Antithrombotics Linked to Complications With Hematuria

October 10, 2017

Use of antithrombotic drugs is associated with a high rate of complications due to hematuria, many of which may be preventable with better medical management, authors of a new study assert.

The study, published in the October 3 issue of JAMA, showed that among older adults, use of antithrombotic medications was significantly associated with higher rates of complications requiring emergency department visits, hospitalizations, and urologic procedures to manage gross hematuria.

"Our bottom-line message is that physicians need to counsel patients on hematuria with antithrombotic drugs to prevent them from ending up in hospital," senior author, Robert K. Nam, MD, Division of Urology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, told Medscape Medical News.

"Visible hematuria is a recognized side effect of antithrombotic agents but varies in severity, and can usually be managed by reducing the dose of antithrombotic or temporarily stopping the medication. It can be an indication of some other underlying issue, such as bladder cancer, and can also lead to kidney failure and infection, so always needs to be taken seriously," he said. 

"While doctors are generally very efficient about considering the risks of serious bleeding complications, such as intracerebral hemorrhage or GI [gastrointestinal] bleeds with antithrombotic drugs, they may not take a little blood in the urine as a major problem. Patients are often not warned about it. It is an obvious side effect, but the prevalence, severity, and risk factors for hematuria associated with the use of antithrombotic agents are largely unknown," Dr Nam explained.

"We were quite surprised by the high rates of hospital admissions and emergency department visits caused by hematuria in patients taking antithrombotics," he added. "Many of these hospital admissions and emergency appointments are preventable."

He added: "Doctors need to tell patients that they always need to seek medical advice if they notice blood in their urine, and they should not regard this as a normal side effect of taking antithrombotic medication. Most cases can be managed and stopped from getting worse, and physicians need to investigate why it is has occurred."

The population-based, retrospective cohort study used data from the Institute of Clinical Evaluative Sciences on all citizens in Ontario, Canada, aged 66 years and older (n = 2,518,064) between 2002 and 2014.

Results showed that 808,897 received at least one prescription for an antithrombotic agent over the study period. During a median follow-up of 7.3 years, the rates of hematuria-related complications were 123.95 events per 1000 person-years among patients actively exposed to antithrombotic agents vs 80.17 events per 1000 person-years among patients not exposed to these drugs, a difference 43.8 per 1000 person-years (P < .001); the incidence rate ratio (IRR) was 1.44.

Patients who had taken antithrombotics also had a higher rate of urologic procedures (IRR, 1.37); hospitalizations (IRR, 2.03); and emergency department visits (IRR, 2.80).

These associations persisted on multivariable analysis, with increasing age, male sex, and increasing comorbidity being significantly associated with rates of hematuria-related complications.

Hematuria-related complications were more common during exposure to anticoagulants than to antiplatelet agents, and patients experienced the lowest rates of complications during exposure to older medications (aspirin and warfarin).

Among anticoagulants, exposure to dabigatran was associated with the lowest rate of complications, while rivaroxaban had the highest rate for each age group.

Other antiplatelet agents, including clopidogrel, prasugrel, ticagrelor, ticlopidine, and dipyridamole, were associated with higher rates of hematuria-related complications than was aspirin.

Patients taking a combination of any antiplatelet agent and any anticoagulant experienced significantly increased rates of  hematuria-related complications, particularly for hospitalizations (range of rate ratios, 2.68 - 4.16) and emergency department visits (range of rate ratios, 6.03 - 10.48).

Patients exposed to antithrombotic agents were more likely to be diagnosed with bladder cancer within 6 months (0.70% vs 0.38%; odds ratio, 1.85).

The authors say that because there is no putative mechanistic linkage, these data suggest that use of antithrombotic agents was likely unmasking otherwise clinically silent bladder cancers.

This study was funded by the Ajmera Family Chair in Urologic Oncology and Sunnybrook Foundation. Two authors report grants and/or personal fees from Astellas, Ipsen, Pfizer, Allergan,  Bayer, Leo Pharma, Bristol-Myers Squibb, Sanofi, and Janssen. The other authors have disclosed no relevant financial relationships.

 JAMA. Published online October 3, 2017. Abstract  

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