Telmisartan effects on insulin resistance in obese or overweight adults without diabetes or hypertension.

Angiotensin receptor blockers (ARBs) are antihypertensive agents associated with reduced risk of new-onset diabetes mellitus. The ARB telmisartan is a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ). This study evaluated the effect of telmisartan on insulin resistance, a known target of PPAR-γ agonism. Overweight/obese persons with body mass index ≥28 kg/m2, waist circumference≥35 inches, and components of the metabolic syndrome without hypertension or diabetes who were not preselected for insulin resistance were enrolled. Patients were randomized to telmisartan or matching placebo for 16 weeks. The primary efficacy measure was changed from baseline in the insulin sensitivity index (SI), calculated from oral glucose tolerance testing. SI was also evaluated in a subset of patients using a hyperinsulinemic euglycemic clamp. Secondary end points included measures of insulin sensitivity and glucose and lipid metabolism. A total of 138 patients were randomized and received ≥1 dose of study medication; 128 completed the study. At end point, no significant difference was found between telmisartan and placebo groups regarding change from baseline in SI or in glucose area under the curve. No significant between-group differences were found regarding glucose metabolism or lipoprotein levels. In the population with abdominal obesity and components of the metabolic syndrome, telmisartan did not increase insulin sensitivity.

Safety, efficacy, and pharmacokinetics of telmisartan in pediatric patients with hypertension.

OBJECTIVE: To assess the safety, pharmacokinetics (PKs), and blood pressure (BP)-lowering efficacy of telmisartan in pediatric (6 to <18 years) patients with hypertension. STUDY DESIGN: Patients with diagnosed hypertension were randomized to 4 weeks of treatment with placebo, or with 1 of 2 nominal telmisartan dose levels (1 mg/kg/d or 2 mg/kg/d). The primary end point was change in seated systolic BP (SBP) from baseline to study end. RESULTS: A total of 77 patients were randomized and received at least 1 dose of study medication (placebo, n = 16; low-dose telmisartan, n = 30; high-dose telmisartan, n = 31). Adjusted mean changes (standard errors) in SBP from baseline to study end were -6 (2.4), -14 (1.7), and -9.7 (1.7) mm Hg, respectively, in the placebo, high-dose telmisartan, and low-dose telmisartan groups. CONCLUSIONS: Telmisartan may be an appropriate therapy for treatment of pediatric hypertension, although more extensive studies are required in patients younger than age 12.

Telmisartan is more effective than losartan in reducing proteinuria in patients with diabetic nephropathy.

In patients with diabetic nephropathy, lowering blood pressure and reducing proteinuria by over 30% correlates with a slower progression to kidney failure. We compared two different angiotensin receptor-blockers in a double blind, prospective trial of 860 patients with type 2 diabetes whose blood pressure levels was over 130/80 mmHg or who were receiving antihypertensive medication(s) and who had a morning spot urinary protein to creatinine ratio of 700 or more. Patients were randomized to telmisartan (a highly lipophilic agent with a long half-life) or losartan (with low lipophilicity and short half-life). The primary endpoint was the difference in the urinary albumin to creatinine ratio between the groups at 52 weeks. The geometric coefficient of variation and the mean of the urinary albumin to creatinine ratio fell in both groups at 52 weeks but both were significantly greater for the telmisartan compared to the losartan cohort. Mean systolic blood pressure reductions were not significantly different between groups at trial end. We conclude that telmisartan is superior to losartan in reducing proteinuria in hypertensive patients with diabetic nephropathy, despite a similar reduction in blood pressure.

Effects of the angiotensin II receptor blockers telmisartan versus valsartan in combination with hydrochlorothiazide: a large, confirmatory trial.

In 2004-2005, the antihypertensive effects of telmisartan 80 mg versus valsartan 160 mg combined with hydrochlorothiazide 25 mg were assessed in a large placebo-controlled trial in patients with stages 1 and 2 hypertension and demonstrated that both agents were highly effective in lowering blood pressure (BP) compared with placebo and that telmisartan lowered BP significantly greater than valsartan. To confirm this finding according to Food and Drug Administration guidelines, we performed a second large trial using the same design in an entirely separate patient population. The trial was double-blind with a 4 : 4 : 1 randomization scheme to compare once daily telmisartan 80 mg plus hydrochlorothiazide 25 mg versus once daily valsartan 160 mg plus hydrochlorothiazide 25 mg versus once daily placebo on reductions in seated clinic BP in patients with stages 1 and 2 hypertension. The primary endpoints were the changes from baseline in seated diastolic and systolic BP at the end of the 8-week treatment period. Safety endpoints included adverse events, changes in laboratory parameters and pulse rate. In total, 1185 patients were randomized (of which 1181 were treated and included in the primary analysis: 528 in the telmisartan-hydrochlorothiazide group, 523 in the valsartan-hydrochlorothiazide group, and 130 in the placebo group), changes from baseline in BP following telmisartan-hydrochlorothiazide (-24.6/-18.2 mmHg) were significantly greater than both placebo (-4.1/-6.1 mmHg) and valsartan-hydrochlorothiazide (-22.5/-17.0 mmHg) (versus placebo, P<0.0001 for systolic and diastolic BP; versus valsartan-hydrochlorothiazide, P=0.017 for systolic BP and P=0.025 for diastolic BP). The total number of patients with at least one adverse event reported was similar among the three treatment groups (placebo, 42%, telmisartan-hydrochlorothiazide, 36%, and valsartan-hydrochlorothiazide, 37%). Thus, this large, second trial confirms that telmisartan-hydrochlorothiazide at doses of 80/25 mg lowered both systolic and diastolic BP to a greater extent than valsartan-hydrochlorothiazide at doses of 160/25 mg in stages 1-2 hypertension. Although these are not the highest doses of these agents at present, at the time that the studies were conducted, they were the maximally approved dosages. Both studies support the strategy of using angiotensin receptor blockers with a higher dose of a thazide diuretic (25 mg) for enhancing the control of hypertension.

The effect of telmisartan and ramipril on early morning blood pressure surge: a pooled analysis of two randomized clinical trials.

OBJECTIVES: The period of early morning blood pressure surge is associated with a higher incidence of cardiovascular events than at other times of the day. Antihypertensive medication given once daily in the morning may not protect against this surge if its duration of action is too short. We compared telmisartan, an angiotensin II receptor blocker with a trough-to-peak ratio >90%, with ramipril, an angiotensin-converting enzyme inhibitor with a trough-to-peak ratio of around 50%. METHODS: Data from two prospective, randomized, open-label, blinded endpoint studies comparing telmisartan force titrated to 80 mg once daily and ramipril 10 mg once daily were pooled. Patients had mild-to-moderate hypertension and were assessed using 24-h ambulatory blood pressure monitoring at baseline and endpoint. Early morning blood pressure surge was defined as the difference between mean blood pressure within 2 h after arising and night-time low. Patients were grouped into quartiles according to their baseline systolic surge. RESULTS: Data from 1279 patients were analyzed. Telmisartan changed the overall mean (SE) systolic surge by -1.5 (0.47) mmHg, and ramipril by +0.3 (0.47) mmHg (P=0.0049). The magnitude of surge reduction was greatest in the quartile with highest baseline systolic surge: telmisartan -12.7 (0.91), ramipril -7.8 (1.02) mmHg (P=0.0004). Telmisartan also reduced the surge compared with ramipril in dippers, but there were no differences between the two groups in nondippers. CONCLUSIONS: Telmisartan significantly reduced the early morning systolic blood pressure surge compared with ramipril. A reduction in this surge may help to reduce cardiovascular events in the morning period.

Novel pharmacological targets for the treatment of Parkinson's disease.

Dopamine deficiency, caused by the degeneration of nigrostriatal dopaminergic neurons, is the cause of the major clinical motor symptoms of Parkinson's disease. These symptoms can be treated successfully with a range of drugs that include levodopa, inhibitors of the enzymatic breakdown of levodopa and dopamine agonists delivered by oral, subcutaneous, transcutaneous, intravenous or intra-duodenal routes. However, Parkinson's disease involves degeneration of non-dopaminergic neurons and the treatment of the resulting predominantly non-motor features remains a challenge. This review describes the important recent advances that underlie the development of novel dopaminergic and non-dopaminergic drugs for Parkinson's disease, and also for the motor complications that arise from the use of existing therapies.

Effects of the angiotensin II receptor blockers telmisartan vs valsartan in combination with hydrochlorothiazide 25 mg once daily for the treatment of hypertension.

To attain recent goals of blood pressure (BP) control, multiple drug therapy combinations are required, including higher doses of thiazide diuretics in combination with other classes of antihypertensive drug therapy. Thus, the authors evaluated the antihypertensive effects of telmisartan vs valsartan when combined with hydrochlorothiazide (HCTZ) 25 mg in a large (N=1066), placebo-controlled trial in patients with stage 1 or 2 hypertension. The primary end points were the changes from baseline in seated diastolic and systolic BP at the end of the 8-week treatment period. Safety end points included adverse events, changes in laboratory parameters, and pulse rate. Changes from baseline in BP following telmisartan-HCTZ (-24.0/-17.6 mm Hg) were significantly greater than both placebo (-4.4/-6.8 mm Hg) and valsartan-HCTZ (-21.2/-16.1 mm Hg) (vs placebo, P<.001 for systolic and diastolic BP; vs valsartan-HCTZ, P=.004 for systolic BP and P=.019 for diastolic BP). The total number of patients with at least 1 adverse event reported were similar among the 3 treatment groups (placebo, 49%; telmisartan-HCTZ, 43%; and valsartan-HCTZ, 38%). In conclusion, telmisartan-HCTZ at doses of 80/25 mg lowered both systolic and diastolic BP to a greater extent than valsartan-HCTZ at doses of 160/25 mg. These data support using a higher dose of a thiazide diuretic (25 mg) with a long-acting angiotensin receptor blocker as a useful strategy for improving hypertension control.

Efficacy and safety of tamsulosin for benign prostatic hyperplasia: clinical experience in the primary care setting.

OBJECTIVE: This study evaluated the efficacy and safety of the alpha(1A)/alpha(1D) subtype-selective blocker tamsulosin for the increasingly common treatment of benign prostatic hyperplasia (BPH) in the primary care setting. METHODS: A total of 493 men (age > or = 45 years), 99.6% of whom had moderate or severe BPH at baseline, were given tamsulosin 0.4 mg/day in a multicenter, open-label study conducted over 45 days by 42 primary care physicians and two urologists. RESULTS: Mean American Urological Association (AUA) Symptom Score decreased by 7.5 from a baseline of 20.0 on day 4, representing a 37.5% improvement over baseline (p < 0.001). AUA Obstructive and Irritative Scores declined significantly by day 4 (-4.7 and -2.7, respectively), as did AUA Bother Score (-5.4, p < 0.001) and mean BPH Impact Score (-2.5, p < 0.001). The Investigator's Global Assessment showed slight or greater improvement in 77.2% of patients (13.7% markedly improved). Effects were maintained from day 4 through day 45. CONCLUSIONS: Overall, patients treated with tamsulosin in a primary care setting experienced rapid, significant improvement in their signs and symptoms of BPH, based upon the change in the AUA Symptom Score. Tamsulosin was well tolerated; no new safety concerns were observed. Tamsulosin was not associated with significant effects on blood pressure or first-dose hypotension.

An effectiveness study comparing algorithm-based antihypertensive therapy with previous treatments using conventional and ambulatory blood pressure measurements.

Effectiveness trials in hypertension enable the efficacy and safety of new drugs to be compared with previous therapy. Since these open-label trials could inadvertently be influenced by observer bias, this study has used ambulatory blood pressure monitoring (ABPM) to provide a rigorous blinded end point to validate the study conclusions. The study was performed in 675 patients with stage 1 or 2 hypertension despite receiving single-agent or fixed-dose combination therapy. After baseline ABPM, the previous treatment was replaced by telmisartan 40 mg daily; if control (office blood pressure <140/90 mm Hg) was not achieved in 2 weeks, the dose was increased to 80 mg, and if necessary, a fixed combination with hydrochlorothiazide 12.5 mg was used after a further 4 weeks. ABPM was repeated after 4 weeks on final therapy. Overall, 50% of patients finished on monotherapy and 50% on combination therapy. By office measurements, there was a decrease (mean +/- SEM) of 16.8+/-0.5/10.3+/-0.3 mm Hg (p<0.001) when telmisartan-based treatment replaced previous treatment; by ABPM, the decrease was 8.2+/-0.4/5.0+/-0.2 mm Hg (p<0.001). The decreases were significant for comparisons with each of the prior drug classes. A treatment algorithm based on the angiotensin receptor blocker, telmisartan, was confirmed by the blinded end point of ABPM as an efficacious alternative to other antihypertensive regimens in clinical practice.

Measuring the efficacy of antihypertensive therapy by ambulatory blood pressure monitoring in the primary care setting.

BACKGROUND: Traditional clinical trials in hypertension measure the efficacy of antihypertensive drugs but may not fully assess their effectiveness in clinical practice. Community-based trials can provide this information but are limited because usually they are of open-label design and potentially subject to observer bias. Therefore, we used ambulatory blood pressure monitoring (ABPM), an automated and objective measure of blood pressure (BP) to overcome these shortcomings in a large community-based trial. METHODS: Patients with hypertension, either untreated or currently on treatment, were started on, or switched to, the angiotensin receptor blocker telmisartan 40 mg daily; after 2 weeks, if office BP remained > or = 140/85 mm Hg, the dose was increased to 80 mg, and if necessary, hydrochlorothiazide 12.5 mg was added after a further 4 weeks and continued for the final 4-week period. Baseline and treatment ABPM measurements were completed in 940 previously untreated patients and 675 previously treated patients. RESULTS: The average reduction of the entire cohort was -10.7/-6.5 mm Hg (P < .0001; mean 24-hour BPs were reduced by 12/8 and 8/5 mm Hg in the untreated and previously treated patients, respectively). In contrast, the office BPs fell by an average of 23/12 and 17/10 mm Hg in previously untreated and treated patients. In 401 patients whose baseline 24-hour BP was > or = 130/85 mm Hg, the mean decrease in 24-hour BP was 16.8/11.4 mm Hg. Based on ABPM criteria, the BP was fully controlled (< 130/85 mm Hg) in 70% of patients, and based on office measurement criteria (< 140/90 mm Hg), in 79%. CONCLUSIONS: Ambulatory BP monitoring demonstrated excellent control rates by telmisartan monotherapy or in combination with hydrochlorothiazide. Observer and measurement bias was substantial based on the changes from baseline by clinical measurements in contrast to ambulatory BP recordings. The successful use of this procedure in primary care research will create further opportunities to define the effectiveness of treatment in the environment in which it is customarily prescribed.

Comparative antihypertensive efficacy of angiotensin receptor blocker-based treatment in African-American and white patients.

Blood pressure (BP) reductions 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 hydrochlorothiazide 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-lowering strategy is effective in previously untreated African-American patients, although a higher proportion will require the use of a diuretic compared with Caucasians.

Ambulatory blood pressure monitoring in the primary care setting: assessment of therapy on the circadian variation of blood pressure from the MICCAT-2 Trial.

BACKGROUND: We conducted a large-scale, practice-based trial (MICCAT-2) to evaluate the effects of telmisartan alone and in combination with a diuretic on 24-h blood pressure (BP) profiles, including the early morning period, a time when cardiovascular risk is excessive. METHODS: Patients with hypertension, either untreated or currently on treatment, were started on, or switched to, the angiotensin receptor blocker telmisartan 40 mg daily; after 2 weeks, if office blood pressure (BP) remained > or =140/85 mmHg, the dose was increased to 80 mg; and if necessary, hydrochlorothiazide 12.5 mg was added after a further 4 weeks and continued for a final 4-week period. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was performed at baseline and at the end of the treatment period. Baseline and treatment ABPM measurements were completed in 1619 patients. RESULTS: There were highly significant reductions in both the daytime (-11.8/-7.2 mmHg) and night-time (-9.6/-5.7 mmHg) mean BP following telmisartan alone or in combination with the diuretic. Evaluation of the 24-h profiles showed evidence for sustained pharmacodynamic effects of telmisartan over the entire dosing period. Ninety-five (6%) patients had a marked surge in early morning BP defined as >30 mmHg post-awakening change in systolic BP. The average reduction of in the early morning (post-awakening) BP in the entire cohort was -11.5/-7.0 mmHg (P<0.001; reductions were similar for monotherapy and combination therapy groups. The early morning post-awakening BPs fell by an average of -17.2/-10.1 mmHg in patients with large morning BP surges (P<0.05 versus non-surge patients). CONCLUSIONS: In a community based study using ambulatory BP monitoring, telmisartan-based therapy induced highly significant reductions in systolic and diastolic BP over 24 h and was particularly effective in reducing BP during the early morning period.

Sustained antihypertensive activity of telmisartan compared with valsartan.

BACKGROUND: Early morning blood pressure (BP) surge and 24 h mean BP are linked to target-organ damage and cardiovascular events. Antihypertensive agents should sustain BP control, particularly in the last 6 h of the dosing interval or if dosing is missed. The efficacies of the long half-life telmisartan compared with shorter half-life valsartan in the last 6 h of the dosing interval following active treatment and during 24 h after a missed dose were compared. METHODS: In two identically designed multinational, randomized, double-blind, forced-titration studies, hypertensive patients (seated diastolic blood pressure (DBP), 95-109 mm Hg, 24 h mean ambulatory DBP, > or = 85 mm Hg) received once-daily telmisartan (40- 80 mg) or valsartan (80-160 mg) for a total of 8 weeks; uptitration occurred after 2 weeks low-dose treatment. After 4 weeks high-dose treatment, patients were given either 1 days double-blind active therapy or placebo (that is, missed dose). Following a further 2 weeks active treatment, a cross-over was performed: patients who had previously received 1 days placebo received active therapy and vice versa. At baseline and after the two active or missed doses, 24 h ambulatory BP monitoring was performed. Data from the studies were pooled, as prospectively planned and analyzed using the intent-to-treat population. RESULTS: After active therapy, last 6 h mean DBP was reduced by 7.6+/-7.9 mm Hg with telmisartan (n=447) compared with 5.8+/-7.8 mm Hg with valsartan (n=430) (P=0.0044). Last 6 h mean systolic blood pressure (SBP) was reduced by 11.1 mm Hg with telmisartan compared with 9.1 mm Hg with valsartan (P=0.0066). After a missed dose, 24 h mean DBP was reduced by 7.2+/-6.5 mm Hg with telmisartan (n=437) compared with 5.5+/-6.2 mm Hg with valsartan (n=431) (P=0.0004). The reduction in 24 h mean SBP after a missed dose was 10.7 mm Hg with telmisartan and 8.7 mm Hg with valsartan (P=0.0024). Absence of treatment-by-study interaction indicated that pooling of studies was appropriate. All 24 hourly mean reductions in DBP and SBP were greater for telmisartan than valsartan. Both treatments were well tolerated. CONCLUSIONS: Due to its longer half-life, telmisartan offers more sustained BP control, especially at the end of the dosing period and provides sustained efficacy in poorly compliant patients in the event of a missed dose with a statistical superiority compared with valsartan.

Effects of the angiotensin II receptor blockers telmisartan versus valsartan on the circadian variation of blood pressure: impact on the early morning period.

BACKGROUND: Ambulatory blood pressure (BP) monitoring has shown that BP typically declines by 10% to 20% during sleep and increases fairly rapidly in the early morning period. Because the early morning period has been associated with both loss of hypertension control and increased rates of myocardial infarction and stroke, there has been interest in evaluating the effects of antihypertensive therapy at this particular time of the day. The purpose of this study was to assess the effects of a long half-life (telmisartan, 24 h) versus intermediate half-life (valsartan, 6 to 9 h) on early morning BP in two scenarios: after an active dose and after a missed dose of each agent. METHODS: The study was a double-blind, randomized trial that compared telmisartan (40 to 80 mg once daily) versus valsartan (80 to 160 mg once daily) on early morning BP in 490 patients with hypertension. Ambulatory BP recordings were performed at baseline after a placebo period and again after 6 and 8 weeks of double-blind therapy in a randomized cross-over design. The monitoring patients received either an active dose or a placebo dose (to mimic a "missed" dose). The primary study end point was reduction in the BP in the early morning period (last 6 h of the dosing period). RESULTS: After the active dose, telmisartan reduced the BP during the last 6 h of the dosing period by -11/-7.6 +/- 0.8/0.6 mm Hg compared to -8.7/-5.8 +/- 0.8/0.6 mm Hg on valsartan (P = .02 for systolic BP and.01 for diastolic BP). On the day of the missed dose, telmisartan reduced the early morning BP by -9.0/-6.3 +/- 0.7/0.6 mm Hg versus -7.4/-5.1 +/- 0.7/0.4 mm Hg on valsartan (P = .09 for systolic BP and.06 for diastolic BP). On the day of the missed dose, reductions in 24-h average BP for the two antihypertensive agents were -10.3/-6.9 mm Hg for telmisartan versus -8.7/-5.9 mm Hg for valsartan (P = .06 for systolic BP and.056 for diastolic BP). CONCLUSIONS: On a day of active therapy, telmisartan lowered both systolic and diastolic BP to a greater extent than valsartan for the last 6 h of the dosing interval. On a day in which a dose was missed, there was a notable trend for greater BP reduction during the latter part of the dosing interval on telmisartan versus valsartan. These results demonstrate that telmisartan achieved a greater effect than valsartan on BP during the early morning period in patients with hypertension.

Quality of life measured in a practice-based hypertension trial of an angiotensin receptor blocker.

Effectiveness of antihypertensive treatment depends not only on drugs that avoid or minimize symptomatic side effects but also on therapy that has a positive effect on quality of life. This study assessed the effect on quality of life of a contemporary agent (an angiotensin receptor blocker) and evaluated the validity and practicality of using a quality-of-life instrument in the practice-based setting. A total of 2716 hypertensive patients, either untreated or on single-agent therapy, were started on or switched to 40 mg telmisartan for 6 weeks; in patients whose blood pressures remained above 130/85 mm Hg after 2 weeks, the dose was increased to 80 mg for the remaining 4 weeks of treatment. Quality of life was measured by patient self-administration of the Psychological General Well-Being Index (GWBI) at baseline and at the end of the study. Sixty-eight percent (n=1858) of patients treated with telmisartan fully completed both GWBI tests; the test score increased by 5.2+/-0.3 (p<0.0001) from 77.7+/-0.4. This improvement was observed across all six emotional and health subscales of the GWBI. White and black patients, those aged <65 or >/=65 years, and men and women had similar increases, though the baseline value in women was sharply lower (p<0.001) than in men. The GWBI rose more in patients whose blood pressure was controlled by treatment (<140/90 mm Hg) than in noncontrolled patients (6.1 vs. 4.1, p<0.0001); for all patients the decreases in systolic and diastolic blood pressures produced by telmisartan correlated significantly (p<0.001 for each) with the increases in the GWBI scores. Controlling blood pressure appears to be an important element in improving subjective health perceptions of hypertensive patients.

Defining the antihypertensive properties of the angiotensin receptor blocker telmisartan by a practice-based clinical trial.

Traditional randomized controlled clinical trials are designed to define the specific properties of individual antihypertensive drugs but do not provide full information about their use in clinical practice. To carry out a large-scale practice-based open-label trial to evaluate the safety and efficacy of an angiotensin receptor blocker (ARB) in controlling blood pressure (BP) in the community setting, 703 practitioners recruited 2705 hypertensive patients. There were three groups: untreated at the time of study entry with uncontrolled BP (>/=140/90 mm Hg) (N = 1957); treated but uncontrolled on current monotherapy (N = 685); and treated and controlled, but with unacceptable side effects (N = 63). After stopping any previous treatment, patients received telmisartan (40 mg daily) for 2 weeks; the dose was increased to 80 mg if BP remained >/=130/85 mm Hg. Participants were then followed for a further 4 weeks. Blood pressure decreased by 18.9/12.3 mm Hg in the untreated group, by 13.1/7.9 mm Hg in the previously treated but uncontrolled group, and increased slightly by 3.5/1.3 mm Hg in the previously controlled group. Patients not responding adequately to the 40-mg telmisartan dose had an initial BP reduction of 7.3/4.5 mm Hg; titration to 80 mg gave an additional 7.5/5.0 mm Hg reduction and controlled BP (<140/90 mm Hg) in 44% of these titrated patients. Overall, control occurred in 56% of white patients; 52% of black patients (who responded well to dose titration); 60% of patients <65 years; and 46% of patients >/=65 years. Thus, in contrast with the relatively flat dose response effects in controlled parallel group trials, this practice-based trial has demonstrated the value of titrating telmisartan to its maximum dose in patients with inadequate BP responses to the initial dose, and has shown its efficacy across major demographic groups.