An attempt by ResMed to show that one of its ventilation therapies could be a lifesaver for heart failure patients has ended poorly, with a postmarket trial showing that the company's technology actually increased cardiovascular deaths.
ResMed's shares fell 15% on Wednesday as investors considered what the trial failure might mean for the company which will, according to EvaluateMedTech's consensus forecasts, lead the global anaesthesia and respiratory market in 2020.
The Europe-based Serve-HF trial enrolled 1,325 patients with moderate to severe predominant central sleep apnoea and congestive heart failure. Around 30-50% of heart failure patients have sleep apnoea, and this is known to be a significant comorbidity.
Serve-HF's purpose was to show that ResMed's adaptive servo-ventilation technology could reduce mortality and morbidity, with its entry in Clinicaltrials.gov suggesting that the intervention could reduce the hazard rate by 20% compared with an untreated control group.
The trial showed no difference between the two groups on the primary endpoint of time to all-cause mortality or unplanned hospitalisation for worsening heart failure, and is therefore a failure on that alone. But worse, a higher annual rate of cardiovascular death was seen in the treatment group, at 10% compared with 7.5% in the control group.
According to Clinicaltrials.gov the devices used in the trial were the AutoSet CS 2 and the VPAP Adapt SV. Adaptive servo-ventilation is an algorithm incorporated by these devices that enables customised therapy by measuring the patient's respiratory rate and volume to determine the degree of pressure support needed. The ventilation level is adjusted through the course of the night.
A cached version of ResMed's website reveals that the AutoSet CS 2 was specifically designed for congestive heart failure patients with Cheyne-Stokes respiration and concomitant obstructive sleep apnoea.
A clinical decision
The devices are sold in Europe, and the company is revising the labelling for the ASV devices to warn against allowing people with symptomatic heart failure with left ventricular ejection fraction less than or equal to 45% to use them.
ResMed recommends that doctors consider discontinuing treatment in patients with symptomatic chronic heart failure and who have reduced left ventricular ejection fraction. "Whether to discontinue is ultimately a clinical decision," the company said in its advice to doctors.
AutoSet CS 2 and the VPAP Adapt SV are classified by ResMed as flow generators, and are part of a segment forecast to break the $1bn sales barrier this year, rising to $1.4bn in 2020, EvaluateMedTech data show. This makes up 57% of the company's total revenues, and the proportion is set to rise – although these forecasts were made before the Serve-HF data were revealed.
True, the products in the trial are just two of the devices in ResMed's dozens-strong flow generator portfolio, and they are not contraindicated for all patients – only in around 25% of the population in which they are used. But an increase in death in a trial intended to show the opposite is an alarming signal. ResMed's ambition to push into heart failure was understandable, but it might find that it has to stick to its core area for now.