indications of improved persistence rates with apixaban over other OACs in the UK. A larger study with longer follow-up is needed to corroborate findings. This study is registered on ClinicalTrials.gov (NCT02488421).

Project description:Background: In the clinical setting, the economic benefits of direct oral anticoagulants (DOACs) in elderly patients with atrial fibrillation (AF) remain unclear. This study aimed to estimate and compare the cost-effectiveness of DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) and vitamin K antagonists (VKAs; warfarin) in preventing stroke among AF patients aged >75 years in real-world practice. Methods: A Markov model with a 10-year span was constructed to estimate the long-term clinical and economic outcomes among AF patients aged >75 years treated with DOACs and warfarin. The study was populated with a hypothetical cohort of 10,000 AF patients aged >75 years. Probabilities of clinical outcomes were obtained from the pooled observational studies (OSs), comparing DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) with VKAs. Other model inputs, including the utilities and the costs, were all estimated from public sources and the published literature. The costs, quality-adjusted life-years (QAYLs), and incremental cost-effectiveness ratios (ICER) were estimated for each treatment strategy. Subgroup analyses of individual DOACs and the scenario analysis were performed. Uncertainty was evaluated by deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA). Results: Compared to warfarin, DOACs were associated with a gain of 0.36 QALY at an additional cost of $15,234.65, resulting in an ICER of $42,318.47 per QALY. Sensitivity analysis revealed that the ICER was sensitive to the cost of DOACs. Direct oral anticoagulants also shifted from dominating to dominated status When their annual costs of DOACs were over $3,802.84 or the risk ratio of death compared to warfarin was over 1.077%/year. Probabilistic sensitivity analysis (PSA) suggested that DOACs had a 53.83 and 90.7% probability of being cost-effective when the willingness-to-pay threshold was set at $50,000 and $100,000, respectively. Among all the four individual DOACs, edoxaban treatment was revealed as the preferred treatment strategy for the AF patients aged over 75 years by yielding the most significant health gain with the relatively low total cost. Conclusions: Despite the high risk for major bleeding in elderly patients with AF, DOACs are more cost-effective treatment options than warfarin in real-world practice. Edoxaban was the preferred treatment strategy among four kinds of DOACs for AF patients aged over 75 years. Furthermore, beyond their safety profiles, the treatment benefits of DOACs assumed greater relevance and importance in older adults.

Project description:BackgroundThe incidence of osteoporotic fracture increases with age, particularly in elderly populations with atrial fibrillation (AF). However, direct oral anticoagulants (DOACs) have less effect on osteoporotic fracture than vitamin K antagonists, it is unclear whether the risk of osteoporotic fracture is affected by different types and doses of DOACs in AF patients.MethodsThis nationwide population-based cohort study included AF patients prescribed DOACs between 2011 and 2016 taken from the Taiwan National Health Insurance database. Adjusted hazard ratios (aHRs) for the risk of osteoporotic, hip, and spine fractures between DOAC users were compared using the Fine and Gray subdistribution hazard model to adjust for possible confounders.ResultsA total of 56,795 patients who were prescribed DOACs were included in the present study. Among them, 24,597 patients received dabigatran, 26,968 received rivaroxaban, and 5230 received apixaban. After 2 years' follow up, there was no significant difference in the incidence of osteoporotic, spine, or hip fracture among those receiving dabigatran, rivaroxaban, or apixaban. Subgroup analysis showed that patients taking dabigatran had a higher incidence of osteoporotic and hip fracture than those taking rivaroxaban and apixaban in cases with concomitant peripheral artery disease (PAD) or a history of hip fracture (p for interaction: 0.004 and 0.030, respectively). However, dabigatran users had a lower incidence of osteoporotic fracture and spine fracture in those receiving standard-dose DOACs compared with rivaroxaban and apixaban; whereas, they had a higher incidence of hip fractures when administered at low dose.ConclusionAF patients with different DOACs did not have different risks of osteoporotic fracture overall. However, additional concomitant morbidities, such as PAD or a history of hip fracture, and standard/low doses might be associated with different risks for different DOACs. These findings should be taken into consideration in the clinic when the DOAC is being chosen.Plain language summaryDifferent direct oral anticoagulants had different impact on osteoporotic fracture Anticoagulation therapy is an essential therapy in atrial fibrillation (AF) patients, but osteoporotic fracture is another important issue in these patients prescribed with anticoagulants. However, no study has been conducted to evaluate the impact of different DOACs on different types of osteoporotic fractures. In our findings, although different DOACs had no significantly different impact on osteoporotic fractures, dabigatran users had a slightly higher incidence of osteoporotic and hip fractures among different DOACs, particularly in those have simultaneously had peripheral artery disease, a history of hip fracture. In addition, when AF patients taking low-dose DOACs, dabigatran users also have higher incidence of hip fracture than those taking other DOACs.

Dataset Information

Indirect comparison of novel Oral anticoagulants among Asians with non-Valvular atrial fibrillation in the real world setting: a network meta-analysis.

Background

Methods

Results

Conclusions

Trial registration

Publications

Indirect comparison of novel Oral anticoagulants among Asians with non-Valvular atrial fibrillation in the real world setting: a network meta-analysis.

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