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Blood Press Monit. 1998 Jun;3(3):189-194.
Various approaches to evaluating the kinetics and efficacy of three antihypertensive drugs in terms of variations in blood pressure and heart rate.

Mallion JM, Siche JP, Baguet JP, Noirclerc M, De Gaudemaris R.

Medecine Interne et Cardiologie, CHU-BP 217 X, 38043 Grenoble, Cedex 9, France.

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.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10212353&dopt=Abstract [PubMed - as supplied by publisher]




Blood Press Monit. 1996 Apr;1(2):115-120.
Weighted Fourier analysis of blood pressure curves after lisinopril versus atenolol administration in young hypertensives.

Veglio F, Rabbia F, Melchio R, Schiavone D, De Micheli AG, Chiandussi L.

Department of Medicine and Experimental Oncology, S. Vito Hospital, University of Turin, Italy.

OBJECTIVE: To evaluate and compare the effects of lisinopril versus atenolol administration on the diurnal blood pressure profile and the nocturnal blood pressure fall in young mild-to-moderate essential hypertensives.METHODS: Thirty patients were studied. After a 2-week placebo run-in period, they were single-blind randomly assigned to receive 20 mg lisinopril or 100 mg atenolol. Using a SpaceLabs 90207 device, their ambulatory blood pressure was measured before and after 12 weeks of therapy. The readings were analysed using Fourer series with four harmonics. RESULTS: Lisinopril and atenolol administration significantly decreased office and ambulatory blood pressure values compared with the placebo period. The daily blood pressure curves obtained from Fourier analysis showed that the circadian rhythm was not altered by lisinopril and atenolol administration. From the night:day ratio for the nocturnal blood pressure fall, we found that atenolol administration minimized the average night-time blood pressure dip by increasing the number of non-dippers. In contrast, lisinopril administration did not modify the day-night difference, preserving the nocturnal blood pressure fall. CONCLUSION: Lisinopril and atenolol administration as a first-step treatment of young essential hypertensives produced comparable degrees of diurnal control of arterial pressure. The blood pressure fall at night in patients treated with atenolol was slightly less than that found with lisinopril treatment.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10226212&dopt=Abstract [PubMed - as supplied by publisher]




Blood Press Monit. 1996 Jun;1(3):263-266.
Individual smoothing of blood pressure profiles to define responders or non-responders to drugs.

Siche JP, de Gaudemaris R, Boutelant S, Baguet JP, Comparat V V, Mallion JM.

Department of Internal Medicine and Cardiology, University Hospital of Grenoble, France.

OBJECTIVE: To compare different methods of individual therapyh efficacy assessment in order to define responding subjects. METHODS: Hypertensive patients were included in three double-blind clinical trials (placebo versus bisoprolol, lisinopril and amlodipine) and ambulatory blood pressure measurements (four per hour) were performed at the end of each month. We analysed the effect of therapy (placebo minus treatment) according to the following criteria: type of model (hourly mean, moving average, fast Fourier analysis), determination of the time to the peak effect (the lowest value of the modelled blood pressure) and the sampling time around this peak (1, 2,., 24 h). RESULTS: Regardless of the type of model, the level of individual therapy efficacy is significantly higher than that of the overall subjects (group efficiency), when the sampling time around this peak decreases. The proportion of responders decreases as the sampling time used to calculate the drop in blood pressure increases, whatever the kind of model and the threshold used to define responders (5 or 10 mmHg in systolic blood pressure). CONCLUSION: By this method, it is possible to appreciate the percentage of subjects considered individuallyas responders according to the time around the peak. This evaluation complements information given by the trough: peak ratio.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10226241&dopt=Abstract [PubMed - as supplied by publisher]





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