Another Way to Save a Life: the MANAGE Trial

Melissa Walton-Shirley, MD


March 12, 2018

It's the story within the story. The MANAGE trial treated patients with postoperative ischemia-driven troponin elevation after noncardiac surgery using 110 mg of dabigatran twice daily. It was a positive trial that produced a 28% reduction in vascular events at 16 months. Despite the terrifying idea of anticoagulating freshly operated patients, there was no increase in major bleeding. But that wasn't the big story. Dr Pamela Douglas, a commentator on the trial, said, "Congratulations on describing a new disease entity. It has never had a trial and it's extremely common. There is an opportunity to impact outcomes." And so it begins.

What? Another Consult for Troponin-emia?

Cardiologists are commonly called to see patients with type II myocardial infarctions (MIs).[1] These are the patients with racing hearts, raging fevers, and bone-dry vascular spaces languishing from blood and volume loss. Sympathetic troponin creeps into the bloodstream, crying foul at the imbalance of myocardial oxygen supply and demand. On some days, that "detectable but nondiagnostic troponin" drives yet another consult request. Cardiologists shore up a few things, bring down the heart rate, get an echo. Many of the patients with type II MI are the sickest of the sick. They are frail, elderly, and sometimes destined for long-term care. We do our best in that situation. The focus of this trial, however, was a different population.

Heart Injury Often Undetected After Surgery

The cohorts in the MANAGE trial developed more classic ischemia-driven troponin elevations detected via a protocol that could vary. Dr PJ Devereaux, from Hamilton, Ontario, Canada, speaking by phone, said, "The order set protocols usually included a troponin assessment somewhere between 6 and 12 hours postoperatively and again on postop days 1, 2, and 3." After the usual suspects that drive type II infarctions were excluded, the patients were enrolled.

According to Devereaux, more than 8 million patients worldwide will experience myocardial infarction during or after noncardiac surgery (MINS). Although almost always silent, it is associated with an increase in cardiovascular events and death in the first 2 years after surgery. It is humbling to know that in many patients we've checked and given a cheeky thumbs-up postoperatively, the silent but damning event has already happened. Those largely asymptomatic patients (>90% in this study) simply smile back and are as much in the dark about their prognosis as we are. The MANAGE trial is among the first trials to warn us not to be complacent.

We're Good at Checking for Postop DVT

Since a nasty deep-vein thrombosis (DVT) can produce devastating complications and a costly prolonged hospital stay, we've become socialized to do great venous complication prevention and good follow-up. I'm proud of my history of having a slick trigger to request a DVT assessment. Concerning, though, is that arterial events were 10-fold more common in this trial population than venous events. It's just another reason to check postop troponins routinely.

What to Do?

I don't know where we will go from here with dabigatran. MANAGE is just one trial, but it will lay the groundwork for many more. The dabigatran dose of 110 mg twice daily is not available in the United States, and the drug doesn't have an approved indication for use in this setting. I'm optimistic that these data will change postop care for many patients in the future. I hope we can identify subsets who benefit most to save others from having to receive full-on anticoagulation.

For now, MANAGE exposes the need for cardiologists to sit down with the quality folks at our institutions and change our postop orders to survey patients for missed asymptomatic infarctions. The traditional "don't ask, don't tell" approach in the pos-op noncardiac surgery patient isn't working. A simple change in our postoperative order sets could be our next opportunity to save another life.


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