Biomedical subjects

JM Mallion

Publications and source records attributed to JM Mallion.

6 recordsLinked to original sources

PubMed1998

Various approaches to evaluating the kinetics and efficacy of three antihypertensive drugs in terms of variations in blood pressure and heart rate.

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.

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PubMed1997

Valsartan, a new angiotensin II antagonist; blood pressure reduction in essential hypertension compared with an angiotensin converting enzyme inhibitor, enalapril.

OBJECTIVE: To compare the blood pressure reduction induced by valsartan, a new angiotensin II receptor antagonist, with that induced by enalapril, an angiotensin converting enzyme (ACE) inhibitor in essential hypertension. METHODS: In total 189 adult outpatients with uncomplicated essential hypertension participated in this double-blind study. Patients were allocated randomly in equal numbers to be administered 80 mg valsartan or 20 mg enalapril daily for 12 weeks. Patients whose blood pressure had not been controlled adequately despite 8 weeks of monotherapy were administered additional therapy with 12.5 mg hydroclorothiazide (HCTZ) daily thereafter. Patients were assessed aftger 4, 8 and 12 weeks of therapy. The primary efficacy variable was the change from baseline in mean sitting diastolic blood pressure (SDBP) after 8 weeks of therapy. Other variables analyzed included the change in sitting systolic blood pressure and percentage responses after 8 weeks of therapy. RESULTS: Valsartan and enalapril were both effective at lowering the blood pressure. Similar falls were induced in the two groups with a similar time course of blood pressure reduction. The mean decreases in SDBP after 8 weeks of therapy were 13.2 mmHg for valsartan and 12.0 mmHg for enalapril. There was no significant difference between the treatments [P = 0.475, 95% confidence interval of the estimated difference (SBP after therapy - SDBP before therapy) -3.5 to 1.6 mmHg]. After 8 weeks of therapy 60.6% had responded to valsartan and 52.6% to enalapril (P = 0.267). Both treatments were tolerated well. Three patients administered enalapril and one patient administered valsartan discontinued their treatment because it made them cough. CONCLUSION: The data show that 80 mg valsartan is as effective as 20 mg enalapril in the treatment of moderate hypertension and that it is tolerated well.

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PubMed1996

Acceptability and tolerance of ambulatory blood pressure measurement in the hypertensive patient.

OBJECTIVE: To establish the acceptability and tolerance of ambulatory blood pressure monitoring (ABPM). METHODS: A two-part questionnaire was completed by the doctor; one part before ABPM and the second after the recording. The pre-recording data concern the demographic data of the patient: previous illness, symptoms, reaction of the patient, anthropometric data, treatment details and the reason for ABPM. The second part of the questionnaire records the type of monitor used, the conditions of the recording and any difficulties for, or adverse effects on, the patient. SUBJECTS: Six hundred and seventy-two patients considered hypertension by World Health Organization criteria (diastolic blood blood pressure >/=90 mmHg, systolic blood pressure >/=140 mmHg), were considered for the first descriptive part of the study; a total of 654 patients were considered for the second part related to tolerance; 18 patients refused to reply to the questions concerning the second questionnaire. The general characteristics of the population were as follows: 345 men (51.5%), 327 women (48.5%) and mean age 54+/- 15 years. RESULTS: The devices used were SpaceLabs (63%), Novacor (19.3%), Nippon Collin (6.3%) and other machines (11.2%). The difficulties caused by the machine were classified as 'nul', 'moderate' or 'important'. The levels of difficulty defined as 'important' were 32% related to the cuff, 14% to the awkwardness of the machine and 6% to the noise of the monitor. Difficulty in driving was reported in 9% of cases and difficulty related to comments by colleagues in 6%. Analysis during sleep hindered sleep in 55%, with a very disturbed sleep pattern (more than three reported awakenings) in 14% of cases. Regression analysis allowed examination of the links among the different variables, taking into account the type of machine or the profile of the subject. Thus, it was possible to differentiate among the elements that could influence or predict intolerance. CONCLUSION: Recording-related problems are not negligible but can be reduced by an approach oriented towards each individual patients, taking into account specific information for particular circumstances.

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PubMed1996

Individual smoothing of blood pressure profiles to define responders or non-responders to drugs.

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.

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PubMed1996

Errors in trough: peak ratio determinations induced by patient behaviour.

BACKGROUND: Trough: peak ratio is often used to evaluate the duration of antihypertensive action. Whatever the method of measurement chosen, trough effect has to be measured 24 h after the last drug intake for a once daily regimen. Peak effect is usually measured 4-6 h after drug intake. If patients' compliance to therapeutic instructions is perfect, then the 'intrinsic' trough: peak ratio of the drug is equal to the measured trough: peak ratio. Some patients do not follow these instructions, leading to biases in the evaluation of the ratio. For trough evaluation, all patients (N) are supposed to take the last dose of the drug the day before blood pressure measurement. However, if some patients (n1) wrongly take the drug in the morning of the visit, they will be evaluated at peak (type A error). For peak evaluation, all patients (N) are supposed to take the drug a few hours before blood pressure measurement. If some patients (n2) miss their morning dose, they will be evaluated at trough (type B error). METHODS: In the MACH 1 study, the use of an electronic pill count monitor allowed us to quantify n1/N and n2/N. A total of 452 hypertensive patients were randomly assigned to two groups. Patients in group 1 received written instructions to take their last dose during the morning of the day before the visit, whereas patients of group 2 had to take their last dose on the morning of the visit. RESULTS: Electronic pill-box recording revealed that 32.9%: of patients in group 1 committed type A error, whereas 27.7% of patients in group 2 committed type B error. The resulting 'pill-box corrected' trough: peak ratio was lower (87.5% for diastolic blood pressure and 93.1% for systolic blood pressure) than the uncorrected trough: peak ratio (95.2% for diastolic blood pressure and 96.0% for systolic blood pressure) of the population. CONCLUSION: The random behaviour of patients, with respect to treatment compliance, results in a systematic overestimation of the measured trough: peak ratio. The computation of this ratio may be optimized by improving patient compliance. Alternatively, only data from a patient subpopulation that complies with the therapeutic protocol, as reported by readings from electronic pill boxes, should be taken into account for its calculation.

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PubMed1996

Repeated measurements of non-invasive ambulatory blood pressure: distinction between reproducibility and the proper effect of placebo.

OBJECTIVE: To determine whether non-invasive ambulatory blood pressure is more reproducible and less affected by the placebo treatment than are clinic blood pressure measurements. METHOD: Thirty-four essential hypertensive outpatients were randomly allocated after a 4-week preselection period in two groups in a cross-over study design. One group received placebo for 4 weeks while the other formed the control group (reproducibility), then the treatments were exchanged for another 4 weeks. Clinic and ambulatory blood pressures were measured at three different times for each patient, namely bnefore the random allocation to groups and at the end of each period, using a mercury sphygmomanometer and 24 h non-invasive ambulatory blood pressure monitoring. RESULTS: Administration of placebo was accompanied by a significant reduction in systolic and diastolic clinic blood pressures (by 3.4+/-13 and 3.6+/-8 mmHg, respectively), but not in 24 h, daytime and night-time blood pressures. Circadian hourly blood pressure and heart rate curves were virtually superimposable. In the 13 placebo responder patients selected on the basis of clinic blood pressure, placebo decreased the clinic blood pressure and also reduced systolic and diastolic ambulatory blood pressures, mainly during the day period (by 5.2+/-6.2 and 4.89+/-7.8 mmHg, respectively). This effect is specific and related to the placebo administration because repetition of the measurements without any treatment showed no significant difference. To characterize at baseline the placebo responder patients, comparison with the non-placebo responders showed lower baseline values of ambulatory systolic blood pressure recorded during 24 h daytime and night-time in the placebo responder group. CONCLUSION: The 24 h ambulatory blood pressure average is not affected by placebo in the present group of patients but that a placebo effect occurs mainly during the daytime in patients who decreased their clinic blood pressure under placebo (placebo responders); the placebo-induced reduction in blood pressure is related to a specific effect of placebo and is independent from any alerting reaction or reproducibility hypothesis. This study clearly indicates the necessity of including placebo and ambulatory blood pressure monitoring in the therapeutic and pharmacological trials of antihypertensive drugs.

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