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|Family Medicine (FM)/General Practice (GP)|
|General Internal Medicine-Primary Care(US)|
|Surgery - Thoracic|
|Hemostasis and Thrombosis|
|Surgery - General|
|Surgery - Orthopaedics|
|Surgery - Vascular|
BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) increases the risk of cardiovascular events and deaths, which anticoagulation therapy could prevent. Dabigatran prevents perioperative venous thromboembolism, but whether this drug can prevent a broader range of vascular complications in patients with MINS is unknown. The MANAGE trial assessed the potential of dabigatran to prevent major vascular complications among such patients.
METHODS: In this international, randomised, placebo-controlled trial, we recruited patients from 84 hospitals in 19 countries. Eligible patients were aged at least 45 years, had undergone non-cardiac surgery, and were within 35 days of MINS. Patients were randomly assigned (1:1) to receive dabigatran 110 mg orally twice daily or matched placebo for a maximum of 2 years or until termination of the trial and, using a partial 2-by-2 factorial design, patients not taking a proton-pump inhibitor were also randomly assigned (1:1) to omeprazole 20 mg once daily, for which results will be reported elsewhere, or matched placebo to measure its effect on major upper gastrointestinal complications. Research personnel randomised patients through a central 24 h computerised randomisation system using block randomisation, stratified by centre. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary efficacy outcome was the occurrence of a major vascular complication, 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 was a composite of life-threatening, major, and critical organ bleeding. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01661101.
FINDINGS: Between Jan 10, 2013, and July 17, 2017, we randomly assigned 1754 patients to receive dabigatran (n=877) or placebo (n=877); 556 patients were also randomised in the omeprazole partial factorial component. Study drug was permanently discontinued in 401 (46%) of 877 patients allocated to dabigatran and 380 (43%) of 877 patients allocated to placebo. The composite primary efficacy outcome occurred in fewer patients randomised to dabigatran than placebo (97 [11%] of 877 patients assigned to dabigatran vs 133 [15%] of 877 patients assigned to placebo; hazard ratio [HR] 0·72, 95% CI 0·55-0·93; p=0·0115). The primary safety composite outcome occurred in 29 patients (3%) randomised to dabigatran and 31 patients (4%) randomised to placebo (HR 0·92, 95% CI 0·55-1·53; p=0·76).
INTERPRETATION: Among patients who had MINS, dabigatran 110 mg twice daily lowered the risk of major vascular complications, with no significant increase in major bleeding. Patients with MINS have a poor prognosis; dabigatran 100 mg twice daily has the potential to help many of the 8 million adults globally who have MINS to reduce their risk of a major vascular complication.
FUNDING: Boehringer Ingelheim and Canadian Institutes of Health Research.
This needs to be reproduced before being applied widely.
Thought-provoking study in that the management of post-operative ischemic events has not been thoroughly evaluated. Future trials, however, might include more assessment and/or therapeutic strategies.
More relevant to hospitalists and cardiologists.
Interesting trial - composite endpoint.
Really important situation. This is important info, but honestly I would like to see it repeated as results look too good to be true (no increase in bleeding, for example).
This international, randomised, placebo-controlled study of the use of dabigatran in patients with myocardial injury after non-cardiac surgery addresses an important question - that of cardiovascular events and deaths after surgery that anticoagulation therapy could prevent. The results will most likely lead to changes in practice at the international level.
Myocardial injury after non cardiac surgery (MINS) according to the definitions of the authors and reference provided includes myocardial infarction(MI) and isolated ischemic troponin elevation, yet the first line of the abstract states MINS can lead to a cardiovascular event, not that MINS is a cardiovascular event itself! Myocardial infarction has a specific, well evidenced treatment protocol and it is unclear why patient with MI, post surgery should be treated differently. Dabigatran is an anticoagulant used to prevent venous thromboembolic events and it is, therefore, no surprise that this paper showed reduced number of thromboembolic events in a high risk group of patients (post MI).
This new information is offered to a wide physician spectrum. Physicians should routinely measure troponin in at-risk patients undergoing non-cardiac surgery and, in those with MINS, should consider using dabigatran 110 mg twice daily for two years. Nevertheless, it could be convinient to have a more powerful randomized trial before to widespread this regime among all the medical community.