Management of Myocardial Injury After Noncardiac Surgery - MANAGE

Contribution To Literature:

The MANAGE trial showed that dabigatran 110 mg BID among patients with mostly biochemical evidence of myocardial injury after noncardiac surgery had lower major vascular event rates compared with placebo; bleeding complications were similar.


The goal of the trial was to compare the safety and efficacy of dabigatran compared with placebo in reducing major vascular events among patients with evidence of myocardial injury after noncardiac surgery.

Study Design

Patients with evidence of myocardial injury after noncardiac surgery were randomized in a 1:1 fashion to either dabigatran 110 mg (n = 877) or placebo (n = 877).

  • Total number of enrollees: 1,754
  • Duration of follow-up: 16 months
  • Mean patient age: 70 years
  • Percentage female: 49%

Inclusion criteria:

  • Included patients ≥45 years of age
  • Had undergone noncardiac surgery
  • Were within 35 days of suffering myocardial injury after noncardiac surgery

Exclusion criteria:

  • History of bleeding diathesis or prior intracranial, intraocular, or spinal bleeding
  • Condition that required anticoagulation
  • Estimated glomerular filtration rate <35 ml/min

Other salient features/characteristics:

  • Myocardial injury after noncardiac surgery criteria: MI 20%, isolated troponin elevation: 80%
  • Aspirin 74%, P2Y12 inhibitor use 8%, statin 69%

Principal Findings:

The trial was terminated early due to loss of funding and slow enrollment. The primary outcome, composite of vascular death, MI, nonhemorrhagic stroke, peripheral arterial thrombosis, amputation, symptomatic venous thromboembolism (VTE), for dabigatran vs. placebo, was 11% vs. 15%, p = 0.012

  • Vascular mortality: 6% vs. 7%
  • MI: 4% vs. 5%
  • Symptomatic VTE: 1% vs. 2%

The primary safety outcome, composite of life-threatening, major, critical organ bleeding, was 3% vs. 4%, p = 0.78.

There was no interaction with omeprazole use in 2 x 2 factorial design (p = 0.93).

Secondary outcomes, for dabigatran vs. placebo:

  • Arterial components of primary composite outcome: 10% vs. 14%, p < 0.05
  • All-cause mortality: 11% vs. 13%
  • Symptomatic VTE: 1% vs. 2%
  • Drug discontinuation: 46% vs. 43%


The results of this trial indicate that addition of dabigatran 110 mg BID among patients with evidence of myocardial injury post-noncardiac surgery had lower major vascular event rates compared with placebo; bleeding complications were similar. These results are interesting, but need to be viewed with the caveat that the trial was terminated early and the primary outcome definition was changed midway through the trial. Rates of discontinuation of the drug were also high (>40%). This is likely a heterogeneous patient group, and the utility of routinely measured troponins in asymptomatic patients without ECG changes is unclear. Aspirin, statin use in the current trial was low, and may also be targets for improvement.


Devereaux PJ, Duceppe E, Guyatt G, et al., on behalf of the MANAGE Investigators. Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial. Lancet 2018;391:2325-34.

Editorial Comment: Adriaenssens T, Sinnaeve P. Direct oral anticoagulants for postoperative myocardial injury. Lancet 2018;391:2297-8.

Presented by Dr. P.J. Devereaux at the American College of Cardiology Annual Scientific Session (ACC 2018), Orlando, FL, March 11, 2018.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Dyslipidemia, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and ACS, Anticoagulation Management and Venothromboembolism, Nonstatins, Novel Agents, Statins

Keywords: ACC18, ACC Annual Scientific Session, Acute Coronary Syndrome, Antithrombins, Electrocardiography, Hemorrhage, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Myocardial Infarction, Stroke, Surgical Procedures, Operative, Thrombosis, Troponin, Venous Thromboembolism, Secondary Prevention, Vascular Diseases

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