Self-managed oral anticoagulant therapy: a call for implementation

Oral anticoagulant therapy (OAT) with vitamin K antagonists (VKA), for example, warfarin or phenprocoumon, remains the mainstay to prevent thromboembolism in a variety of clinical conditions. Mechanical heart valves, atrial fibrillation, and recurrent venous thromboembolism are the most frequent clinical indications for long-term treatment [1].

VKA impedes coagulation and consequently increases the risk of bleeding; hence, meticulous monitoring of the anticoagulant effect measured using the international normalized ratio (INR) and appropriate dosage adjustments are mandatory for patients prescribed VKA [1]. General practitioners and hospital departments generally perform conventional management of VKA therapy, but the risk of bleeding complications is an important concern during conventional management [2].

Patient self-management (PSM) of OAT is a concept empowering trained patients to monitor and adjust their treatment in home settings [3]. A blood sample is drawn using a finger prick, and the INR is measured using a point-of-care coagulometer; based on this measurement, the patient will accordingly make dose adjustment. A related concept is patient self-testing (PST), when patients take the blood sample themselves, and a health-care provider takes responsibility for dose adjustment of the VKA [3]. In general, the quality of the OAT treatment is highly dependent on the type of management. The lowest quality is found in conventional management performed by the general practitioner or a hospital department, intermediary quality is found in a highly specialized anticoagulation center or using computer dosing of the VKA, whereas the highest quality is found in PSM and PST [4–8]. This editorial will focus on PSM.

In order to perform PSM in Denmark, patients are required to attend an educational program containing a minimum of three teaching lessons, including basic theoretical and practical skills, including use of a coagulometer, interpretation of INR values, and VKA dose adjustments [9]. Over a period of 6 months, patients gradually become self-managed. Finally, the patients are requested to demonstrate their skills in a multiple-choice exam. The total time (three sessions spread out over 6 month) required for training is approximately 4 h in total in our setup. Other methods exist, for example, with fewer lessons, group-based teaching, or no laboratory INR measurements during training. It must be foreseen that in the future, there will be an increased use of web-based teaching, including interactive lessons and an increased use of mobile apps.

In our institutions, we find it essential to follow the patients after training and exam in order to continuously monitor the quality of the treatment, the accuracy of the coagulometer, and to provide continuous patient support, if questions arise or if, for example, the patient is to undergo surgery, or are prescribed concomitant medication. After passing the exam, follow-up and quality control of the treatment is achieved by patients reporting their dose of warfarin and INR values every 3rd month to the center, predominantly done online to a database.

It has been demonstrated to be possible to perform PSM safely in both adults and a pediatric setting, the latter, of course, with the support of the parents [10]. In adults, it is estimated that approximately 50% of all patients prescribed OAT are able to perform PSM. However, this number is highly dependent on the indication for OAT: ranging from 30% in atrial fibrillation up to 80% in mechanical heart valve patients [3].

The requirement for the patient to perform PSM is based on an evaluation often with four dimensions: physical health, mental suitability, interest in OAT, and expected level of compliance with PSM. All these aspects should be evaluated and recorded with the patient present and monitored continuously, including ambulatory visits for the patient [11].

An initial concern regarding the widespread use of PSM was the precision and accuracy of the coagulometer, potentially resulting in patients making dose adjustments based on incorrect INR values. The precision of coagulometers is generally adequate for clinical use. Their performance in terms of accuracy has to be viewed in respect of the inherent inaccuracies of INR measurements. The accuracy of coagulometers is generally acceptable, and they can be used in a clinical setting. However, external quality control is advisable [12–14].

Randomized controlled trials (RCTs) have demonstrated the efficacy and safety of PSM, with self-managed patients achieving a significant reduction in major thromboembolism compared to conventionally monitored patients [3]. The risk of thromboembolism can also be halved without a concomitant significant increase in mortality or bleeding. However, the advantages of PSM in RCT represent the efficacy of PSM under ideal circumstances.

Looking at the efficacy (results under daily clinical practice) of PSM, numerous papers have been published. We have recently shown that PSM results in overall excellent results for all OAT indications [9]. We included 2068 patients representing 6900 patient-years and found an incidence of major bleeding events of 1.6% per year, major thromboembolism of 0.7% per year, and a risk of all-cause death on 0.5% per year [9].

In patients with mechanical heart valves, we found that PSM results in a significantly lower 5-year mortality compared to conventional management and a nonsignificant reduction in major thromboembolic and bleeding events [15]. Mechanical heart valve patients are solely dependent on VKA treatment and there is growing evidence that this group of patients should perform PSM as standard treatment [3,15].

Importantly, trials have demonstrated that PSM leads to an increased quality of life compared to conventional management [16]. It is also important to stress that patients performing PSM is a selected group of patients and it is not a treatment offer for all patients receiving OAT.

The approval of non-vitamin K antagonist oral anticoagulants (NOAC) (e.g. dabigatran, apixaban, and rivaroxaban) for patients with atrial fibrillation and venous thromboembolism has increased the number of treatment options for these patient groups [17,18]. These drugs have advantages in terms of, for example, a fixed daily dose, no need for monitoring, markedly fewer interactions, and a consistent lower risk of intracranial bleedings compared to VKA treatment. However, disadvantages exist in terms of, for example, a high cost, dependency on renal function for drug elimination, and no antidote for most of these drugs (although these are under development). Yet, it has been suggested that some patients treated with dabigatran etixilate may benefit from a tailoring of the dose beyond the ones already proposed by the manufacturer [19].

The quality of the OAT treatment in the VKA group in the atrial fibrillation studies regarding NOAC has not been optimal, displaying a time within therapeutic INR target range (TTR) of 55–64%. TTR is a surrogate marker for the quality of the VKA treatment, and in PSM, a TTR of at least 70% is found in most trials [9]. In most trials of NOAC, none or marginal differences were found between NOAC and VKA regarding major bleedings in the group of patients with the highest TTR (>70%) [20]. So, there is likely limited advantage for NOAC compared to PSM in terms of clinically relevant end points. However, a consistent lower risk of intracranial bleedings compared to VKA treatment is found. However, superiority of VKA in patients with a high TTR (e.g. PSM patients) compared to NOAC has not yet been proven in a large study. Again, it is important to emphasize that PSM is only an option for a selected segment (~50%) of all patients prescribed OAT.

The quality of the VKA treatment in the NOAC trials differs from what is observed in PSM, but probably reflects daily clinical practice very well. Thus, an NOAC agent is being recommended as first-choice drug in contemporary European guidelines for OAT in atrial fibrillation. However, in mechanical heart valve patients, children, and in severe thrombophilia, only VKA is an option.

For the majority of indications for OAT, both VKA and NOAC can be used. What should the physician then advice the patient to choose? It clearly depends on the patient’s indication for OAT (see above regarding mechanical heart valves) and comorbidity. Many patients will undoubtedly benefit from NOAC. If a VKA drug is to be a real alternative, it needs to be a high-quality treatment. Accordingly, VKA treatment should be managed as PSM given the improved quality (in terms of TTR), and if that is not feasible, then PST. That latter can be applied to approximately 80% of patients.

Treatment with VKA will probably persist for many years, and we need to further improve the quality of treatment in terms of an increased use of PSM. The scientific evidence in favor of PSM is convincing, regarding both effectiveness and efficacy in addition to safety aspects.

Financial & competing interests disclosure

TD Christensen has been on the speaker bureaus for AstraZeneca, Boehringer Ingelheim, Pfizer, Takeda, Bristol-Myers Squibb and Roche Diagnostics. EL Grove has received speaker honoraria from AstraZeneca, Baxter, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb and Pfizer and has participated in advisory board meetings for AstraZeneca, Bayer, Boehringer Ingelheim and Bristol-Myers Squibb. TB Larsen has served as an investigator for Janssen Scientific Affairs, LLC and Boehringer Ingelheim and has been on the speaker bureaus for Bayer, BMS/Pfizer, Roche Diagnostics, Takeda and Boehringer Ingelheim. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.