“Using CPAP” Improves Cardiovascular Outcomes: Physicians Must Look Behind the RCT Veil and Focus on Long-Term Adherence
- 1. Sleep Centers of Middle Tennessee and Middle Tennessee State University Sleep Research Consortium, USA
- 2. Division of Cardiovascular Health and Disease, University of Cincinnati, USA
Abstract
While obstructive sleep apnea (OSA) has a mortality and prevalence similar to hypercholesterolemia, few patients with cardiovascular disease (CVD) undergo evaluations for OSA. Historically poor adherence to continuous positive airway pressure (CPAP) and the failure of CPAP to reduce cardiovascular (CV) events in randomized controlled trials (RCTs), may be responsible.
Observational data, including secondary analysis of RCTs, showed improvement in CV outcomes in patients who used CPAP 4 or more hours per night longterm. RCTs were limited by exclusions for ethical constraints and poor CPAP adherence. “Wearing” CPAP clearly improves CV outcomes despite confounding factors and considering the low cost and low risk of CPAP, patients with CVD should be evaluated for OSA and not denied the likely benefits of CPAP.
Poor long-term CPAP adherence likely results from lack of focus from sleep medicine providers and lack of requirements for medical equipment companies. However, utilizing motivational enhancement, patient education, and remote monitoring, long-term adherence rates for CPAP may exceed that of many CV medications.
Therefore, physicians, particularly cardiologists, should consider OSA screening when assessing other CV risk factors and choose a sleep medicine program that provides convenient and cost-efficient testing and has ample trained staff to produce long-term CPAP adherence which is required for improved CV outcomes.
Keywords
Obstructive sleep apnea, Cardiovascular disease
Citation
Noah WH, Cook JL (2021) “Using CPAP” Improves Cardiovascular Outcomes: Physicians Must Look Behind the RCT Veil and Focus on LongTerm Adherence. J Cardiol Clin Res 9(1): 1165
ABBREVIATIONS
OSA: Obstructive Sleep Apnea; CVD: Cardiovascular Disease; HTN: Hypertension; AF: Atrial Fibrillation; HF: Heart Failure; CPAP: Continuous Positive Airway Pressure; RCT: Randomized Controlled Trial; HSAT: Home Sleep Apnea Testing
INTRODUCTION
Obstructive sleep apnea (OSA) is associated with increased morbidity and mortality from cardiovascular disease (CVD)[1- 3] and strongly associated with hypertension (HTN), resistant HTN, pulmonary HTN, atrial fibrillation (AF), stroke, transient ischemic attack, heart failure (HF), coronary heart disease, myocardial ischemia, myocardial infarction, and sudden death [4-6]. Central sleep apnea is associated with HF, stroke, and AF [4-6]. The mechanisms have been extensively reviewed [4].
Based on a hazard ratio of 5.2, patients with severe OSA are five times more likely to experience cardiovascular mortality than those without sleep disordered breathing [7]. In comparison, middle aged patients (the highest risk group with a total cholesterol of >300) have a similar hazard ratio for cardiovascular mortality [8]. Perhaps surprisingly, the cost of CPAP over five years is similar to the cost of a statin [9].
RISK FOR CARDIAC EVENTS
OSA and hyperlipidemia are both highly prevalent in patients with CVD [4,10,11], however while most patients with CVD are screened for elevated TC, only a small percentage of patients with CVD undergo evaluations for OSA [10].This is likely because the main treatment of OSA, continuous positive airway pressure (CPAP), has had historically poor adherence [12], and recent meta-analyses [13-16] of randomized controlled trials (RCTs) utilizing CPAP to treat OSA have failed to show improvement in CV outcomes.
IMPACT OF OSA THERAPY
However, two recent exhaustive reviews [17,18] summarize a preponderance of observational data, including the secondary analyses of three RCTs, that show improvement in CV outcomes in those patients who used CPAP 4 or more hours per night long-term. CPAP usage, which has been shown to be dose dependent, was clearly higher in observational studies than in RCTs. This could have accounted for the improved outcomes, but confounding factors were possible. RCTs were also limited by ethical constraints requiring exclusions of many patients (i.e. sleepy patients) more likely to use CPAP and patients with more severe disease who were more likely to benefit from the treatment. Despite the poor adherence, the RCTs still had secondary outcomes of improved blood pressure (lowering risk of CVD), daytime sleepiness, and quality of life.
RCTs refer to a population, not an individual. In the largest RCT [19], the average CPAP usage was 3.3 hours per night, and only 42% used CPAP 4 or more hours long-term. There were just not enough users to improve CV outcomes for the whole population. But this does not address outcomes for participants in the trial with excellent adherence. Observational studies and secondary analyses of RCTs clearly showed those using CPAP > 4 hours per night had improved CV outcomes whether the improvement was from the CPAP or a confounding factor. Considering the low cost and low risk of harm of CPAP relative to a CV event, patients with CVD should be evaluated for OSA and not denied the likely benefits of CPAP found in the observational data and the clear benefits of the secondary outcomes in RCTs.
Again, CPAP adherence is historically low [12], as reflected in the RCTs, despite efforts to improve adherence in the treatment groups. The largest RCT [19], used a trial of CPAP (below therapeutic levels), before randomization which eliminated 14% of patients from the treatment group likely not to use CPAP. This suggests “real world usage” [20], is even worse than the RCTs, with possibly less than 30% of CPAP patients using long term.
Most sleep medicine physicians (many who also practice another specialty and only spend part of their time in sleep medicine) are paid to perform sleep consultations, interpret polysomnograms, and limited follow-up visits. Medical equipment providers are paid to provide CPAP equipment and obtain a minimal short-term adherence [21], which translates to only 2.8 hours per night. Currently, there is little incentive for sleep medicine providers and medical equipment companies to focus on long-term usage. Without long-term CPAP usage, the value of a sleep consultation, polysomnogram, and CPAP equipment in OSA patients become limited. Again, this perceived limited value among referring physicians may account for the small percentage of patients with CVD undergoing OSA evaluations [11], especially considering the high cost of polysomnography in hospital-owned sleep laboratories [22].
There is a solution. A recent RCT [23], showed that motivational enhancement increased average CPAP usage from 3.3 hours (similar to the largest RCT) [15] to 4.4 hours per night at 6 months, with similar results at 12 months. Motivational enhancement (part of cognitive behavioral theory), patient education, remote monitoring, and troubleshooting CPAP problems are each associated with increased CPAP adherence [16]. Sleep medicine practices which utilize these practices in their care-model are likely to achieve better outcomes.
Our group presented a large, retrospective cohort study [24], evaluating CPAP adherence in a community setting (age 18-64), where the treatment group (n=1881) had 66% still using CPAP after 12 months. The usual care group (n=2182), had 44% still using after 12 months, similar to the largest RCT [19], and the usual care group in the RCT mentioned above [23]. If we had included patients over age 65 our number of long-term users would have been higher [25]. Furthermore, the treatment group only had intervention for three months, and there is evidence [26] that extending the intervention longer may have produced 80% still using CPAP at 12 months. We believe our results are obtainable in community practice settings but will first require a change of focus among many sleep medicine providers, and possibly a change of incentives. Our results could possibly improve the outcomes of patients with CVD on CPAP in future RCTs, but the behavioral interventions to increase adherence could become a confounding factor (encouraging other healthy behaviors) as well. But are future RCTs ethical? Is it ethical to randomize a patient with severe OSA to a lengthy trial knowing the untreated mortality approaches 40% over 12-15 years [27, 28]?
For comparative purposes, long-term adherence rates to many CV medications are also poor [29], and may be worse than CPAP adherence in the largest RCT [19]. The 12-month CPAP adherence we found in our treatment group [24] was nearly twice that of many CV medications [26]. With poor adherence to many CV medications being associated with increased cardiovascular morbidity and mortality [29], patient interventions may be warranted similar to those needed to improve adherence with CPAP.
NEXT STEPS FOR OSA AND
CVD In the meantime, physicians, particularly Cardiologists, should consider home sleep apnea testing (HSAT) in the same way they consider ordering a lipid profile and select a sleep medicine program in the way they select a CV medication. Providers select the most cost-efficient medications expected to provide the best outcome for their patients. Physicians should also select a sleep medicine program that performs cost-efficient testing and has the systems and trained staff to focus on long-term CPAP usage, for only with proven long-term usage can providers expect improved outcomes for their patients with CVD. The sleep medicine program must also offer alternative treatments for nonusers of CPAP [30].
CONFLICT OF INTEREST
1 Noah WH: None
2 Cook JL: Itamar Medical (Global Medical Director)
