RESUMEN
AIM: Many hypertensive subjects travel to high altitudes, but little is known on ambulatory blood pressure (ABP) changes and antihypertensive drugs' efficacy under acute and prolonged exposure to hypobaric hypoxia. In particular, the efficacy of angiotensin receptor blockers in this condition is unknown. This may be clinically relevant considering that renin-angiotensin system activity changes at altitude. The HIGHCARE-HIMALAYA study assessed changes in 24 h ABP under acute and prolonged exposure to increasing altitude and blood pressure-lowering efficacy and safety of an angiotensin receptor blockade in this setting. METHODS AND RESULTS: Forty-seven healthy, normotensive lowlanders were randomized to telmisartan 80 mg or placebo in a double-blind, parallel group trial. Conventional and Ambulatory BPs were measured at baseline and on treatment: after 8 weeks at sea level, and under acute exposure to 3400 and 5400 m altitude, the latter upon arrival and after 12 days (Mt. Everest base camp). Blood samples were collected for plasma catecholamines, renin, angiotensin, and aldosterone. In both groups, exposure to increasing altitude was associated with: (i) significant progressive increases in conventional and 24 h blood pressure, persisting throughout the exposure to 5400 m; (ii) increased plasma noradrenaline and suppressed renin-angiotensin-aldosterone system. Telmisartan lowered 24 h ABP at the sea level and at 3400 m (between-group difference 4.0 mmHg, 95% CI: 2.2-9.5 mmHg), but not at 5400 m. CONCLUSION: Ambulatory blood pressure increases progressively with increasing altitude, remaining elevated after 3 weeks. An angiotensin receptor blockade maintains blood pressure-lowering efficacy at 3400 m but not at 5400 m.
Asunto(s)
Altitud , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Bencimidazoles/farmacología , Benzoatos/farmacología , Presión Sanguínea/efectos de los fármacos , Adulto , Monitoreo Ambulatorio de la Presión Arterial , Ritmo Circadiano/fisiología , Método Doble Ciego , Femenino , Humanos , Masculino , Telmisartán , Factores de TiempoRESUMEN
BACKGROUND: Patients with hereditary C1-inhibitor deficiency have recurrent attacks of angioedema, preferably treated with C1-inhibitor concentrate. A recombinant human C1-inhibitor (rHuC1INH) was developed, derived from milk from transgenic rabbits. This study was undertaken to investigate the effects of rHuC1INH in the treatment of acute angioedema attacks in patients with a hereditary C1-inhibitor deficiency. STUDY DESIGN AND METHODS: Patients with hereditary C1-inhibitor deficiency were treated with rHuC1INH (at a dose of 100 U/kg) within 8 hours after onset of an acute attack. Time to initiation of relief and time to minimal symptoms were reported by both the patient and the treating physician. RESULTS: Thirteen severe angioedema attacks in 9 patients with hereditary C1-inhibitor deficiency were treated with rHuC1INH. There was rapid improvement of clinical conditions for all attacks, with approximately 80 percent of treated patients experiencing symptom relief within 2 hours and minimal symptoms within 12 hours. There were no drug-related adverse events or immunogenic reactions to C1-inhibitor or rabbit proteins. CONCLUSION: The transgenically produced rHuC1INH was successfully used in the treatment of acute angioedema attacks in patients with hereditary C1-inhibitor deficiency.
Asunto(s)
Angioedema/tratamiento farmacológico , Proteína Inhibidora del Complemento C1/administración & dosificación , Enfermedades Genéticas Congénitas/tratamiento farmacológico , Enfermedad Aguda , Adulto , Angioedema/diagnóstico por imagen , Angioedema/genética , Animales , Proteína Inhibidora del Complemento C1/efectos adversos , Proteína Inhibidora del Complemento C1/genética , Femenino , Enfermedades Genéticas Congénitas/diagnóstico por imagen , Enfermedades Genéticas Congénitas/genética , Humanos , Masculino , Persona de Mediana Edad , Conejos , Radiografía , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/genética , Factores de Tiempo , Resultado del TratamientoRESUMEN
Hereditary angioedema (HAE) is a rare condition, resting on attacks of edema in various localizations, potentially life-threatening if in facial, laryngeal, pharyngeal or gastrointestinal area. The disease is caused by deficiency or impaired activity of C1 inhibitor, therefore C1 inhibitor infusion is the the essential treatment and the only efficient method in an acute attack of HAE. Nowadays C1 inhibitor applied in our patients is obtained from human plasma, what restricts the availability of the drug and carries relevant risks. After many years of research it came to the synthesis of the recombinant protein with features of human C1 inhibitor. Its first usage in Poland took place-in two HAE patients with severe edema in 2004. The course and efficiency of this treatment is reported in the paper. Recombinant human C1 inhibitor occurred efficient and safe in presented case of severe angioedema.