Before initiating oral antithrombotic therapy, the benefits of treatment must be weighed against the risks of bleeding. Relevant risk assessment tools, such as CHA2DS2-VASc and HAS-BLED (see modules 3 and 4), can be used to determine a patient’s thrombotic and individual bleeding risks, and to guide management decisions (e.g. whether to start antithrombotic therapy, if so with what drugs, the duration of therapy, and whether gastroprotection is required).
It is good practice before initiating antithrombotics to ensure a full coagulation screen has been undertaken (including INR and activated partial thromboplastin time [APTT]), as well as a full blood count, and renal and liver function tests to identify any inherent bleeding issues.
Pharmacists play an integral role as members of a multidisciplinary team, ensuring that patients receive the correct drug and dose in a timely manner. They must also consider patient factors such as renal and hepatic dysfunction, as well as drug factors, such as interactions or drugs predisposing the patient to a greater risk of adverse effects (e.g. bleeding with non-steroidal anti-inflammatory drugs [NSAIDs]).
- to ensure the anticoagulant is appropriate for the individual patient (involving the patient in decision making)
- to initiate anticoagulant treatment with appropriate liaison between prescribers and anticoagulation clinics for ongoing monitoring and supply. This should take into consideration the needs of the patient (which may include home monitoring and initial supply of reagent strips)
- to ensure the patients receive the relevant anticoagulant card, and particularly for warfarin, the monitoring book, which allows any healthcare professional to review INR control.
Commissioning effective anticoagulation services
There are approximately 1.25 million people in the UK on anticoagulant therapy.1 Although the need for anticoagulation is expected to increase in coming years as the UK population ages and the rates of atrial fibrillation (AF) rise, it is estimated that 40% of people with AF at risk of stroke are not being anticoagulated. Evidence suggests that without adequate anticoagulation, one in 20 AF patients will suffer a stroke every year.2 This has led to the improvement of anticoagulation becoming a national quality, innovation, productivity and prevention (QIPP) initiative.
Anticoagulation Europe has a resource pack for commissioners involved in commissioning anticoagulation services for the future, which may be particularly relevant for pharmacists involved in this process.1
The relatively newer non-vitamin K antagonist oral anticoagulants (NOACs) require initiation by clinicians within secondary care before transferring care to GPs. Before patients are discharged, an agreement – also referred to as a shared care guideline (SCG) – is sent to the GP. This SCG outlines the responsibilities of the patient, clinicians in secondary and primary care, the duration of treatment supplied by the hospital, and monitoring requirements (if any). Shared care guidelines can be found locally within hospitals and Clinical Commissioning Groups (CCGs).
Counselling patients initiated on warfarin and NOACs
Due to their unpredictable pharmacokinetics and narrow therapeutic windows, routine coagulation monitoring using INR is essential for vitamin K antagonist anticoagulants. NOACs demonstrate predictable and stable pharmacokinetics and do not require routine coagulation monitoring.
The need for regular monitoring must be explained to the patient. The INR can define how quickly the blood clots in relation to someone who is not on warfarin, i.e. a value of three indicates that it will take three times longer for someone’s blood to clot in comparison to someone not on warfarin. The patient will appreciate that too low an INR (INR <2) will not give the full benefit of preventing strokes, whereas too high an INR (INR >4) can put the patient at risk of bleeding heavily should they cut themselves, or bruising badly if they fall.
When patients first start taking warfarin, they will attend the anticoagulant clinic frequently, as they adjust their dosage to an appropriate level. Most people find that once they are established on warfarin their INR is fairly stable, and they need only attend the clinic every six to 12 weeks.
There are multiple factors that can influence the efficacy of warfarin, including: liver function; age; concomitant medicines; dietary intake of leafy vegetables; and alcohol. As such, the required dose of warfarin needs to be tailored to each individual and may change from time to time, for example when drinking more alcohol, going on holiday, or taking a course of antibiotics.
WARFARINISED (see table 1) is a good acronym to remember the important counselling points for patients starting therapy with warfarin.
Considerations for use of NOACs
The NOACs are covered in previous modules (modules 3 and 4). In October 2011 the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended an update to the product information for dabigatran following reports of increased bleeding and bleeding fatalities in the elderly and those with poor renal function. The recommended updated product information includes advice that renal function should be assessed in all patients before starting treatment (dabigatran is 85% renally metabolised). During treatment, renal function should be assessed at least yearly in patients over 75 years of age and in those with known renal impairment. It should also be assessed whenever a decline in function is suspected.
Rivaroxaban, apixaban, and the newer edoxaban, are renally metabolised to a lesser extent, but caution (e.g. dose reduction) and, as appropriate, close monitoring in patients with moderate-to-severe renal impairment should still be applied.
The newer antiplatelet agents (ticagrelor and prasugrel) are more potent than clopidogrel, but are associated with increased bleeding rates, while the NOACs range from being non-inferior to superior to warfarin, and offer the benefit of less intracranial haemorrhage with variable major bleed rates (ranging from equivalent to less bleeding versus warfarin). Refer to the latest British National Formulary and Summaries of Product Characteristics (SPCs)3,4 for side effects, cautions, contraindications and interactions.
Note that for dabigatran and rivaroxaban, indigestion is a known adverse effect and, as such, patients should be counselled and gastric protection considered as appropriate. All of the newer agents have a shorter half-life than warfarin, such that the drug concentration (and, thus, anticoagulant effect) would decline soon after one or more doses are missed. If the patient misses a dose of rivaroxaban or edoxaban, it is recommended that they take it as soon as possible. However, not more than one tablet in a single day should be taken to make up for a missed dose. For dabigatran, patients should immediately take the missed dose unless the next is due within six hours, in which case it should be discounted. For apixaban, if a dose is missed, the patient should take it immediately and then continue with twice daily intake as before.
Lastly, ensure patients receive their respective anticoagulant alert card and carry it with them at all times, to present to any relevant healthcare professional who is managing their care.
Switching between anticoagulants
The National Institute for Health and Care Excellence (NICE) guideline5 on anticoagulation in AF recommends the use of either NOACs or vitamin K antagonists. It is, however, patient preference, cognitive function, co-morbidities and liable INR that can determine choice of anticoagulant. These parameters can change throughout a patient’s clinical condition, which may require an anticoagulation switch.
Instances where vitamin K antagonists may need to be switched to a NOAC can be determined by time in therapeutic range (TTR). NICE highlights the following factors to reassess therapy and possibly to switch to a NOAC:
- Two INR values higher than 5 or one INR value higher than 8 within the past six months
- Two INR values less than 1.5 within the past six months
- TTR less than 65%.
On the flip side, patients well-established on a NOAC, may need to switch to a vitamin K antagonist, for example, if they are having a mechanical valve replacement since NOACs are only being licensed for non-valvular AF.
The dosing recommendations on switching can be found in the summary of product characteristics (SPCs).
Role of the community pharmacist in optimising this patient’s care
Patients have regular access to community pharmacists, who can add to the care of a patient medicated with anticoagulation and antiplatelet therapy. Anticoagulants are one of the classes of medicines most frequently identified as causing preventable harm and admission to hospital.
Following the National Patient Safety Agency guidance6 issued in March 2007 on the safe use of anticoagulant therapy, pharmacists are in a prime position to provide both medication and disease-state counselling. The guidance recommends that patients receive appropriate information throughout the course of their treatment, and that their INRs (for warfarin) are monitored regularly, to ensure they are at a safe level (see figure 1), before repeat prescriptions for oral anticoagulation are dispensed.
The guidance also suggests that pharmacists dispensing clinically significant interacting medicines, such as antibiotics, or another medication that may increase the risk of bleeding (e.g. selective serotonin re-uptake inhibitors, or non-steroidal anti-inflammatory drugs (NSAIDs)), should take additional safety precautions. These include:
- informing the anticoagulant service that an interacting medicine has been prescribed
- ensuring additional INR blood tests have been arranged to monitor any changes.
More recently, the New Medicines Service (NMS)7 has been introduced as an advanced service to the community pharmacy contract. The service provides support for people with long-term conditions newly prescribed a medicine, helping to improve medicine adherence. The optimal use of appropriately prescribed medicines is vital to the self-management of most long-term conditions, but reviews conducted across disease states are consistent in estimating that between 30–50% of prescribed medicines are not taken as recommended. This represents a failure to translate the technological benefits of new medicines into health gain for individuals. Sub-optimal medicine use can lead to inadequate management of long-term conditions, and a cost to the patient, the NHS, and to society.
The NMS currently focuses on specific patient groups and conditions, including antiplatelet and anticoagulant therapy.
The service is such that all patients newly prescribed an anticoagulant, for example, will be eligible to receive it. The NMS provides an interview schedule to facilitate discussions between pharmacist and patient. These include:
- Have you had a chance to start taking your new medicine yet?
- How are you getting on with it?
- Are you having any problems with your new medicine, or concerns about taking it?
If you are a hospital-based pharmacist or prescriber, consider referral to the new medicine service. This will provide the reassurance that any information provided to the patient is reinforced by community pharmacy colleagues, and that any problems patients experience will be addressed and discussed.
1. Commissioning effective anticoagulation services for the future: a resource pack for commissioners. Anticoagulation Europe 2013. Available from http://anticoagulationeurope.org/publications (accessed 20/02/13)1. Commissioning effective anticoagulation services for the future: a resource pack for commissioners. Anticoagulation Europe 2013. Available from http://anticoagulationeurope.org/publications (accessed 20/02/13)
2. Dorian P, et al. The Impairment of health related quality of life in patients with intermittent AF; implications of the assessment of investigational therapy. J Am Coll Cardiol 2000;36:1303–9. http://dx.doi.org/10.1016/S0735-1097(00)00886-X
3. Summary of product characteristics for apixaban, rivaroxaban, dabigatran, and warfarin. Electronic Medicines Compendium 2012. Available from http://emc.medicines.org.uk/ (accessed 20/02/13)
4. Summary of product characteristics for edoxaban. Electronic Medicines Compendium 2015. Available from http://emc.medicines.org.uk/ (accessed 09/08/15)
5. National Institute for Health and Care Excellence. Atrial fibrillation: the management of atrial fibrillation. Clinical guideline 180. Issued June 2014, last modified: August 2014. https://www.nice.org.uk/guidance/cg180/resources/guidance-atrial-fibrillation-the-management-of-atrial-fibrillation-pdf
6. National Patient Safety Agency. Patient safety alert: actions that can make anticoagulant therapy safer(Alert 18), 2007. Available from http://www.nrls.npsa.nhs.uk/resources/?entryid45=59814 (accessed 20th February 2013)
7. Outline service specification – New Medicine Service. Pharmaceutical Services Negotiating Committee 2011. Available from http://www.psnc.org.uk/pages/nms.html (accessed 20/02/13)
Hicks T, Stewart F, Eisinga A. NOACs versus warfarin for stroke prevention in patients with AF: a systematic review and meta-analysis. Open Heart 2016;3:e000279. http://dx.doi.org/10.1136/openhrt-2015-000279