Treating Patients with Renal Impairment

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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

With so many patients at risk for atrial fibrillation and stroke also at risk for renal impairment and kidney disease, it is important for physicians treating these patients to understand the performance of oral anticoagulants in patients with creatinine clearance levels of 30 or less.

Peter Salgo, MD, noted that renal impairment and chronic kidney disease are also prevalent in the aging patient population at higher risk for atrial fibrillation and stroke. Given that the newer oral anticoagulant drugs are excreted renally, he asked the panel for insight into using these medications in patients with impaired renal function.

Seth Bilazarian, MD, who was an investigator for 3 of the 4 agents, said the trials excluded patients with creatinine clearances less than 30, meaning “we actually don’t have any event trial data for that patient population.” However, physicians can prescribe these drugs because the FDA has given permission to use them in patients with creatinine less than 30.

“Renal excretion issues are really important. We know that dabigatran is the one that’s most dependent on renal excretion, and we know that apixaban is the least dependent, with the other two sort of in the middle. The real question is how should we go forward? Should that be part of the selection process?” Bilazarian asked.

When these medications first started being used four years ago, they could only be prescribed for patients with creatinine clearances above 30, but many physicians were hesitant to use them in patients who had creatinine clearances in the 30-40 range. Bilazarian said he chose not to use them at all in those patients.

“We’ve all seen those patients. The paradigm might be the little old lady who has a urinary tract infection and her creatinine doubles. Now, creatinine clearance has fallen precipitously. She’s not clearing the drug. Is she going to be at greater risk for bleeding? That was my concern,” he said.

The conversation up until this point has focused on the benefits associated with the oral anticoagulants‑‑they lower intracranial hemorrhage by 50%, they’re more convenient, etc.

Bilazarian asked the other panelists, “Is renal impairment an area where we’re starting to parse differences between the medications?”

Scott Kaatz, DO, said the initial clinical trials used the Cockcraft-Gault equation with actual body weight to measure creatinine clearance in patients. However, he said physicians should be careful because “that is not what we’re seeing on our biochemical profiles in the labs. Those I usually got done differently.” He said for patients whose creatinine clearance gets close to 30, “I usually pull out my iPhone and the National Kidney Foundation’s app and actually calculate it to see where I am.”

He added, “Sub-30 I get worried a little bit. I know we have the kinetic modeling that let us go down with dabigatran 75 mg with, etc. But I think it is important to be aware there are nuances with each of the drugs from the FDA package labeling right now, including if your creatinine clearance is ‘too good’ with edoxaban.”

Christian T. Ruff, MD, said patients with renal dysfunction are at elevated risk of both stroke and bleeding, so they’re particularly vulnerable. Interestingly, he also noted that “although warfarin is not a renally cleared drug, warfarin performs terribly in patients who have impaired renal function.”

Even though the new oral anticoagulants are renally cleared, as renal function becomes more impaired the differential between bleeding starts to be even more favorable with the new drugs. “All of these drugs incorporate a step-down in dose by renal function. It’s not that you don’t have to monitor drug levels, but you have to monitor patients. And one of the critical things if you put a patient on one of these agents is you should know what their renal function is, and you should know what their Cockcroft-Gault renal function is” because once creatinine clearance is about 50 for many of the drugs, there’s a step-down in dose, said Ruff.

“I think we have to be cautious in using these new agents and make sure that patients are on the appropriate dose,” he said.

Gerald Naccarelli, MD, said physicians must decide which medication option is most appropriate for a given patient. By way of example, he said to consider a patient with a creatinine clearance of 32. You could prescribe dabigatran in that patient, but dabigatran is 80% renally excreted. “I’m not totally comfortable putting a patient on dabigatran with a creatinine clearance of 32 when I can use apixaban or edoxaban, which have less renal excretion and actually have a dose adjustment for a lower dose in those patients,” he said.

“I think we need to have some data in these patients,” Naccarelli continued, “because if these drugs are a better idea adjusted against warfarin, we need to know that. The guidelines aren’t there yet.”

Bilazarian said this conversation has been truly beneficial and useful, adding that it appears “a consensus is forming amongst us that we probably should favor apixaban or edoxaban for lower creatinine clearance. For the higher creatinine clearance, we actually have a package label to avoid edoxaban. I think it’s helpful to know that others are thinking about this.”