Tolerability of bedtime diuretics: a prospective cohort analysis

Abstract

Objectives: We sought to validate, or refute, the common belief that bedtime diuretics are poorly tolerated due to nocturia.

Design: Prespecified prospective cohort analysis embedded within the randomised BedMed trial, in which hypertensive participants are randomised to morning versus bedtime antihypertensive administration.

Setting: 352 community family practices across 4 Canadian provinces between March 2017 and September 2020.

Participants: 552 hypertensive patients (65.6 years old, 57.4% female) already established on a single once-daily morning antihypertensive and randomised to switch that antihypertensive to bedtime. Of these, 203 used diuretics (27.1% thiazide alone, 70.0% thiazide/non-diuretic combinations) and 349 used non-diuretics.

Intervention: Switching the established antihypertensive from morning to bedtime, and comparing the experience of diuretic and non-diuretic users.

Primary and secondary outcome measures: Primary outcome: Adherence to bedtime allocation time at 6 months (defined as the willingness to continue with bedtime use, not an assessment of missed doses). Secondary 6-month outcomes: (1) nocturia considered to be a major burden and (2) increase in overnight urinations/week. All outcomes were self-reported and additionally collected at 6 weeks.

Results: At 6 months: Adherence to bedtime allocation time was lower in diuretic users than non-diuretic users (77.3% vs 89.8%; difference 12.6%; 95% CI 5.8% to 19.8%; p<0.0001; NNH 8.0), and more diuretic users considered nocturia a major burden (15.6% vs 1.3%; difference 14.2%; 95% CI 8.9% to 20.6%; p<0.0001; NNH 7.0). Compared with baseline, diuretic users experienced 1.0 more overnight urinations/week (95% CI 0.0 to 1.75; p=0.01). Results did not differ between sexes.

Conclusions: Switching diuretics to bedtime did promote nocturia, but only 15.6% found nocturia a major burden. At 6 months, 77.3% of diuretic users were adherent to bedtime dosing. Bedtime diuretic use is viable for many hypertensive patients, should it ever become clinically indicated.

Trial registration number: NCT02990663.

Keywords: CLINICAL PHARMACOLOGY; Cardiology; Hypertension; PRIMARY CARE.

Figure 1

Study flow diagram for analysis of adherence. ACEI, ACE inhibitor; BB, beta-blockers; BP, blood pressure; CCB, calcium channel blocker.

Figure 2

Medication frequency at baseline. ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; BB, beta blocker; HCTZ, hydrochlorothiazide; ER/XL/XR, extended release.