More Bleeding on NOACs Seen in Kidney Disease? (CME/CE) | IUK Med Online
Wednesday, July 18, 2018
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More Bleeding on NOACs Seen in Kidney Disease? (CME/CE)

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More Bleeding on NOACs Seen in Kidney Disease?

Stroke prevention similar to warfarin in observational study

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  • by MedPage Today Intern

Action Points

  • Note that this observational study suggests that, among patients with chronic kidney disease and atrial fibrillation, the use of DOACs may have slightly higher bleeding risk than warfarin.
  • Be aware that less than 2% of the population studied was non-white.

Patients with chronic kidney disease (CKD) who took direct oral anticoagulants (DOACs, also known as NOACs) to treat atrial fibrillation (Afib) had a “slightly” higher risk of bleeding than those on warfarin, researchers found.

Within a cohort with estimated glomerular filtration rates (eGFR) under 60 ml/min/1.72 m2, DOAC users experienced similar rates of ischemic stroke (HR 1.02, 95% CI 0.76-1.37) but had a 23% higher risk of bleeding (HR 1.23, 95% CI 1.02-1.48) compared to warfarin users, reported Jung-Im Shin, MD, of Johns Hopkins University in Baltimore, and colleagues in the Clinical Journal of the American Society of Nephrology.

Patients with eGFRs of at least 60 ml/min/1.72 m2 shared similar bleeding rates whether they took DOACs or warfarin (17.3 [15.7-19.3] versus 16.8 [15.3-18.6] per 100 person-years). This cohort also showed no difference in ischemic stroke rates between groups (HR 0.94, 95% CI 0.74-1.18).

However, neither interaction between bleeding and anticoagulant type by CKD status nor between stroke and anticoagulant type by CKD status was significant.

“One could say there’s no interaction and that means these two groups are not different,” Shin told MedPage Today. “But my argument is we don’t think this is the proper interpretation, because we have a small sample size. We didn’t have the power to detect for significant interaction but I think if we had a bigger sample size we could have found a significant interaction. The findings, we think, are meaningful.”

While DOAC use has proven to be more effective than warfarin in preventing ischemic stroke and decreasing risk of bleeding in the general population, DOAC clearance is slower in patients with CKD, which may result in drug accumulation and a greater risk of bleeding.

“Anticoagulation is always tricky because CKD populations are increased in the risk of stroke but at the same time have an increased risk of bleeding in the context of anticoagulants,” Shin said. “There’s a lot of enthusiasm about DOACs, but we need to make sure to balance the risk and benefits, just like we do for any new drug.”

FDA approval of several DOACs, including dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis), for patients with severe kidney disease, was based on small, single-dose pharmacokinetics studies that did not use clinical trials, the researchers said. All previous randomized trials of DOACs used to treat Afib have excluded patients with severe kidney disease.

And although the American Heart Association, American College of Cardiology, and European Society of Cardiology guidelines recommend not using DOACs when creatinine clearance is less than 30 ml/min, previous studies have observed an increase in DOAC prescriptions among Afib patients with advanced CKD.

To conduct this study, the researchers collected 20,727 Afib patient records from October 2010 through February 2017 using an electronic health record from the Geisinger Health System. They selected 3,206 propensity-score matched Afib patients who used DOACs and 3,206 who used warfarin.

The DOAC group had a mean age of 73 years, with 47% women, and an average eGFR of 69 ml/min/1.73m2. The sample of warfarin users had a mean age of 72 years, was 46% female, and reported an average eGFR of 68 ml/min/1.73m2.

More patients were prescribed rivaroxaban (43%) than dabigatran (24%) or apixaban (33%). Rivaroxaban users were on average older, more often women, and had slightly lower eGFRs, and higher HAS-BLED scores than other DOAC users, the investigators reported.

Researchers also conducted analysis excluding dialysis and valvular Afib patients, exploring potential effects of misclassification of baseline eGFR, and using a 30-day gap to define medication discontinuation, and found similar results.

Shin and colleagues acknowledged that there may have been some undetected differences between DOAC and warfarin groups in their retrospective study, citing medication compliance as one possibility. Other limitations were that only 2% of the patient population was non-white and that there were few with eGFR under 30 ml/min/1.73 m2.

Lastly, the study did not take into account the risk of site-specific bleeding, such as GI or intracranial hemorrhage, the authors pointed out.

As more patients are being prescribed DOACs and data accumulates, Shin called on further research to study the safety of DOAC use in older populations as well as those with durable Afib.

Shin disclosed no relationships with industry.

One co-author is on the FDA’s Peripheral and Central Nervous System Advisory Committee and reported relationships with IQVIA, Monument Analytics, MesaRx Innovations, and OptumRx.

  • Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner
2018-07-12T17:00:00-0400
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Medpage Today

More Bleeding on NOACs Seen in Kidney Disease?

Stroke prevention similar to warfarin in observational study

MedpageToday

  • register today

    Earn Free CME Credits by reading the latest medical news in your specialty.

    sign up

  • by MedPage Today Intern

Action Points

  • Note that this observational study suggests that, among patients with chronic kidney disease and atrial fibrillation, the use of DOACs may have slightly higher bleeding risk than warfarin.
  • Be aware that less than 2% of the population studied was non-white.

Patients with chronic kidney disease (CKD) who took direct oral anticoagulants (DOACs, also known as NOACs) to treat atrial fibrillation (Afib) had a "slightly" higher risk of bleeding than those on warfarin, researchers found.

Within a cohort with estimated glomerular filtration rates (eGFR) under 60 ml/min/1.72 m2, DOAC users experienced similar rates of ischemic stroke (HR 1.02, 95% CI 0.76-1.37) but had a 23% higher risk of bleeding (HR 1.23, 95% CI 1.02-1.48) compared to warfarin users, reported Jung-Im Shin, MD, of Johns Hopkins University in Baltimore, and colleagues in the Clinical Journal of the American Society of Nephrology.

Patients with eGFRs of at least 60 ml/min/1.72 m2 shared similar bleeding rates whether they took DOACs or warfarin (17.3 [15.7-19.3] versus 16.8 [15.3-18.6] per 100 person-years). This cohort also showed no difference in ischemic stroke rates between groups (HR 0.94, 95% CI 0.74-1.18).

However, neither interaction between bleeding and anticoagulant type by CKD status nor between stroke and anticoagulant type by CKD status was significant.

"One could say there's no interaction and that means these two groups are not different," Shin told MedPage Today. "But my argument is we don't think this is the proper interpretation, because we have a small sample size. We didn't have the power to detect for significant interaction but I think if we had a bigger sample size we could have found a significant interaction. The findings, we think, are meaningful."

While DOAC use has proven to be more effective than warfarin in preventing ischemic stroke and decreasing risk of bleeding in the general population, DOAC clearance is slower in patients with CKD, which may result in drug accumulation and a greater risk of bleeding.

"Anticoagulation is always tricky because CKD populations are increased in the risk of stroke but at the same time have an increased risk of bleeding in the context of anticoagulants," Shin said. "There's a lot of enthusiasm about DOACs, but we need to make sure to balance the risk and benefits, just like we do for any new drug."

FDA approval of several DOACs, including dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis), for patients with severe kidney disease, was based on small, single-dose pharmacokinetics studies that did not use clinical trials, the researchers said. All previous randomized trials of DOACs used to treat Afib have excluded patients with severe kidney disease.

And although the American Heart Association, American College of Cardiology, and European Society of Cardiology guidelines recommend not using DOACs when creatinine clearance is less than 30 ml/min, previous studies have observed an increase in DOAC prescriptions among Afib patients with advanced CKD.

To conduct this study, the researchers collected 20,727 Afib patient records from October 2010 through February 2017 using an electronic health record from the Geisinger Health System. They selected 3,206 propensity-score matched Afib patients who used DOACs and 3,206 who used warfarin.

The DOAC group had a mean age of 73 years, with 47% women, and an average eGFR of 69 ml/min/1.73m2. The sample of warfarin users had a mean age of 72 years, was 46% female, and reported an average eGFR of 68 ml/min/1.73m2.

More patients were prescribed rivaroxaban (43%) than dabigatran (24%) or apixaban (33%). Rivaroxaban users were on average older, more often women, and had slightly lower eGFRs, and higher HAS-BLED scores than other DOAC users, the investigators reported.

Researchers also conducted analysis excluding dialysis and valvular Afib patients, exploring potential effects of misclassification of baseline eGFR, and using a 30-day gap to define medication discontinuation, and found similar results.

Shin and colleagues acknowledged that there may have been some undetected differences between DOAC and warfarin groups in their retrospective study, citing medication compliance as one possibility. Other limitations were that only 2% of the patient population was non-white and that there were few with eGFR under 30 ml/min/1.73 m2.

Lastly, the study did not take into account the risk of site-specific bleeding, such as GI or intracranial hemorrhage, the authors pointed out.

As more patients are being prescribed DOACs and data accumulates, Shin called on further research to study the safety of DOAC use in older populations as well as those with durable Afib.

Shin disclosed no relationships with industry.

One co-author is on the FDA's Peripheral and Central Nervous System Advisory Committee and reported relationships with IQVIA, Monument Analytics, MesaRx Innovations, and OptumRx.

  • Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner
2018-07-12T17:00:00-0400
Take Posttest Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.



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