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.

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 4,512 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 4,227 patients for analysis. In most instances, premature withdrawal from the study (16.3% [690/4,227]) was due to loss to follow-up (37.2% [257/690]), followed by the development of AEs (27.8% [192/690]). Fifty-nine percent (2,493/4,226) of patients analyzed were men and 41.0% (1,733/4,226) 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% (2,316/4,227) presented with some type of associated disease. The percentage of patients undergoing monotherapy was 70.7% (2,987/4,227); the remainder (29.3% [1,240/4,227]) underwent a combined-therapy regimen using another antihypertensive drug in conjunction with doxazosin. The mean initial systolic and diastolic BPs were 160 +/- 10.63 mm Hg and 95.26 +/- 7.21 mm Hg, respectively. Reduction in systolic BP was 20.9 mm Hg in phase 1 and 3.8 mm Hg in phase 2. In the case of diastolic BP, the reduction was 13.3 mm Hg in phase 1 and 2.6 mm Hg in phase 2. The percentage of patients with controlled disease was 47.9% (1,891/3,949) by the end of phase 1 and 63.4% (2,242/3,537) by the end of phase 2. A total of 322 (7.6%) patients presented with 343 AEs. 37 (0.9%) of which were deemed severe (0.6% in phase 1 and 0.3% in phase 2). Limitations included the following: (1) the design of this study did not allow comparison of the 2 formulations regarding effectiveness or tolerability: (2) the patients who remained in the study after phase 1 were those less susceptible to toxicity from doxazosin; and (3) it is probable that the nonresponders were more likely to drop out of the study. CONCLUSIONS: Doxazosin in the standard formulation was effective and well tolerated for the purpose of lowering BP. Patients who tolerated the standard formulation also tolerated the switch to the GITS formulation. Finally, this substitution did not negatively impact the effectiveness of treatment of AHT.

[Association between herpetic burden and chronic ischemic heart disease: matched case-control study]. / Asociación entre la carga herpética y la enfermedad isquémica crónica del corazón: estudio de casos y controles.

BACKGROUND AND OBJECTIVES: Previous studies showed a plausible association between herpetic burden and ischemic heart disease. Our aim is to test this hypothesis in an spanish seroepidemiological context. PATIENTS AND METHODS: Sex and age matched case-control study (1:1) including patients with chronic ischemic heart disease and healthy controls. Herpetic burden was defined as the aggregate number of antibody seropositivities (IgG) for Epstein Barr Virus, cytomegalovirus, varicella zoster virus, Herpes simplex type 1 and type 2. RESULTS: We found that 90.7% of cases and 70,7% of controles (P=.002), were seropositive to 4 or more herpesvirus (high herpetic burden). Within control group, hypercholesterolemic subjects had a higher proportion of high burden (88,5% vs. 61,2%, P=.02). High herpetic burden was associated with ischemic heart disease, even after adjusting for diabetes, smoking, hypertension and literacy level, (OR: 4,5 [1,23-16,53]), but not when hypercholesterolemia was included in the model (OR 2,2 [0,45-10,62]). CONCLUSION: The hypothesized relationship is independent from most but not all classical cardiovascular risk factors.

[The epidemiology of hospital admissions due to leishmaniasis in Spain (1999-2003)]. / Epidemiología de los ingresos hospitalarios por leishmaniasis en España (1999-2003).

OBJECTIVE: The aim of this study was to determine the epidemiology of patients hospitalized for leishmaniasis during the period 1999 to 2003. PATIENTS AND METHODS: This is a retrospective study using the Minimum Data Set for Hospital Discharge (CMBD, Conjunto Mínimo Básico de Datos al alta hospitalaria), a national surveillance system database. RESULTS: There were 1,180 hospital admissions with a primary diagnosis of leishmaniasis, 34% of which were readmissions, yielding a total of 786 new cases of leishmaniasis and an incidence rate of 0.4 per 100,000 population/year. The disease mainly affected children under five years of age and adults between 25 and 44. The most frequent form of presentation was visceral leishmaniasis, which was documented in 83.6% of hospitalizations. Among the autonomous communities of Spain, Madrid and Castilla-La Mancha showed the highest incidence rates, whereas Galicia and Extremadura presented the lowest rates. Patients coinfected with HIV accounted for 42% of hospital admissions for leishmaniasis. Nonetheless, between 2000 and 2003, a decrease was observed in the number of hospitalizations in this subgroup and an increase of patients without HIV coinfection. CONCLUSION: The increase in hospitalization rates for leishmaniasis in Spain indicates that this avoidable zoonosis remains a considerable public health problem in our country.