Author + information
- Gregory Y.H. Lip, MD∗ (, )
- Flemming Skjøth, MSc, PhD,
- Lars Hvilsted Rasmussen, MD, PhD,
- Peter B. Nielsen, PhD and
- Torben Bjerregaard Larsen, MD, PhD
- ↵∗University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, United Kingdom
Whether to anticoagulate patients with atrial fibrillation (AF) and 1 stroke risk factor (i.e., CHA2DS2-VASc [congestive heart failure, hypertension, age >75 years, diabetes mellitus, stroke, vascular disease, age 65–75 years, and female sex] score = 1 in men, or 2 in women) is controversial, but many studies report ischemic stroke rates of >1.5% per year, even with 1 stroke risk factor (1). We estimated the net clinical benefit (NCB) of aspirin or warfarin compared with no antithrombotic therapy among such patients on the basis of a nationwide Danish cohort, with incident AF diagnosed between 1998 and 2012 (2). Men with a CHA2DS2-VASc score ≠ 1 and women with score ≠ 2 at the date of discharge after diagnosis were excluded, as were patients who initiated nonvitamin K antagonist (VKA) oral anticoagulants (OACs), phenprocoumon, or who had warfarin or aspirin prescriptions between 4 and 12 months and before the date of AF diagnosis. Others were stratified according to: 1) no treatment, if there was no prescription for warfarin or aspirin within 1 year; 2) aspirin; or 3) warfarin prescriptions within 4 months.
Endpoint rates were calculated as events per 100 person-years. NCB was calculated for aspirin or warfarin versus no treatment, and for aspirin versus warfarin under intention-to-treat as a weighted sum of rate differences ΔR = Ratenot treated – Ratetreated: NCB = w1 × ΔRischemic stroke + w2 × ΔRICH + w3 × ΔRmajor bleeding + w4 × ΔRMI. When contrasting aspirin and warfarin, the rate difference was given as ΔR = Rateaspirin – Ratewarfarin. Positive NCB favored treatment (i.e., warfarin compared with aspirin, or no treatment, respectively). Weights in hazard ratios (HRs) were estimated from the entire Danish AF cohort by Cox proportional hazards models (3), on the basis of 1-year follow-up. NCB with 95% confidence intervals (CIs) were calculated from rate differences and SEs using Poisson regression.
NCBs for 1 follow-up are presented in Figure 1, on the basis of weights: w1 = 1, w2 = 2.44, w3 = 0.67, and w4 = 0.86. NCBs were positive for warfarin versus no treatment (HR: 1.68; 95% CI: 0.55 to 2.81) and for warfarin versus aspirin (HR: 2.22; 95% CI: 0.59 to 3.85). The NCB for aspirin versus no treatment was negative (HR: –0.54; 95% CI: –1.84 to 0.75).
This analysis supports a positive advantage for stroke prevention with OACs compared with no therapy or with aspirin among patients with AF who have a single stroke risk factor other than a sex factor (i.e., CHA2DS2-VASc score = 1 in men or 2 in women). The analysis by Friberg et al. (4) excluded patients who received OACs during follow-up, which introduced bias away from the null hypothesis that patients with 1 additional risk factor benefit from OAC treatment.
Ischemic stroke rates among such AF patients have varied in reports from different cohorts, reflecting the populations and settings from which the data are derived (1,5). However, clinical risk status changes over time, and hospitalized AF patients face greater mortality and morbidity, whereas OAC reduces stroke and all-cause mortality compared with placebo and/or control drugs. Finally, NCB may be greater with the non-VKA OACs than warfarin, because of their better efficacy and safety compared with the VKAs in clinical trials.
The Obel Family Foundation supported this study. The sponsor had no role in the study design; in the collection, analysis, and interpretation of the data; in the writing of this paper; or in the decision to submit the paper for publication.
Please note: Dr. Lip has served as a consultant for Bayer, Astellas, Merck, AstraZeneca, Sanofi, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, Medtronic, Biotronik, Portola, and Boehringer Ingelheim; and has been on the speakers bureau for Bayer, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, Medtronic, Daiichi-Sankyo, and Sanofi. Dr. Rasmussen has served on the speaker bureaus for Bayer, Bristol-Myers Squibb/Pfizer, Roche Diagnostics, Janssen Pharmaceuticals, Boehringer Ingelheim, and Takeda Pharma. Dr. Larsen has served as an investigator for Janssen Scientific Affairs, LLC, and Boehringer Ingelheim; and has served on the speaker bureaus for Bayer, Bristol-Myers Squibb/Pfizer, Roche Diagnostics, Boehringer Ingelheim, and Takeda Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Lip G.Y.H.,
- Skjøth F.,
- Rasmussen L.H.,
- et al.
- Friberg L.,
- Skeppholm M.,
- Terént A.