Use of combination antiplatelets and anticoagulants

Antiplatelets and anticoagulants are widely used as effective therapies to lower the risk of a range of events. The aim of this section is to ensure that these are prescribed safely.

These treatments are effective in a variety of conditions with a range of magnitude of benefit.

The highest effect and most essential indications include:

• reduction of risk of clot in adults with metal heart valves²⁸¹
• initial treatment of pulmonary embolism²⁸²
• antiplatelet treatment following coronary artery stenting^283,284

Medication to reduce the blood's ability to clot are commonly used to reduce the risk of major adverse outcomes in a range of conditions:

• heart attack (acute coronary syndromes)
• stroke
• pulmonary embolism (PE)
• deep venous thrombosis (DVT)
• atrial fibrillation (AF)²⁸⁵
• reducing clotting in adults with metal heart valves

Medications that reduce the blood's ability to clot come in different drug classes

• antiplatelets e.g. aspirin, clopidogrel
• anticoagulants e.g. warfarin, or direct oral anticoagulants (DOACs) – e.g. apixaban, dabigatran, edoxaban, rivaroxaban
• injected antithrombotics e.g. enoxaparin, dalteparin, fondaparinux

Risk of bleeding

• should always be balanced against potential benefit when prescribing antiplatelets or anticoagulants (see NNT table)
• increases if more than one agent is used at the same time
• increases with age²⁸⁶

• Risk of bleeding increases with age as well as the number of agents used
• Indication and duration should be clear both at commencing treatment and with continuing use
• Particular care is needed in ensuring that if an individual is on more than one agent that:
  • a clear indication exists and is still valid
  • if the indication for more than one agent was time limited, that has not expired
  • change in bleeding risk over time has not altered the risk/ benefit ratio

Do not stop antiplatelets or anticoagulants in situations where the indication is clear, remains within specified duration, and bleeding risk has been considered, e.g. still within the recommended time post coronary artery stenting.

• When commencing treatment, both indication and duration of treatment should be clearly stated
• Combination antiplatelets and anticoagulants can be inappropriate in situations including:
  • An individual already on an agent develops a second indication for a different agent and two are prescribed rather than using one for both e.g.
    • an adult with previous stroke is prescribed clopidogrel then develops atrial fibrillation and is commenced on edoxaban. Clopidogrel should be stopped.
    • an adult with previous heart attack is prescribed aspirin and later develops a pulmonary embolism and is prescribed rivaroxaban. Aspirin should be stopped for duration of rivaroxaban treatment.
    • an adult is admitted to hospital with pneumonia and is prescribed enoxaparin to reduce the risk of DVT but is already on apixaban due to AF. Concomitant treatment with heparin agents and DOAC is contra-indicated
  • The indication for using more than one agent was time limited and has elapsed e.g. an adult has a coronary artery stent inserted and required to be on dual antiplatelet treatment (DAPT) for 12 months but remains on it after this time. One of the antiplatelet drugs should stop^287,288
  • The indication for using more than one agent is no longer common practice e.g.
    • adding an antiplatelet agent to an anticoagulant to reduce risk of stroke in an adult with AF is no longer current practice. Stop antiplatelet agent
    • using an anticoagulant to reduce stroke in an adult in sinus rhythm is no longer current practice. Use an antiplatelet agent instead

Managing bleeding risk:

Ensure that bleeding risk is not increased by co-prescription of agents that increase risk of bleeding e.g.

• non-steroidal anti-inflammatory drugs (NSAID)
• selective serotonin re-uptake inhibitors (SSRI) antidepressants e.g. citalopram, fluoxetine

Consider use of gastroprotection.²⁸⁹ Proton pump inhibitors are felt to be the most effective N.B. adults on clopidogrel should avoid omeprazole or esomeprazole.

There is little randomised controlled trial evidence examining to what degree bleeding risk can be reduced by the addition of gastroprotection.²⁹⁰ Guidelines and meta-analyses (largely based on observational trials) generally advise addition of gastroprotection if there is increased risk of bleed, including:

• use of high dose aspirin
• older age (consider in those over 65 years)
• history of gastroduodenal ulcer or perforation
• Helicobacter pylori infection
• concomitant use of medicines known to increase risk of gastrointestinal bleed
• use of one or more antiplatelet or anticoagulant agents

Consider effect of kidney function

• DOACs are affected by kidney function
  • calculate creatinine clearance and adjust dose accordingly
  • kidney function can improve as well as deteriorate so dose may need to increase or decrease
  • at least annual assessment of kidney function is recommended while taking DOACs

• If an antiplatelet or anticoagulant is no longer indicated or safe, it should be stopped. There is no need to reduce the dose before stopping.
• If gastroprotection was started to reduce the risk of bleeding with an antiplatelet or anticoagulant and that agent is then stopped, consider stopping gastroprotection.

Supporting people who do not or cannot reduce/stop

• advise on bleeding risk
• provide alert card if taking oral anticoagulant
• annually review benefit/risk
• discuss importance of taking medication as prescribed.

Specific areas/situations where medication may need to be introduced or increased

• DOACs are affected by kidney function e.g. apixaban, dabigatran, edoxaban, rivaroxaban. Therefore:
  • calculate creatinine clearance and adjust dose accordingly - refer to SPC²⁹¹
  • kidney function can improve as well as deteriorate so dose may need to increase or decrease
• A change in clinical condition will require review, e.g. development of AF
• A change requiring gastroprotection

Polypharmacy: Manage Medicines app

Does the person understand the outcomes of the review, including risk and benefits?

• DOACs thin the blood in a stable predictable way, so do not need blood tests for monitoring unlike agents such as warfarin

Is drug therapy tailored to the individual?

• To be effective, DOACs need to be taken at the same time each day. DOACs that are taken twice daily, e.g. apixaban need to be 12 hours apart

Agree the plan

• Adults on DOACs need at least annual review including renal function
• For adults on complicated regimens, repeated education and reminders may be required

• self-management/support tools
• decision aids

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CHA ₂DS₂VASc tool

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