title: Evening versus morning dosing of antihypertensive drugs in hypertensive patients with sleep apnoea: a cross-over study.
abstract: OBJECTIVE
  Beneficial effects of continuous positive airway pressure (CPAP) on both blood pressure (BP) levels and variability have been documented in patients with obstructive sleep apnoea (OSA). We investigated the relevant impact of different dosing times of antihypertensive drugs beyond CPAP application.
  
  
  METHODS
  In this prospective, cross-over trial, we included 41 patients with newly diagnosed hypertension and never treated OSA (apnoea-hypopnea index ≥15/h), without increased daytime somnolence (Epworth Score ≤10 points). Patients first received treatment with valsartan or with a fixed combination of amlodipine and valsartan in a single morning dose for 8 weeks. In the following 8-week period, patients received the same therapeutic regimen in a single evening dose. Office and ambulatory BP were measured at baseline and after each treatment period.
  
  
  RESULTS
  Compared with morning administration, evening dosing induced a greater decrease in office SBP (by 3.7 ± 6.5 mmHg, P = 0.001). The decrease in 24-h SBP/DBP was significant and similar after morning and evening dosing (-16.4 ± 11/11.0 ± 7.5 and -18.4 ± 11/12.1 ± 7.5 mmHg, respectively, P < 0.001 for both). Evening compared with morning dosing further reduced night-time SBP/DBP by 4.4 ± 8.6/2.9 ± 5.6 mmHg (P = 0.007 and P = 0.006, respectively). Night-time dippers increased from 24% at baseline to 34% with morning dosing and to 61% with evening dosing. There was no significant interaction between concurrent CPAP application and drugs dosing time on BP changes.
  
  
  CONCLUSIONS
  Evening dosing of antihypertensive drugs improves night-time BP and dipping status in nonsleepy patients with OSA, irrespective of CPAP application.
authors.affiliation: aFirst Cardiology Clinic, University of Athens, Hippokration Hospital, Athens, Greece bDepartment of Cardiology, IRCCS Ospedale San Luca, Istituto Auxologico Italiano and Department of Health Sciences, University of Milano Bicocca, Milan, Italy cDivision of Vascular Surgery, First Department of Propaedeutic Surgery, University of Athens Medical School, Hippokration Hospital, Athens, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Kasiakogias
authors.forename: Costas
authors.initials: C
authors.lastname: Tsioufis
authors.forename: Costas
authors.initials: C
authors.lastname: Thomopoulos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Andrikou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Aragiannis
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Dimitriadis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsiachris
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Bilo
authors.forename: Skevos
authors.initials: S
authors.lastname: Sideris
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Filis
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Parati
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Stefanadis
mesh_terms: D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D045422:Continuous Positive Airway Pressure; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020181:Sleep Apnea, Obstructive / Q000150:complications*; D000068756:Valsartan / Q000008:administration & dosage*
chemical_list: D000959:Antihypertensive Agents; D017311:Amlodipine; D000068756:Valsartan