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How important is 24-hour control of blood pressure?
1Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Insights
Achieving consistent 24-hour blood pressure control is vital for preventing cardiovascular complications. Understanding a drug
Area of Science:
- Cardiovascular Medicine
- Clinical Pharmacology
Background:
- 24-hour blood pressure control is crucial for preventing cardiac and vascular hypertrophy.
- Sudden cardiac events, myocardial infarction, and stroke incidence peak during the morning blood pressure surge.
- Current once-daily hypertension therapies present challenges in maintaining consistent blood pressure control and assessing new drugs.
Purpose of the Study:
- To evaluate the importance of 24-hour blood pressure control in hypertension management.
- To explore the concept of the trough: peak ratio in assessing antihypertensive drug efficacy.
- To identify strategies for achieving optimal 24-hour blood pressure control with antihypertensive medications.
Main Methods:
- Analysis of pharmacokinetic and pharmacodynamic interactions of antihypertensive drugs.
- Examination of the trough: peak ratio as a measure of drug efficacy over a dosing interval.
- Review of drug properties, including elimination half-life and pharmaceutical delivery systems.
Main Results:
- The trough: peak ratio is a key factor in assessing a drug's ability to provide 24-hour blood pressure control.
- Drugs with an elimination half-life approximating or exceeding the dosing interval are preferred.
- Pharmaceutical modifications or drugs inducing persistent physiological effects can improve 24-hour control.
Conclusions:
- Consistent 24-hour blood pressure control is essential for cardiovascular health and prognosis.
- The trough: peak ratio provides valuable insight into a drug's suitability for once-daily dosing.
- Strategies focusing on drug half-life and delivery systems are necessary to achieve effective 24-hour blood pressure management.
Abstract:
Control of blood pressure over the full 24-hour period is important to prevent, or allow resolution of, cardiac and vascular hypertrophy. In addition, the peak incidence of sudden death, myocardial infarction and stroke occurs at the time of the blood pressure increase associated with awakening and arising. There is at present no objective evidence that "good' 24-hour blood pressure control will improve prognosis. Once-daily therapy has created problems in hypertension management. The problem in assessing new drugs was that, in order to achieve blood pressure control before the next drug dose, excessive falls in blood pressure occurred at peak drug concentrations or excessive blood drug concentrations were produced. This led to the concept of a trough: peak ratio. This is not a unique property of a drug and if drugs have an Emax effect (i.e. the drug produces a plateau response) it is dose dependent. Interpreting a trough: peak ratio requires an understanding of the interaction between the pharmacokinetics and pharmacodynamics of a drug. The answer is to use drugs with an elimination half-life close to or greater than the dose interval (24 hours); to use drugs with an "effective' half-life close to or greater than the dose interval, which can be achieved either by modification of the pharmaceutical delivery system or by using drugs that produce a persistent effect because of physiological changes induced; or to give drugs more frequently than once a day. 24-hour blood pressure control is important and the trough: peak ratio of a drug gives a guide as to whether it can be achieved.