AT SLEEP 2016
DENVER (FRONTLINE MEDICAL NEWS) – Long-term continuous positive airway pressure (CPAP) for treatment of sleep apnea in patients with a recent mild stroke or transient ischemic attack resulted in improved cardiovascular and metabolic risk factors, better neurologic function, and a reduction in the recurrent vascular event rate, compared with usual care in the SLEEP TIGHT study.
“Up to 25% of patients will have a stroke, cardiovascular event, or death within 90 days after a minor stroke or TIA [transient ischemic attack] despite current preventive strategies. And, importantly, patients with a TIA or stroke have a high prevalence of obstructive sleep apnea – on the order of 60%-80%,” explained Dr. H. Klar Yaggi at the annual meeting of the Associated Professional Sleep Societies.
SLEEP TIGHT’s findings support the hypothesis that diagnosis and treatment of sleep apnea in patients with a recent minor stroke or TIA will address a major unmet need for better methods of reducing the high vascular risk present in this population, said Dr. Yaggi of Yale University in New Haven, Conn.
SLEEP TIGHT was a National Heart, Lung, and Blood Institute–sponsored phase II, 12-month, multicenter, single-blind, randomized, proof-of-concept study. It included 252 patients, 80% of whom had a recent minor stroke, the rest a TIA. These were patients with high levels of cardiovascular risk factors: two-thirds had hypertension, half were hyperlipidemic, 40% had diabetes, 15% had a prior MI, 10% had atrial fibrillation, and the group’s mean body mass index was 30 kg/m2. Polysomnography revealed that 76% of subjects had sleep apnea as defined by an apnea-hypopnea index of at least 5 events per hour. In fact, they averaged about 23 events per hour, putting them in the moderate-severity range. As is common among stroke/TIA patients with sleep apnea, they experienced less daytime sleepiness than is typical in a sleep clinic population, with a mean baseline Epworth Sleepiness Scale score of 7.
Participants were randomized to one of three groups: a usual care control group, a CPAP arm, or an enhanced CPAP arm. The enhanced intervention protocol was designed to boost CPAP adherence; it included targeted education, a customized cognitive intervention, and additional CPAP support beyond the standard CPAP protocols used in sleep medicine clinics. Patients with sleep apnea in the two intervention arms were then placed on CPAP.
At 1 year of follow-up, the stroke rate was 8.7 per 100 patient-years in the usual care group, compared with 5.5 per 100 person-years in the combined intervention arms. The composite cardiovascular event rate, composed of all-cause mortality, acute MI, stroke, hospitalization for unstable angina, or urgent coronary revascularization, was 13.1 per 100 person-years with usual care and 11.0 in the CPAP intervention arms. While these results are encouraging, SLEEP TIGHT wasn’t powered to show significant differences in these hard events.
Outcomes across the board didn’t differ significantly between the CPAP and enhanced CPAP groups. And since the mean number of hours of CPAP use per night was also similar in the two groups – 3.9 hours with standard CPAP and 4.3 hours with enhanced CPAP – it’s likely that the phase III trial will rely upon the much simpler standard CPAP intervention, according to Dr. Yaggi.
He deemed CPAP adherence in this stroke/TIA population to be similar to the rates typically seen in routine sleep medicine practice. Roughly 40% of the stroke/TIA patients were rated as having good adherence, 30% made some use of the therapy, and 30% had no or poor adherence.
Nonetheless, patients in the two intervention arms did significantly better than the usual care group in terms of 1-year changes in insulin resistance and glycosylated hemoglobin. They also had lower 24-hour mean systolic blood pressure and were more likely to convert to a favorable pattern of nocturnal blood pressure dipping. However, no differences between the intervention and usual care groups were seen in levels of high-sensitivity C-reactive protein and interleukin-6, the two markers of systemic inflammation analyzed. Nor did the CPAP intervention provide any benefit in terms of heart rate variability and other measures of autonomic function.
Fifty-eight percent of patients in the intervention arms ended up with a desirable National Institutes of Health Stroke Scale score of 0-1, compared with 38% of the usual care group. In addition, daytime sleepiness as reflected in Epworth Sleepiness Scale scores was reduced at last follow-up to a significantly greater extent in the CPAP groups, Dr. Yaggi noted.
Greater CPAP use was associated with a favorable trend for improvement in the modified Rankin score, a measure of functional ability: a 0.3-point reduction with no or poor CPAP use, a 0.4-point decrease with some use, and a 0.9-point reduction with good use.
The encouraging results will be helpful in designing a planned much larger, event-driven, definitive phase III trial, Dr. Yaggi said.
Dr. Yaggi reported having no financial conflicts regarding this National Heart, Lung and Blood Institute-sponsored study.