Low-Sodium Oxybate Demonstrates Meaningful Blood Pressure Reductions in Patients With Narcolepsy

In an interview with Pharmacy Times®, Richard Kovacs, MD, QE and Sally Russell professor of cardiology and professor of clinical medicine at Indiana University School of Medicine, discusses results from the phase 4 XYLO trial (NCT05875974) comparing high-sodium (Xyrem; Jazz Pharmaceuticals) and low-sodium oxybate (Xywav; Jazz Pharmaceuticals) in patients with narcolepsy. Kovacs explains that lowering sodium intake produced clinically significant reductions in systolic blood pressure—comparable to the effects of modest antihypertensive therapy—while improving overall cardiovascular risk profiles. Kovacs highlights the importance of these findings for a population already at heightened cardiovascular risk.

This transcript was lightly edited for flow and clarity using artifical intelligence.

Pharmacy Times: Could you summarize the key findings of the XYLO trial and their clinical significance in patients with narcolepsy?

Richard Kovacs, MD: The XYLO trial was a phase 4 trial where we replaced high-sodium oxybate with low-sodium oxybate, with the primary endpoints being the effects on blood pressure. We measured both ambulatory blood pressure as well as office blood pressures. We looked at sodium intake, which, as expected, was reduced, and we looked at urinary sodium excretion, which also was reduced. The key findings were as expected—with reducing sodium intake in these patients, we had clinically meaningful reductions in blood pressure.

Pharmacy Times: From a cardiovascular standpoint, how meaningful is a 4 to 9 mmHg reduction in systolic blood pressure for this patient population?

Kovacs: It’s really important, and it’s probably more important in this population than it might be in others. People with narcolepsy have other risk factors for cardiovascular disease, so anything we can do to reduce that risk for cardiovascular events—meaningful cardiovascular events like stroke, heart attack, or heart failure—are things we should be doing. A reduction of 4 to 9 millimeters of mercury in blood pressure is clinically relevant. These kinds of reductions are similar to what we see with modest doses of antihypertensive agents, like 2.5 to 5 milligrams of amlodipine, for example. In addition, these reductions in blood pressure have an impact on lowering cardiovascular risk for major cardiac events.

Pharmacy Times: How might these results influence prescribing decisions for patients currently using high-sodium oxybate?

Kovacs: Well, hopefully they will make us all realize—wherever we sit in the care team for these patients—I’m a cardiologist, so I’m very interested in cardiovascular outcomes for people with narcolepsy. I would hope that we all aim to lower their sodium intake, reduce their cardiovascular risk, and demonstrably show a reduction in their blood pressure.