The 2020 American College of Cardiology, together with the World Congress of Cardiology, hosted the first-ever virtual Scientific Sessions from March 28-30. Here’s a handy guide to some of the big trials you might have missed.

VOYAGER PAD

Participants

  • 6,564 patients with symptomatic peripheral artery disease (PAD) who had lower limb revascularization

Trial Design

  • International, double-blind trial
  • Half of patients received rivaroxaban 2.5 mg twice daily + 100 mg of aspirin daily.
  • The other half received placebo + 100 mg of aspirin daily.
  • Patients were followed for a median of 28 months.
  • Note: Half of participants took clopidogrel at the discretion of the physician treating them. (The use of clopidogrel was not part of the study design.)

Study Endpoints

  • Primary endpoint: Composite of acute limb ischemia, major amputation for vascular causes, ischemic stroke, myocardial infarction (MI), or death from cardiovascular causes
  • Primary safety endpoint: Rate of major bleeds according to the Thrombolysis in Myocardial Infarction (TIMI) bleeding classification*

*Fatal bleeding, overt bleeding with drop in hemoglobin ≥5 g/dl or a 15% drop in hematocrit, and any intracranial hemorrhage

Key Findings

  • There were lower event rates in patients taking rivaroxaban + aspirin vs. aspirin alone (17.3% vs. 19.9%, respectively), resulting in a 15% absolute risk reduction.
  • The rivaroxaban + aspirin group had more bleeding (2.7%) than the aspirin group (1.9%), but the difference was not statistically significant.
  • There was no excess in severe or fatal bleeding (e.g., intracranial hemorrhage).

Study Limitations

  • More patients prematurely discontinued treatment than anticipated.

The Bottom Line

  • Dual therapy with rivaroxaban + aspirin safely and effectively reduced the rate of ischemic events and was superior to aspirin alone in patients with symptomatic PAD.
  • Patients with PAD who have undergone revascularization are at high risk for acute limb ischemia; this trial provides an evidence-based treatment strategy for these patients.
  • VOYAGER PAD further supports findings from the COMPASS trial, which showed that low-dose rivaroxaban + aspirin significantly decreased major adverse heart events in patients with coronary artery disease (CAD) and PAD.

Corresponding Publication

Bonaca MP, Bauersachs RM, Anand SS, et al. N Engl J Med. 2020. [Epub ahead of print].


CARAVAGGIO

Participants

  • 1,170 patients with cancer-associated thrombosis (CAT)

Trial Design

  • Multinational, noninferiority trial
  • Half of patients received 10 mg of apixaban twice daily for seven days followed by 5 mg twice daily.
  • The other half received 200 units/kg of subcutaneous (SQ) dalteparin once a day for one month, followed by 150 units/kg once daily.
  • Patients were followed for 6 months (the total course of treatment in both study arms).

Study Endpoints

  • Primary endpoint: Recurrent venous thromboembolism (VTE)
  • Primary safety endpoint: Major bleeding

Key Findings

  • In the apixaban group, 5.6% of patients had recurrent VTE vs. 7.9% of patients in the dalteparin group.
  • Major bleeding occurred in 3.8% of patients in the apixaban arm vs. 4.0% of patients in the dalteparin arm.
  • Apixaban was not associated with increased gastrointestinal (GI) bleeding compared with dalteparin.

Study Limitations

  • The sample size was only powered for the primary outcome and not powered to drive conclusions about bleeding.
  • Findings cannot be generalized to all types of cancer. (Patients with basal-cell or squamous-cell skin cancer, brain tumors, known intracerebral metastases, or acute leukemia were excluded from the study.)

The Bottom Line

  • Apixaban is at least as effective as dalteparin—the current standard of care—in treating CAT.
  • Apixaban was not associated with excess major bleeding or increased GI bleeding, both of which are concerns in patients on anticoagulation.
  • The data may broaden the use of apixaban in patients with CAT and provide them with a less cumbersome treatment option than dalteparin.

Corresponding Publication

Agnelli G, Becattini C, Meyer, G, et al. N Engl J Med. 2020. [Epub ahead of print.]


PRONOMOS

Participants

  • 3,604 patients undergoing nonmajor orthopedic limb surgery*

*Achilles tendon repair, knee surgery, tibial or ankle fractures, or other similar procedures requiring >14 days of thromboprophylaxis; hip/knee replacements or hip fracture repair were excluded

Trial Design

  • International, double-blind trial
  • Half of patients received 10 mg of rivaroxaban daily + placebo injection.
  • The other half received 40 mL of SQ enoxaparin daily + placebo tablet.
  • The median duration of treatment was 28 days. (Treatment duration ranged from 2-8 weeks based on the discretion of the treating clinician and the anticipated timeframe of postsurgical immobilization.)

Study Endpoints

  • Primary endpoint: Major VTE*
  • Prespecified secondary outcomes: Major and clinically relevant nonmajor bleeding, overt thrombocytopenia, and death from any cause

*Composite of symptomatic distal or proximal DVT, pulmonary embolism (PE), or VTE-related death during the treatment period or asymptomatic proximal DVT at the end of treatment

Key Findings

  • A major VTE event occurred in 0.24% of patients taking rivaroxaban vs. 1.1% of patients receiving enoxaparin.
  • Bleeding rates did not differ between the study arms:
    • Major + nonmajor clinically relevant bleeding: 1.08% in rivaroxaban arm vs. 1.04% in enoxaparin arm
    • Major bleeding: 0.57% in rivaroxaban arm vs. 0.69% in enoxaparin arm

Study Limitations

  • Study enrollment was halted early, leading to a smaller sample size than investigators planned.
  • The study population was young and healthy (median age = 41), limiting generalizability to older populations.
  • A discussant at the ACC session noted that enoxaparin is not frequently used for VTE prophylaxis outside the US.

The Bottom Line

  • Compared with enoxaparin, rivaroxaban reduced the risk of major VTE by 75% in young patients requiring immobilization after lower limb orthopedic surgery.
  • Rivaroxaban was not associated with an increased incidence of major bleeding or other bleeding events.
  • The study showed that a once-daily oral anticoagulant can safely be used for postsurgical VTE prophylaxis instead of an injection.

Corresponding Publication

Samama CM, Laporte S, Rosencher N, et al. N Engl J Med. 2020. [Epub ahead of print.]


TICO

Participants

  • 3,056 patients in South Korea with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI)

Trial Design

  • Open-label trial
  • All patients received dual antiplatelet therapy (DAPT) with ticagrelor + aspirin for 3 months (the current standard of care).
  • After 3 months, half of patients received DAPT and the other half received ticagrelor monotherapy.
  • Patients were followed for 12 months.

Study Endpoints

  • Primary endpoint: Net adverse clinical events* at 12 months
  • Secondary outcomes:
    • Major bleeding at 12 months
    • Stent thrombosis at 12 months

*Death, MI, stent thrombosis, stroke, target vessel revascularization, or TIMI major bleeding

Key Findings

  • Approximately 4% of patients in the monotherapy group had a primary-endpoint event vs. nearly 6% of patients receiving DAPT.
  • There was a reduced risk of major bleeding in the monotherapy group vs. the DAPT group (1.7% vs. 3%, respectively).

Study Limitations

  • The trial had an open-label design without placebo.
  • Patients with an elevated bleeding risk* were excluded.

*Age ≥80, a history of stroke in past year, or traumatic brain injury or brain surgery in past 6 months

The Bottom Line

  • After 3 months of DAPT, ticagrelor monotherapy was superior to DAPT in preventing bleeding and ischemic events in patients who underwent PCI for ACS.
  • This study builds on findings from last year’s TWILIGHT trial and positions ticagrelor monotherapy as an emerging treatment option in post-PCI patients who receive DAPT for 90 days.

Additional studies you may be interested in:

  • REDUCE-IT EPA trial: In this major prevention trial, patients who took 4 grams of prescription fish oil daily had increased blood levels of EPA, which correlated with a significant reduction in CV events and CV death.
  • Insights from the COMPASS trial (diabetes subset): Patients with stable coronary disease, PAD, and diabetes who took 2.5 mg of rivaroxaban daily + aspirin had a larger absolute benefit on CV endpoints—including a 3-fold greater reduction in all-cause mortality—compared with the general population.

Consumer-friendly trial summaries for your patients can be found below and at the ACC Media Center.