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Canadian Journal of Cardiology

Insufficient Use of Anticoagulation for Frail Patients With Atrial Fibrillation: Still Stuck in the "Early Majority" Phase

Published:December 20, 2021DOI:https://doi.org/10.1016/j.cjca.2021.10.010
      In 1952, Professor Everett M. Rogers published his classic text “Diffusion of Innovations,” describing the typical journey of a new idea or technology as it becomes incorporated into the framework of society.
      • Rogers E.
      Diffusion of Innovations.
      Such an item is typically "disruptive" and often first assumed to present high risk and uncertain benefit. Rogers explained that a successful technology would manage to persist through 5 stages of implementation: the innovators-disruptors, early adopters, early majority, late majority, and the laggards. The time required to pass through these stages entails some complex variables, including the risk-to-benefit ratio, the nature of those being asked to change habits and beliefs, communication and diffusion of the new idea, and the economic and political influences of the current society. In October 2010, dabigatran was approved by Health Canada and the US Food and Drug Administration for prevention of atrial fibrillation (AF) stroke. The disruptors argued that this new approach, binding thrombin to prevent its activation of clotting, rather than targeting the production of the clotting factors themselves, presented an opportunity to expand prevention of AF stroke by standardizing dosing and eliminating the inconvenience of regular laboratory visits. One might assume that this would be of particular benefit to patients who are most frail: those with difficulty getting to the laboratory for bloodwork and making dose adjustments. In this issue of the Canadian Journal of Cardiology, Orlandi et al.
      • Orlandi M.
      • Dover D.C.
      • Sandhu R.K.
      • Hawkins N.M.
      • Kaul P.
      • McAlister F.A.
      The introduction of direct oral anticoagulants has not resolved treatment gaps for frail patients with nonvalvular atrial fibrillation.
      show us that a decade later we remain stuck in the "early majority" phase when considering direct oral anticoagulant (DOAC) uptake in frail subjects and, perhaps even more striking, when considering any anticoagulation at all for these high-risk patients.
      Orlandi et al. used standard Canadian and Alberta administrative databases to identify a large cohort of 75,796 patients (about one-fifth of whom were frail) 20 years of age or older with newly diagnosed, nonvalvular atrial fibrillation, and seeking care between 2009 and 2019. Among these patients, 88% appeared to have an indication for anticoagulation according to Canadian guidelines.
      • Andrade J.G.
      • Aguilar M.
      • Atzema C.
      • et al.
      The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation.
      A greater proportion of frail patients had indications for anticoagulation than the proportion of nonfrail (92% vs 74%, respectively). A small proportion of patients—1.5%—had contraindications to anticoagulation, and they were excluded from the analysis. Of those eligible, 49.4% had evidence of filling any prescription for anticoagulation over the following 120 days. Furthermore, the subset of frail patients had odds ratios of 0.61 of receiving an anticoagulant when indicated, compared with the nonfrail patients. Among the one-half of patients who did receive anticoagulation, use of DOAC comprised 49% of all prescriptions and a lower 43% of prescriptions in the subset of frail patients. Compared with nonfrail patients, those who were frail had odds ratios of 0.66 for receiving a DOAC in place of warfarin or low- molecular-weight heparin.
      The study by Orlandi et al. is sobering on several fronts. It continues to tell the well-known story that only approximately one-half of patients with AF with a guideline indication are being anticoagulated,
      • Ogilvie I.M.
      • Newton N.
      • Welner S.A.
      • Cowell W.
      • Lip G.Y.
      Underuse of oral anticoagulants in atrial fibrillation: a systematic review.
      ,
      • Hernandez I.
      • He M.
      • Chen N.
      • Brooks M.M.
      • Saba S.
      • Gellad W.F.
      Trajectories of oral anticoagulation adherence among Medicare beneficiaries newly diagnosed with atrial fibrillation.
      with an even lower proportion among those who are most frail and likely have the highest risk of stroke. Over the time since DOACs were introduced, there has been an increase in overall anticoagulation, but it has been modest: from 41% to 67% in the nonfrail population and from 28% to 51% in the frail population. It is interesting to consider the reasons that frailty may correlate with exaggerated undertreatment in the AF population. We hypothesize that clinicians may be more reluctant to anticoagulate elderly frail patients, based on the risk of bleeding. Indeed, the frail population will, on average, have high HAS-BLED scores and associated risk of bleeding complications.
      • Wilkinson C.
      • Clegg A.
      • Todd O.
      • et al.
      Atrial fibrillation and oral anticoagulation in older people with frailty: a nationwide primary care electronic health records cohort study.
      However, they will also have higher risk of stroke. In this double-edged scenario, we suspect that clinicians err on the side of withholding anticoagulation, especially those without reversal agents, to avoid "causing" bleeds, even if it means failure to prevent some strokes. This may indicate a difference in viewpoint between physicians who wish to do no harm vis à vis bleeds and their patients who often view stroke as the greater of two evils. It also may bring out a nuanced difference in approach to healthier patients in whom we may overlook anticoagulation because of an error of omission, vs more frail patients in whom we may intentionally choose to avoid anticoagulation and its inherent risks—arguably, an error of commission—perhaps understandable in the most frail population.
      Some methodology questions must be considered. Are the patients in this study truly frail? The Hospital Frailty Risk Score (HFRS) was used rather than the more clinically predictive
      • Rockwood K.
      • Andrew M.
      • Mitnitski A.
      A comparison of two approaches to measuring frailty in elderly people.
      Clinical Frailty Scale (CFS), a reality of database research, as the CFS requires in-person assessment and must be collected prospectively. The senior author is an expert in the field of frailty assessment and has previously expressed that although CFS is the standard, HFRS is a promising instrument for studies that use health services data.
      • McAlister F.A.
      • Lin M.
      • Bakal J.A.
      Prevalence and postdischarge outcomes associated with frailty in medical inpatients: impact of different frailty definitions.
      His group published a direct comparison of the 2 instruments,
      • McAlister F.A.
      • Lin M.
      • Bakal J.A.
      Prevalence and postdischarge outcomes associated with frailty in medical inpatients: impact of different frailty definitions.
      showing that among patients deemed frail by CFS, fewer than one-half are also considered frail by HFRS, suggesting a higher degree of frailty when determined by HFRS, as in the current study. Are the other estimates derived in this retrospective study of large databases accurate? There are the usual reservations about administrative data— such as coding problems, definition problems, and missing data—that can give rise to some degree of systematic bias. One can imagine circumstances that may circumvent the definitions used in the study, such as a patient who has had AF for 6 years, presents for some change in their symptoms, and is already taking a DOAC that does not need to be renewed in the following 4 months. But, in spite of such anecdotes, a sample of 75,796 subjects is likely to have a fairly high signal-to-noise ratio, especially when the case definitions used in the study have been previously validated.
      • Hawkins N.M.
      • Daniele P.R.
      • Humphries K.H.
      • et al.
      Empirical insights when defining the population burden of atrial fibrillation and oral anticoagulation utilization using administrative data.
      Are the practice patterns of Alberta generalizable to Canada as a whole, or elsewhere? Canada has a single set of national practice guidelines that have been well disseminated to practitioners over the course of a decade of DOAC availability. Medication plans are similar across the country, with insurance plans covering a majority of those employed and government programs picking up the bill for those 65 years of age and older. As the authors point out, this gives rise to one potential vulnerability in the elderly, as these plans often require evidence of failed warfarin use as a requirement to cover DOAC costs. This requirement to fail a therapy that is clearly less convenient—and, arguably, less effective—is a poignant example of tension between economic and health interests that can arise with a safer but more expensive alternative for therapy. Indeed, Orlandi et al. did find increased use of DOACs in subjects younger than 65 years of age, and this may have been related to such financial considerations in addition to frailty-related risks of bleeding. The latter has been related to widespread concern regarding lack of reversal agents, a concern that is being alleviated in recent years as they become more widely available.
      In summary, Orlandi et al. present a well-designed, clinically important study that is a wake-up call for clinicians on several fronts. One-half of patients with AF and guideline indications are not filling prescriptions for anticoagulation, either because of lack of prescriptions or a choice not to fill one that was provided. This is even more an issue in the frail portion of the population. And when prescriptions are filled, approximately one-half are DOACs–even less in those that are frail and possibly have the most to gain from safe, effective, fixed-dose anticoagulation. The explanations for these findings are undoubtedly multifactorial and complicated, possibly related as much to the opinions of those filling the prescriptions as those writing them. It is getting late in the game to consider DOACs an innovation, yet we seem stuck in the "early majority" stage of their uptake. Even more shocking, we may be languishing in the same stage when considering anticoagulation in general for at-risk patients with AF. Orlandi et al. remind us that there remains considerable work to be done to prod us forward to the "late majority" stage of accepting DOAC therapy for prevention of AF stroke.

      Funding Sources

      No funding was provided for this article.

      Disclosures

      The authors have no conflicts of interest to disclose.

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