Trial Tidbits: ESC 2020

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The European Society of Cardiology hosted their first-ever virtual 2020 Congress from August 29 to September 1. Here’s a handy guide to some of the big thrombosis-related trials you might have missed.

EAST-AFNET 4

Participants

  • 2,789 patients with recently diagnosed* atrial fibrillation (AFib) and an average CHA2DS2-VASc** score of 3.4 

*Recently diagnosed = diagnosis within ≤1 year before study enrollment    ** CHA2DS2-VASc risk score

Trial Design

  • International, prospective, blinded-outcome-assessment trial
  • Patients randomly assigned to either:
    • An early rhythm-control strategy with an antiarrhythmic medication or ablation
    • Usual care with rate-control therapy (in a minority of patients, rhythm-control therapy only initiated to mitigate uncontrolled AFib symptoms with adequate rate control)
  • Median 5.1-year follow-up

Study Endpoints

  • Co-primary endpoint 1: Composite of cardiovascular (CV) death, stroke, acute coronary syndrome, or hospitalization for worsening heart failure (HF)
  • Co-primary endpoint 2: Mean number of nights spent in the hospital each year (a measure to approximate the cost of treatment)
  • Primary safety endpoint: Stroke, death, or serious adverse events related to rhythm-control therapy

Key Findings

  • The primary outcome occurred at a rate of 3.9% each year in the rhythm-control group compared to 5% per year in the rate-control group, resulting in a statistically significant 21% relative risk reduction in favor of early rhythm control.
    • Results appeared consistent across predefined subgroups (i.e., asymptomatic patients, patients with obesity, and patients with or without HF).
  • The mean number of nights in the hospital was roughly the same in both arms (about 5 days/year).
  • The primary safety outcome didn’t differ between groups, but serious adverse events were more common in the rhythm-control group (4.9% vs. 1.4%), translating to about a 1% serious event rate annually in the rhythm-control group.
  • More than 70% of patients in both treatment groups were asymptomatic at 1 and 2 years, suggesting that both rate and rhythm control can help mitigate symptoms in patients with early AFib. 

Study Limitations

  • Open trial design
  • Not designed to evaluate the safety or effectiveness of specific components of early rhythm control
  • Results may not be generalizable to patients who initiate rhythm-control therapy later in AFib course

The Bottom Line

  • Early rhythm-control therapy can play an important role in managing patients with early AFib at risk of CV complications.

Corresponding Publication: Kirchhof P, Camm AJ, Goette A, et al. N Engl J Med. 2020. DOI: 10.1056/NEJMoa2019422.

LoDoCo2

Participants

  • 5,522 patients with chronic coronary disease
  • Most patients treated with secondary prevention therapies at baseline (e.g., antiplatelet agents or anticoagulants, statins, beta-blockers, etc.)

Trial Design

  • International, double-blind trial
  • Half of patients received 0.5 mg of colchicine once daily and half received a matching placebo
  • There was a 30-day run-in period for tolerance (no loading dose)
  • Median 28.6-month follow-up

Study Endpoints

  • Primary endpoint: Composite of CV death, spontaneous (nonprocedural) myocardial infarction (MI), ischemic stroke, or ischemia-driven coronary revascularization
  • Secondary endpoints (ranked in order):
    • CV death, MI, or ischemic stroke (key secondary endpoint)
    • MI or ischemia-driven coronary revascularization
    • CV death or MI
    • Ischemia-driven coronary revascularization
    • MI
    • Ischemic stroke
    • Death from any cause
    • CV death

Key Findings

  • The primary endpoint occurred in 6.8% of the colchicine arm compared to 9.6% in the placebo arm, resulting in a 31% lower risk and 77 fewer events in patients taking colchicine vs. placebo.
  • Colchicine benefits were also observed in several of the secondary endpoints, including MI and ischemia-driven coronary revascularization.
  • Non-CV death was significantly higher with colchicine compared to placebo (0.7 vs. 0.5 events per 100 person-years).

Study Limitations

  • C-reactive protein or other inflammatory markers not routinely measured at baseline
  • BP and lipid levels not collected at baseline or during trial
  • Small percentage of female participants

The Bottom Line

  • These findings were consistent across subgroups and build on evidence from previous trials (LoDoCo and COLCOT) supporting the potential benefits of anti-inflammatory treatments in patients with coronary disease.

Corresponding Publication: Nidorf SM, Fiolet ATL, Mosterd A, et al. N Engl J Med. 2020; DOI: 10.1056/NEJMoa2021372

HOME-PE

Participants

  • 1,974 patients presenting to the emergency department (ED) with non-high-risk (hemodynamically stable) pulmonary embolism (PE)

Trial Design

  • International, open-label, noninferiority trial
  • Half of patients randomized to risk stratification with the HESTIA* rule
  • The other half randomized to risk stratification with the simplified Pulmonary Embolism Severity Index (sPESI)** score
  • Low-risk patients discharged home; patients not deemed low risk were hospitalized

*HESTIA rule; **sPESI score

Study Endpoints

  • Primary endpoint: All-cause death, recurrent venous thromboembolism (VTE), or major bleeding at 30 days
  • Secondary endpoints: Proportion of patients managed as outpatients, the rate of low-risk patients eligible for outpatient care, cumulative event rate, and rates of recurrent VTE, suspected recurrent VTE, major bleeding, nonmajor bleeding, death, and serious adverse events

Key Findings

  • Nearly 40% of patients in the HESTIA group were eligible for outpatient care (“no”answers to all 11 criteria); nearly half of sPESI-scored patients had a score of 0 and were deemed eligible for outpatient management.
  • Physicians could overrule the discharge decision; 38% of patients were discharged home within 24 hours in the HESTIA group and 37% in the sPESI group.
  • The primary endpoint occurred in:
    • 3% of the HESTIA outpatients vs. 1.1% of the sPESI outpatients.
    • 6% of the HESTIA hospitalized patients vs. 4.7% of the sPESI outpatients.

Study Limitations

  • Successful outpatient management depends on access to healthcare and social support (not examined in the study)
  • Role of additional imaging or laboratory criteria to exclude more severe PE was not addressed

The Bottom Line

  • In patients with PE, the HESTIA rule was noninferior to the sPESI score regarding all-cause death, recurrent VTE, or major bleeding. The two strategies didn’t differ as far as the proportion of patients treated at home.
  • Risk stratification can identify approximately one-third of low-risk PE patients that can be safely managed at home.

Reference: Presented by Dr. Pierre-Marie Roy at the European Society of Cardiology Virtual Congress, August 31, 2020.

IMPACT-AFib

Participants

  • >47,000 patients with AFib and a CHA2DS2-VASc score of at least 2 who had not initiated oral anticoagulation (OAC)

Trial Design

  • US-based, prospective, randomized, open-label educational intervention trial
  • Half of patients received a single educational mailing at the start of the trial and half received usual care
  • The mailing included:
    • A letter about the patient’s AFib diagnosis
    • A statement about why OAC is a suitable medication option
    • A suggestion that patients discuss OAC with their healthcare provider
  • Additional components of the mailing included information on stroke risk in AFib, a chart to manually calculate one’s CHA2DS2-VASc score, and an overview of the potential risks of OAC, possible drug-drug interactions, and the limited availability of reversal agents

Study Endpoints

  • Primary endpoint: The proportion of patients initiating OAC within 1 year of follow-up

Key Findings

  • Nearly 10% of patients in both study arms began OAC within 1 year of follow-up (9.89% and 9.80% in the intervention and usual care groups, respectively; OR, 1.01, 95% CI 0.95-1.07).
  • There was a non-statistically significant numerical uptick in patients starting OAC early after the mailing.

Study Limitations

  • The mailing did not overtly address the benefits of OAC in patients with AFib.

The Bottom Line

  • OACs remain under-prescribed and underused in patients with AFib.
  • A single mailing/intervention is likely inadequate to capture attention and change patient behavior. Repeated messaging or multi-component interventions targeting both patients and providers may yield better outcomes.

Reference: Presented by Dr. Sean Pokorney at the European Society of Cardiology Virtual Congress, September 1, 2020.

Additional studies you may be interested in:

  • The POPular TAVI trial: In patients not taking OAC, aspirin alone vs. aspirin + clopidogrel following transcatheter aortic valve implantation (TAVI) significantly reduced bleeding rates and did not increase thromboembolic events.
  • The EMPEROR-Reduced trial: Patients receiving recommended therapy for HF who also received empagliflozin had a lower risk of CV death or hospitalization for HF, regardless of their diabetes status.
  • The DAPA-CKD trial: Dapagliflozin prolonged survival and significantly reduced the risk of kidney failure, HF hospitalization and CV death in patients with CKD regardless of their diabetes status

Consumer-friendly trial summaries can be found at the ACC Media Center:

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