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Abstract

  1. Top of page
  2. Abstract
  3. METHODS Study Design
  4. RESULTS
  5. DISCUSSION
  6. References

Blood pressure (BP) reuctions with agents that block the renin-angiotensin system are regarded as less effective as monotherapy in African Americans than other ethnic groups. This practice-based study compares the efficacy of an angiotensin receptor blocker-based regimen in African-American and Caucasian patients. Included in the 10-week study were 173 African-American and 1296 Caucasian patients. Efficacy was based on differences in 24-hour ambulatory BP. After baseline ambulatory BP monitoring and office BPs were obtained, all patients were started or switched to the angiotensin receptor blocker telmisartan, 40–80 mg daily, plus hydro-chlorothiazide 12.5 mg daily (if needed for office BP control: <140/90 mm Hg). More African Americans required the addition of a low-dose thiazide diuretic than Caucasians (47.3% vs. 34.9%; p=0.021). Once patients with white coat hypertension were excluded (i.e., those with baseline ambulatory BP monitoring <130/80 mm Hg), ambulatory BP monitoring changes were similar between groups. A greater proportion of African Americans than Caucasians without white coat hypertension also needed combination therapy (52.1% vs. 39.5%; p=0.04). While achievement of BP goal was similar between groups by office criterion (<140/90 mm Hg), differences were noted by ambulatory BP monitoring (<130/80 mm Hg) (48.0% in African American vs. 63.2% in Caucasians; p=0.01) despite the same BP reductions, reflecting higher baseline values in African Americans. We conclude that an angiotensin receptor blocker as part of a BP-lower-ing strategy is effective in previously untreated African-American patients, although a higher proportion will require the use of a diuretic compared with Caucasians.

Guidelines for the treatment of hypertension now emphasize the importance of achieving rigorous blood pressure (BP) goals.1,2 In particular, the target for hypertensive patients in general is <140/90 mm Hg and <130/80 mm Hg for those with diabetes or impairment of kidney function. Recent clinical trials in hypertension have established the importance of these recommendations. For example, in the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial3 it was shown that achieving a systolic BP of <140 mm Hg, as compared with failing to reach this target, was associated with highly significant decreases in cardiac and stroke events and mortality. This finding was independent of the class of antihypertensive agent used. Other trials have also established the clinical outcomes benefits of rigorous BP control.4,5

These recommendations are of particular importance in African-American patients. Not only is hypertension more common in this population, but it appears to carry higher risks of major end points, especially strokes and end-stage renal disease.6,7 Although African Americans have been included proportionately in most hypertension clinical trials carried out in the United States, these trials are often not of sufficient size to fully determine the effects of treatment in patient subgroups.

Data from the most recent National Health and Nutrition Examination Survey 1999–2000 (NHANES) note that only 34% of patients with hypertension are at the goal of <140/90 mm Hg.1–8 This finding applies to all ethnic groups, including African Americans. It is difficult to generalize the results of formal clinical trials in hypertension to the actual practice of medicine in the community. A recent detailed review of this problem indicates that although randomized control trials are, in general, internally valid, the results may be of limited relevance to the actual practice of medicine.9 For these reasons, we conducted a study to determine the response of African-American patients to a well-accepted antihypertensive treatment regimen. The overall results of this trial were reported previously.10 Treatment was based on an angiotensin receptor blocker (ARB) given as monotherapy or in combination with a thiazide diuretic. Such combinations have been shown to be effective in lowering BP in clinical trials.11,12 Specifically, we performed a clinical trial in the community setting, conducted predominately by primary care physicians. Large cohorts of both white and African-American patients were treated based on an algorithm using the ARB, telmisartan, to which low-dose hydrochlorothiazide (HCT) could be added if required to achieve BP targets. A key feature of this study was the use of ambulatory BP monitoring (ABPM), a technique that is free from observer bias and minimizes the so-called placebo effect in hypertension trials. We also analyzed the treatment effects in the African-American and white patient groups from which individuals with white coat hypertension had been excluded.

METHODS Study Design

  1. Top of page
  2. Abstract
  3. METHODS Study Design
  4. RESULTS
  5. DISCUSSION
  6. References

This is a prospective, randomized, open-label, blinded-end point, phase 4, practice-based trial designed to compare the antihypertensive efficacy of telmisartan alone or in combination with HCT on 24-hour BP control in African-American and Caucasian patients. ABPM was used to record each patient's BP over 24 continuous hours at baseline and at the end of treatment. To avoid measurement bias, the study employed a remote data transfer function that ensured the investigators were blinded to the 24-hour ABPM data. All investigators were trained in appropriate techniques of ABPM placement, proper measurement of office BP according to American Heart Association guidelines,13 as well as details of data collection and protocol implementation.

Study Patients

Patients were considered for study enrollment if they met the following inclusion criteria: uncontrolled, treated stage I or II essential hypertension, defined by diastolic office BP ≥90 and ≤109 mm Hg or systolic office BP ≥140 and ≤179 mm Hg, age 18 years or older, and not of childbearing potential. Any of the following were exclusion criteria: known hypersensitivity to ARBs or thiazide diuretics; history of angioedema associated with use of an angiotensin-converting enzyme inhibitor; history of hypertensive encephalopathy, stroke, or transient ischemic attack within the past 6 months; history of coronary heart disease events within the past 3 months; congestive heart failure, or clinically significant hepatic or renal disease. Medications other than study drugs not allowed after baseline measurements included: angiotensin-converting enzyme inhibitors and ARBs; β blockers (ophthalmic preparations were allowed); calcium channel antagonists; peripheral α blockers and central α agonists; diuretics; antiar-rhythmic medication, including digoxin use within 5 days of study entry; antipsychotic medications (although chronic use of serotonin uptake inhibiting agents was allowed); and amphetamines or amphetamine-derivative agents.

The protocol was approved by the appropriate institutional review boards and conducted in accordance with the ethical principles originally described in the Declaration of Helsinki. All patients provided signed informed consent before enrolling in the study.

Study Protocol

Each patient had five to seven clinic visits, depending on drug titration needed, with all visits occurring between 6 a.m. and 10 a.m. over the 10-week period of the study. Only patients not on antihypertensive therapy or receiving only single-agent antihypertensive therapy or two-drug fixed combinations (most commonly with a diuretic as the second agent) were eligible for enrollment. A baseline 24-hour ABPM was performed on all patients (previously treated or untreated). At completion of the ABPM, any previous antihypertensive medication was discontinued, and all patients were immediately started on telmisartan 40 mg once daily. After 2 weeks, an up-titration to 80 mg of telmisartan occurred and, after 4 weeks, conversion to telmisartan/HCT (telmisartan 80 mg/HCT 12.5 mg) would occur if office BP goal, i.e., <140/90 mm Hg, was not achieved. After the final titration step, patients remained on treatment for four additional weeks, when ABPM was repeated. Adverse events from study entry to study exit were also evaluated and recorded at each visit.

BP Measurements

For office BP measurements, investigators were instructed to use the same BP monitor and the same observer for each patient visit, as well as to measure BP in the nondominant arm throughout the study to optimize consistency. BP was measured after at least 5 minutes in the examination room, during which time the patient remained seated and quiet. Two seated BP measurements were taken at least 2 minutes apart, allowing the cuff to fully deflate between readings. BP was expressed as the mean of the two readings.

Measurement of ambulatory BP was performed using monitoring devices (Spacelabs model 90207, Spacelabs Medical, Inc., Redmond, WA)13,14 with the appropriately sized cuff and bladder. The units were programmed to take measurements every 20 minutes throughout the 24-hour period. With this technique, the first five BP measures appeared on the device''s display screen, but all subsequent measures were blinded. If the recording device was unable to obtain BP data at a particular time point, the measurement was repeated within 1–2 minutes according to the standard algorithm of the ABPM unit.

The 24-hour ABPM procedure began at 8:00 a.m. ± 2 hours on a normal workday. In order for the 24-hour test to be considered successful, at least 80% of the total readings for the 24-hour period had to be valid, and no more than two consecutive hours were allowed without valid readings. One hour was considered valid if at least one valid reading was captured during that hour. Each patient''s mean systolic and diastolic BPs derived from 24-hour ABPM were calculated by averaging the valid readings over each 24-hour period. All data from the ABPMs were downloaded to a central site where initial editing was performed by computer, and then the entire record was reviewed by a trained technician.

Data Analyses

The study end points included the changes in mean 24-hour ABPM systolic and diastolic BPs from baseline to study end, changes in office diastolic and systolic BPs, and BP control rates. The criteria for BP control at study end were a 24-hour diastolic pressure average <80 mm Hg, systolic pressure <130 mm Hg, and office diastolic BP <90 and systolic BP <140 mm Hg. The principal comparisons were of BP changes in the African-American and white patient subgroups. Only those patients with successful baseline and end-of-treatment ABPM procedures were included in the analyses.

Discrete variables, such as BP control rates, were summarized by frequencies and percentages and compared by group using the chi-square test. Continuous variables were summarized by descriptive statistics and compared using analysis of variance if the data were normally distributed; if the data were not normally distributed, the Kruskal-Wallis test was used. Adjusted differences for continuous efficacy variables were calculated using an analysis of covariance, with baseline values as a covariate and treatment group as a factor in the model. If the data were not normally distributed, the Wilcoxon rank sum test was used for the comparison of the groups. Within each group, the hypothesis of no mean change from baseline was tested using a paired t test. The analyses were performed using SAS software, version 8.0 (SAS Institute, Inc., Cary, NC). For all analyses, p<0.05 was considered statistically significant.

RESULTS

  1. Top of page
  2. Abstract
  3. METHODS Study Design
  4. RESULTS
  5. DISCUSSION
  6. References

ABPM was successfully carried out at baseline and at the end of the treatment period in 173 African-American patients and in 1296 white patients. The main clinical characteristics of the two groups are shown in Table I. The African-American group was younger and had a higher proportion of women compared with the Caucasian group. Over 50% of each group was not receiving antihypertensive agents at the time of entering the trial. The two groups had virtually identical office systolic BP values, although the baseline office diastolic BP was slightly higher in the African Americans.

Table I.  Baseline Characteristics
CharacteristicsAfrican American (N=173)Caucasian (N= 1296)p Valve*
Age at enrollment (yr) (mean ± SD)51.4±13.356.5±13.0<0.0001
Male (n [%])62 (36.0)643 (49.8)0.0007
Female (n [%])110(64.0)649 (50.2) 
Prior treatment (n [%])   
Previously untreated92 (54.1)771 (59.7)0.1625
Previously treated78 (45.9)520 (40.3) 
Body mass index (kg/m2) (mean ± SD)30.9±5.930.1±6.00.1251
Office systolic blood pressure (mm Hg) (mean ± SD)150.3±13.5150.2±12.80.9206
Office diastolic blood pressure (mm Hg) (mean ± SD)92.3±8.790.9±8.90.0513
*p values are based on the comparison of the values between the African-American and Caucasian groups using a two-sided t test for continuous variables and a two-sided chi-square test for categoric variables.

In the African-American group, 81 patients (46.8%) remained on monotherapy (telmisartan 40 mg or 80 mg) by the end of the study, 90 (52.6%) finished on combination therapy (telmisartan plus HCT), including three patients who were missing prior treatment data, and two who were missing final treatment assessment data. For the white group, 749 (57.8%) remained on monotherapy, including two patients who were missing prior treatment data, and 526 (40.6%) received combination treatment, including three patients who were missing prior treatment data and 21 who were missing final treatment assessment data. The proportion of African-American patients receiving combination therapy was greater than that for the Caucasian patients (p=0.0047). The baseline BP values, both for ABPM and office measurements, for all the patients in the two groups, as well as those who finished with either monotherapy or combination therapy (shown separately) are listed in Table II. It is clear that those patients who required combination therapy had baseline values that were significantly greater than those for the patients who remained on monotherapy. This applied to patients previously untreated and those previously on antihypertensive therapies. The baseline values, particularly for ABPM, also tended to be slightly higher in African-American patients than in Caucasians.

Table II.  Baseline ABPM and Office BP Measurements by Prior Treatment and Race
 Previously UntreatedPreviously Treated
 African AmericanCaucasianAfrican AmericanCaucasian
ALL PATIENTS (n)9277178520
Baseline SBP (mm Hg)*    
ABPM138.0±13.6135.5±11.6134.1±16.1135.3±13.6
Office152.2±12.3150.4±11.7148.6±14.7150.0±14.3
Baseline DBP (mm Hg)*    
ABPM83.8±8.5**80.3±8.778.7±10.077.1±9.9
Office94.0±7.592.3±8.190.7±9.488.9±9.7
MONOTHERAPY† (n)4849433253
Baseline SBP (mm Hg)*    
ABPM135.5±11.3133.7±10.8127.6±11.7††131.7±11.9
Office151.0±12.5148.4±10.9145.8±15.4146.1±13.2
Baseline DBP (mm Hg)*    
ABPM81.7±8.079.0±8.476.6±7.875.2±9.0
Office92.8±7.390.9±8.089.4±10.387.2±9.7
COMBINATION† (n)4326544258
Baseline SBP (mm Hg)*    
ABPM141.1±15.4138.8±11.9138.4±17.2139.1±14.2
Office153.6±12.3154.4±12.2150.8±14.1153.9±14.3
Baseline DBP (mm Hg)*    
ABPM86.3±8.4tt82.6±8.979.8±10.979.0±10.5
Office95.6±7.594.9±7.791.9±8.790.3±9.4
ABPM=ambulatory blood pressure monitoring; BP=blood pressure; SBP=systolic BP; DBP=diastolic BP; *Values are reported as mean ± SD. **p<0.01 comparing African-American and Caucasian populations within prior treatment category; Tinal treatment was defined as the treatment at the end of study. Monotherapy included all subjects who ended the study on telmisartan 40 mg or 80 mg. Combination included all subjects who ended the study with telmisartan/hydrochlorothiazide. Final treatment assessment data were missing for 23 subjects. ††p<0.05 comparing African-American and Caucasian populations within prior treatment category

The mean hourly BP over the 24-hour period at baseline and the final visit in previously untreated patients as measured by ABPM are shown in Figure 1. Data are shown for the two racial groups as a whole, as well as separately for those patients who remained on monotherapy or received combination therapy. These results were similar in the African-American and white patients, although the BP reductions in the monotherapy subgroups were slightly greater for systolic BP in the white patients (p=nonsignificant). In the previously untreated patients, overall reductions in office BPs in the white patients were 22.9±0.5/13.5±0.3 mm Hg and 22.8±1.4/13.3±0.9 mm Hg in the African-American patients.

image

Figure 1. Hourly means over 24-hour period for systolic and diastolic blood pressure at baseline and the final visit as measured by ambulatory monitoring. Data are shown for untreated patients as a whole (a) (African American: n=92; Caucasian: n=771), those who remained on monotherapy during the study (b) (African American: n=48; Caucasian: n=494), and those who required combination therapy (c) (African American: n=43; Caucasian: n=26S).

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In previously treated patients, the overall reduction in BP in white patients was 17.1±0.7/9.3±0.4 mm Hg by office measurements and 8.8±0.5/4.6±0.3 mm Hg by ABPM measurements. For African Americans, the reductions were 12.4±1.8/8.5±1.1 mmHg (office) and 2.7±1.3/1.7±0.8 mm Hg (ABPM). The reductions in white patients were greater than those in African-American patients for office systolic (p=0.0162) and diastolic (p=nonsignificant) measurements and for ABPM systolic (p<0.0001) and diastolic (p=0.0012) measurements.

To better assess true antihypertensive treatment effects, we repeated these analyses only in those patients whose baseline ABPM values were ≥130/80 mm Hg, thereby excluding patients with white coat hypertension. In the African-American patients, 73 of the 92 (79%) patients previously untreated met this criterion and 44 of 78 (56%) of the previously treated patients met this criterion. For white patients, the respective values were 574 of 771 (74%) and 366 of 520 (70%). The proportion of patients in the African-American and white groups excluded because of white coat hypertension were not significantly different.

The baseline values for ABPM and office BPs for the two treatment groups (excluding white coat hypertensives), divided according to whether they had previously been untreated or on therapy, and also divided according to whether they had remained on monotherapy or received combination therapy, are shown in Table III. Again, as for the cohort as a whole, baseline values in the patients receiving combination therapy were significantly higher than those who remained on monotherapy. Moreover, there was a nonsignificant trend for baseline values to be higher in the African-American patients than in the whites.

Table III.  Baseline ABPM and Office BP Measurements by Prior Treatment and Race Excluding Those Patients Who Were White Coat Hypertensive*
 Previously UntreatedPreviously Treated
 African AmericanCaucasianAfrican AmericanCaucasian
HYPERTENSIVE PATIENTS* (n)7357444366
Baseline SBP (mm Hg)**    
ABPM142.2±12.0140.0±9.6144.5±13.6141.4±10.8
Office154.2±12.4152.1±11.7152.0±115.6153.0±13.7
Baseline DBP (mm Hg)**    
ABPM86.1±7.8†82.7±8.484.2±9.1††80.5±9.0
Office94.3±8.092.7±8.492.9±9.3††89.8±9.3
MONOTHERAPY‡ (n)3534313153
Baseline SBP (mm Hg)**    
ABPM140.3±9.1138.7±8.5138.2±10.8138.8±9.1
Office154.1±12.4††149.9±11.1150.4±17.6149.4±12.7
Baseline DBP (mm Hg)**    
ABPM84.2±7.781.8±8.282.9±6.578.9±8.5
Office92.6±8.291.0±8.593.9±11.0††87.9±9.3
COMBINATION* (n)3822430208
Baseline SBP (mm Hg)**    
ABPM144.0±14.0141.7±10.5146.8±13.9143.6±11.5
Office154.4±12.7155.8±11.7153.0±15.0155.9±13.8
Baseline DBP (mm Hg)**    
ABPM87.9±7.6††84.2±8.584.3±9.781.7±9.3
Office95.9±7.595.4±7.792.8±8.591.3±9.2
ABPM=ambulatory blood pressure monitoring; BP=blood pressure; SBP=systolic BP; DBP=diastolic BP; *patients who had a baseline ABPM SBP <130 mm Hg and baseline ABPM DBP <80 mm Hg were considered to have white coat hypertension and were excluded for this analysis; **values are reported as mean ± SD; †p <0.01 comparing African-American and Caucasian populations within prior treatment category; ††p <0.05 comparing African-American and Caucasian populations within prior treatment category; ‡final treatment was defined as the treatment at the end of study. Monotherapy included all subjects who ended the study on telmisartan 40 mg or 80 mg. Combination included all subjects who ended the study on telmisartan hydrochlorothiazide. Final treatment assessment data were missing for 13 subjects.

For the groups of patients with white coat hypertension excluded from analysis, the changes in BP in previously untreated individuals as measured by ABPM are shown in Figure 2. Data are shown for the two ethnic groups as a whole as well as separately for those patients who remained on monotherapy or received combination therapy. The results are similar in the African-American and white patients. In these previously untreated patients, overall reductions in office BPs for the white patients were 23.0±0.6/13.4±0.4 mm Hg, and 23.5±1.6/13.2±1.0 mm Hg in the African-American patients. The overall reductions by ABPM for the white patients were 14.7±0.4/9.2±0.3 mm Hg and 14.8±1.2/9.7±0.8 mm Hg in the African-American patients.

image

Figure 2. Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBF) as measured by 24-hour ambulatory blood pressure monitoring (ABPM) in African-American and Caucasian hypertensive patients. Individuals with white coat hypertension (average blood pressure by ambulatory monitoring <130/80 mm Hg at baseline) were excluded from this analysis. Data are shown for the patients as a whole, those who remained on monotherapy during the study, and those who required combination therapy. Values are mean ± SD.

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In the previously treated patients, the overall reduction in BP in the white patients was 18.1±0.9/9.7±0.5 mm Hg by office measurements, and 11.4±0.616.l±0.4 mm Hg by ABPM measurements. For African Americans, the reductions were 10.5±2.5/7.3±1.5 mm Hg and 4.3±1.9/2.6±1.1 mm Hg. The changes in white patients were significantly greater than those in the African-American patients for office systolic (p=0.0039) measurements, but not for office diastolic BPs, and for ABPM systolic (p=0.0003) and diastolic (p=0.0033) measurements.

BP control in this study was defined as <140/90 mm Hg by office readings and <130/80 mm Hg for the 24-hour ABPM average. For previously untreated patients, 75.0% of African Americans achieved BP control by office readings (<140/90 mm Hg) and 55.4% by ABPM (<130/80 mm Hg). Among previously untreated white patients, the respective rates were 85.1% (p<0.05 vs. African Americans) and 70.7% (p<0.01 vs. African Americans). In the true hypertensive patients (white coat hypertensives excluded), the rates in the previously untreated African-American patients was 48.0% and 74.0%, and in the previously untreated white patients 63.2% (p<0.05 vs. African Americans) and 80.8% (p=NS vs. African Americans).

The treatment employed in this study was well tolerated. The frequency of drug-related adverse events is shown in Table IV. It is evident that there were no meaningful differences between the two ethnic groups.

DISCUSSION

  1. Top of page
  2. Abstract
  3. METHODS Study Design
  4. RESULTS
  5. DISCUSSION
  6. References

This study demonstrates that an antihypertensive treatment algorithm based on an ARB, with use of a thiazide diuretic when necessary, is efficacious in achieving recommended BP treatment goals in previously untreated hypertensive patients. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) office BP goal of <140/90 mm Hg1 was achieved by 75% of African-American patients and 85% of Caucasian patients. The difference in response rates was significant. The 24-hour ABPM target of <130/80 mm Hg15 was achieved in 55% of African Americans and 71% of whites.

Decreases in BP achieved by the one- or two-drug regimens in this study were similar to previous reports as assessed by either office measurements16 or ABPM.17 The present study, however, extends observations of previous trials by comparing responses in African-American and nonblack (predominantly white) hypertensive patients. Of note is that patients who entered this trial on no antihypertensive treatment demonstrated similar BP reductions regardless of race. The use of an ARB with a diuretic appears to be effective in controlling BP in different racial groups.

Use of ABPM in this primary care, practice-based trial allows for both an evaluation of white coat hypertension as well as reduction of BP recording bias and digit preference.18 We noted that more than 20% of previously untreated patients who met the criteria for hypertension diagnosed in the office had normal BPs as assessed by ABPM.

When patients with white coat hypertension were excluded, baseline ABPM values in previously untreated African-American patients were slightly higher compared with white patients (3.4 mm Hg difference in DBP). Therefore, it is not surprising that a higher proportion of African-American patients required combination therapy with a diuretic compared with whites (53% vs. 47%). The overall reductions in BP during treatment between groups, however, were similar. These ambulatory BP changes, which averaged 15/10 mm Hg in previously untreated African-American patients and 15/9 mm Hg in previously untreated white patients, indicated comparable BP effects consistent with a previous report using similar therapy.17 An antihypertensive treatment effect can be achieved in black patients as well as in whites using an ARB alone, although response rates may be lost. The use of a thiazide diuretic in combination with an ARB tends to eliminate any overall racial differences in response rates. The findings of this study add support to treatment guidelines issued by the International Society on Hypertension in Blacks (ISHIB). These guidelines state that drug selection for hypertension in African Americans should be based on individual patient needs and tolerability rather than traditional recommendations.2

In addition to some differences between groups in baseline BP values, an additional reason for the need of combination therapy in African Americans may relate to a higher body mass index. It is known that hypertension in obese patients is driven largely by increased sodium reabsorption secondary to higher insulin levels and increased sympathetic tone,19 thus, the need for a diuretic is more important to achieve BP reduction.

The subgroup of African-American patients switched to the ARB regimen, with or without a diuretic, demonstrated less BP lowering efficacy than the white cohort. One explanation for this may be that a relatively large proportion of patients had been receiving calcium antagonists or diuretics, which tend to be more effective in lowering BP in African Americans.20 This observation would make it less likely that African Americans as compared with whites would benefit when switched to an ARB-based regimen. It should be noted, however, that practitioners who entered a large proportion of patients already on treatment into this trial selected those whose ongoing regimens were relatively unsatisfactory.

In summary, this study demonstrates that an anti-hypertensive treatment regimen based on an ARB was effective in lowering BP in African-American and Caucasian patients as assessed by both office measurements and 24-hour ABPM. Combination therapy with a diuretic is often needed to achieve goal BPs in African-American patients.

Disclosures: Dr. Bakris provides speaking and consulting services for AstraXeneca Pharmaceuticals LP, AusAm Biotechnologies Inc., Abbott Laboratories, Alteon Inc., Biovail Pharmaceuticals, BMS/Sanofi, Boerhinger Ingelheim Pharmaceuticals, Inc., Eli Lilly & Company, GlaxoSmithKline, Merck & Company, Novartis, and Takeda Pharmaceuticals North America; Dr. Giles and Dr. White provide speaking or consulting services for Boehringer Ingelheim Pharmaceuticals, Inc., Novartis, BMS, Pfizer Inc., Sanofi, and Sankyo; Dr. Smith and Dr. Weber provide speaking and consulting services for Boehringer Ingelheim Pharmaceuticals, Inc., Novartis, Merck & Company, BMS, Pfizer, Sanofi, and Sankyo. They also have an interest and provide consulting services to Integrium, a contract research organization that provided clinical management for this trial. Dr. Davidai is an employee of Boehringer Ingelheim Pharmaceuticals, Inc., the sponsor of this study.

References

  1. Top of page
  2. Abstract
  3. METHODS Study Design
  4. RESULTS
  5. DISCUSSION
  6. References
  • 1
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    McGill JB, Rilly PA. Telmisartan plus hydrochlorothiazide versus telmisartan or hydrochlorothiazide monotherapy in patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled parallel-group trial. Clin Ther. 2001;23:833850.
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    Giles TD, Bakris GL, Smith DH, et al. Defining the antihypertensive properties of the angiotensin receptor blocker telmisartan by a practice-based clinical trial. Am J Hypertens. 2003;16:460466.
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    Perloff D, Grim C, Flack J, et al. Human blood pressure determination by sphygmomanometry. Circulation. 1993;88:24602467.
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    O'Brien E, Mee F, Atkins N, et al. Accuracy of the Spacelabs 90207 determined by the British Hypertension Society Protocol. J Hypertens. 1991;9(suppl 5):S25S31.
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    White WB. Ambulatory blood pressure monitoring in clinical practice. N Engl J Med. 2003;348:23772378.
  • 16
    Neutel JM, Smith DHG, Weber MA, et al. Use of olmesartan medoxomil-based treatment algorithm for hypertension control. J Clin Hypertens (Greenwich). 2004;6:168174.
  • 17
    White WB, Lacourciere Y, Davidai G. Effects of the angiotensin II receptor blockers telmisartan vs valsartan on the circadian variation of blood pressure: impact on the early morning period. Am J Hypertens. 2004;17:347353.
  • 18
    Weber MA, Byyny RL, Pratt JH, et al. Blood pressure effects of the angiotensin II receptor blocker losartan. Arch Intern Med. 1995;155:405411.
  • 19
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