Roberto Dischinger Miranda

An 18-Week, Prospective, Randomized, Double-Blind, Multicenter Study of Amlodipine/Ramipril Combination Versus Amlodipine Monotherapy in the Treatment of Hypertension : The Assessment of Combination Therapy of Amlodipine/Ramipril (ATAR) Study

BACKGROUND A combination of antihypertensive agents of different drug classes in a fixed-dose combination (FDC) may offer advantages in terms of efficacy, tolerability, and treatment compliance. Combination of a calcium channel blocker with an angiotensin-converting enzyme inhibitor may act synergistically to reduce blood pressure (BP). OBJECTIVE The aim of this study was to compare the efficacy and tolerability of an 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 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 then 10/10 mg (amlodipine/ramipril) and 5 then 10 mg (amlodipine). The primary end point was BP measured in the intent-to-treat (ITT) 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 (SD) changes in systolic BP (SBP) and diastolic BP (DBP), as measured using 24-hour ambulatory blood pressure monitoring (ABPM) and in the physicians office, were significantly 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 and DBP, -16.48 [0.78] vs -14.48 [0.75] mm Hg [both, P = NS]). Twenty-nine patients (22.1%) treated with combination therapy and 41 patients (30.6%) treated with monotherapy experienced > or =1 adverse event considered possibly related to study drug. The combination-therapy group had lower prevalence of edema (7.6% vs 18.7%; P = 0.011) and a similar prevalence 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 of patients with essential hypertension, the amlodipine/ramipril FDC was associated with significantly reduced ambulatory and office-measured BP compared with amlodipine monotherapy, with the exception of office DBP. Both treatments were well tolerated.

Decrease in blood pressure and improved psychological aspects through meditation training in hypertensive older adults: A randomized control study

The present study aimed to evaluate the effects of Zen meditation on blood pressure (BP) and quality of life in elderly subjects.

I posicionamento brasileiro em hipertensão arterial e diabetes mellitus

The association between AH and DM was first described in the 70s, observed in both sexes and at any age range. The prevalence of hypertension is two to three-fold higher in diabetics than in the general population5, and about 70% of diabetics are hypertensive3,6. A meta-analysis of 102 prospective studies and 698,782 individuals showed that the presence of DM increases by two-fold the risk of coronary artery disease (CAD), cerebrovascular accident (CVA) and CV death. According to this meta-analysis, 10% of CV deaths in developed countries can be attributed to the presence of DM7.

I Posicionamento Brasileiro sobre Pre-Hipertensao, Hipertensao do Avental Branco e Hipertensao Mascarada: Diagnostico e Conduta

Repeated BP measurement at the office allows the diagnosis of hypertension and normotension. To better assess BP behavior, there are methods that analyze BP by using a higher number of measurements, minimizing interferences of the environment, situation and observer. Those alternatives are as follows: 24-hour ambulatory BP monitoring (ABPM); and dwelling BP measurement [home BP monitoring (HBPM) and BP self-measurement (BPSM)]. Based on those methods, two other BP classifications were adopted: white coat hypertension (WCH) and masked hypertension (MH)1,3-5 (Figure 1).

I Posicionamento Brasileiro sobre Combinação de Fármacos Anti-Hipertensivos

Arterial hypertension (AH) is a highly prevalent disease, and is a major cardiovascular (CV) risk factor1; therefore, achieving blood pressure (BP) control goals as soon as possible is paramount to reduce that risk2. That means that approximately 70% of hypertensive individuals will need antihypertensive drug combination3, and up to 30% of hypertensive individuals are estimated to use four or more drugs to achieve BP control4. Thus, drug combination is currently described as an important strategy to manage AH, providing effective and safe BP reduction. Drug choice is based on effective BP reduction and CV outcomes. Despite the existence of a significant number of drugs to treat AH, their control rates are still very low, contributing to the high CV morbidity and mortality rates observed in Brazil and worldwide1,2. According to the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and the Hypertension Optimal Treatment (HOT) Study, only 26% and 33% of the patients, respectively, could control their BP with monotherapy, while in the Losartan Intervention for Endpoints Reduction (LIFE) Study, 90% of the patients needed combined therapy for that purpose3 . Drug combination is mainly aimed at increasing antihypertensive efficacy, with fewer adverse events. It is worth noting the importance of considering therapy adherence. The pathophysiology of AH involves multiple factors and mechanisms, making its control difficult when only one drug is used, because counterregulatory mechanisms that attenuate the antihypertensive effect of the drug can occur. The association of drugs with different mechanisms of action has a greater impact on BP reduction as long as there is pharmacokinetic compatibility and no disparity of effects and properties3-5. Thus, the choice of the drugs to be combined should contemplate two aspects: synergism of the mechanisms of action and opposition to counterregulatory mechanisms triggered after the beginning of therapy with a certain drug. The desired antihypertensive efficacy is more likely to be achieved by using lower doses of the drugs involved. Thus, fewer adverse events are observed, with no loss of antihypertensive drug potency3-5. Another important aspect is that drugs should be preferably combined in a single galenic presentation, facilitating their administration, and assuring lower cost, with a consequent improvement in treatment adherence2,6.

7th Brazilian Guideline of Arterial Hypertension: Chapter 11 - Arterial Hypertension in the elderly

Arterial hypertension is the most common chronic noncommunicable disease among the elderly. 1 Its prevalence increases progressively with aging, AH being considered the major modifiable CVRF in the geriatric population. 2 From the chronological viewpoint, elderly are individuals aged 65 years and older, living in developed countries, or individuals aged 60 years and older, living in developing countries. 3 Within that age group, the very elderly are those in their eighth decade of life. 4 There is a direct and linear relationship between BP and age, the prevalence of AH being greater than 60% in the age group older than 65 years. 5 The Framingham Study has reported that 90% of the individuals with normal BP levels up to the age of 55 years will develop AH throughout life. 6 In addition, that study has shown that both SBP and DBP, in both sexes, increase up to the age of 60 years, when DBP begins to decrease. Systolic BP, however, continues to increase linearly. 7 The high prevalence of other concomitant RFs in the elderly and the consequent increase in the rate of CV events, in addition to the presence of comorbidities, compound the relevance of AH with aging. 8 Vascular aging is the major aspect related to BP elevation in the elderly, characterized by changes in the microarchitecture of vascular walls, with consequent arterial stiffening. Large vessels, such as the aorta, lose their distensibility, and, although the precise mechanisms are not clear, they primarily involve structural changes in the media layer of the vessels, such as fracture due to elastin fatigue, collagen deposition and calcification, resulting in increased vascular diameter and IMT. Clinically, arterial wall stiffness is expressed as ISH, highly prevalent in the geriatric population, and considered an independent RF for the increase in CV morbidity and mortality. 6,9-11 Other consequences are increased PWV and elevated PP. 12 Changes inherent in aging determine different aspects in that populations BP, such as the higher frequency of auscultatory gap, which consists in the disappearance of the Korotkoff sounds during cuff deflation, usually between the end of phase I and beginning of phase II, resulting in falsely low SBP levels or falsely high DBP levels. The wide BP variability in the elderly throughout 24 hours makes ABPM useful. Pseudohypertension, which is associated with the atherosclerotic process, can be detected by use of Oslers maneuver, that is, the radial artery remains palpable …

7ª Diretriz Brasileira de Hipertensão Arterial: Capítulo 11 - Hipertensão Arterial no Idoso

Arterial hypertension is the most common chronic noncommunicable disease among the elderly. 1 Its prevalence increases progressively with aging, AH being considered the major modifiable CVRF in the geriatric population. 2 From the chronological viewpoint, elderly are individuals aged 65 years and older, living in developed countries, or individuals aged 60 years and older, living in developing countries. 3 Within that age group, the very elderly are those in their eighth decade of life. 4 There is a direct and linear relationship between BP and age, the prevalence of AH being greater than 60% in the age group older than 65 years. 5 The Framingham Study has reported that 90% of the individuals with normal BP levels up to the age of 55 years will develop AH throughout life. 6 In addition, that study has shown that both SBP and DBP, in both sexes, increase up to the age of 60 years, when DBP begins to decrease. Systolic BP, however, continues to increase linearly. 7 The high prevalence of other concomitant RFs in the elderly and the consequent increase in the rate of CV events, in addition to the presence of comorbidities, compound the relevance of AH with aging. 8 Vascular aging is the major aspect related to BP elevation in the elderly, characterized by changes in the microarchitecture of vascular walls, with consequent arterial stiffening. Large vessels, such as the aorta, lose their distensibility, and, although the precise mechanisms are not clear, they primarily involve structural changes in the media layer of the vessels, such as fracture due to elastin fatigue, collagen deposition and calcification, resulting in increased vascular diameter and IMT. Clinically, arterial wall stiffness is expressed as ISH, highly prevalent in the geriatric population, and considered an independent RF for the increase in CV morbidity and mortality. 6,9-11 Other consequences are increased PWV and elevated PP. 12 Changes inherent in aging determine different aspects in that populations BP, such as the higher frequency of auscultatory gap, which consists in the disappearance of the Korotkoff sounds during cuff deflation, usually between the end of phase I and beginning of phase II, resulting in falsely low SBP levels or falsely high DBP levels. The wide BP variability in the elderly throughout 24 hours makes ABPM useful. Pseudohypertension, which is associated with the atherosclerotic process, can be detected by use of Oslers maneuver, that is, the radial artery remains palpable …