Short-term effects of withdrawing angiotensin converting enzyme inhibitor therapy on home self-measured blood pressure in hypertensive patients.

The aim of this study was to compare blood pressure rise after interruption of two angiotensin converting enzyme (ACE) inhibitors in hypertensive patients. After a 2-week placebo run-in period, hypertensive patients were treated with either trandolapril 2 mg once daily or perindopril 4 mg once daily for 4 weeks in a double-blind design. A placebo was then administered for 1 week. Three periods of 1-week home self-measured blood pressure (SMBP) were programmed: end of placebo run-in period, end of treatment period, and final withdrawal placebo period. Every day, three consecutive measurements were requested both in the evening and in the morning. Individual reversion to baseline BP level was studied in the subgroup of patients responding to therapy (evening diastolic SMBP decrease > or =6 mm Hg). The ratio (R) of mean post-drug DBP lowering (residual effect) over evening on-drug DBP lowering (full effect) was used to study reversion to baseline. Patients exhibiting a lower value than the median of this ratio were called Reverters, whereas others were called Nonreverters. One hundred-nineteen patients entered the analysis. During the treatment period, mean SMBP decreased significantly, from 150 +/- 14/97 +/- 7 mm Hg to 139 +/- 15/91 +/- 9 mm Hg (all P < .001). The on-drug BP level was similar in the evening in the two treatment groups. However, both systolic and diastolic morning SMBP levels were significantly lower in the trandolapril group. After drug discontinuation, the mean BP level significantly rose to 144 +/- 14/94 +/- 9 mm Hg (all P = .01) but remained lower than the baseline BP values (P = .003 for SBP and P = .002 for DBP). The post-drug BP level was significantly lower in the trandolapril group than in the perindopril group. Seventy-four patients were responders to therapy. In this subgroup, the median of the R ratio used to analyze reversion to baseline after drug discontinuation was 44%. Nonreverters were characterized by a sustained on-drug BP decrease, compared to Reverters. We therefore conclude that ACE inhibitor treatment withdrawal is accompanied by a rapid rise in BP (within 48 h), followed by a 5-day BP plateau that is lower than the initial level. Reverters to baseline after drug discontinuation were more likely to be insufficiently controlled during therapy, particularly in the morning. The longer duration of action of trandolapril was associated with a lower BP level during both the morning during the active treatment phase and the 1-week posttreatment phase.

Superiority of home blood pressure measurements over office measurements for testing antihypertensive drugs.

OBJECTIVE: To compare the effects on office blood pressure and home blood pressure of placebo and active drug administration. DESIGN: After a 2-week wash-out period, patients with mild-to-moderate hypertension entered a 2-week single-blind placebo period and then a 4-week double-blind period. Patients were randomly assigned to be administered either 2 mg trandolapril once daily or its placebo in a 2:1 proportion. Office blood pressure was measured by a physician at the end of each period, using a mercury sphygmomanometer (mean of three consecutive measurements). Home blood pressure was measured during the last week of each period according to standard procedure carefully taught to each patient by the physician. Compliance was checked by using electronic pill boxes. RESULTS: Data for 34 of the 44 patients who entered the study were eligible for analysis. Baseline systolic blood pressure/diastolic blood pressure were significantly (P = 0.0001/P = 0.0001) higher for office blood pressure (161/101 mmHg) than they were for home blood pressure (145/93 mmHg). There was no statistically significant difference between the placebo and active-treatment groups at baseline. During the single-blind period, blood pressures measured at the office and at home did not change significantly. Office blood pressure decreased by 2.7 +/- 10 mmHg for systolic blood pressure and by 0.5 +/- 4 mmHg for diastolic blood pressure whereas home blood pressure increased by 0.8 +/- 6 mmHg for systolic blood pressure and by 0.7 +/- 4 mmHg for diastolic blood pressure. During the double-blind period, office blood pressure fell significantly with trandolapril treatment (systolic by 10.2 +/- 12 mmHg, diastolic by 8.3 +/- 6 mmHg; P = 0.0005/0.0001, versus single-blind placebo period) but this decrease was not significantly different (P = 0.45/0.92) from the fall in members of the placebo group (systolic by 6.9 +/- 9 mmHg, diastolic by 8.0 +/-6 mmHg; P = 0.04/0.002, versus single-blind placebo period). Thus, no antihypertensive effect of trandolapril was demonstrated. The fall lin home blood pressure with trandolapril treatment was significant (systolic by 10.7 +/- 8 mmHg, diastolic by 5.8 +/- 5 mmHg; both P = 0.0001, versus single-blind placebo period) and was significantly greater (P = 0.0004/0.004) than the minimal change observed with placebo (systolic fell by 0.2 +/- 5mmHg, diastolic fell by 0.6 +/- 4 mmHg; P = 0.90/0.62, respectively, versus single-blind placebo period). The evening decrease in home blood pressure was similar to the morning decrease in home blood pressure in members of the trandolapril-treated group. The resulting morning:evening decrease in blood pressure ratio was 0.83 for diastolic blood pressure and 0.95 for systolic blood pressure. For the subgroup of responders, mean of individual ratios was 0.77 +/- 0.43 for diastolic blood pressure and 0.70 +/- 0.39 for systolic blood pressure. CONCLUSION: The placebo effect observed with office blood pressure measurements does not occur with home blood pressure measurements. Expected treatment effect can alter a physician's blood pressure readings. The precision of measurements is greater with home blood pressure (there is a lower SD). Use of home blood pressure measurements increases the power of comparative trials, allowing one either to study fewer subjects or to detect a smaller difference in blood pressure.

[Demonstration of differences in the effect of 2 antihypertensive agents by self blood pressure measurement: comparison of trandolapril and perindopril]. / Mise en évidence de différences dans l'effet de deux antihypertenseurs par automesure tensionnelle: comparaison du trandolapril et du périndopril.

In this double blind randomized study, blood pressure lowering effects and duration of action of two angiotensin converting enzyme (ACE) inhibitors were compared using home self blood pressure measurement (SBPM). After a two-week placebo run-in period, 128 hypertensive patients received during four weeks a daily morning dose of either perindopril (P) 4 mg or trandoplapril (T) 2 mg. One week of SBPM was planned at the end of both the run-in and the treatment period. Three consecutive measurements, with printed results, were requested in the morning before drug intake and in the evening. Run-in period home systolic (SBP) and diastolic (DBP) blood pressures were comparable in both groups: 149.9 +/- 14.5/97.3 +/- 8.1 mmHg in the P group (n = 63), 148.9 +/- 14.3/96.7 +/- 6.9 mmHg in the T group (n = 65). During the treatment period, evening BP was similar in the 2 groups: 139.1 +/- 14.3/89.9 +/- 9.1 mmHg in P group, 137.5 +/- 15.3/89.4 +/- 9.1 mmHg in T group (NS). On the other hand, morning BP was higher in the P group: 143.1 +/- 16.3/93.8 +/- 9.6 mmHg vs 137.4 +/- 16.7/90.3 +/- 9.7 mmHg (p < 0.05 for SBP and DBP-Student's t test). These results were confirmed by co-variance analysis after adjustment on initial BP. Due to standardized conditions of measurement, home SBPM was able to show a difference in BP lowering effects at the end of the inter-dose interval between two ACE inhibitors.

[Risk factors of adverse effects of angiotensin-converting enzyme inhibitors. Apropos of 30,072 patients treated by trandolapril]. / Facteurs de risque de survenue d'effets indésirables sous inhibiteur de l'enzyme de conversion: à propos de 30,072 patients traités per trandolapril.

SUMMARY: The aim of the present study was to investigate the incidence of adverse effects and the prognostic value of various risk factors in a large population of unselected hypertensive patients treated with the ACE inhibitor trandolapril. Among the 30 072 patients investigated in this post marketing retrospective study, 1813 patients (6.0 per cent) reported an adverse effect. The five most frequent side effects were coughing (3.1 per cent), dizziness (0.7 per cent), headache (0.6 per cent) asthenia (0.5 per cent) and nausea (0.3 per cent). Intolerance risk factors for trandolapril were researched using both univariate and multivariate analysis. In the univariate analysis, a prior intolerance of an ACE inhibitor and female gender were strongly correlated with either overall intolerance or coughing. The most relevant variables for the occurrence of adverse effects, listed according to their entry order in the multivariate analysis, were: prior intolerance of ACE inhibitors (OR: 4.19, 95 per cent CI: 3.66-4.78), female gender (OR: 1.46, 95 per cent CI: 1.31-1.63), prior intolerance of other antihpertensive agents (OR: 1.27, 95 per cent CI: 1.14-1.41), smoking (OR: 0.76, 95 per cent CI: 0.66-0.87) and combination with a beta blocker (OR: 1.31, 95 per cent CI: 1.08-1.58). A prior intolerance of an ACE inhibitor appears to be a very strong predictor of coughing (OR: 6.14, 95 per cent CI: 5.24-7.19). The following variables, namely female gender (OR: 1.61, 95 per cent CI: 1.40-1.85), age 60-80 (OR: 1.25, 95 per cent CI: 1.09-1.44) and prior intolerance of other antihypertensive agents (OR: 1.20, 95 per cent CI: 1.03-2.39) appear less significant.

Home self blood pressure measurement in general practice. The SMART study. Self-measurement for the Assessment of the Response to Trandolapril.

The SMART study (Self-Measurement for the Assessment of the Response to Trandolapril) was performed in general practice and enrolled 1710 patients in order to assess on a large scale the feasibility and informative value of self-measurement of blood pressure at home (SMBP), define home blood pressure (BP) levels in comparison to office readings, and determine the number of home measurements necessary to provide an accurate and precise BP value. After a 2-week washout period, patients with office diastolic blood pressure within the range 95 to 119 mm Hg received 2 mg trandolapril once daily in the morning for 4 weeks. Four days of SMBP were performed both at the end of the washout period and the end of the treatment period, with an automatic printer-equipped oscillometric device (A&D UA751). The first day values were not analyzed. Thus, the maximum number of BP measurements obtained per patient and per period was 18. Four hundred and twenty-four patients (25%) did not perform any measurements. One thousand one hundred and nine patients (65%) performed at least 4 measurements. Among them, 619 (36%) correctly performed all 18 measurements. A preference for digits 0 and 5 was detected in physicians' measurements (three consecutive values, during a single office visit). This digit preference was not found with the semiautomatic device. When the number of measurements selected for analysis was increased from 1 to 18, in the 604 patients who provided all recordings and fullfilled all protocol criteria, the standard deviation of the mean BP of the cohort was reduced by 17% for SBP and by 23% for DBP. Eighty-five percent of this reduction was already achieved by six home measurements taken at random. BP was significantly lower at home than at the office by 13 +/- 15 mm Hg for systolic BP (SBP), and 8 +/- 10 mm Hg for diastolic BP (DBP). This difference was independent of age, more marked in women (P < .001 for SBP and P < .05 for DBP), and had a Gaussian distribution. Under treatment, office SBP/DBP decreased from 166.4 +/- 14.8/101.4 +/- 5.7 mm Hg to 144.7 +/- 14.2/86.1 +/- 8.3 mm Hg, while SMBP decreased from 153.2 +/- 17.8/93.8 +/- 10.1 mm Hg to 139.4 +/- 16.4/85.1 +/- 9.5 mm Hg (all P < .0001). A major aim in research studies and individual care is to reduce BP measurements variability. This study demonstrates the ability to evaluate baseline SMBP level in two-thirds of patients previously unfamiliar with the method, the ability to evaluate treatment effect in about one-half of the patients, the improvement in the measurement precision obtained with the repetition of measures (at least six home measurements), and the absence of bias of SMBP as compared to office measurements.

Assessment of drug efficacy using home self-blood pressure measurement: the SMART study. Self Measurement for the Assessment of the Response to Trandolapril.

UNLABELLED: The SMART study (Self Measurement for the Assessment of the Response to Trandolapril) was a large scale trial conducted by general practitioners in order to assess the informative value of home self-measured blood pressure (BP) for the evaluation of therapeutic intervention. After a 2-week wash-out period, patients with office diastolic blood pressure (DBP) between 95 and 120 mm Hg received trandolapril, 2 mg once daily for 4 weeks. Four days of self-recorded BP were performed both at the end of the wash-out period and at the end of the treatment period with an automatic printerequipped device using the oscillometric method (A&D UA 751). Every day, a series of three consecutive measurements was planned in the morning before drug intake and repeated in the evening. A total of 1710 patients (946 men, 764 women) aged 56 +/- 11 entered the study. In the 816 patients who correctly performed self-measured blood pressure (SMBP) during both periods and followed the protocol schedule, office BP (SBP/DBP) decreased from 166.4 +/- 15/101.4 +/- 6 mm Hg to 144.7 +/- 14/86.1 +/- 8 mm Hg while SMBP decreased from 153 +/- 18/94 +/- 10 mm Hg to 139 +/- 16/85 +/- 10 mm Hg. A weak correlation was found between the two methods with regard to systolic (r = 0.47, P < 0.0001) and diastolic (r = 0.36, P < 0.0001) BP lowering. Individual response to therapy varied between the two methods: 633 patients (77.6%) exhibited at least a 10 mm Hg office DBP decrease while 493 (60.4%) presented at least a 6 mm Hg self measured DBP decrease in the evening; 65% of patients were considered as responders with both methods. The 24-h therapeutic coverage was assessed by the morning to evening BP decrease ratio (M/E ratio) which represents the ratio of the trough effect to the 12-h post dosing efficacy. Both population and individual M/E ratios ranged between 73% and 86% thus confirming the long duration of action of trandolapril. IN CONCLUSION: (1) discrepancies between office and self-measured BP evaluation of therapeutic response have been pointed out: agreement between the two methods is obtained in only 65% of patients, mainly due to intra-individual BP variability and recording conditions; and (2) self-measured BP could be a potential tool to explore the 24-h therapeutic coverage.

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.

Antihypertensive effects of trandolapril and nitrendipine in the elderly: a controlled trial with special emphasis on time effect profiles.

The aim of this double-blind randomized study was to compare the antihypertensive effects of trandolapril and nitrendipine in the elderly. After a 2-week placebo period, patients received either trandolapril 0.5 mg or nitrendipine 10 mg, once daily for 15 days. At the end of this period, according to a forced titration, the dose was increased to 2 mg of trandolapril or 20 mg of nitrendipine once daily for 2 months. Seventy-three hypertensive patients, aged 65 and over, entered the study. Demographic data and initial blood pressure (BP) level were comparable in the two groups. The antihypertensive effect, measured with a mercury sphygmomanometer, was assessed in 64 patients: SBP decreased by 18.6 +/- 12.1 mm Hg in the trandolapril (P < 0.001) and by 21.0 +/- 13.7 mm Hg in the nitrendipine group (P < 0.001); DBP decreased by 13.4 +/- 8.5 mm Hg in the trandolapril group (P < 0.001) and by 15.4 +/-8.2 mm Hg in the nitrendipine group (P < 0.001). No statistically significant difference was seen between the two treatment groups. A sub-group of 42 patients were evaluated by 24 h ambulatory BP monitoring. Mean 24 h ambulatory SBP/DBP decreases were 6.6 +/- 18.0/8.4 +/- 8.5 mm Hg in the trandolapril group (P < 0.001) and 5.7 +/- 11.1/7.2 +/-9.6 mm Hg in the nitrendipine group (P < 0.001). The differences between the two treatment groups were not statistically significant. The antihypertensive action of trandolapril was sustained throughout the 24 h period with a trough-to-peak ratio of 70.2% for SBP and 70.9% for DBP. Nitrendipine exerted its action mainly during the day, with a very modest antihypertensive effect during the night and early morning; its trough/peak ratio was 25.9% for SBP and 28% for DBP. The tolerance of both treatments were good; seven patients were withdrawn from the trial for adverse events (four in the nitrendipine group, three in the trandolapril group).

Benefits of electronic pillboxes in evaluating treatment compliance of patients with mild to moderate hypertension.

OBJECTIVE: This study was designed to assess the compliance of hypertensive patients with a once-daily regimen of the angiotensin converting enzyme (ACE) inhibitor trandolapril and to evaluate the antihypertensive efficacy of the drug in relation to the time interval between taking the final dose and measuring the blood pressure (BP). DESIGN: After a 2-week wash-out period, hypertensive patients, recruited by cardiologists, received trandolapril 2 mg once daily in the morning for 4 weeks. METHODS: In order to assess compliance, each patient's supply of trandolapril capsules was presented in a pillbox that incorporated in its lid a microprocessor that recorded the date and time of each occasion that it was opened. BP was measured using validated semi-automatic devices, at the end of both the wash-out and the treatment period. RESULTS: A total of 590 patients entered the study. Compliance data were evaluable for 501 patients. Overall compliance, defined as the ratio of the number of openings recorded to the number of doses prescribed was less than 80, 80-100, and more than 100% in 17, 63 and 20% of patients, respectively. The average number (+/- SD) of missed doses was 4.5 +/- 8 (median 2). The average interval between successive openings was 25 h 07 min mean +/- 13 h (median 24 h). The average number of delayed doses (a delayed dose being defined as the box being opened 25-36 h after the previous occasion) was 5.6 +/- 3 (median 6). Patients living in the Paris area had more forgotten and delayed doses than those living in the provinces (7.9 versus 3.8 forgotten; P<0.0001 and 6.3 versus 5.5 delayed; P<0.005). Doses were forgotten and delayed more often during weekends than on weekdays. The greatest number of delayed doses occurred in those patients under 60 years of age (6.0 versus 5.2; P<0.01). Decreases in systolic blood pressure (SBP and diastolic blood pressure (DBP) were 20.3/12.8 mmHg, for patients whose final drug was taken on the same day as the BP measurement, and 18.9/11.2 mmHg for patients whose final dose was taken on the previous day. CONCLUSIONS: Electronic compliance monitoring allows refined analysis of the behaviour of hypertensive patients. In this study doses were missed and delayed frequently during the first month of treatment, depending on the patient's lifestyle.

[Behavior of patients with mild-to-moderate arterial hypertension in relation to their treatment. Contribution of an electronic pillbox]. / Comportement des patients ayant une hypertension artérielle légère à modérée vis-à-vis de leur traitement. Apport du pilulier électronique.

The objective of the MACH1 study (MEMS for the Assessment of Compliance of Hypertensives) was to evaluate the real behaviour of patients in relation to antihypertensive treatment administered as a single daily dose. After a 2-week period during which no other antihypertensive was allowed to be administered, 590 patients with mild-to-moderate hypertension received 2 mg of trandolapril as a single daily dose in the morning between 7:00 a.m. and 9:00 a.m. for 4 weeks. Treatment was packaged in electronic pillboxes recording the date and time of each opening. Various profiles were distinguished on the basis of the individual chronograms for the 501 patients able to be analysed in terms of compliance, and as a function of the deviations observed in relation to the treatment regimen prescribed. One hundred and two patients (20%) omitted more than 20% of the prescribed doses, either consecutive doses or scattered throughout the month of treatment; these patients were referred to as "omitters". The other patients were classified according to the scatter of openings in relation to the mean time of the dose: 10 "metronome" patients (2%), 126 "regular" patients (25%), 221 "irregular" patients (44%) and 42 "anarchic" patients (8%). Irregularities of dose times were more frequent on public holidays than on week days and in patients living in Paris or the Paris region. "Metronome" patients were older than the overall patient population. The use of an electronic pillbox could allow the attending physician to more adequately adapt his therapeutic approach and management of specific problems of compliance observed in hypertensive patients.

[Evaluation of trandolapril alone or in combination with a calcium channel blocker in hypertensive patients over 60 years of age]. / Evaluation du trandolapril seul ou en association à un inhibiteur calcique chez l'hypertendu âgé de plus de 60 ans.

The efficacy and safety of trandolapril alone and in combination with a calcium channel blocker were evaluated in 13,147 hypertensive patients over 60 years old. Two patient groups were constituted. After a 2-week wash-out period, the patients in group I received monotherapy with trandolapril 2 mg/day for 4 weeks. Trandolapril was continued for another 4 weeks in responding patient, otherwise the dosage of trandolapril was doubled or another antihypertensive was added. Group 2, composed of patients previously treated with a calcium channel blocker with insufficient efficacy, was treated according to the same treatment regimen, but the calcium channel blocker was maintained throughout the study. 13,147 patients (group 1: 11,329 patients, group 2: 1,818 patients) with a mean age of 68 +/- 7 years were followed. After 4 weeks of treatment, the blood pressure measured by mercury sphygmomanometer decreased from 176 + 11/99 +/- 8 mmHg to 164 +/- 12/87 +/- 7 mmHg (p < 0.0001). This blood pressure fall was similar in group 1 (-22 +/- 12/-12 +/- 8 mmHg) and in group 2 (-21 +/- 11/-12 +/- 8 mmHg). In the pure systolic HT subgroup treated by trandolapril monotherapy, the antihypertensive effect predominantly affected the SBP (-23 +/- 12/- 4 +/- 6 mmHg). The antihypertensive effect was correlated with the initial blood pressure. In group 1, in the case of insufficient response to trandolapril monotherapy, the addition of a calcium channel blocker was the strategy which achieved the most marked antihypertensive effect (ANOVA, p < 0.0001). This bitherapy was more effective than the trandolapril+diuretic combination (-18 +/- 11/- 11 +/- 8 mmHg and -15 +/- 10/- 9 +/- 7 mmHg, respectively (p < 0.001). A total of 1,270 adverse events were reported by 996 patients (7.6%), leading to discontinuation of treatment in 372 patients (2.8%). The most frequent adverse effects were cough (2.8%), headache (0.8%), vertigo (0.8%) and nausea (0.5%). Only one minor equivalent of angioneurotic oedema was reported. In conclusion, trandolapril is effective and well tolerated in elderly hypertensive patients. In the case of pure systolic HTA, its action is essentially exerted on SBP. The combination of trandolapril+calcium channel blocker appears to be the most effective strategy in the case of incomplete blood pressure control by trandolapril alone.

Differential effects of a missed dose of trandolapril and enalapril on blood pressure control in hypertensive patients.

A double blind randomised comparison of two angiotensin-converting enzyme (ACE) inhibitors was made in a study in which ambulatory blood pressure was monitored over a steady-state dosage interval and the subsequent 24-h period, the latter being designed to mimic a missed dose of drug. The blood pressure responses on active therapy were compared to an identical recording made at the end of a 3-week placebo run in period. Eighty-eight essential hypertensives were treated with a morning dose of either trandolapril 2 mg or enalapril 20 mg. Mean systolic (SBP) and diastolic blood pressure (DBP) were calculated on each of the following periods: daytime (8:31 a.m.-10:30 p.m.), nighttime (10:31 p.m.-6:30 a.m.), and early morning (6:31 a.m.-8:30 a.m.). Trough/peak was calculated for each group both on active treatment and after a missed dose. Twelve patients were excluded from analysis before opening the randomisation code because of inadequate ambulatory blood pressure monitoring (ABPM) recordings. Demographic data, placebo-period office blood pressure, and ABPM recordings were not significantly different between the two groups. Both trandolapril and enalapril effectively reduced blood pressure over the 24-h period. Twenty four-hour ambulatory SBP and DBP decreased from 148 +/- 14/92 +/- 10 mm Hg to 135 +/- 14/83 +/- 10 mm Hg in the trandolapril group (p < 0.001). The same parameters decreased to a quite similar extent after enalapril, from 143 +/- 13/91 +/- 5 mm Hg to 133 +/- 15/83 +/- 8 mm Hg (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Duration of action of trandolapril in mild to moderate hypertensive patients evaluated by ambulatory measurement of blood pressure]. / Durée d'action du trandolapril chez l'hypertendu léger á modéré, évaluée par mesure ambulatoire de la pression artérielle.

The duration of the antihypertensive action of transdolapril, a new angiotensin converting enzyme inhibitor, was studied in 23 patients using ambulatory blood pressure monitoring (ABPM) over 48 hours. After a 20-day placebo period (D1 to D20), mild to moderate hypertensive patients received 2 mg trandolapril once daily for 30 days (D21 to D50). The first 24-hour ABPM recording was performed on day 14, during the placebo run-in period. Two additional recordings were done successively on days 50 and 51 corresponding to a normal dosing day and a following day with a simulated missed dose, respectively. The three blood pressure recordings (placebo, treatment, missed dose) were compared. The average 24-hour systolic (SBP) and diastolic (DBP) blood pressure were significantly decreased by trandolapril. The mean +/- s.d. decrease between day 14 and day 50 were - 8.0 +/- 7.2 mmHg for the DBP and -13.3 +/- 7.8 mmHg for the SBP. Blood pressure was also consistently decreased during the daytime period (-8.7 +/- 7.9 mmHg for the DBP and - 15.6 +/- 8.5 mmHg for the SBP), nighttime period (-5.6 +/- 9.1 mmHg for the DBP and - 8.5 +/- 11.3 mmHg for the SBP) and early morning (- 12.3 +/- 9.7 mmHg for the DBP and - 15.9 +/- 15.1 mmHg for the SBP). The normal circadian pattern of blood pressure was maintained under treatment. The antihypertensive effect of trandolapril was sustained beyond 24 hours after the last intake: there were no significant difference beetween days 50 and 51 in terms of 24-hour, daytime and nighttime average blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the converting enzyme inhibitor trandolapril on short-term variability of blood pressure in essential hypertension.

Short-term fluctuations in blood pressure and heart rate were analysed in a group of eight males with essential hypertension. Indirect finger blood pressure was measured by a non-invasive device (Finapres). Analogue-to-digital conversion of the blood pressure was used to determine systolic and diastolic blood pressure and heart rate every second. The equidistant sampling allowed a direct spectral analysis using a fast Fourier transformation algorithm. The effect of 7-day administration of the angiotensin converting enzyme inhibitor, transolapril (2 mg/day), was assessed in a double-blind, randomized, placebo-controlled cross-over study. After trandolapril there was a significant reduction in systolic blood pressure levels (-15 mmHg). The reduction in diastolic blood pressure did not reach significance. The standard deviation of systolic and diastolic blood pressure levels were significantly reduced (-20% and -22% for systolic and diastolic respectively). Neither average heart rate nor standard deviations of heart rate time series was affected by the angiotensin converting enzyme inhibitor. Spectral analysis of fluctuation in blood pressure showed a reduction in the variability underlying the standard deviation changes of systolic and diastolic blood pressure. Trandolapril selectively reduced the amplitude of systolic and diastolic oscillations in the 66-129 mHz region, corresponding to Mayer waves. The significant decrease in the 10 s period oscillations of blood pressure after chronic angiotensin converting enzyme blockade with trandolapril could reflect reduced sympathetic outflow to vascular smooth muscle.