In March 2020, as COVID-19 was declared a pandemic and efforts were made to reduce face-to-face consultations with patients, NHS England (2020) devised a rapid plan to switch patients who had previously had a blood clot and were on warfarin therapy to a direct oral anticoagulant (DOAC).
The goal of warfarin—a vitamin K antagonist and the most widely prescribed anticoagulant therapy—is to prevent blood clotting. It does this by delivering the lowest effective dose of anticoagulant to maintain the target international normalised ratio (INR). This measures how long it takes a person's blood to clot. Warfarin thins the blood to prevent blood clots, but not so much that bleeding risk increases. Trying to get this delicate balance right requires regular INR monitoring—a tall order for overextended healthcare resources during a pandemic.
Like most decisions made during the COVID-19 pandemic, the decision to switch as many patients on warfarin therapy as possible to a DOAC to reduce INR blood testing frequency while still keeping patients safe, was made quickly. It made sense, but without the time to consider all aspects or potential consequences, it was not without its challenges. There were many aspects to be weighed and considered in switching patients' anticoagulant therapy.
For example, a small (but, according to Curtis et al (2021), ‘substantial’) number of patients who were switched to a DOAC also continued on warfarin therapy (Robinson, 2021). Subsequently, a national safety alert was issued, as well as guidance to health professionals, to ensure that any patients being switched over stop their warfarin treatment prior to starting on a DOAC, in order to reduce any risk of over-anticoagulation and bleeding (Curtis et al, 2021; Medicines and Healthcare products Regulatory Agency (MHRA), 2020a; Robinson, 2021).
Curtis et al (2021) carried out a cohort study, making use of routine clinical data from 24 million patients in England. Between March and May 2020, 12% of patients (20000 of 164000) on warfarin therapy were switched to a DOAC, with the most common being edoxaban and apixaban (Curtis et al, 2021). A sharp rise in inappropriate coprescribing of warfarin and DOACs was observed in April 2020 (from 50–100 to 246 instances per month) (Curtis et al, 2021). INR testing fell by 14%, and a very small increase in elevated INR was noted during April 2020 when compared with January 2020 (Curtis et al, 2021). Certain factors were found by Curtis et al (2021) to be associated with patients switching from warfarin to DOACs in response to national guidance at the pandemic's outset, including older age, a higher number of recent INR tests, a diagnosis of atrial fibrillation, normal renal function and care home residency.
DOACs, like warfarin, can have interactions with other medications, which is also worth consideration (MHRA, 2020b). For many patients, such as those with a prosthetic mechanical valve, those who are pregnant or breastfeeding, or those who have moderate-to-severe mitral stenosis, a DOAC is not an appropriate option (NHS England, 2020). For those who are deemed suitable for a switch, a phased approach is recommended over the 12-week INR monitoring cycle in order to avoid affecting the supply chain for other patients (National Institute for Health and Care Excellence (NICE), 2020).
Interestingly, and importantly, patients on anticoagulant therapy who have had changes made to their treatment have reported feeling excluded from decision-making around their therapy (Pharmaceutical Journal, 2020). While it is acknowledged that the pandemic required emergency decision-making in the interest of public health and safety, this patient concern is still worthy of consideration.
Researchers from the Canadian city of Vancouver, British Columbia, analysed telephone interview notes from 388 patients with atrial fibrillation, who were contacted every 3 months for a 2-year period. Of these, 56 patients had undergone a change to their therapy, such as a switch or discontinuation. These patients not only had limited knowledge about their anticoagulant therapy, they also had a generally negative attitude towards taking medicines. The researchers highlighted that these experiences appeared to affect these patients' adherence to their anticoagulant therapy and their perceptions of their care provider, as well as the healthcare system overall (Pharmaceutical Journal, 2020; Salmasi et al, 2020).
Patients on warfarin or any other vitamin-K antagonist require regular blood testing, which may be particularly frequent at the beginning of treatment as adjustments are made to ensure the correct dosage. However, another instance in which testing becomes especially important is when patients display symptoms of COVID-19 (for example, high temperature, a new continuous cough, loss of sense of smell or taste) or who have tested positive for the virus (MHRA, 2020b). To reduce any risk of overcoagulating and bleeding, patients displaying symptoms of COVID-19 must be identified as soon as possible and receive the appropriate care early on (MHRA, 2020b). Furthermore, it must be highlighted that patients who test positive for COVID-19 may be prescribed antibiotics or antivirals, which may interact with warfarin or other vitamin-K antagonists (MHRA, 2020a).
