Join more than 1.500 of your peers to stay up to date with the latest in thrombosis.
Sign up now!
Consider the following fictional patient case:
Having just become a grandmother for the second time, Louisa wants to ensure that she will still be able to play with her grandchildren in the future. How can you help to conserve the benefits of her revascularization?
Until recently, guideline recommendations to protect patients from thrombotic events following surgical or endovascular revascularization included SAPT with aspirin or clopidogrel, DAPT with both drugs or the use of vitamin K antagonists.1,2 However, many of these recommendations carry a level of evidence C, reflecting a lack of robust evidence to support clinical decision making, or level of evidence B, indicating data derived from a single randomized clinical trial or large non-randomized studies.1,2 Furthermore, these guideline recommendations are typically extrapolated from clinical data in coronary revascularization.2,3
Recommendations for antithrombotic therapy following revascularization in previous guidelines are based on limited evidence, typically based on clinical data from coronary revascularization trials1-3
LoE, level of evidence; PAD, peripheral artery disease
Despite the use of these therapies, patients with PAD remain at high risk of major adverse limb and cardiovascular (CV) events. Cardiologist and vascular medicine specialist Dr Marc Bonaca from the University of Colorado, USA, noted in an interview: ‘Even with known therapies such as aspirin, statins, P2Y12 inhibitors, ACE [angiotensin-converting enzyme] inhibitors…rates of major adverse cardiovascular and limb outcomes are extremely high in this population and particularly after revascularization.’
The VOYAGER PAD trial aimed to evaluate the efficacy and safety of dual pathway inhibition (DPI) with rivaroxaban 2.5 mg twice daily (bid) plus aspirin 100 mg once daily (od), compared with aspirin alone, to reduce the risk of thrombotic events in patients with PAD undergoing peripheral revascularization procedures.4
The trial involved over 6500 patients and found that patients receiving DPI were significantly better protected from the primary composite efficacy outcome of acute limb ischaemia (ALI), major amputation of vascular aetiology, myocardial infarction, ischaemic stroke or CV death compared with aspirin alone. This benefit did not compromise the risk of major bleeding for patients, with a similar rate of Thrombolysis In Myocardial Infarction (TIMI) bleeding observed in both treatment groups.3
DPI reduced the combined risk of major adverse limb and CV events* following revascularization versus aspirin, with comparable rates of TIMI major bleeding3
*Primary composite efficacy outcome of ALI, major amputation of vascular aetiology, MI, ischaemic stroke or CV death. #A significant increase in the secondary safety outcome of ISTH major bleeding was observed; HR=1.42, 95% CI 1.10–1.84, p=0.007
ALI, acute limb ischaemia; bid, twice daily; CI, confidence interval; CV, cardiovascular; DPI, dual pathway inhibition; HR, hazard ratio; ISTH, International Society on Thrombosis and Haemostasis; KM, Kaplan–Meier; MI, myocardial infarction; od, once daily; RRR, relative risk reduction; TIMI, Thrombolysis In Myocardial Infarction
A consistent benefit across different types of major adverse limb and CV events was also demonstrated in patients receiving DPI versus those receiving aspirin alone, including unplanned limb revascularization for recurrent limb ischaemia, hospitalization for coronary or peripheral events, arterial and venous thrombotic events and ALI events.3,5,6 Regardless of your patients’ age, prior critical limb ischaemia, type of revascularization or bypass conduits, or use of clopidogrel, VOYAGER PAD provides reassuring evidence for a consistent effect of DPI with rivaroxaban 2.5 mg bid plus aspirin 100 mg od compared with aspirin alone.7-13
A consistent benefit of DPI versus aspirin in the reduction of major adverse limb and cardiovascular events following revascularization was observed in VOYAGER PAD, in addition to a consistent effect across patient subgroups5-13
ALI, acute limb ischaemia; CI, confidence interval; CLI, critical limb ischaemia; DPI, dual pathway inhibition; HR, hazard ratio
The findings from VOYAGER PAD have resulted in updates to the European label for rivaroxaban 2.5 mg bid plus aspirin 100 mg od for the prevention of atherothrombotic events in adult patients with symptomatic PAD at high risk of ischaemic events, which has been expanded to include a specific recommendation for patients with a recent lower-extremity revascularization.14
Guidance on DPI use according to the European rivaroxaban label14 DAPT, dual antiplatelet therapy; DPI, dual pathway inhibition; PAD peripheral artery disease; TIA, transient ischaemic attack
The promising results from the VOYAGER PAD trial, including results across key patient subgroups, are also reflected in a broad recommendation in the European Atherosclerosis Society/European Society of Vascular Medicine joint statement for therapy in patients with arterial disease: ‘Based on results from the VOYAGER [PAD] study, combination therapy with aspirin (100 mg od) and rivaroxaban (2.5 mg bid) should be considered for DAPT post‑intervention.’15
Moreover, the 2021 European Society of Cardiology expert consensus on antithrombotic therapies in aortic and peripheral arterial diseases states that rivaroxaban 2.5 mg bid plus aspirin 100 mg od should be considered in patients undergoing surgical or endovascular revascularization for lower extremity artery disease, unless there is an obvious concern regarding bleeding; for example, frail or extremely old patients, patients with a history of ischaemic stroke or intracranial haemorrhage who have experienced recent gastrointestinal bleeding or have an estimated glomerular filtration rate <15 ml/min/1.73 m2.16
The consistent results across key patient subgroups provide reassurance that DPI with rivaroxaban 2.5 mg bid plus aspirin 100 mg od is a treatment option with a favourable efficacy and safety profile for many of your patients, like Louisa.
The significance of the results from VOYAGER PAD and the subsequent label update and guideline recommendations for DPI with rivaroxaban 2.5 mg bid and low-dose aspirin was highlighted in the interview with Dr Marc Bonaca. Regarding patients with PAD, he states: ‘even when they’re being revascularized for claudication, they have extremely high rates of acute limb ischaemia and the need for unplanned index revascularizations. That’s where new data from VOYAGER PAD, from rivaroxaban, are so exciting… for the first time we have an agent labelled for preventing these thrombotic vascular events in the setting of revascularization for peripheral artery disease; and rivaroxaban presents a new option in our toolkit to improve outcomes for these patients.’