Nocturnal antihypertensive treatment in patients with type 1 diabetes with autonomic neuropathy and non-dipping: a randomised, placebo-controlled, double-blind cross-over trial

• Published in: BMJ open 2016-12, Vol.6 (12), p.e012307-e012307
• Main Authors: Hjortkjær, Henrik Øder, Jensen, Tonny, Kofoed, Klaus F, Mogensen, Ulrik M, Sigvardsen, Per Ejlstrup, Køber, Lars, Hilsted, Karen Lisa, Corinth, Helle, Theilade, Simone, Hilsted, Jannik
• Format: Article
• Language: English
• Subjects: Aged; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - therapeutic use; Antihypertensives; Autonomic Nervous System; Autonomic Nervous System Diseases - drug therapy; Autonomic Nervous System Diseases - etiology; Autonomic Nervous System Diseases - physiopathology; Blood pressure; Blood Pressure - physiology; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - etiology; Circadian Rhythm; Cross-Over Studies; Diabetes; Diabetes and Endocrinology; Diabetes Mellitus, Type 1 - complications; Double-Blind Method; Drug Administration Schedule; Drug dosages; Enalapril - administration & dosage; Enalapril - therapeutic use; Female; Humans; Hypertension; Hypertension - drug therapy; Hypertension - etiology; Hypertension - physiopathology; Ischemia; Male; Middle Aged; Morbidity; Mortality; Pharmacy; Risk Factors
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2016-012307

ObjectivesCardiovascular autonomic neuropathy (CAN) and abnormal circadian blood pressure (BP) rhythm are independent cardiovascular risk factors in patients with diabetes and associations between CAN, non-dipping of nocturnal BP and coronary artery disease have been demonstrated. We aimed to test if bedtime dosing (BD) versus morning dosing (MD) of the ACE inhibitor enalapril would affect the 24-hour BP profile in patients with type 1 diabetes (T1D), CAN and non-dipping.SettingSecondary healthcare unit in Copenhagen, Denmark.Participants24 normoalbuminuric patients with T1D with CAN and non-dipping were included, consisting of mixed gender and Caucasian origin. Mean±SD age, glycosylated haemoglobin and diabetes duration were 60±7 years, 7.9±0.7% (62±7 mmol/mol) and 36±11 years.InterventionsIn this randomised, placebo-controlled, double-blind cross-over study, the patients were treated for 12 weeks with either MD (20 mg enalapril in the morning and placebo at bedtime) or BD (placebo in the morning and 20 mg enalapril at bedtime), followed by 12 weeks of switched treatment regimen.Primary and secondary outcome measuresPrimary outcome was altered dipping of nocturnal BP. Secondary outcomes included a measurable effect on other cardiovascular risk factors than BP, including left ventricular function (LVF).ResultsSystolic BP dipping increased 2.4% (0.03–4.9%; p=0.048) with BD compared to MD of enalapril. There was no increase in mean arterial pressure dipping (2.2% (−0.1% to 4.5%; p=0.07)). No difference was found on measures of LVF (p≥0.15). No adverse events were registered during the study.ConclusionsWe demonstrated that patients with T1D with CAN and non-dipping can be treated with an ACE inhibitor at night as BD as opposed to MD increased BP dipping, thereby diminishing the abnormal BP profile. The potentially beneficial effect on long-term cardiovascular risk remains to be determined.Trial registration numberEudraCT2012-002136-90; Post-results.