Author + information
- Hendrika A. van den Ham, PharmD∗ (, )
- Olaf H. Klungel, PharmD, PhD,
- Daniel E. Singer, MD,
- Hubert G.M. Leufkens, PharmD, PhD and
- Tjeerd P. van Staa, MD, PhD
- ↵∗Address for correspondence:
Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, Utrecht, Utrecht none, The Netherlands
We tested the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke), and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65 to 74 years, female) stroke risk scores in the CPRD (Clinical Practice Research Datalink) cohort of incident atrial fibrillation (AF) patients not using oral anticoagulants (OAC) because these are the patients for whom physicians must make the OAC treatment decision (1). The mean patient follow-up of 0.74 years over a study period of 15 years indicates that a large proportion eventually received OAC. In the first year, the rate of warfarin prescription was 38%. The on- and off-warfarin cohorts did not differ much in stroke risk at index date. This illustrates that, in clinical practice, risk score–based decisions are not fully implemented.
An important message from our study (1) is that reported stroke rates in different cohorts can differ substantially. This is illustrated by national AF cohorts in Sweden and in Denmark (2,3), where the Danish point score-specific stroke rates are multiple times the Swedish rates. Considering the similarities in burden of disease and healthcare setting in these 2 Nordic countries, these differences in rates are likely largely explained by methodological choices in the study, such as outcome definition (4). Our paper also illustrated that optimal risk score cut points will differ with different rates. It will be important to standardize analytic approaches to be sure differences in reported stroke rates reflect truly different stroke rates.
A major advantage of the ATRIA score over the CHA2DS2-VASc score is its use of additional age categories and formal statistical weighting of these risk factors. The CHA2DS2-VASc score was not founded on a formal statistical approach. As a result, AF patients can have a CHA2DS2-VASc score of 1 from hypertension or from being age 65 to 74 years; the former risk factor conveys little additional stroke risk, whereas the latter increases risk multifold. The better risk prediction of the ATRIA score is also clinically valuable at higher point scores in patients with contraindications to OAC, where accurate absolute stroke risk must be balanced against risk of toxicity.
The argument of the importance of simplicity of a risk score is in our opinion not valid in a world in which technology is completely integrated in our daily lives. A patient who will be put on a long-term treatment deserves the best informed decision that optimally integrates patient data. Undoubtedly, we will build on current risk scores (e.g., with biomarkers). It is important that we start with our most rigorously developed and accurate AF stroke risk score.
Please note: Dr. Klungel has received unrestricted funding for pharmacoepidemiological research from the Dutch private-public TI pharma Mondriaan project. Dr. Singer has served as a consultant to Boehringer Ingelheim, Bristol-Myers Squibb, CVS Health, Johnson & Johnson, Medtronic, and Merck; and has received research support from Boehringer Ingelheim, Bristol-Myers Squibb, and Medtronic. Dr. Leufkens is a researcher at The WHO Collaborating Centre for Pharmaceutical Policy & Regulation, which receives no direct funding or donations from private parties, including pharma industry. Research funding from public-private partnerships, for example, IMI, TI Pharma, is accepted under the condition that no company-specific product or company related study is conducted. The Centre has received unrestricted research funding from public sources, for example, Netherlands Organisation for Health Research and Development, the Dutch Health Care Insurance Board, EU 7th Framework Program, Dutch Medicines Evaluation Board, and Dutch Ministry of Health. Dr. van Staa has participated in an expert meeting on simple trials for Boehringer Ingelheim. Dr. van den Ham has reported that she has no relationships relevant to the contents of this paper to disclose.
- 2016 American College of Cardiology Foundation
- van den Ham H.A.,
- Klungel O.H.,
- Singer D.E.,
- Leufkens H.G.,
- van Staa T.P.
- Friberg L.,
- Skeppholm M.,
- Terént A.