Estudo duplo-cego e randomizado para avaliar a eficácia e a tolerabilidade da combinação fixa Anlodipina/Ramipril comparada ao Anlodipino isolado em pacientes hipertensos

• Ano de defesa: 2009
• Autor(a) principal: Miranda, Roberto Dischinger [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Anlodipino; Ramipril; Terapia combinada; Hipertensão arterial
• Link de acesso: http://repositorio.unifesp.br/handle/11600/9577

Background: Antihypertensive agents of different drug classes in a fixed-dose combination (FDC) may offer advantages in terms of efficacy, tolerability, and treatment compliance. A combination of a calcium channel blocker with an angiotensin-converting enzyme inhibitor may act synergistically to reduce blood pressure (BP). Objectives: This study aims to compare the efficacy and tolerability of amlodipine/ramipril FDC with those of amlodipine monotherapy. Methods: This 18-week, prospective, randomized, double-blind study was conducted at 8 centers across Brazil. Patients with stage 1 or 2 essential arterial hypertension were enrolled. After a 2-week placebo run-in phase, patients received amlodipine/ramipril 2.5/2.5 mg or amlodipine 2.5 mg, after which the doses were titrated based on BP to 5/5 or 10/10 mg (amlodipine/ramipril) and 5 or 10 mg (amlodipine). The primary end point was the difference between basal and final BP measurements by the intention to treat (ITT) analysis in the randomized population. Hematology and serum biochemistry were assessed at baseline and study end. Tolerability was assessed using patient interview, laboratory analysis, and physical examination, including measurement of ankle circumference to assess peripheral edema. Results: A total of 222 patients completed the study (age range, 40–79 years; FDC group, 117 patients [mean dose, 7.60/7.60 mg]; monotherapy, 105 patients [mean dose, 7.97 mg]). The mean (SE) changes in systolic BP (SBP) and diastolic BP (DBP), as measured using 24-hour ambulatory blood pressure monitoring (ABPM) and in the physician’s office, were greater with combination therapy than monotherapy, with the exception of office DBP (ABPM: –20.76 ±1.25 vs –15.80 ±1.18 mm Hg and –11.71 ±0.78 vs –8.61 ± 0.74 mm Hg, respectively [both, P = 0.004]; office: –27.51 ±1.40 vs –22.84 ±1.33 mm Hg [P = 0.012] and –16.41 ±0.79 vs –14.64 ± 0.75 mm Hg [P = NS], respectively). In the ITT analysis the mean changes in ambulatory, but not office-based, BP were statistically significant (ABPM: SBP, –20.21 ±1.14 vs –15.31 ±1.12 mm Hg and DBP, –11.61 ±0.72 vs – 8.42 ±0.70 mm Hg, respectively (both, P = 0.002); office: SBP, –26.60 ±1.34 vs – 22.97 ±1.30 mm Hg (P = 0.068) and –16.48 ±0.78 vs –14.48 ±0.75 mm Hg (P = NS), respectively. Twenty-nine patients (22.1%) treated with combination therapy and 41 patients (30.6%) treated with monotherapy reported e1 adverse events considered possibly related to study drug. The combination-therapy group had a lower incidence of edema (7.6% vs 18.7%; P = 0.011) and a similar of dry cough (3.8% vs 0.8%; P = NS). No clinically significant changes in laboratory values were found in either group. Conclusions: In this population with essential arterial hypertension, the amlodipine/ramipril FDC significantly reduced the BP compared to amlodipine monotherapy. Both treatments were well tolerated, however amlodipine/ramiprilgroup showed much less peripheral edema.