Filling an Important Knowledge Gap: The DOAC Score

HomeCirculationVol. 148, No. 12Filling an Important Knowledge Gap: The DOAC Score Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBFilling an Important Knowledge Gap: The DOAC Score Michael D. Ezekowitz and Mohammed Kamareddine Michael D. EzekowitzMichael D. Ezekowitz Correspondence to: Michael D. Ezekowitz, MBChB, DPhil, Ste 301, 830 Old Lancaster Rd, Bryn Mawr, PA 19010. Email E-mail Address: [email protected] https://orcid.org/0000-0003-3623-2252 Sydney Kimmel Medical School, Thomas Jefferson University, Philadelphia, PA (M.D.E.). Cardiology Department, Lankenau Medical Center, Bryn Mawr Hospital/Mainline Health, Wynnewood, PA (M.D.E.). Search for more papers by this author and Mohammed KamareddineMohammed Kamareddine Internal Medicine Department, Lankenau Medical Center/Mainline Health, Wynnewood, PA (M.K.) Search for more papers by this author Originally published25 Aug 2023https://doi.org/10.1161/CIRCULATIONAHA.123.066316Circulation. 2023;148:947–949This article is a commentary on the followingDevelopment and Validation of the DOAC Score: A Novel Bleeding Risk Prediction Tool for Patients With Atrial Fibrillation on Direct-Acting Oral AnticoagulantsOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: August 25, 2023: Ahead of Print In this issue of Circulation, Aggarwal et al1 report the development of the first bleeding risk score for patients with atrial fibrillation prescribed a direct-acting oral anticoagulant (DOAC). The neurological bleed rate in patients receiving all DOACs is low; thus, the DOAC score is driven by nonneurological bleeds.2–6 The new DOAC score represents a significant scientific advancement in anticoagulation management that balances the benefit of preventing stroke and systemic embolization with the risk of bleeding in patients with atrial fibrillation.Article, see p 936Existing stroke risk scoring systems, particularly the CHA2DS2-VASc score, have been incorporated into American and European atrial fibrillation guidelines7,8 and are broadly adopted in clinical practice, defining the threshold above which patients with atrial fibrillation would benefit from anticoagulation. On the other hand, currently available bleeding risk scoring systems are considered much less reliable.9 The current leading bleeding risk score is the HAS-BLED score. This scoring system was developed for patients prescribed warfarin and assigns 1 point for each of the following bleeding risk factors: uncontrolled hypertension (systolic blood pressure >160 mm Hg), abnormal renal function (chronic dialysis, transplantation, or creatinine >2.26 mg/dL) or liver function, prior stroke, bleeding history or predisposition, labile international normalized ratios, elderly (≥65 years of age), concomitant aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and alcohol excess. Scores range from 0 to 9, with scores of ≥3 indicating a high risk of bleeding. Compared with other available bleeding scores, HAS-BLED offers better prediction of bleeding.9,10 The HAS-BLED score has been validated in real-world and clinical trial patient cohorts,11 but its predictive accuracy is highly variable.9,12 The most relevant limitation of the HAS-BLED score is that it was derived from warfarin-treated patients, not those prescribed any of the approved DOACs. Because DOACs are currently the preferred anticoagulation choice for most patients with atrial fibrillation except those with mechanical heart valves or moderate to severe mitral stenosis,8 developing a bleeding risk scoring system for patients prescribed DOACs is of paramount importance.Therefore, the scoring system developed by Aggarwal et al fills a critical unmet need for patients receiving a DOAC. The DOAC score is derived from the following variables: age 65 to 69 counts as 2 points; age 70 to 74 years counts as 3 points; age 75 to 79 years counts as 4 points; and age ≥80 years counts as 5 points. Kidney function using creatinine clearance assigns 0 points if ≥60 mL/min, 1 point if 30 to 59 mL/min, and 2 points if ≤30 mL/min. The following variables each count for 1 point: underweight (body mass index <18.5 kg/m2), stroke and systemic embolization/transient ischemic attack history, history of diabetes, history of hypertension, and current NSAID use. Liver disease counts for 2 points, and bleeding history counts for 3 points. Antiplatelet use with aspirin counts for 2 points, and aspirin+P2Y12 inhibitor counts for 3 points. Scores are categorized as very low (0–3), low (4–5), moderate (6–7), high (8–9), or very high (10).The DOAC score, as described by Aggarwal et al, was initially developed from patients randomized to dabigatran 150 mg twice daily in the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). The scoring system was then tested in patients randomized to both doses of dabigatran 150 mg twice daily and the lower dose of dabigatran 110 mg twice daily; it was superior in predicting major bleeds compared with the HAS-BLED score. It is notable that dabigatran 75 mg twice a day was not evaluated in the RE-LY trial, but it was approved in the United States on the basis of pharmacokinetic data and has not been evaluated with the DOAC score. The DOAC score was then refined from data obtained from GARFIELD-AF (Global Anticoagulant Registry in the Field–Atrial Fibrillation), a multinational registry of adults with recently diagnosed atrial fibrillation receiving dabigatran, apixaban, rivaroxaban, and edoxaban (N=12 296). The DOAC score was found to be superior to the HAS-BLED score for predicting major bleeding in this cohort. The DOAC score was then validated in COMBINE-AF (A Collaboration Between Multiple Institutions to Better Investigate Non–Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation), a cohort that consisted of 5 randomized controlled trials with patients from all the DOAC classes (N=25 586), and RAMQ (Régie de l'assurance maladie du Québec), an administrative database of Canadian patients who were prescribed standard doses of rivaroxaban 20 mg daily or apixaban 5 mg twice a day (N=11 945). The DOAC score also outperformed HAS-BLED.Compared with HAS-BLED, the DOAC score not only is derived from DOAC-treated patients and superior in performance but also considers variables such as age, kidney function, and concomitant high-bleeding-risk medication use on a spectrum rather than binary entities, as shown in the Table 1. For example, age is the most prominent risk factor for atrial fibrillation, and there is an increased risk of major bleeding with DOAC use as age increases.13 Aligning with this approach and unlike prior scoring systems, the DOAC score assigns distinct levels of bleeding risk on the basis of various age categories, allowing enhanced and personalized estimates of bleeding risk. Furthermore, DOACs exhibit 25% to 80% renal clearance,3–6 and as renal function worsens, the risk of major bleeding increases. Because DOACs are dosed according to creatinine clearance, the use of creatinine clearance as a marker of chronic kidney disease in the DOAC score not only is more accurate than HAS-BLED but also leads to more accurate quantification of bleeding risk in these patients (Table 1). One other clear pitfall of HAS-BLED is that it attributes the same singular risk of bleeding to concomitant use of an NSAID, aspirin, or a combination of both despite the known increased risk with multiple agents. Furthermore, other antiplatelet agents are not incorporated into HAS-BLED. On the other hand, the DOAC score accounts for this increased cumulative risk of NSAID and antiplatelet use with DOACs both individually and when used in combination. Last, there are notable exclusions from HAS-BLED that are incorporated into the DOAC score such as underweight status (body mass index <18.5 kg/m2), which is important because of the known increased risk of major bleeding in underweight patients with atrial fibrillation taking DOACs.14Table 1. Comparing the DOAC Score With the HAS-BLED Score in Patients With Atrial FibrillationDOAC scoreHAS-BLED scoreImplicationsDerivationDOAC-treated patientsWarfarin-treated patientsThe DOAC score is superior to the HAS-BLED score in predicting major bleeding in DOAC-treated patients.Risk factor assignmentAssigns risk of major bleeding differently for each risk factor.Assigns risk of major bleeding similarly for all risk factorsThe DOAC score assigns bleeding risk more accurately than the HAS-BLED score.Quantification of bleeding riskVery low: 0–3 pointsScores range from 0–9, with scores ≥3 indicating a high risk of bleeding.The DOAC score provides patients and clinicians with a clearer understanding of major bleeding risk from very low to very high.Low: 4–5 pointsModerate: 6–7 pointsHigh: 8–9 pointsVery high: 10 pointsAge stratification, y65–69: 2 points<65: 0 pointsThe DOAC score provides better correlation with the known increased risk of bleeding with increased age.70–74: 3 points75–79: 4 points≥65: 1 point≥80: 5 pointsRenal impairment classificationCrCl 30–60 mL/min: 1 pointChronic dialysis: 1 pointBy using CrCl, the DOAC score more accurately estimates bleeding risk in patients with kidney disease, especially because these drugs are dosed according to CrCl and are 25%–80% renally cleared.Renal transplantation: 1 pointCrCl <30 mL/min: 2 pointsCreatinine >2.26 mg/dL: 1 pointImpact of concomitant medicationsNSAID use: 1 pointNSAIDs and aspirin use individually or in combination: 1 pointThe DOAC score accurately quantifies the increased cumulative risk of bleeding in DOAC-treated patients taking NSAIDs and antiplatelet agents individually or in combination.Antiplatelet use Aspirin: 2 points Dual antiplatelet: 3 pointsCrCl indicates creatinine clearance; DOAC, direct-acting oral anticoagulant; HAS-BLED, hypertension, abnormal renal/liver function, stroke history, bleeding history, labile international normalized ratio, elderly, drugs or alcohol excess; and NSAID, nonsteroidal anti-inflammatory drug.In conclusion, the DOAC score was developed and validated using high scientific standards. The transition from warfarin to DOACs has led to improved patient outcomes, with an enhanced safety and efficacy profile.2–6 However, the absence of a widely accepted bleeding risk score for DOAC-treated patients has remained a crucial knowledge gap.8 The DOAC score can be applied in clinical practice given that it relies on clinical data typically available before the initiation of anticoagulation. A critical point is that its adoption by clinicians, similar to the CHA2DS2-VASc score, will depend on its endorsement by atrial fibrillation guideline committees both in the United States and in Europe with global implications. The DOAC score allows the clinician to accurately quantify bleeding risk in patients taking DOACs while also helping identify bleeding risk factors and to correct those that are modifiable such as better controlling blood pressure, removing concomitant unnecessary antiplatelet or NSAID use, and counseling the patient about such factors. Thus, the bleeding risk assessment with the DOAC score and its clinical adoption will improve patient care, highlight patients in whom risks are reversible, and provide caution when needed. With the recent emergence of nonpharmacological options for stroke and systemic embolization prevention in patients with atrial fibrillation, namely left atrial appendage closure procedures, the DOAC score could also potentially serve as a quantifiable measure with respect to selecting patients who might benefit from these procedures in the modern era.15ARTICLE INFORMATIONSources of FundingFunding provided by the Sharpe-Strumia Foundation, Bryn Mawr Hospital.Disclosures Dr Ezekowitz is a LIBREXIA-AFIB Trial (A Study of Milvexian Versus Apixaban in Participants With Atrial Fibrillation) national leader. His role is limited to finding sites for other investigators to enroll patients. Dr Kamareddine reports no conflicts.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Disclosures, see page 949.Circulation is available at www.ahajournals.org/journal/circCorrespondence to: Michael D. Ezekowitz, MBChB, DPhil, Ste 301, 830 Old Lancaster Rd, Bryn Mawr, PA 19010. Email michael.ezekowitz@comcast.netREFERENCES1. Aggarwal R, Ruff CT, Virdone S, Perreault S, Kakkar AK, Palazzolo MG, Dorais M, Kayani G, Singer DE, Secemsky E, et al. Development and validation of the DOAC score: a novel bleeding risk prediction tool for patients with atrial fibrillation on direct-acting oral anticoagulants.Circulation. 2023; 148:936–946. doi: 10.1161/CIRCULATIONAHA.123.064556LinkGoogle Scholar2. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, et al. 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Circulation. 2023;148:936-946 September 19, 2023Vol 148, Issue 12 Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.123.066316PMID: 37621202 Originally publishedAugust 25, 2023 KeywordsEditorialsatrial fibrillationbleeding riskdirect acting anticoagulantsPDF download Advertisement SubjectsAtrial Fibrillation