Novel Anticoagulation Options:Target-Specific Oral Agents an - Episode 6

Triple Therapy Risks and Rewards


The MD Magazine Peer Exchange “Novel Anticoagulation Options: Target-Specific Oral Agents and Their Antidotes” features leading physician specialists discussing key topics in anticoagulation therapy, including the clinical characteristics of current and emerging agents and criteria for use in specific patient populations.

This Peer Exchange is moderated by Peter Salgo, MD, professor of medicine and anesthesiology at Columbia University and an associate director of surgical intensive care at the New York-Presbyterian Hospital in New York City.

The panelists are:

  • Scott Kaatz, DO, MSc, Chief Quality Officer at Hurley Medical Center in Flint, Michigan, and clinical associate professor at Michigan State University
  • Seth Bilazarian, MD, clinical and interventional cardiologist at Pentucket Medical and instructor of medicine at Harvard Medical School
  • Gerald Naccarelli, MD, Bernard Trabin Chair in Cardiology, professor of medicine and chief of the Division of Cardiology at Penn State University School of Medicine, and associate clinical director at Penn State Heart and Vascular Institute in Hershey, Pennsylvania
  • Christian T. Ruff, MD, associate physician in the cardiovascular medicine division at Brigham and Women’s Hospital, and assistant professor of medicine at Harvard Medical School in Boston

In this segment of the Peer Exchange, the panelists discuss patients’ misconceptions of the risks associated with use of anticoagulants, and the risks and benefits of using triple therapy with antiplatelets, antithrombotics, and the newer drugs.

The panelists agreed that the volume of stories patients have heard from friends and family members about bad experiences with warfarin has resulted in many patients being quite aware of the hazards associated with that drug. “Whether it’s nuisance bleeding, bruising on the skin, or more serious GI bleeding or intracranial hemorrhage, I think people are aware of the hazards of these drugs.”

But all bleeds are not the same, said Nacarrelli. Although bleeding rates overall “are the same for warfarin compared to rivaroxaban or dabigatran, it’s where the bleeds are different” that counts, he said.

“A GI bleed doesn’t kill you; bleeding in your head does,” he said. And not only is treatment with edoxaban and apixaban associated with fewer bleeds, those drugs “don’t have bleeds that cause fatalities,” Nacarrelli added. Apixaban is approved for reducing mortality, and if you “look at all the numbers in every one of these trials, it’s very favorable in mortality because you’re reducing hemorrhagic stroke, you’re reducing big strokes and people are living longer.”

“What about triple therapy?” asked Salgo. “What are we talking about and which agents that we’re talking about are best for that?”

“All blood thinners are going to cause bleeding, no matter which ones you use,” said Ruff. “That’s part of using antiplatelets and antithrombotics. Now, the issue with triple therapy is that all anticoagulants cause bleeding, so if you add another drug or two that also causes bleeding (in triple therapy generally you use two antiplatelet agents, with aspirin and clopidogrel being the most common) now they’re on three drugs that together dramatically, exponentially increase your rates of serious bleeding.”

The clinical community is nervous about these patients because they have very, very high rates of bleeding,” Ruff said. But, in trials with these new agents, there were very few patients who actually ended up on triple therapy.”

“We have good data showing that when one of these new agents is combined with a single antiplatelet agent (say aspirin) that generally it’s still favorable because they cause less bleeding than warfarin overall,” he said. Ruff suspects that adding two agents on top of warfarin or two agents on top of one of these new agents, “is still going to favor these new agents because they’re much safer with respect to serious bleeding.”

There are several ongoing studies involving the new anticoagulants and patients who have coronary disease or stenting who require dual antiplatelet therapy. In Ruff’s opinion, these trials will likely provide a large amount of data showing that many patients who are on single antiplatelet or double antiplatelet therapy shouldn’t be on it.’

In a small subset of patients, “you’re forced to tackle this, but we should be taking many of these patients off their antiplatelet because you’re exposing them to dramatically unnecessary bleeding risks,” Ruff added.

“I think this is huge, because we know from the trials that anywhere from 25-40% of the patients in the trials were on aspirin on top of warfarin or one of the newer agents. I tell you this as a hospitalist: I spend a lot of time trying to remove unnecessary aspirin that’s sitting on top of an anticoagulant,” said Kaatz.