Tools for Practice

#59 Taking blood pressure-lowering medications at night

Will taking one or more antihypertensive drugs at night improve cardiovascular disease (CVD) outcomes and reduce drug side-effects?

Taking one or more BP meds at bedtime may help reduce cardiovascular risk, but due to limitations of the evidence, strong recommendations are difficult.

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MAPEC1, a 5.6 year trial of 2,156 hypertensive patients (52% female, mean age 56, 20% diabetes, 13% smoker): 
  • Randomized to antihypertensives taken upon awakening versus one or more medications taken at bedtime (47% took all antihypertensives at bedtime). 
  • Blood pressure (BP) results: No difference at start. After:  
    • Daytime BP: Both groups ~125/75. 
    • Nighttime BP: Bedtime medication group 5/2 lower than awakening medication group (111/63 versus 116/65). 
  • Outcomes: Statistically significant reduction in: 
    • Mortality: Awakening 2.6% versus bedtime 1.1%, Number Needed to Treat (NNT)=67. 
    • Total CVD events: Awakening 17.3% versus bedtime 6.3%, NNT=9. 
  • Limitations: Poorly described randomization and allocation of patients, lack of blinding, no reporting of adverse events, no correction for multiple analysis, CVD event rates inexplicably higher than expected (very unusual in clinical trials), and outcome research from one group only.   
  • Diabetic2 and chronic kidney disease3 patients had similar benefits. 
  • Observational studies4-6 have demonstrated that nighttime ambulatory BP is a better predictor of CVD events than either in-office BP or daytime BP. 
  • A Cochrane systematic review of 21 RCTs of various BP medications shows that BP medications taken in the evening (versus morning) resulted in a greater 24-hour BP reduction (1-2 mmHg) using most antihypertensive classes.7 
  • We could not identify any other large trials specifically addressing CVD for antihypertensives taken at bedtime. 
    • However, ramipril was given at bedtime in the HOPE trial. The daytime office BP changed little (3/2mmHg) so the benefits (3.8% reduction in CVD events in five years) were assumed due to a unique property of ramipril.8 However, the night-time BP was 17/8 mmHg better.9 
june 8 2015 by adrienne

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  • G. Michael Allan MD CCFP
  • Ricky Turgeon BScPharm

1. Hermida RC, Ayala DE, Mojon A, et al. Chronobiol Int. 2010;27(8):1629-51.

2. Hermida RC, Ayala DE, Mojon A, et al. Diabetes Care. 2011;34(6):1270-6.

3. Hermida RC, Ayala DE, Mojon A, et al. J Am Soc Nephrol. 2011;22(12):2313-21

4. Kikuya M, Ohkubo T, Asayama K, et al. Hypertension. 2005;45(2):240-5.

5. Hansen TW, Li Y, Boggia J, et al. Hypertension. 2011;57(1):3-10.

6. Minutolo R, Agarwal R, Borrelli S, et al. Arch Intern Med. 2011;171(12):1090-8.

7. Zhao P, Xu P, Wan C, et al. Cochrane Database Syst Rev. 2011; 10:CD004184.

8. Yusuf S, Sleight P, Pogue J, et al. N Engl J Med. 2000;342(3):145-53.

9. Svensson P, de Faire U, Sleight P, et al. Hypertension 2001, 38:e28-e32.

Authors do not have any conflicts of interest to declare.