Direct Oral Anticoagulants: An Updated Systematic Review of Their Clinical Pharmacology and Clinical Effectiveness and Safety in Patients With Nonvalvular Atrial Fibrillation.

Direct oral anticoagulants have been an increasingly used class of drugs in the setting of nonvalvular atrial fibrillation, defying vitamin K antagonists' monopoly when it comes to anticoagulation due to its several limitations. Direct oral anticoagulants (DOACs) have entered the market as a noninferior and safer option in comparison with vitamin K antagonists, as their respective phase III clinical trials proved. The aim of this article was to update and summarize data on their clinical pharmacology and to review real-world data to know their comparative effectiveness and safety. We performed a systematic review using PubMed, Google Scholar, Embase, and Web of Science as search engines. Regarding pharmacodynamics, there were no substantial changes reported from their original profile. There were many advances in the knowledge about clinical pharmacokinetics of DOACs that have had a direct impact on their clinical use, mainly related to drug-drug interactions. In a real-world setting, DOACs have shown to be noninferior in preventing thromboembolic events compared to vitamin K antagonists. In regards to safety, DOACs have shown a lower bleeding risk relative to warfarin. Comparison between DOACs has demonstrated rivaroxaban to have the highest bleeding risk. Overall, the evidence gathered showed few changes from the original data presented in phase III clinical trials, concluding that their real-world use coincides greatly with them.

Real-world data meta-analysis: procedural success and clinical outcomes after radiofrequency ablation of atrial fibrillation in South America.

OBJECTIVE: To profile patients' characteristics, in-hospital results, and recurrence rates after radiofrequency ablation of atrial fibrillation (RAAF) in South America. METHODS: We comprehensively searched for single-center studies from South America with ≥10 patients receiving RAAF, published or presented from January 1, 2010, through June 29, 2020, excluding those reports aimed to specific populations such as permanent atrial fibrillation, structural cardiopathies, or re-do procedures. RESULTS: Main pooled estimates from a random-effects meta-analysis that included 3909 patients from 27 cohorts (from 5 countries): a) Patients characteristics: age 57.6 years (95% CI 55.7-59.5), male gender 71.5% (95% CI 67.0-75.6%), hypertension 54.2% (95% CI 45.4-62.8%), paroxysmal atrial fibrillation 79.8% (95% CI 71.3-94.5%), CHADS score 1.2 (95% CI 0.5-1.9), b) Acute procedural success 91.1% (95% CI 82.2-95.8%), c) In-hospital complications: stroke 0.6% (95% CI 0.3-1.2%), cardiac tamponade 2.3% (95% CI 1.4-3.7), hematoma 3.5% (95% CI 2.0-6.1), pseudoaneurysm 1.2% (95% CI 0.6-2.3), arteriovenous fistula 2.5% (95% CI 1.6-4.1). There were no cases of esophageal-atrial fistula nor death. Pooled estimate for arrhythmia recurrence (excluded 3-months blanking period) at 12 months was 19.9% (95% CI 17.0-23.1). CONCLUSION: In-hospital results of RAAF reported for South American centers were worse than published international registries, even when included populations profile was of lower risk, as reflected in younger age and less prevalence of non-paroxysmal AF. Late recurrence rates seemed appropriate. This study provides a real-life framework for the analysis of the performance of this technology in the region.

Temporal Trends in Self-Expandable Transcatheter Aortic Valve Replacement in South America: A Systematic Review and Meta-Analysis.

OBJECTIVES: This study aimed to estimate temporal trends in clinical presentation and short-term outcomes of transcatheter aortic valve replacement (TAVR) with self-expandable prostheses in South America through a systematic review and meta-analysis of observational data. METHODS: We comprehensively searched for articles published in peer-reviewed medical journals and for abstracts presented in medical conferences of the region from September 1, 2008, to June 29, 2020. We included single-center studies on self-expandable TAVR populations with ≥ 10 patients from South America. RESULTS: A total of 28 cohorts from 6 countries pooling 1780 patients were included in a random-effects meta-analysis. Pooled estimates of age changed during time (period 2011-2015, 81.6 years; 95% confidence interval [CI] 80.7-82.4; period 2016-2018, 80.6 years; 95% CI 79.8-81.3; period 2019: 78.5 years; 95% CI 77.0-80.0; P = .0003); no other temporal trends in patient characteristics were ascertained. Temporal trends in short-term mortality pooled estimates were in-hospital mortality (11.8% [95% CI 8.2-16.7] for the period 2011-2015, 6.6% [95% CI 4.5-9.6] for the period 2016-2018, and 4.4% [95% CI 1.9-9.8] for the period 2019 [P = .007]) and 30-day mortality (12.8% [95% CI 7.7-20.4], 9.7% [95% CI 7.0-13.3], and 5.7% [95% CI 2.8-11.3], respectively [P =.044]). These associations between reporting year of the study and lower mortality remained after adjusting by age and surgical risk (multivariate meta-regression). CONCLUSIONS: In studies reported between 2011 and 2019 in South America, we demonstrated a clear time trend toward reduction of short-term mortality after self-expandable TAVR, independently of age and surgical risk of populations. These findings are relevant to the local reassessment of cost-effectiveness of TAVR.

Clinical outcomes after transcatheter aortic valve replacement in South America: A centre-level systematic review and meta-analysis of observational data.

OBJECTIVES: To estimate in-hospital and 30-day outcomes after transcatheter aortic valve replacement (TAVR) in South America through a systematic review and meta-analysis of observational data. METHODS: We comprehensively searched for papers published in peer-reviewed medical journals and for abstracts presented in medical conferences of the region from 1 September 2008, through 29 June 2020, using predefined criteria. We included single-centre studies on TAVR populations with ≥10 patients from South America reporting any in-hospital or 30-day clinical outcome. RESULTS: Fifty-five cohorts from seven countries, pooling 3001 patients, were included in a random-effects meta-analysis. Self-expandable prostheses were the most frequently implanted. Pooled estimate of procedure success by VARC2 criteria was 90.0% (95%CI 81.8%-94.7%; I2 75.0%). The pooled estimate rates of the outcomes were as follow: post-procedure moderate or severe aortic regurgitation, 9.7% (95%CI 6.0%-15.4%; I2 65.4%), in-hospital cardiac tamponade, 4.0% (95%CI 2.5%-6.6%; I2 0%), in-hospital stroke, 4.1% (95%CI 2.9%-5.7%; I2 0%), in-hospital major vascular complication, 7.8% (95%CI 5.2%-11.5%; I2 22.3%), in-hospital permanent pacemaker implantation, 19.4% (95%CI 15.9%-23.4%; I2 53.8%), in-hospital mortality, 8.0% (95%CI 6.7%-9.6%; I2 0%), and 30-day mortality, 9.7% (95%CI 7.9%-11.8%; I2 26.4%). CONCLUSION: As compared with published international registries, the overall results of TAVR in South America seemed underrated. Significant heterogeneity was observed in procedural success, pacemaker requirement, and post-procedure moderate or severe aortic regurgitation. This study provides a real-life framework for the analysis of the performance of this technology in the region, intended to be a starting point for quality improvement.

Estimation of the cost-effectiveness of apixaban versus vitamin K antagonists in the management of atrial fibrillation in Argentina.

Apixaban, a novel oral anticoagulant which has been approved for the prevention of stroke and systemic embolism in non-valvular atrial fibrillation, reduces both ischemic and haemorrhagic stroke and produces fewer bleedings than vitamin K antagonist warfarin. These clinical results lead to a decrease in health care resource utilization and, therefore, have a positive impact on health economics of atrial fibrillation. The cost-effectiveness of apixaban has been assessed in a variety of clinical settings and countries. However, data from emergent markets, as is the case of Argentina, are still scarce.We performed a cost-effectiveness analysis of apixaban versus warfarin in non-valvular atrial fibrillation (NVAF) in patients suitable for oral anticoagulation in Argentina. A Markov-based model including both costs and effects were used to simulate a cohort of patients with NVAF. Local epidemiological, resource utilization and cost data were used and all inputs were validated by a Delphi Panel of local experts. We adopted the payer's perspective with costs expressed in 2012 US Dollars.The study revealed that apixaban is cost-effective compared with warfarin using a willingness to pay threshold ranging from 1 to 3 per capita Gross Domestic Product (11558 - 34664 USD) with an incremental cost-effectiveness ratio of 786.08 USD per QALY gained. The benefit is primarily a result of the reduction in stroke and bleeding events.The study demonstrates that apixaban is a cost-effective alternative to warfarin in Argentina.