Antithrombotic agents (anticoagulants and antiplatelets)

Anticoagulants

Anticoagulants are indicated for deep vein thrombosis, pulmonary embolism, ischaemic stroke, transient ischaemic attack, and during the acute hospitalisation phase of acute coronary syndromes (ACS) [177]. Independent risk factors for the long-term risk of major bleeding include age > 65 years, concomitant antiplatelet therapy, renal impairment (creatinine clearance < 50 mL/min), anaemia, and history of major bleeding [233, 234]. In clinical practice, anticoagulants for stroke prevention are often under-prescribed in older people with newly diagnosed atrial fibrillation (AF), likely due to the perceived risk of severe haemorrhage outweighing anticoagulation benefits [235, 236].

The factors influencing the prescribing of direct oral anticoagulants and warfarin in older people with AF include a history of dementia, falls, major bleeds, and fractures [237]. Optimal prescribing of anticoagulants requires the healthcare provider to assess the benefits of reduced thromboembolic events against the risk of major bleeding. In people who require long-term anticoagulation, at least an annual reassessment of risks and benefits is essential [233]. Excessive anticoagulation may lead to serious harm including anticoagulant-related nephropathy and bleeding [177]. Anticoagulant-related nephropathy is a type of acute kidney injury, but it may also result in permanent kidney damage and increased mortality [177].

Antiplatelets

Antiplatelets are indicated for the prevention of ACS or cerebral vascular disease [177]. Its use can be separated into primary (without established cardiovascular disease) or secondary prevention (with a prior cardiovascular event).

Dual antiplatelet therapy (DAPT)

Other antiplatelet agents (P2Y12 antagonists e.g. clopidogrel, ticagrelor, prasugrel) are often used as secondary prevention agents to prevent the recurrence of cardiovascular events. DAPT, consisting of aspirin and P2Y12 receptor antagonists, is often initiated post-hospitalisation for ACS or stroke. Recommended duration varies depending on the initial indication, and individual bleeding and ischaemic risks.

The 2025 Australian clinical guideline for the diagnosis and management of ACS provided a strong recommendation that DAPT (with aspirin and a P2Y12 inhibitor) should be prescribed for [238]:

• Six to 12 months in people discharged post-ACS who are at high ischaemic and/or low bleeding risk
• One to three months post-ACS in low ischaemic and/or high bleeding risk, followed by single antiplatelet therapy (SAPT)

In addition, the 2025 American College of Cardiology (ACC) and American Heart Association (AHA) joint guideline for the management of ACS provides updated recommendations on dual antiplatelet therapy (DAPT) duration and strategies to reduce the risk of bleeding [239]:

• For people not at high bleeding risk, a standard 12-month DAPT regimen consisting of aspirin and an oral P2Y12 inhibitor is recommended to reduce the risk of major adverse cardiovascular events (MACE)
• In patients with ACS who have tolerated DAPT (aspirin and ticagrelor), discontinuation of aspirin and continuation with ticagrelor monotherapy after one to three months post-PCI may be considered to lower bleeding risk. Alternatively, de-escalation of P2Y12 inhibitor potency (from aspirin + ticagrelor/prasugrel to aspirin + clopidogrel) can be considered to reduce bleeding risk
• In patients with ACS at high bleeding risk, early transition to single antiplatelet therapy (either aspirin or a P2Y12 inhibitor) after one month post-PCI may be reasonable

Evidence supports shortened DAPT durations in selected post-PCI populations to balance the risks of bleeding and MACE. A 2024 systematic review and meta-analysis of 14 RCTs found that abbreviated DAPT regimens of one or three months were associated with significantly lower bleeding risk compared to six months of DAPT, without an increase in net adverse clinical events or MACE [240]. Additionally, three months of DAPT was associated with a lower risk of bleeding compared to 12 months [240]. Additionally, when comparing aspirin monotherapy with clopidogrel monotherapy, a secondary analysis of the STOPDAPT-3 trial found no significant difference in cardiovascular or bleeding outcomes beyond 1 month and up to 12 months after PCI with drug-eluting stents [241].

Concurrent antiplatelet and anticoagulant therapy

Certain clinical situations necessitate the temporary use of combined antiplatelet therapy and oral anticoagulants (OAC), after which a clinical decision should be made to discontinue either therapy. Combining antiplatelet with OAC should only occur in people who require anticoagulation for thromboembolic prevention (e.g. AF, venous thromboembolism) but also have an indication for antiplatelet therapy (e.g. recent ACS or percutaneous coronary intervention) [242].

Triple antithrombotic therapy (an oral anticoagulant, aspirin and a P2Y12 inhibitor) is commonly indicated for people requiring long-term anticoagulation therapy (e.g. for AF, venous thromboembolism, and prosthetic heart valves) plus an indication for dual antiplatelet therapy following coronary stent insertion for ACS. The balance between ischaemic and bleeding risks must be carefully considered.

Refer to the narrative evidence summary, the GRADE Summary of Findings table in the guidelines, and the Technical Report for a complete presentation of the deprescribing evidence based on the GRADE framework (including other factors considered in developing the recommendations).

1. Anticoagulants

Although AF primarily affects older people, they are often under-represented in RCTs, particularly those who are frail. Australian clinical guidelines recommend anticoagulation for all people aged 75 years and older with non-valvular AF [243]. In people with acute ischemic stroke and AF, OAC is often switched to antiplatelet therapy until the risk of haemorrhagic transformation is low, normally up to two weeks, depending on the size of the infarcted area, after which the OAC is re-started [244]. The risk of major bleeding in people taking OAC for stroke prophylaxis is 2-3% per year, with approximately half of these events being gastrointestinal bleeding [245]. Similar rates were observed when OAC was used for venous thromboembolism prophylaxis [246]. However, anticoagulant-related major bleeding is more likely to be fatal than recurrent venous thromboembolism [234]. In people with AF, anticoagulation is only recommended when the net clinical benefit of reducing ischaemic stroke risk outweighs the potential harm from major bleeding. The bleeding risk in people prescribed long-term anticoagulation for atrial fibrillation can be estimated using the HAS-BLED score. In older people with advanced chronic kidney disease (CKD IV-V/ESKD), the risk of bleeding complications with warfarin use often outweighs the potential benefits of anticoagulation [247].

CHA2DS2-VASc is a point-based tool that can be used to calculate stroke risk in people with atrial fibrillation [248]. The tool was validated to predict the patients at high risk for mortality within three to five years in people with atrial fibrillation [248]. The scores for stratifying risk levels were score 0 (low risk), score 1 (medium risk), and score ≥ 2 (high risk) [248]. For people with a CHA2DS2-VASc score of ≥ 2 (high risk), anticoagulant therapy is recommended, whereas in those with a CHA2DS2-VA score of 1 (medium risk), anticoagulant therapy should be considered following a person-centred approach and careful assessment of other thromboembolic risk factors if present [242].

However, the tools are not sufficient on their own to justify withholding anticoagulants in AF [243]. A study involving approximately 25,000 people with AF found that for those with a HAS-BLED score of 3 or more, continuing OAC was associated with better clinical outcomes, including stroke prevention, reduced major bleeding, and lower all-cause mortality [249]. Higher HAS-BLED scores may be used as a prompt to identify and address modifiable bleeding risk factors, such as uncontrolled hypertension, excessive alcohol intake, concomitant antiplatelet use, and the need for fall prevention. Restarting anticoagulation after a bleeding episode must balance stroke prevention with the risk of recurrent bleeding. A systematic review reported that many people with AF were willing to accept a moderate increase in the risk of bleeding to reduce stroke risk [250]. However, recommendations for clinical practice are rarely straightforward, especially in the care of people who are frail. An individualised approach should be implemented, involving informed decision-making with the person, their carer and/or family.

The anticoagulant effect of warfarin diminishes upon cessation, with normal coagulation typically restored in a few days. Warfarin has a mean half-life of 40 hours and the duration of effect is typically two to five days [251]. When stopping warfarin, routine monitoring of the international normalised ratio (INR) is generally not required, particularly if the INR is within the therapeutic range at the time of discontinuation. However, closer monitoring a few days after cessation may be appropriate in the presence of concurrent illness or changes in medications, including prescribed, over-the-counter, complementary, or alternative therapies. For individuals who require reinitiation of warfarin, close INR monitoring is essential to ensure a return to and maintenance of the therapeutic range.

2. Antiplatelets

Older people who are otherwise well, functionally independent, and have a life expectancy of five years or more are likely to derive the most benefits from antiplatelet therapy as secondary prevention [252]. However, the net benefit in primary prevention declines with advanced age due to underlying comorbidities. In older people without a history of cardiovascular, cerebrovascular, or peripheral arterial disease, the risk of major gastrointestinal or intracranial bleeding from aspirin often offsets the risk reduction in preventing cardiovascular events [177].

Coronary artery calcium (CAC) scoring, used for predicting future cardiovascular risk, may be useful in identifying a subgroup of people who are more likely to benefit from antiplatelet therapy for primary prevention. People with a CAC score of more than 100 were estimated to have a favourable risk/benefit profile for aspirin use in the primary prevention of coronary heart disease, with the greatest benefit observed in those with a score exceeding 400. However, these effects have not been well studied in people over the age of 70 [257, 258].

The use of DAPT beyond six to 12 months (or beyond one to three months in certain people post-PCI) is rarely indicated [238, 239], as it increases bleeding risk without additional benefit in reducing cardiovascular or all-cause mortality for most people [259]. However, individual assessment of bleeding and ischemic risk is essential to guide DAPT duration. For stroke, DAPT is recommended to be used for only 21 days following an acute ischaemic stroke or transient ischaemic attack. A meta-analysis of four trials has found the net benefit of DAPT occurred within the first 21 days and DAPT beyond three months significantly increased bleeding and mortality risk with no reduction in major vascular events [260]. DAPT therapy to reduce ischaemic risks needs to be weighed against the higher bleeding risk and all-cause mortality [259]. The PRECISE-DAPT score, validated in 21 studies, was developed to assess bleeding risk in people treated with DAPT following coronary stent insertion for coronary artery disease. Older people with either prior bleeding, anaemia Hb < 100g/L or CKD stage IV or V are recommended to have a shortened DAPT duration [261].

3. Concurrent antiplatelet and anticoagulant therapy

In people with an indication for oral anticoagulation (e.g. AF) undergoing percutaneous coronary intervention, triple therapy should be continued for up to seven days or extended up to one month in people at high ischaemic risk [239]. After this, the person should transition (i.e. step down) to OAC plus SAPT, preferably with a P2Y12 inhibitor (clopidogrel) due to its lower bleeding risk, for up to six months (in people not at high ischaemic risl) or 12 months (in people at high ischaemic risk) post-event (including duration of triple therapy), then stepping down to OAC alone ongoing for the oral anticoagulation indication [238, 239, 262]. During the first 12 months of therapy, any new ischemic or bleeding event should prompt a re-evaluation of antithrombotic therapy [243].

We identified one study related to anticoagulant deprescribing from the systematic review and meta-analysis [266]. Additionally, we identified five studies (two cohort studies and three before-and-after studies) related to antiplatelet deprescribing [254, 267-270].

Overall, the current evidence supporting the deprescribing of antithrombotic agents is of very low certainty. Available studies suggest that discontinuing low-dose aspirin used for primary prevention in patients without cardiovascular comorbidities may reduce the risk of mortality and bleeding. In contrast, for individuals with cardiovascular comorbidities, stopping low-dose aspirin prescribed for secondary prevention may increase the risk of mortality or acute cardiovascular events, particularly within the first six months of discontinuation. However, there is a lack of quality evidence to inform evidence-based recommendations. If deprescribing is considered appropriate, close monitoring of ongoing risk factors, such as bleeding risk and cardiovascular risk, is essential. Regular follow-up, ideally at least monthly during the first six months may be necessary while concurrently addressing modifiable cardiovascular risk factors through lifestyle optimisation.

The method of deprescribing was not described in all studies, but it appears to have involved abrupt discontinuation.