The European Society of Cardiology (ESC) Congress 2017 took place in sunny Barcelona, Spain last month from August 26th to August 30th. The event provided the setting for cardiologists, industry, and academia to come together for nearly five days of networking. Over the five days, over 500 thought leader sessions and more than 4,500 abstracts were presented on latest trends and advancements in cardiovascular medicine. A bevy of trials were presented at ESC 2017 congress providing new clinical evidence on Atrial Fibrillation (AF) management. Among the announcements that were of particular interest, several results from late-breaking clinical trials for current and emerging therapies were presented.
RACE 3: Racing to the Top
Results from the RACE 3 trial demonstrated that risk-factor upstream therapy is superior to conventional therapy in the maintenance of sinus rhythm in patients with persistent AF and/or heart failure. Upstream therapies comprising of cardiac rehabilitation, mineralocorticoid receptor antagonists, statins, and ACE inhibitors/ARBs were started at least three weeks before electrical cardioversion and were continued for 12 months. At one year follow-up, sinus rhythm was present in 75% patients in the upstream therapy group compared to 63% patients in the control group. The understanding of etiology and pathophysiology of AF is still in its early developmental stages. Positive results from the study will help physicians understand the role of upstream therapies in management of AF patients. AF is a progressive disease and its progression is primarily caused by structural remodeling. Upstream therapy may modify atrial remodeling and help prevent the progression of AF.
EMANATE: Apixaban for AF Patients Undergoing Cardioversion
According to the results from the EMANATE trial, AF patients receiving apixaban before their scheduled cardioversion had fewer strokes and similar bleeding risk when compared with warfarin and heparin. The EMANATE trial enrolled 1,500 AF patients who were anticoagulation-naïve and were scheduled for elective cardioversion. The current standard of care (heparin and warfarin) requires monitoring and potential dose adjustments. Positive results from this study will help Bristol-Myer-Squib/Pfizer to position apixaban as an alternative treatment option to conventional therapies for AF patients undergoing cardioversion. Currently, apixaban is not approved for use in anticoagulation-naive patients before cardioversion.
CASTLE-AF: Pharmacotherapy versus Catheter Ablation
Results from CASTLE-AF trial demonstrated catheter ablation improves outcomes for AF patients with left ventricular dysfunction. Patients who received catheter ablation had lower mortality and less hospitalization for worsening heart failure compared to those receiving conventional drug treatment. The trial included 397 patients with symptomatic paroxysmal or persistent AF and heart failure ejection fraction less than 35%. These results highlight the importance of restoring and maintaining regular heart rhythm in AF patients. CASTLE-AF is the only randomized clinical trial which compares catheter ablation and pharmacological therapy for patients with coexisting heart failure and AF with primary endpoints of hospitalizations and mortality. The positive results can have major cost implications for AF treatment by reducing the overall rates of hospitalization.
RE-DUAL PCI: Dual Therapy versus Triple Therapy
Boehringer Ingelheim presented the results from RE-DUAL PCI which evaluated dual therapy with Pradaxa versus triple therapy with warfarin in AF patients who have undergone PCI with stenting. The primary safety endpoint of the trial was defined as time to major bleeding events and clinically-relevant non-major bleeding events. Bleeding risk was found to be lower with dabigatran plus P2Y12 inhibitor compared with triple therapy with warfarin. The dual therapy also met the non-inferiority threshold or the composite efficacy endpoint. RE-DUAL PCI results will help Boehringer Ingelheim highlight superior efficacy of Pradaxa in managing AF patients over conventional therapies. Additionally, in light of impending patent expiry and increasing competition from other NOACs, positive results from RE-DUAL PCI and other recent large studies such as RE-CIRCUIT and RE-VERSE AD can provide the much needed sales boost for the drug.
AFFIRM Post-hoc Analysis: Blood Pressure Control Pivotal in SPAF
Results from the sub-analysis of AFFIRM trial demonstrated that blood pressure plays an important role in reducing risk of major bleeding events and stroke in AF patients. The patients were categorized into four quartiles based on their mean standard deviation in systolic blood pressure. After a mean follow-up of 3.6 years, a clear pattern of increasing risk with each elevation in quartile emerged from the study with recorded 149 strokes and 248 major bleeding events. The findings from the study indicate that blood pressure control is a pivotal aspect of managing AF patients to improve outcomes and reduce overall morbidity and mortality associated with the disease.
IMPACT-AF: Improving Outcomes with Education
IMPACT-AF study assessing whether educating providers and AF patients could increase the use of oral anticoagulation compared to usual care concluded that monitoring and feedback led to a 9% absolute increase in the use of anticoagulation therapies to reduce stroke. The study demonstrated that education and feedback boosted the treatment rate from 68% at baseline to 80% at one year. If the finding from the trial is broadly implemented, it can have a substantial impact on managing the burden from AF, specifically from an economic perspective.
GARFIELD-AF Registry: Insights from Real World Practices
Insights from GARFIELD-AF registry study featuring one-year outcomes from 52,000 prospective patients were presented at the ESC 2017 congress. Data highlighted that AF imposes high financial, and economic burden on societies across Europe and the type of health services used varies significantly across geographies. The study highlighted that rate of anticoagulant use has increased markedly to 71% and the prescription trends have grown massively for NOACs. Mortality was cited as the most frequent adverse event in AF. According to the outcomes, rate of anticoagulation use was found to be suboptimal in the patients with severe form of AF. Additionally, it was reported that more than two-thirds of patients received no anticoagulant treatment after 4 months. Overall, GARFIELD-AF registry study helps in identifying gaps between real-world antithrombotic prescribing practices and the current clinical guidelines. These findings can help in devising clinical strategies that can reduce AF-related hospitalization and improve clinical outcomes, thereby translating into more efficient use of healthcare resources.
The results from these clinical studies make atrial fibrillation a dynamic indication to watch, and we will be covering this exciting indication in an upcoming Disease Landscape & Forecast report to be published in December 2017.
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