NOAC reduces major CV complications in patients with myocardial injury after noncardiac surgery
Dabigatran in myocardial injury after noncardiac surgery
Presented at ACC.18 by dr. PJ Devereaux (McMaster University in Hamilton, ON, Canada)
MINS refers to myocardial injury after noncardiac surgery, and includes myocardial infarction (MI) and isolated ischemic troponin elevation that occur within the first 30 days after noncardiac surgery. MINS is independently associated with increased risk of CV events and death over the first two years after surgery.
Anticoagulation therapy is beneficial in non-operative patients at risk of thrombotic events, but no published trial has evaluated treatment for MINS. This study evaluated the potential of the oral direct thrombin inhibitor dabigatran, to avoid a broad range of vascular complications in patients with MINS. The international MANAGE trial randomized 1754 patients (mean age 70 years old) with MINS to dabigatran 110 mg BID or placebo. In a partial 2x2 factorial design, patients not already on PI treatment, were randomized to omeprazole 20 mg daily or placebo. Patients were followed for a maximum of 2 years or until the trial was terminated. The primary efficacy outcome was a composite of vascular death and nonfatal MI, non-hemorrhagic stroke, peripheral arterial thrombosis, amputation and symptomatic VTE. The primary safety outcome was a composite of life-threatening, major, and critical organ bleeding.
- 46% Of patients in the dabigatran group and 43% of patients in the placebo group discontinued the study drug, mostly with patient request as the reason for stopping.
- 97 Of 877 (11%) patients randomized to dabigatran experienced a primary efficacy outcome event, as compared with 133 of 877 (15%) patients on placebo, resulting in a risk reduction of 28% (HR: 0.72, 95%CI: 0.55-0.93, P=0.012).
- There was not significant effect of omeprazole study drug on the effects of dabigatran in the primary efficacy analysis (P-interaction=0.79).
- The primary safety outcome occurred in 29 (3%) of patients on dabigatran and in 31 94%) patients on placebo, which was not significantly different (HR: 0.92, 955CI: 0.55-1.53, P=0.79).
- Omeprazole study drug did not significantly interact with the effect of dabigatran on the primary safety outcome.
This study shows that patients who have MINS are at substantial risk of major vascular complications. Without routine post-operative troponin measurement, most cases of MINS will go unnoticed. Among patients with MINS, dabigatran 100 mg BID resulted in lower risk of major vascular complications as compared with placebo.
Almost half of patients discontinued study drug. The most common reason for drug discontinuation was patient request; however, 14 percent of these patients had a major complication (e.g., heart attack, stroke, bleeding). Devereaux notes in a press release that analyses that counted patients up to seven days after they discontinued the study drug showed even larger treatment effects, with 46 percent reductions in major CV complications with dabigatran and no excess of life-threatening, major or critical organ bleeding.
Our coverage of ACC.18 is based on the information provided during the congress.