Tags

Type your tag names separated by a space and hit enter

Comparison of fixed-dose combinations of telmisartan/hydrochlorothiazide 40/12.5 mg and 80/12.5 mg and a fixed-dose combination of losartan/hydrochlorothiazide 50/12.5 mg in mild to moderate essential hypertension: pooled analysis of two multicenter, prospective, randomized, open-label, blinded-end point (PROBE) trials.
Clin Ther. 2005 Nov; 27(11):1795-805.CT

Abstract

BACKGROUND

High incidences of cardiovascular events coincide with a surge in blood pressure (BP) that occurs in the early morning hours at the time of arousal. Thus, control of BP at this time of day, using oral fixed-dose combinations (FDCs) as required, is important in reducing cardiovascular risk in hypertensive patients.

OBJECTIVE

The aim of this analysis was to compare the antihypertensive efficacy in the early morning hours and tolerability of oral FDCs of telmisartan/hydrochlorothiazide (HCTZ) (40/12.5 mg [T40/H12.5] and 80/12.5 mg [T80/H12.5]) versus a low-dose FDC of losartan 50 mg/HCTZ 12.5 mg (L50/H12.5).

METHODS

Data from 2 similarly designed prospective, randomized, open-label, blinded-end point (PROBE) studies were pooled and analyzed. The studies were conducted at 72 centers across the United States, and 70 centers in Canada, Europe (9 countries), and the Philippines. Adult male and female patients with mild to moderate essential hypertension (24-hour mean ambulatory diastolic BP [DBP], > or =85 mm Hg; seated cuff DBP, 90-109 mm Hg) were enrolled. Patients were randomly assigned to receive T40/H12.5, L50/H12.5, or T80/H12.5, QD (morning) for 6 weeks. Antihypertensive efficacy was assessed using 24-hour ambulatory BP monitoring (ABPM) and cuff sphygmomanometry at trough, performed at baseline and on completion of active treatment. The primary end point was the reduction from baseline in mean ambulatory DBP over the last 6 hours of the dosing interval. Secondary end points included other ABPM- and clinic-derived changes in DBP and systolic BP (SBP), and control and response rates (SBP response defined as 24-hour mean SBP <130 mm Hg and/or reduction from baseline > or =10 mm Hg; DBP response defined as 24-hour mean DBP <85 mm Hg or reduction from baseline > or =10 mm Hg; DBP control defined as 24-hour mean DBP <85 mm Hg). Tolerability was assessed using patient interview, spontaneous reporting, and clinical evaluation.

RESULTS

A total of 1402 patients were enrolled(876 men, 525 women; mean [SD] age, 53.1 [9.9] years) (T40/H12.5, n = 517; L50/H12.5, n = 518; and T80/H12.5, n = 367). With T40/H12.5, the mean reduction in last-6-hour mean ambulatory DBP was 1.8 mm Hg greater compared with that achieved with L50/H12.5 (-11.3 [0.4] vs -9.4 [0.4] mm Hg; P < 0.001), and with T80/H12.5, the mean reduction was 2.6 mm Hg greater compared with that achieved with L50/H12.5 (-12.0 [0.4] vs -9.4 [0.4] mm Hg; P < 0.001). Analysis of secondary end points found that greater BP reduction occurred with T40/H12.5 and T80/H12.5 compared with L50/H12.5. ABPM SBP control and response rates were similar between the 3 groups, but the ABPM DBP control and response rates were significantly higher with T80/H12.5 compared with L50/H12.5 (46.6% vs 34.0% [P < 0.002] and 69.4% vs 55.0% [P < 0.001], respectively). Clinic SBP and DBP control and response rates were higher with T40/H12.5 and T80/H12.5 compared with L50/H12.5 (SBP response, 80.4% and 80.8% vs 68.5% [both, P < 0.001]; DBP response, 66.1% and 67.4% vs 54.4% [both, P < 0.001]; DBP control, 56.5% and 56.4% vs 44.1% [both, P < 0.001]). The 2 most commonly recorded adverse events (AEs) were headache (T40/H12.5, 2.9%; L50/H12.5, 3.3%; and T80/H12.5, 3.0%) and dizziness (1.2%, 2.1%, and 3.0%, respectively). Most AEs were mild to moderate.

CONCLUSIONS

The results of this pooled analysis of2 PROBE studies in adult patients with mild to moderate essential hypertension suggest that T40/H12.5 and T80/H12.5 conferred greater DBP and SBP control compared with low-dose L50/H12.5, including during the last 6 hours of the dosing interval. All 3 treatments were well tolerated.

Authors+Show Affiliations

Unité d'hypertension, Centre Hospitalier de l'Université Laval, Université Laval, 2705 Boulevard Laurier (S-120), Sainte-Foy, Québec G1V 4G2, Québec, Canada. YvesLacourciere@crchul.ulaval.caNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16368450

Citation

Lacourcière, Yves, et al. "Comparison of Fixed-dose Combinations of Telmisartan/hydrochlorothiazide 40/12.5 Mg and 80/12.5 Mg and a Fixed-dose Combination of Losartan/hydrochlorothiazide 50/12.5 Mg in Mild to Moderate Essential Hypertension: Pooled Analysis of Two Multicenter, Prospective, Randomized, Open-label, Blinded-end Point (PROBE) Trials." Clinical Therapeutics, vol. 27, no. 11, 2005, pp. 1795-805.
Lacourcière Y, Neutel JM, Schumacher H. Comparison of fixed-dose combinations of telmisartan/hydrochlorothiazide 40/12.5 mg and 80/12.5 mg and a fixed-dose combination of losartan/hydrochlorothiazide 50/12.5 mg in mild to moderate essential hypertension: pooled analysis of two multicenter, prospective, randomized, open-label, blinded-end point (PROBE) trials. Clin Ther. 2005;27(11):1795-805.
Lacourcière, Y., Neutel, J. M., & Schumacher, H. (2005). Comparison of fixed-dose combinations of telmisartan/hydrochlorothiazide 40/12.5 mg and 80/12.5 mg and a fixed-dose combination of losartan/hydrochlorothiazide 50/12.5 mg in mild to moderate essential hypertension: pooled analysis of two multicenter, prospective, randomized, open-label, blinded-end point (PROBE) trials. Clinical Therapeutics, 27(11), 1795-805.
Lacourcière Y, Neutel JM, Schumacher H. Comparison of Fixed-dose Combinations of Telmisartan/hydrochlorothiazide 40/12.5 Mg and 80/12.5 Mg and a Fixed-dose Combination of Losartan/hydrochlorothiazide 50/12.5 Mg in Mild to Moderate Essential Hypertension: Pooled Analysis of Two Multicenter, Prospective, Randomized, Open-label, Blinded-end Point (PROBE) Trials. Clin Ther. 2005;27(11):1795-805. PubMed PMID: 16368450.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of fixed-dose combinations of telmisartan/hydrochlorothiazide 40/12.5 mg and 80/12.5 mg and a fixed-dose combination of losartan/hydrochlorothiazide 50/12.5 mg in mild to moderate essential hypertension: pooled analysis of two multicenter, prospective, randomized, open-label, blinded-end point (PROBE) trials. AU - Lacourcière,Yves, AU - Neutel,Joel M, AU - Schumacher,Helmut, PY - 2005/09/30/accepted PY - 2005/12/22/pubmed PY - 2006/3/21/medline PY - 2005/12/22/entrez SP - 1795 EP - 805 JF - Clinical therapeutics JO - Clin Ther VL - 27 IS - 11 N2 - BACKGROUND: High incidences of cardiovascular events coincide with a surge in blood pressure (BP) that occurs in the early morning hours at the time of arousal. Thus, control of BP at this time of day, using oral fixed-dose combinations (FDCs) as required, is important in reducing cardiovascular risk in hypertensive patients. OBJECTIVE: The aim of this analysis was to compare the antihypertensive efficacy in the early morning hours and tolerability of oral FDCs of telmisartan/hydrochlorothiazide (HCTZ) (40/12.5 mg [T40/H12.5] and 80/12.5 mg [T80/H12.5]) versus a low-dose FDC of losartan 50 mg/HCTZ 12.5 mg (L50/H12.5). METHODS: Data from 2 similarly designed prospective, randomized, open-label, blinded-end point (PROBE) studies were pooled and analyzed. The studies were conducted at 72 centers across the United States, and 70 centers in Canada, Europe (9 countries), and the Philippines. Adult male and female patients with mild to moderate essential hypertension (24-hour mean ambulatory diastolic BP [DBP], > or =85 mm Hg; seated cuff DBP, 90-109 mm Hg) were enrolled. Patients were randomly assigned to receive T40/H12.5, L50/H12.5, or T80/H12.5, QD (morning) for 6 weeks. Antihypertensive efficacy was assessed using 24-hour ambulatory BP monitoring (ABPM) and cuff sphygmomanometry at trough, performed at baseline and on completion of active treatment. The primary end point was the reduction from baseline in mean ambulatory DBP over the last 6 hours of the dosing interval. Secondary end points included other ABPM- and clinic-derived changes in DBP and systolic BP (SBP), and control and response rates (SBP response defined as 24-hour mean SBP <130 mm Hg and/or reduction from baseline > or =10 mm Hg; DBP response defined as 24-hour mean DBP <85 mm Hg or reduction from baseline > or =10 mm Hg; DBP control defined as 24-hour mean DBP <85 mm Hg). Tolerability was assessed using patient interview, spontaneous reporting, and clinical evaluation. RESULTS: A total of 1402 patients were enrolled(876 men, 525 women; mean [SD] age, 53.1 [9.9] years) (T40/H12.5, n = 517; L50/H12.5, n = 518; and T80/H12.5, n = 367). With T40/H12.5, the mean reduction in last-6-hour mean ambulatory DBP was 1.8 mm Hg greater compared with that achieved with L50/H12.5 (-11.3 [0.4] vs -9.4 [0.4] mm Hg; P < 0.001), and with T80/H12.5, the mean reduction was 2.6 mm Hg greater compared with that achieved with L50/H12.5 (-12.0 [0.4] vs -9.4 [0.4] mm Hg; P < 0.001). Analysis of secondary end points found that greater BP reduction occurred with T40/H12.5 and T80/H12.5 compared with L50/H12.5. ABPM SBP control and response rates were similar between the 3 groups, but the ABPM DBP control and response rates were significantly higher with T80/H12.5 compared with L50/H12.5 (46.6% vs 34.0% [P < 0.002] and 69.4% vs 55.0% [P < 0.001], respectively). Clinic SBP and DBP control and response rates were higher with T40/H12.5 and T80/H12.5 compared with L50/H12.5 (SBP response, 80.4% and 80.8% vs 68.5% [both, P < 0.001]; DBP response, 66.1% and 67.4% vs 54.4% [both, P < 0.001]; DBP control, 56.5% and 56.4% vs 44.1% [both, P < 0.001]). The 2 most commonly recorded adverse events (AEs) were headache (T40/H12.5, 2.9%; L50/H12.5, 3.3%; and T80/H12.5, 3.0%) and dizziness (1.2%, 2.1%, and 3.0%, respectively). Most AEs were mild to moderate. CONCLUSIONS: The results of this pooled analysis of2 PROBE studies in adult patients with mild to moderate essential hypertension suggest that T40/H12.5 and T80/H12.5 conferred greater DBP and SBP control compared with low-dose L50/H12.5, including during the last 6 hours of the dosing interval. All 3 treatments were well tolerated. SN - 0149-2918 UR - https://www.unboundmedicine.com/medline/citation/16368450/Comparison_of_fixed_dose_combinations_of_telmisartan/hydrochlorothiazide_40/12_5_mg_and_80/12_5_mg_and_a_fixed_dose_combination_of_losartan/hydrochlorothiazide_50/12_5_mg_in_mild_to_moderate_essential_hypertension:_pooled_analysis_of_two_multicenter_prospective_randomized_open_label_blinded_end_point__PROBE__trials_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(05)00293-6 DB - PRIME DP - Unbound Medicine ER -