A postmarketing, open-label study to evaluate the tolerability and effectiveness of replacing standard-formulation doxazosin with doxazosin in the gastrointestinal therapeutic system formulation in adult patients with hypertension

• Published in: Clinical therapeutics 2002-05, Vol.24 (5), p.786-797
• Main Authors: Anegón, Maria, Esteban, Jesus, Jiménez-García, Rodrigo, Sanz de Burgoa, Veronica, Martínez, Javier, Gil de Miguel, Angel
• Format: Article
• Language: English
• Subjects: Adult; Antihypertensive agents; Antihypertensive Agents - adverse effects; Antihypertensive Agents - therapeutic use; Antihypertensives; arterial hypertension (AHT); Biological and medical sciences; Blood pressure; Blood Pressure - drug effects; Cardiovascular system; Chemical compounds; Chemistry, Pharmaceutical; Clinical Trials as Topic; Delayed-Action Preparations; Disease control; doxazosin; Doxazosin - adverse effects; Doxazosin - therapeutic use; Drug dosages; Drug Tolerance; Female; Formulations; gastrointestinal therapeutic system (GITS); Health care; Humans; Hypertension; Hypertension - drug therapy; Male; Medical sciences; Middle Aged; Patients; Pharmacology; Pharmacology. Drug treatments; Posture; Product Surveillance, Postmarketing - methods; Serum levels; Syncope; Therapy; tolerability; Toxicity; Vasodilation
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(02)85152-9

Background: The antihypertensive doxazosin works to decrease perivascular muscular tone, causing vasodilatation and hence a decrease in peripheral vascular resistance. To prevent the sharp decrease in blood pressure (BP), syncope, and other postural effects that may occur at the beginning of therapy with this drug, the dose must be adjusted. A new formulation, doxazosin gastrointestinal therapeutic system (GITS), allows slow release of the active agent so therapeutic serum levels are reached within 24 hours, rendering dose adjustment unnecessary and eliminating any first-dose effects. Objectives: The goals of this study were to evaluate the tolerability and effectiveness of (1) using doxazosin in the standard and new GITS formulations in adult patients with hypertension who either had uncontrolled or newly diagnosed disease, and (2) replacing standard-formulation doxazosin with doxazosin in the GITS formulation. Methods: This was a postmarketing, open-label, noncomparative, multicenter clinical study covering primary care patients diagnosed with essential uncontrolled arterial hypertension (AHT). Subjects could be patients who were undergoing drug therapy before enrollment or those diagnosed with AHT and/or treated for the disease for the first time on entering the study. The study covered a period of 6 to 9 months, divided into 2 phases. Phase 1 involved a minimum of 3 and maximum of 6 months of treatment with standard-formulation doxazosin. Phase 2 commenced with the changeover from standard-formulation doxazosin to the GITS formulation and lasted 12 weeks. The principal study variables included BP and the development of adverse events (AEs). At every visit, the patients were asked by an investigator whether they had suffered any AEs since the previous contact. Results: Of the total of 4512 patients initially enrolled, 3537 (78.4%) completed the study. A total of 285 patients were excluded for failing to comply with the inclusion criteria, leaving 4227 patients for analysis. In most instances, premature withdrawal from the study (16.3% [690/4227]) was due to loss to follow-up (37.2% [257/690]), followed by the development of AEs (27.8% [192/690]). Fifty-nine percent (2493/ 4226) of patients analyzed were men and 41.0% (1733/4226) were women (sex data not recorded for 1 patient), with a mean age of 62.4 years (SD, 10.6). Among the patients participating, 54.8% (2316/4227) presented with some type of associated disease. The percentage of patients undergoin