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Saline nose spray may reduce chronic nosebleeds as effectively as medications

The topical intranasal therapies bevacizumab, estriol and tranexamic acid each failed to reduce nosebleed frequency in patients with hereditary hemorrhagic telangiectasia compared with placebo, according to recent findings published in JAMA.

“None of the three topical therapies was any better at decreasing epistaxis frequency than twice-daily saline sprays,” Kevin J. Whitehead, MD, associate professor of cardiovascular medicine at the University of Utah, and colleagues wrote. “No serious adverse events were seen in this study.”

Recurrent and spontaneous nosebleeds, or epistaxis, are seen in 90% to 95% of patients with hereditary hemorrhagic telangiectasia (HHT), the researchers wrote. As treatment, researchers have studied oral estrogen, topical estriol plus argon plasma coagulation, oral tamoxifen, oral tranexamic acid, submucosal bevacizumab, topical bevacizumab and sclerotherapy. However, the studies have demonstrated conflicting results.

Whitehead and colleagues assessed whether bevacizumab, estriol and tranexamic acid could reduce HHT-related epistaxis. Bevacizumab (Avastin, Genentech) inhibits vascular endothelial growth factor and is FDA-approved for patients with colorectal cancer. Estriol induces the squamous metaplasia of the nasal mucosa. Tranexamic acid stabilizes blood clots and upregulates endoglin and ACVRL1 expression in endothelial cells.

The researchers performed The North American Study of Epistaxis in HHT (NOSE), a double-blind, placebo-controlled randomized clinical trial at six HHT centers. Between 2011 and 2014, they assessed 121 adult patients (mean age, 52.8 years) with HHT who had experienced HHT-related epistaxis with an Epistaxis Severity Score of at least 3. Patients received twice-daily nasal sprays for 12 weeks with either 0.4 mg per day of estriol, 4 mg per day of bevacizumab, 40 mg per day of tranexamic acid or saline placebo.

The primary outcome was median weekly epistaxis frequency from weeks 5 through 12. Secondary outcomes were epistaxis duration, Epistaxis Severity Score, hemoglobin levels, ferritin levels, transfusions, ED visits and treatment failure.

Before the study, the median frequency of weekly epistaxis episodes was 7. Of the 121 patients, 106 completed the study. The researchers found that none of the therapies significantly reduced epistaxis frequency, which remained at 7 episodes per week for bevacizumab, 8 for estriol, 7.5 for tranexamic acid and 8 for placebo. For epistaxis duration, no drug treatment was significantly different than placebo. There were no significant differences between groups in hemoglobin levels, ferritin levels, treatment failure, transfusions, ED visits or treatment failure. However, all groups showed significant improvement at weeks 12 and 24 in Epistaxis Severity Score.

“Therapy for [HHT-related epistaxis] has evolved over the years through mostly trial and error, supported by anecdotal reports of benefit,” the researchers wrote. “The optimal treatment for [HHT-related epistaxis] remains uncertain.”

"This research highlights that there could be a benefit even in the simplest of interventions," Whitehead said in a press release. "No drug proved to be any better than the saline placebo, but the majority of patients improved over the course of treatment — even those using saline." – by Will Offit

Disclosure: One researcher reported receiving institutional grant funding from GlaxoSmithKline. Please see the full study for all other researchers’ relevant financial disclosures.