In addition to the treatment of aF, apixaban, dabigatran, and rivaroxaban have been approved by nIce as options for the prophylaxis of venous thromboembolism in adults after elective hip or knee replacement surgery. rivaroxaban has also been approved as an option for prophylaxis of atherosclerotic events (with aspirin alone, or with aspirin and clopidogrel, or ticlopidine) for people with coronary heart disease and after an acute coronary syndrome in people with elevated cardiac biomarkers. It is also indicated for people with symptomatic peripheral artery disease at high risk of ischaemic events.


DOacs have an improved efficacy/safety ratio, a predictable anticoagulant effect without need for routine coagulation monitoring, and fewer food and drug interactions compared with vitamin K antagonists (VKas) like warfarin. That said, individual DOacs have their own unique characteristics, which help determine in what circumstances they are prescribed. In terms of mechanism of action, apixaban, edoxaban and rivaroxaban are all factor xa inhibitors, whilst dabigatran is a direct thrombin inhibitor.


How anticoagulants work anticoagulants work by interfering with the chemicals that are needed to make clots.


Warfarin, acenocoumarol and phenindione block the effects of vitamin K, which is needed to make some clotting factors. Blocking vitamin K prevents blood clots forming so easily by increasing the time it takes to make fibrin, a solid protein which has strands that form a meshwork and trap blood cells and platelets, which form into a solid clot. Dabigatran, apixaban, edoxaban and rivaroxaban work by preventing a blood chemical called thrombin from working. This, in turn, prevents fibrin from being made from fibrogen. While dabigatran binds to thrombin, apixaban and rivaroxaban stop thrombin from being made. DOacs can be used in the prevention of stroke for people with non-valvular aF, which is when aF is not associated with a problem in a heart valve. They can also be used in the management of venous


thromboembolism, which is when a blood clot forms in a vein. non- valvular aF is the type of aF that most people in the uK have and, like


warfarin, DOacs can help to prevent clots from forming in the first place and help protect patients from certain types of stroke.


unlike warfarin, the DOacs do not need regular Inr monitoring. however, regular follow-up and monitoring is still required, at least annually, to assess compliance; enquire about the presence of any adverse effect eg, bleeding; and assess for the presence of thromboembolic events, eg, symptoms of stroke, or breathlessness which might suggest a Pe.


Problems with anticoagulants


unfortunately, while anticoagulants can help to prevent clots in patients, they can also cause problems. Patients, who are on combinations of anticoagulants and non-steroidal anti- inflammatory drugs (nSaIDs), for example, and who are without gastroprotection, are at increased risk of bleeding.


a 2018 study showed that the combination of anticoagulants, nSaIDs and antiplatelets caused more than a third of hospital admissions as a result of avoidable adverse drug reactions. That said, the problems caused by anticoagulants are now being increasingly recognised and pharmacists are viewed as an important part of the solution.


unfortunately, combinations of drugs involving anticoagulants are one of the most frequent causes of medicine-related hospital admissions. That is because patients are often on risky combinations of anticoagulants and medication for other conditions, such as non-steroidal anti- inflammatory drugs, without gastro-protection. This naturally raises the risk of bleeding.


Patients taking any anticoagulant should be advised: • To seek immediate medical advice if spontaneous bleeding occurs and does not stop, or recurs. This includes bruising, bleeding gums, nosebleeds, prolonged bleeding from cuts, blood in urine or stools, haemoptysis, subconjunctival haemorrhage, and vaginal bleeding in postmenopausal women. • To seek medical advice if they get sudden severe back pain, which may indicate spontaneous retroperitoneal bleeding.


A 2018 study showed that the combination of


anticoagulants, NSAIDs and antiplatelets caused more than a third of hospital admissions as a result of avoidable adverse drug reactions


• not to take, or apply, over-the-counter medicines, such as non-steroidal anti-inflammatory drugs. • What to do if there has been a missed dose, or if a double dose has been taken.


The role of the pharmacist In July 2019, anticoagulation was named as one of six ‘headline issues’ that are to be addressed by the nhS Improvement Medicines Safety Programme. as part of this programme, pharmacists will be trained in shared decision making so that they will be able to support patients with atrial fibrillation (aF), who are taking anticoagulants. Various pharmacist-led clinics dealing with anticoagulation have already proved successful in the treatment of patients.


In the London clinical commissioning groups (ccgs) of Lambeth and Southwark, for example, pharmacist- led virtual clinics were held to ensure all aF patients at risk of stroke were offered anticoagulation, if appropriate. Over a twelve-month period, the programme reviewed more than 1500 patients with aF, who were not receiving


anticoagulation. The clinics resulted in an additional 1200 patients being anticoagulated and the two ccgs saw a 25 per cent reduction in the rate of aF-related stroke.


The Stroke association has also estimated that a pharmacist-led review of patients with aF produced nhS savings of more than £82m in its first year. The ongoing review of more than 280,000 aF patients was carried out by a team of pharmacists, who looked at whether patients needed anticoagulants, whether they needed to change their medication and whether they needed to be referred to secondary care.


nIce has also estimated that pharmacists’ intervention has helped prevent more than 1,800 strokes and hundreds of deaths, arguing that ‘around 7,000 strokes and 2,000 premature deaths could be avoided every year through effective detection and protection with anticoagulant drugs’.


Suggested actions that pharmacists can take when dealing with patients on anticoagulants include: • reinforce dosage and regime with each new supply of DOac.


• rivaroxaban must be taken with food, otherwise there’s a 66 per cent reduction in absorption, hence under-coagulation.


• Open discussion of patients’ experiences of missed doses and how to proceed if that should happen in the future.


• check if they have had any experience of unusual and/or uncontrolled bleeding and how they have dealt with that.


• ensure they know what signs they are looking for indicating a hidden bleed, eg, urine, stools, back pain.


• reinforce that, should they have an accident and hit their head, they should report to emergency Department with medication card, and they will be fast-tracked through to examination and scanning.


• Dabigatran should not be put into a compliance aid.


• Take care with other prescribed medications, eg macrolide antibiotics, oral anti-fungals, nSaIDs, etc.


• counsel on OTc medicines. It’s tempting to be more complacent about potential interactions with DOacs compared with warfarin, but caution is still required with the usual suspects, eg, aspirin, oral or topical nSaIDs, etc.


• report back any significant findings from discussions to prescribing gP or practice-based pharmacist.


ScOTTISh PharMacIST - 43


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