title: Various approaches to evaluating the kinetics and efficacy of three antihypertensive drugs in terms of variations in blood pressure and heart rate.
abstract: BACKGROUND: Ambulatory blood pressure measurements allow better evaluation of the effects of antihypertensive drugs on the diurnal profile of blood pressure. Various strategies, such as determining peak: trough ratio and smoothness indexd, with and without smoothing of raw data by Fourier analysis, have been put forward to define the efficacy and duration of action of antihypertensive drugs better. To date there has been little interest in the time scale of maximum effect after intake of the drug and few data regarding effects on variability of heart rate exist.OBJECTIVE: To compare the effects of three antihypertensive agents (10 mg bisoprolol, 2 mg lacidipine and 20 mg lisinopril) on the peak: trough ratio, the smoothness index and the peak response slope for blood pressure and heart rate. METHODS: After a e-week washout period, 99 patients were randomly allocated in double-blind fashion to one of the three drugs. Ambulatory blood pressure measurements were taken upon entry to the study and after 6 weeks of treatment. The diurnal profile of blood pressure was smoothed using fast Fourier analysis. RESULTS: Each of the three treatments had a similar antihypertensive effect over the 24 h. The trough:peak blood pressure ratio for the group as a whole was higher than the value calculated on an individual basis. There was no difference among the peak response slopes for the three treatments; because one integrates three variables (peak, trough and time to maximal effect) this variable expresses large variations in individual cases. We observed differences among the smoothness indices of diastolic blood pressure for the durgs. Studying heart rate during the time of peak effect on blood pressure provides new findings. With bisoprolol, because the heart rate decreased both at the peak and at the trough, the ratio provides a good estimate of a balanced 24 h effect. In contrast, with lacidipine, the rise in heart rate over the 24 h renders use of this ratio impractical. The smoothness index with bisoprolol is significantly higher than those with lacidipine and lisinopril. Examination of individual heart rate slopes shows that there is a large variability for lacidipine and bisoprolol which is not significantly correlated to the slopes of blood pressure. CONCLUSION: To understand the effects of antihypertensive medication fully, various aspects need to be taken into account, namely the trough:peak ratio, the smoothness index and the peak response slope, each one of which is complementary to the analysis of the efficacy. Furthermore, it also seems necessary to study the heart rate, which can be significantly influenced by certain drugs and hence has important implications for the overall haemodynamic state.
authors.affiliation: Médecine Interne et Cardiologie, CHU-BP 217 X, 38043 Grenoble, Cedex 9, France.
authors.initials: JM
authors.lastname: Mallion
authors.initials: JP
authors.lastname: Siché
authors.initials: JP
authors.lastname: Baguet
authors.initials: M
authors.lastname: Noirclerc
authors.lastname: De Gaudemaris R