03245nas a2200385   4500000000100000008004100001653001000042653001100052653001100063653000900074653002400083653000900107653001600116653001700132653001900149653001600168653004000184653002900224653002300253653002800276653004200304653002300346100001900369700002000388700001600408700002100424700001500445700001900460700001900479245013600498300001200634490000700646520219200653022001402845       2017                            d10aAdult10aFemale10aHumans10aAged10aDouble-Blind Method10aMale10aMiddle Aged10aHypertension10aBlood Pressure10aPerindopril10aContinuous Positive Airway Pressure10aSleep Apnea, Obstructive10aCross-Over Studies10aAntihypertensive Agents10aBlood Pressure Monitoring, Ambulatory10aDrug Chronotherapy1 aArima Hisatomi1 aSerinel Yasmina1 aYee Brendon1 aGrunstein Ronald1 aWong Keith1 aCistulli Peter1 aPhillips Craig00aChronotherapy for hypertension in obstructive sleep apnoea (CHOSA): a randomised, double-blind, placebo-controlled crossover trial.  a550-5580 v723 a<p>
<b>BACKGROUND: </b>Obstructive sleep apnoea (OSA) is an important cause of secondary hypertension. Nocturnal hypertension is particularly prevalent in OSA and is a strong predictor of cardiovascular mortality. Studies in patients with essential hypertension have suggested that nocturnal administration of antihypertensives improves nocturnal blood pressure (BP) without elevating daytime BP. We evaluated the efficacy of this technique in patients with OSA with stage I/II hypertension, both before and after the addition of CPAP.
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<b>METHODS: </b>In this double-blind randomised placebo-controlled crossover trial, patients with moderate-to-severe OSA and hypertension received 6 weeks each of evening or morning perindopril with opposing time-matched placebo. CPAP therapy was subsequently added for 8 weeks in addition to either morning or evening perindopril. The primary outcome was sleep systolic BP (SBP) using 24-hour BP monitoring, analysed using linear mixed models.
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<b>RESULTS: </b>Between March 2011 and January 2015, 85 patients were randomised, 79 completed both dosing times, 78 completed the CPAP phase. Sleep SBP reduced significantly from baseline with both evening (-6.9 mm Hg) and morning (-8.0 mm Hg) dosing, but there was no difference between dosing times (difference: 1.1 mm Hg, 95% CI -0.3 to 2.5). However, wake SBP reduced more with morning (-9.8 mm Hg) than evening (-8.0 mm Hg) dosing (difference: 1.8 mm Hg, 95% CI 1.1 to 2.5). Addition of CPAP to either evening or morning dosing further reduced sleep SBP, but by a similar amount (evening: -3.2 mm Hg, 95% CI -5.1 to -1.3; morning: -3.3 mm Hg, 95% CI -5.2 to 1.5).
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<b>CONCLUSIONS: </b>Our findings support combining OSA treatment with morning administration of antihypertensives. Unlike in essential hypertension, our results do not support evening administration of antihypertensives, at least with perindopril. Further research is required before this strategy can be widely adopted into hypertension guidelines and clinical practice.
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<b>TRIAL REGISTRATION NUMBER: </b>ACTRN12611000216910, Results.
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  a1468-3296