When Less is More: How to Provide Less Anticoagulant and Antiplatelet Treatment to Improve Outcomes

As hospitalists, we are often trained to err on the side of doing more, especially in the ways we have historically approached anticoagulation and antiplatelet therapies. Faced with the competing risks of thrombosis and bleeding, it can feel safer to continue therapy longer, combine agents, or pursue additional testing “just in case.” But the evidence increasingly tells a different story.

In daily practice, we routinely manage patients with acute venous thromboembolism (VTE), atrial fibrillation (AF), and coexisting cardiovascular disease. These cases raise practical questions: How long should anticoagulation be continued? When is thrombophilia testing actually useful? How long should triple therapy last after percutaneous coronary intervention (PCI)? And do patients with AF and stable coronary disease really need both anticoagulation and antiplatelet therapy?

De-Escalation After Acute VTE

One of the most common decisions we influence as hospitalists is how patients transition from acute to long-term anticoagulation after VTE. While we may not always follow patients longitudinally, the discharge plan we set often defines their trajectory.

Earlier studies comparing shorter (three months) to longer duration of anticoagulation in unprovoked VTE established a clear tradeoff; extended therapies reduced recurrence but increased bleeding.¹ Recent studies of extended therapies with direct oral anticoagulants (DOACs) such as apixaban and rivaroxaban have demonstrated that prophylactic dose regimens retain much of the benefits without a proportionate increase in bleeding.^2,3

More recently, the API-CAT trial has reinforced the concept that reduced-dose strategies after an initial period of therapeutic dosing of DOACs for VTE, even in patients with active metastatic malignancies, can be effective in preventing recurrence with a lower risk of bleeding.

Taken together, these studies have reshaped our approach. Instead of a binary decision about stopping versus continuing anticoagulation, we now recognize a third path: de-escalation to a prophylactic dose of DOAC. The American College of Chest Physicians’ (ACCP) Chest guidelines support this approach.⁴

Thrombophilia Testing

Thrombophilia testing has historically been performed in patients with provoked and unprovoked VTE subtypes with unclear utility, but studies have shown higher rates of recurrent VTE in patients with unprovoked risk factors, very low rates in patients for whom surgery was a risk factor, but intermediately increased rates in patients for whom there were medical risk factors.⁵

While the ACCP Chest guidelines advise against extended-duration anticoagulation after major or minor transient risk factors, the recent HI-PRO trial did demonstrate a lower risk of recurrent VTE when an extended duration of prophylactic dose apixaban is offered to patients with enduring risk factors, a significant number of which would usually be classified as minor.⁶ American Society of Hematology guidelines have clarified that routine thrombophilia testing is not indicated in surgical risk factors but is recommended in patients with VTE and non-surgical major and/or minor risk factors.⁷ Such testing should be done in the outpatient setting after discharge for patients with VTE. Testing should also be reserved for situations where it meaningfully alters management, such as influencing the duration of anticoagulation or informing family risk.

Triple Therapy: Shorter Is Safer

Few areas illustrate the risks of overtreatment more clearly than triple therapy. Observational data have highlighted the magnitude of bleeding risk, showing markedly higher rates of major bleeding and intracranial hemorrhage with combination regimens.

Randomized trials evaluating anticoagulation plus a P2Y12 inhibitor (with early discontinuation of aspirin) consistently demonstrated significant reductions in bleeding without an increase in ischemic events. Trials such as AUGUSTUS were particularly influential, showing that removing aspirin from the regimen reduced major or clinically relevant nonmajor bleeding while maintaining similar rates of death and hospitalization.⁸

Subsequent meta-analyses and shorter-duration dual antiplatelet therapy trials further reinforced that prolonged exposure to multiple agents offers diminishing returns and increasing harm.

The cumulative impact of these data has been the North American consensus: for most patients, triple therapy should be limited to the shortest duration possible; often just during hospitalization or up to one week after PCI, with extension to one month only in select high-risk cases.

Anticoagulation Plus Antiplatelet Therapy: Simplifying Regimens

Another common scenario we encounter is the patient with AF and stable coronary or vascular disease who remains on both anticoagulation and aspirin. Historically, this approach was rooted in the concept of targeting dual pathophysiology.

However, multiple randomized trials (such as EPIC-CAD, ADAPT AF-DES) have challenged this practice.^9,10 These trials comparing oral anticoagulation alone versus combination therapy have shown that removing antiplatelet therapy reduces major bleeding without a meaningful increase in ischemic events. In fact, the recent AQUATIC trial demonstrated an increased mortality for patients on aspirin and DOAC compared to a DOAC alone six months after PCI (with significant numbers of patients with acute coronary syndrome in this trial).¹¹ The standard practice at this point is to stop the antiplatelet agent for any patient who is already on a therapeutic dose of an oral anticoagulant.

The impact of these trials has been substantial: they have shifted guidelines and clinical practice toward default simplification, reserving combination therapy only for clearly defined, time-limited indications.

For hospitalists, this translates into a simple but high-yield question at every transition of care: “Does this patient still need aspirin?” In many cases, the answer is no.

Dr. Mehta

Dr. Mehta is an associate professor of medicine and vice-chair of inpatient clinical affairs at the University of Cincinnati in Cincinnati. He is also the associate editor for The Hospitalist.

References

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2. Agnelli G, Becattini C. Risk assessment for recurrence and optimal agents for extended treatment of venous thromboembolism. Hematology Am Soc Hematol Educ Program. 2013;2013:471-7. doi:10.1182/asheducation-2013.1.471.
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11. Lemesle G, et al. Aspirin in patients with chronic coronary syndrome receiving oral anticoagulation. N Engl J Med. 2025;393(16):1578-1588. doi:10.1056/NEJMoa2507532.