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. 2023 May 19;3(3):oead051.
doi: 10.1093/ehjopen/oead051. eCollection 2023 May.

Guideline-directed medical therapies for comorbidities among patients with atrial fibrillation: results from GARFIELD-AF

Alan John Camm  1 , Jan Steffel  2 , Saverio Virdone  3 , Jean-Pierre Bassand  3   4 , Keith A A Fox  5 , Samuel Z Goldhaber  6 , Shinya Goto  7 , Sylvia Haas  8 , Alexander G G Turpie  9 , Freek W A Verheugt  10 , Frank Misselwitz  11 , Ramón Corbalán Herreros  12 , Gloria Kayani  3 , Karen S Pieper  3 , Ajay K Kakkar  3 ; GARFIELD-AF Investigators
Affiliations

Guideline-directed medical therapies for comorbidities among patients with atrial fibrillation: results from GARFIELD-AF

Alan John Camm et al. Eur Heart J Open. .

Abstract

Aims: This study aimed to identify relationships in recently diagnosed atrial fibrillation (AF) patients with respect to anticoagulation status, use of guideline-directed medical therapy (GDMT) for comorbid cardiovascular conditions (co-GDMT), and clinical outcomes. The Global Anticoagulant Registry in the FIELD (GARFIELD)-AF is a prospective, international registry of patients with recently diagnosed non-valvular AF at risk of stroke (NCT01090362).

Methods and results: Guideline-directed medical therapy was defined according to the European Society of Cardiology guidelines. This study explored co-GDMT use in patients enrolled in GARFIELD-AF (March 2013-August 2016) with CHA2DS2-VASc ≥ 2 (excluding sex) and ≥1 of five comorbidities-coronary artery disease, diabetes mellitus, heart failure, hypertension, and peripheral vascular disease (n = 23 165). Association between co-GDMT and outcome events was evaluated with Cox proportional hazards models, with stratification by all possible combinations of the five comorbidities. Most patients (73.8%) received oral anticoagulants (OACs) as recommended; 15.0% received no recommended co-GDMT, 40.4% received some, and 44.5% received all co-GDMT. At 2 years, comprehensive co-GDMT was associated with a lower risk of all-cause mortality [hazard ratio (HR) 0.89 (0.81-0.99)] and non-cardiovascular mortality [HR 0.85 (0.73-0.99)] compared with inadequate/no GDMT, but cardiovascular mortality was not significantly reduced. Treatment with OACs was beneficial for all-cause mortality and non-cardiovascular mortality, irrespective of co-GDMT use; only in patients receiving all co-GDMT was OAC associated with a lower risk of non-haemorrhagic stroke/systemic embolism.

Conclusion: In this large prospective, international registry on AF, comprehensive co-GDMT was associated with a lower risk of mortality in patients with AF and CHA2DS2-VASc ≥ 2 (excluding sex); OAC therapy was associated with reduced all-cause mortality and non-cardiovascular mortality, irrespective of co-GDMT use.

Clinical trial registration: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.

Keywords: Atrial fibrillation; Comorbidity; GARFIELD-AF; Guideline-directed medical therapy; Mortality; Oral anticoagulant.

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Conflict of interest statement

Conflict of interest: A.J.C. has received institutional grants and personal fees from Bayer, Boehringer Ingelheim, BMS/Pfizer, and Daichi Sankyo. J.S. has received consultant and/or speaker fees from Abbott, Alexion, AstraZeneca, Bayer, Berlin-Chemie, Biosense Webster, Biotronik, Boehringer Ingelheim, Boston Scientific, BMS, Daiichi Sankyo, Medscape, Medtronic, Menarini, Merck/MSD, Organon, Pfizer, Saja, Servier, and WebMD. He reports ownership of Swiss EP and CorXL. K.A.A.F. has received grants and personal fees from Bayer/Janssen and AstraZeneca. S.Z.G. has received research support from Bayer, BMS, Boston Scientific, BTG, EKOS, Janssen, NHLBI, and Pfizer and has consultancy with Pfizer. S.G. has received a quality fee from the American Heart Association and received a steering committee fee from Duke University. S.H. has received personal fees from Bayer, BMS, Daiichi Sankyo, Pfizer, and Sanofi, outside the submitted work. A.G.G.T. has received personal fees from Bayer Healthcare, Janssen Pharmaceutical Research & Development LLC, Astellas, Portola, and Takeda. F.W.A.V. has received grants from Bayer Healthcare and personal fees from Bayer Healthcare, BMS/Pfizer, Daiichi Sankyo, and Boehringer Ingelheim. K.S.P. has consultancy with Johnson & Johnson, Element Science, Artivion, and Novartis. A.K.K. has received grants and personal fees from Bayer AG, Sanofi, and Anthos Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Distribution of guideline-directed medical therapy use for comorbid conditions in patients with atrial fibrillation and a CHA2DS2-VASc score of ≥2 by antithrombotic treatment. AF, atrial fibrillation; AP, antiplatelet; GDMT, guideline-directed medical therapy; NOAC, non-vitamin K oral anticoagulant; OAC, oral anticoagulant; VKA, vitamin K antagonist.
Figure 2
Figure 2
Hazard ratios with 95% confidence intervals (2-year follow-up) for all vs. no/some comorbidity guideline-directed medical therapy use at enrolment in the overall group, patients receiving oral anticoagulants, and patients not receiving oral anticoagulants. 1Hazard ratios derived from univariable Cox models without stratification of possible comorbidity combinations. 2Hazard ratios derived from univariable Cox models that include stratification by all possible combinations of the five comorbidities used to define guideline-directed medical therapy eligibility. 3Hazard ratios are adjusted for age, sex, ethnicity, type of atrial fibrillation, prior stroke/transient ischaemic attack/systemic embolism, history of bleeding, moderate-to-severe chronic kidney disease, anticoagulation at baseline, smoking status, and heavy alcohol consumption. A robust covariance estimate is included in order to account for correlation within each country. Models include stratification by all possible combinations of the five comorbidities used to define guideline-directed medical therapy eligibility. GDMT, guideline-directed medical therapy; OAC, oral anticoagulant; SE, systemic embolism.
Figure 3
Figure 3
Hazard ratios (2-year follow-up) for baseline oral anticoagulant treatment by comorbidity GMDT use (see Supplementary material online, Table S2 for covariates). Hazard ratios are obtained using an overlap-weighted Cox model. Variables included in the weighting scheme are country and cohort enrolment, sex, age, ethnicity, type of atrial fibrillation, care setting speciality and location, acute coronary syndromes, carotid occlusive disease, prior stroke/transient ischaemic attack/systemic embolism, prior bleeding, venous thromboembolism (VTE), hypercholesterolaemia, cirrhosis, moderate-to-severe chronic kidney disease, dementia, hyperthyroidism, hypothyroidism, current smoking, heavy alcohol consumption, body mass index, heart rate, systolic and diastolic blood pressure at diagnosis, and baseline antiplatelet use. A robust covariance estimate is included in order to account for correlation within each country. GDMT, guideline-directed medical therapy; OAC, oral anticoagulant; SE, systemic embolism.
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