Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial

Lancet 2018;391:2325-34 doi:10.1016/S0140-6736(18)30832-8

Presented by: Dr James Lloyd


  • Myocardial injury after non-cardiac surgery (MINS) is a relatively newly described diagnosis, having only been described about 4 years ago
  • The diagnosis includes myocardial infarction and isolated ischaemic troponin elevation occurring within 30 days after surgery, but does not include perioperative myocardial injury due to non-ischaemic causes for example caused by sepsis, or rapid heart rate.
  • It is common, estimated at around 8 million cases internationally every year, and carries an increased risk of mortality.
  • This is the first randomised controlled trial to address this group of patients.

Design & Setting

  • A multicentre, international, placebo controlled randomised control trial involving 1754 patients


  • Patients over 45, who had received non cardiac surgery, and were within 35 days of what the authors term MINS (Myocardial Injury after Non cardiac Surgery).
  • MINS is defined as having either elevated troponin with ischaemic signs or symptoms, ischaemic electrocardiographic changes, or new or presumed new ischaemic abnormality on cardiac imaging or an isolated elevated troponin measurement without an alternative explanation.


  • Patients were assigned either the intervention arm which was 110mg of Dabigatran twice daily for up to two years, or matched placebo.
  • Patients were then also randomised to receive either 20mg of omeprazole once daily, or placebo, as part of a separate study.


  • The primary outcome was a major vascular complication (This was defined as a composite of vascular mortality, and non-fatal myocardial infarction, non-haemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism).
  • The primary safety outcome, to monitor the side effect profile of the intervention, were a composite of life-threatening, major, and critical organ bleeding.


  • A major vascular complication occurred in 97 (11%) of 877 patients allocated to dabigatran and in 133 (15%) of 877 patients allocated to placebo (HR 0·72, 95% CI 0·55–0·93, p=0·0115)
  • In addition, Dabigatran did not increase the risk of life-threatening, major, or critical organ bleeding (primary safety outcome) compared with placebo (HR 0·92, 95% CI 0·55–1·53, p=0·78)
  • In the analysis of the secondary outcomes Dabigatran was shown to increase the risk of minor bleeding, clinically non-significant lower gastrointestinal bleeding, and dyspepsia.
  • The subgroup analysis shows that the hazard ratios are not statistically significant for patients receiving dual antiplatelet therapy, or for patients who showed only an isolated troponin rise.


  • In patients identified as having MINS, instigating a treatment of 110mg BD dabigatran reduced the probability of a major vascular complication, without increasing the risk of major, or life threatening bleeding.
  • The number needed to treat with dabigatran to prevent one major vascular complication was 24, whereas the number needed to harm (i.e. to cause major, rather than life threatening bleeding) is 54.
  • The subgroup analysis fails to reinforce the concept of routine monitoring of troponin, as the patients identified only by a troponin rise did not show any benefit from the intervention.


  • A large, well blinded randomised control trial, with good length of follow up


  • Trial terminated early due to slow recruitment and withdrawal of funding
  • Because of the early termination the primary outcome measures for the trial were altered part way through
  • The subgroup analysis shows benefit for one group, but not another, suggesting two different sets of pathology


  • That unless routine screening of perioperative troponin levels is instigated 90% of MINS events will be missed.
  • That treating these patients with BD Dabigatran 110mg will reduce vascular complications.

Potential for impact

I don’t think this is really very clear, for two main reasons;

  1. Although the subgroup of patients who had ischaemic changes on ECG showed benefit from the treatment, they also had quite low levels of treatment with traditional secondary prevention medication, for which there is already lots of evidence.
  2. The group of patients who were only identified with troponin changes did not show any benefit from the intervention, which means there is little point starting this costly screening process when the authors are keen to point out that this is the only trial investigating the treatment of this group of patients.