Effects of Morning versus Evening Administration of Perindopril on the Circadian Control of Blood Pressure in Cameroonian Type 2 Diabetes Individuals: A Crossover Randomized Trial

Abstract

Background: Renin-angiotensin system antagonists are the mainstays of blood pressure (BP) lowering strategies in people with diabetes. Perindopril a long half-life Angiotensin Converting Enzyme (ACE) inhibitor offers the advantage of a single daily dose, usually empirically taken in the morning. We therefore aimed to assess the influence of time of administration on the effect of Perindopril on circadian BP in type 2 diabetes (T2D) individuals with previously untreated stage 1 hypertension. Methods: Twenty T2D patients (9 being women) with a mean age of 58.7 years, newly diagnosed with stage 1 hypertension, were randomly allocated to receive perindopril 10 mg/day as monotherapy either in the morning or in the evening for 28 days, with crossover without washout period on day 29th and additional 28 days follow-up. A 24hour ambulatory BP monitoring (ABPM) was performed at baseline, days 28 and 56. This study was retrospectively registered having a trial registration: ClinicalTrials.gov Identifier: NCT03393715. January 8, 2018. Results: Median diagnosed duration of diabetes was 2.0 years. At baseline, mean 24-hour systolic and diastolic BP were 137.0 mmHg and 84.5 mmHg, and mean albumin/ creatinine ratio (ACR) was 132.6 mg/g. There was no difference in the 24-hour systolic blood pressure pattern between the patients on morning perindopril and patients on evening perindopril (p = 0.61). The chronotherapeutic scheme did not influence neither ACR (p = 0.58) nor uric acid level (p = 0.32). However, the administration of 10 mg Perindopril lowered the ACR in both treatment allocation sequences; with an overall treatment effect of -41.7 (95% CI: -92.6 to 9.2) mg/g. Conclusions: The morning administration of perindopril did not prove to be superior to night time regimen for BP control in this group of sub-Saharan type 2 diabetes patients with stage 1 hypertension. However, the administration of perindopril seems to lower the ACR which is suggestive of the reno-protective effect of ACE inhibitors in patients presenting with hypertension and type 2 diabetes. RESEARCH ARTiCLE