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Management of antihypertensive treatment with Lisinopril: a chronotherapeutic approach
C Macchiarulo1, R Pieri, D C Mitolo
1Dept Clinical Methodology and Medico-Surgical Technologies, Medical School, University of Bari, Italy.
Insights
Optimizing hypertension treatment, taking Lisinopril at 10:00 PM offers better cardiovascular protection. This chronotherapy approach aligns drug delivery with the body's natural blood pressure rhythms, reducing morning cardiovascular risk.
Area of Science:
- Cardiology
- Pharmacology
- Chronobiology
Background:
- Cardiovascular events peak in the early morning due to circadian blood pressure (BP) variability.
- Traditional once-daily antihypertensive medication, often taken in the morning, shows diminished efficacy towards the end of the dosing interval.
- Optimizing drug timing based on circadian BP patterns and chronorisk is crucial for hypertensive patients with vascular conditions.
Purpose of the Study:
- To evaluate the impact of administering ACE-inhibitor Lisinopril (20 mg/day) at different times (8:00 AM, 4:00 PM, 10:00 PM) on blood pressure control.
- To determine the optimal dosing time for Lisinopril to enhance therapeutic effects and mitigate morning cardiovascular risk.
Main Methods:
- 40 patients with mild to moderate primary hypertension underwent 24-hour ambulatory blood pressure monitoring (ABPM).
- Patients were randomized to receive Lisinopril at 8:00 AM, 4:00 PM, or 10:00 PM, with ABPM repeated every two months while adjusting the dosing time.
- Chronobiological analysis was performed on ABPM data before and after treatment to assess BP changes and circadian rhythm patterns.
Main Results:
- Lisinopril administration at all tested times resulted in a significant reduction in systolic and diastolic BP without altering the circadian BP rhythm.
- A more pronounced reduction in BP was observed between 6:00 AM and 11:00 AM following the 10:00 PM dosing regimen.
- Nighttime administration (10:00 PM) provided superior protection against morning cardiovascular risk compared to morning or afternoon dosing.
Conclusions:
- Administering Lisinopril at 10:00 PM is more effective in managing hypertension and reducing cardiovascular risk.
- This chronotherapeutic approach, by aligning medication with the circadian BP pattern, offers enhanced protection against morning vascular events and the Cruickshank effect.
- Chronobiologist antihypertensive treatment represents a valuable strategy to augment the efficacy of traditional hypertension management.
Abstract:
Risk for cardiovascular events seems to be higher in the early morning, also as consequence of a rise in blood pressure (BP) values due to the characteristic circadian pattern of BP variability. Therefore, a suitable therapeutic BP control should be tightest during the early morning. On the basis of the ambulatory blood pressure monitoring (ABPM) studies, it has been previously demonstrated that the antihypertensive effect of once daily drug, generally administrated in the morning, decreases at the end of the dosing period. A chronotherapeutic approach to the management of hypertension (this field has been pourly investigated so far) would allow the assessment of the optimum timing of drug dosing, according to the circadian BP rhythm and to the chronorisk maps, in hypertensive patients affected by associated vascular pathologies. This would increase the therapeutic effects. The aim of this study was to assess BP changes due to ACE-inhibitor (Lisinopril 20 mg/die) once daily administration at three different times (8.00 AM, 4.00 PM, 10.00 PM), in order to optimise the dosing time. 40 subjects (mean age +/- SD: 45 +/- 10) affected by primary mild to moderate hypertension were submitted to ABPM for 24 hours, by means of Spacelabs 90207, before and after pharmacological treatment. Patients were randomised to take the drug at 8.00 AM, 4.00 PM or 10.00 PM, and they repeated ABPM every two months, by changing the dosing time. The chronobiological analysis showed: 1) a sensible decrease both in Systolic (S)BP and Diastolic (D)BP without affecting the circadian rhythm, in all evaluations; 2) a greater reduction of SBP and DBP from 6.00 AM to 11.00 AM, period in which cardiovascular risk is higher, after 10.00 PM dosing; 3) no other sensible reduction in SBP and DBP occurred after night administration as compared to that caused by other dosing times. Lisinopril administration at 10.00 PM. has been shown to be much more useful since, although BP circadian rhythm was unmodified, it protects hypertensive patients from both vascular chronorisk and Cruickshank effect (J-curve). Therefore, a chronobiologist antihypertensive treatment in order to increase the therapeutic effect already obtained with the traditional statistic methods.