March 11, 2018
Dabigatran Shown to Reduce Major Cardiovascular Complications in Patients With Myocardial Injury After Noncardiac Surgery
March 11, 2018—Treatment with the anticoagulant drug dabigatran significantly reduced the risk of death, heart attack, stroke, and other heart or blood vessel complications among patients who were at elevated risk for these events due to heart damage that occurred after major noncardiac surgery. These findings were presented by P.J. Devereaux, MD, in a Late Breaking Trial session at the American College of Cardiology's (ACC) 67th annual scientific session held March 10–12 in Orlando, Florida.
This randomized controlled trial evaluated a treatment for myocardial injury after noncardiac surgery (MINS). The investigators found that patients treated with dabigatran twice daily were 28% less likely to die, have a heart attack or stroke, develop blood clots, or need an amputation because of cardiovascular disease, compared with patients who received a placebo.
In the ACC press release, Dr. Devereaux commented, "We have shown for the first time that dabigatran reduces the risk of major cardiovascular complications and offers an option for improving outcomes in a large at-risk population who have MINS." Dr. Devereaux is Director of Cardiology at McMaster University in Hamilton, Canada.
The background of the study is that approximately 8 million people every year develop MINS after undergoing surgery such as a hip or knee replacement, bowel resection, or abdominal aortic aneurysm repair. These findings build on research that Dr. Devereaux and his colleagues presented at the ACC conference in 2017 showing that MINS may account for approximately one in four deaths during the first 30 days after surgery. That research also showed a blood test for high-sensitivity troponin T protein, which is released into the bloodstream when injury to the heart occurs, can identify patients with MINS whose lives could potentially be saved with timely treatment.
Dr. Devereaux advised that most cases of MINS currently go undetected because it is not standard practice in most centers to monitor blood levels of troponin in patients who had major noncardiac surgery. He hopes this may change now that this study has shown treatment with dabigatran can improve outcomes for patients with MINS. He stated, "Our findings reaffirm that patients who develop MINS are at high risk for bad outcomes. We owe it to our patients to identify this risk and do what we can to reduce it."
As summarized in the ACC announcement, the MANAGE trial enrolled 1,754 patients (51% men; average age, 70 years) in 19 countries. The primary efficacy outcome was the combined rate of death from a cardiovascular cause, heart attack, stroke caused by inadequate blood supply, blood clots, or amputation caused by cardiovascular disease. The primary safety outcome was the combined rate of life-threatening, major, and critical organ bleeding.
During the study, patients, health care providers and research staff were blinded to which group received dabigatran and which received a placebo.
The investigators found that after an average follow-up of 16 months, 11.1% of patients treated with dabigatran experienced one or more of the primary efficacy outcome events, compared with 15.2% of patients who received a placebo. This translates to a 28% reduction in risk for patients receiving dabigatran.
When analyzing occurrence rates for the events comprising the primary efficacy outcome, the investigators found trends of benefit for each component. For example, patients treated with dabigatran versus those treated with placebo were 20% less likely to die of a cardiovascular cause, 20% less likely to have a heart attack, 30% less likely to have an amputation, and 53% less likely to have a venous blood clot. The result for nonhemorrhagic stroke also demonstrated a benefit with an 80% reduction in risk, a difference that was statistically significant compared with patients who were randomized to placebo.
There were no statistically significant differences between the two groups in life-threatening, major, or critical organ bleeding. Compared with the placebo group, however, more patients in the dabigatran group experienced bleeding in the lower gastrointestinal tract and minor bleeding. An increased risk of bleeding is an expected complication of treatment with an anticoagulant. Dr. Devereaux noted, "It's encouraging that we did not see an increase in major or life-threatening bleeding in patients on dabigatran."
The investigators advised that although nearly all patients (98.9%) completed follow-up, 45.3% of those on dabigatran had discontinued the study drug. The most common reason for drug discontinuation was patient request; however, 14% of these patients had a major complication (eg, heart attack, stroke, bleeding).
According to Dr. Devereaux, analyses that counted patients up to 7 days after they discontinued the study drug showed even larger treatment effects, with 46% reductions in major cardiovascular complications with dabigatran and no excess of life-threatening, major, or critical organ bleeding. He said that future research is needed to evaluate other treatment options for this high-risk group of patients.