Table 1 Ingestion upon awakening vs. at bedtime differences in effects of six classes of BP-lowering medications and their combinations quantified by changes from baseline in awake and asleep SBP/DBP means (mm Hg) and sleep-time relative SBP/DBP decline (%) in hypertensive patients adhering to a normal daytime activity–nocturnal rest routine

From: Chronotherapy with conventional blood pressure medications improves management of hypertension and reduces cardiovascular and stroke risks

   

Treatment-time reducton in awake SBP/DBP mean

Treatment-time reduction in asleep SBP/DBP mean

Treatment-time effect on sleep-time relative SBP/DBP decline

Medication

Dose, mg

No. of patients

Awakening R x

Bedtime R x

Awakening R x

Bedtime R x

Awakening R x

Bedtime R x

ACEI

 Ramipril

5

115

−10.1/−6.9

−10.5/−9.0

−4.5/−4.1

−13.5/−11.5*

−3.3/−1.8

3.4/4.9*

 Spirapril

6

165

−9.9/−8.0

−8.5/−5.7

−5.7/−4.6

−12.8/−8.6*

−2.5/−2.7

4.1/4.5*

ARB

 Valsartan

160

559

−13.4/−9.4

−14.1/−10.5

−12.4/−8.9

−18.4/−12.6

0.3/1.0*

4.5/4.8*

 Olmesartan

20–40

203

−14.8/−10.9

−14.5/−10.4

−11.6/−8.3

−16.4/−12.0

−1.1/−0.8*

3.0/4.4*

 Telmisartan

80

215

−11.7/−8.8

−11.3/−8.2

−8.3/−6.4

−13.8/−9.7

−1.6/−1.0*

3.1/3.9*

CCB

 Amlodipine

5

194

−10.2/−7.7

−11.8/−7.2

−9.6/−5.5

−11.2/−6.7

0.1/−1.6

0.2/0.7‡

 Nifedipine GITS

30

238

−9.4/−6.3

−12.8/−7.7‡

−7.5/−5.1

−12.8/−7.8

−0.7/−0.2*

1.0/1.5‡

β-Blocker

 Nebivolol

5

173

−14.7/−12.4

−13.4/−10.9

−7.9/−7.4

−10.2/−8.1

−3.6/−3.0

−1.2/−1.4‡

Diuretic

 Torasemide

5

113

−7.3/−3.7

−15.6/−9.9*

−4.3/−2.5

−12.5/−8.0*

−1.6/−0.7

−1.3/−0.2

α-Blocker

 Doxazosin GITS

4

91

−3.5/−3.4

−5.6/−4.7

0.3/−0.8

−6.1/−5.7†

−2.6/−2.6

0.5/1.7‡

Combination R x

 Valsartan/amlodipine

160/5

203

−18.3/−14.5

−22.6/−12.7

−14.4/−10.1

−28.1/−14.7*

−1.3/−2.1

5.5/5.2*

 Valsartan/hydrochlorothiazide

160/12.5

204

−17.4/−11.5

−16.7/−11.4

−16.0/−12.0

−20.1/−13.6‡

0.5/2.4

3.9/4.7*

  1. Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin-II receptor blocker; BP, blood pressure; CCB, calcium-channel blocker; DBP, diastolic blood pressure; GITS, gastrointestinal therapeutic system; SBP, systolic blood pressure.
  2. All cited studies were conducted by some of the authors utilizing a prospective, randomized, open-label, blinded endpoint (PROBE) design and entailing grade 1 or 2 essential hypertension participants (2473 patients in total) evaluated by simultaneous 48 h ambulatory BP monitoring (ABPM) and wrist actigraphy before and after timed treatment to accurately derive awake and asleep SBP/DBP means and sleep-−time relative BP decline (([awake BP mean−asleep BP mean]/awake BP mean) × 100), that is, percent decline in mean BP during nighttime sleep relative to mean BP during daytime activity. Statistical significance of comparison of between treatment-time effects on BP: *P<0.001; †P<0.01; ‡P<0.05.
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