(A) and major bleeding
Gli anticoagulanti diretti nel mondo reale Il neurologo: Efficacia e sicurezza Antonio Carolei* e Cindy Tiseo Clinica Neurologica e Stroke Unit Avezzano - Sulmona Università degli Studi dell’Aquila *Presidente Italian Stroke Organization Roma, 15 febbraio 2016 Natural history of AF J Am Heart Assoc 2016;5:e002984 doi: 10.1161/JAHA.115.002984 …despite a great unmet need for safer antiarrhythmic drugs, developments in this field are expected to be much slower Two potential antiarrhythmic drugs are forecast to enter the market within the next decade. Both drugs candidates are expected to launch late in the forecast period and will not reach peak sales until after 2023 The low level of activity in the pipeline is expected to continue due to the high risk involved in developing antiarrhythmic drugs VKAs vs NOACs Decision tree for antithrombotic therapy in patients with nvAF Antithrombotic therapy Eur Heart J 2012;33:2719-2747 & Europace 2015;17:1467-507 Why should we care about any real world data versus clinical trial? Efficacy (Clinical trial data) Effectiveness (Real-world data) Does it work under ideal circumstances? Controlled clinical trial environment Geared to get FDA approval Fixed regimen with highly motivated patients Compliance usually high External validity - low to medium Does it work under usual circumstances? Real world clinical practice Drug performance in the real world Flexible regimen with your regular day to day clinic patient Low to high compliance External validity - medium to high Favourable risk-benefit profile Lancet 2014;383:955-962 Efficacy of NOAC in the SPAF Trials Ischemic stroke or Systemic embolism RRR 19% Major bleeding RRR 14% Lancet 2014;383:955-962 * Efficacy of NOAC in the SPAF Trials Secondary efficacy and safety outcomes Ischemic vs hemorrhagic stroke RRR 8% RRR 51% RRR 52% Lancet 2014;383:955-962 * * Stroke or SE Major bleeding Compared OR for all-cause with standard stroke oradjusted systemicdose embolism VKA, (A) newand oralmajor anticoagulants bleeding (B) were in associated Bayesian network with modest meta-analysis reductions versus in standard the absolute adjusted riskdose of stroke VKA. CrI, andcredible major bleeding. interval; VKA, vitamin K antagonist. BMJ Open 2014;4:e004301 What do these meta-analyses tell us? Overall the results appear reassuring for the NOACs NOACs are associated with significant reduction in major bleeding, fatal bleeding, intracranial bleeding, clinically relevant non-major bleeding and total bleeding However, results should be interpreted in the context that these analyses included patients that participated in major randomized trials where the environment was more controlled They may not reflect the “true” incidence of bleeding in the real day to day clinical practice world The EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot Registry has provided systematic collection of contemporary data regarding the management and treatment of AF by cardiologists in ESC member countries Oral anticoagulant use has increased, but novel OAC use was still low (8%). Compliance with the treatment guidelines for patients with the lowest and higher stroke risk scores remains suboptimal Europace 2014:16,308-319 Between February 2012 and March 2013 Europace 2014:16,308-319 * J Am Coll Cardiol 2013 ;61:2264-73 Major bleedings Warfarin vs Apixaban MARKETSCAN REAL-WORLD Studio ARISTOTLE HR=0.69 (95% CI: 0.60–0.80) HR=0.52 (95% CI: 0.30–0.89) RRR 31% RRR 48% 3.09 2.13 N=9052 N=9088 Incidenza dell’evento (%/anno) 4.66 N Engl J Med 2011;365:981-92 & Lip ESC 2015 2.35 N=12,713 N=2402 Major bleedings Warfarin vs Apixaban - Rivaroxaban - Dabigatran RRR 48% Lip ESC 2015 RRR 12% XANTUS vs ROCKET-AF Eur Heart J 2015 [Epub ahead of print] Comparison of Major Bleeding, Stroke and Associated Medical Costs among Treatment-naïve Non-valvular Atrial Fibrillation Patients Initiating Apixaban, Dabigatran, Rivaroxaban or Warfarin within One Year of Treatment Initiation Major bleedings Adjusted HR: 0.87; 95% CI: 0.74 – 1.03 P = 0.109 Adjusted HR: 0.71, RRR 29%; 95% CI: 0.62– 0.82 P < 0.001 * Adjusted HR: 0.71, RRR 29%; 95% CI: 0.62 – 0.80 P < 0.001 Favours Apixaban Favours comparator Adjusted HR *ARISTOTLE: HR=0.69 (95% CI 0.60–0.80) RRR 31%, P< 0.001 for superiority Comparison of Major Bleeding, Stroke and Associated Medical Costs among Treatment-naïve Non-valvular Atrial Fibrillation Patients Initiating Apixaban, Dabigatran, Rivaroxaban or Warfarin within One Year of Treatment Initiation Stroke and SE Adjusted HR: 0.91; 95% CI: 0.81 – 1.02 P = 0.120 Adjusted HR: 0.94; 95% CI: 0.86 – 1.04 P = 0.215 * Adjusted HR: 0.74, RRR 26%; 95% CI: 0.68 – 0.81 P <0.001 * Favours Apixaban Favours comparator Adjusted HR *ARISTOTLE: HR 0.79 (95% CI: 0.66-0.95) RRR 21%, P=0.01 for superiority Circ Cardiovasc Qual Outcomes 2016;DOI: 10.1161/CIRCOUTCOMES.115.002369 Circ Cardiovasc Qual Outcomes 2016;DOI: 10.1161/CIRCOUTCOMES.115.002369 Conclusions Registries and trials are complementary Randomized clinical trials determine the efficacy and safety compared with VKA Registries test how these drugs work in the real world Some patients are overtreated and do not need anticoagulation (patients at very low risk for stroke) Other patients at high risk for stroke do not receive the treatment they need THANKS!