Marco Antonio Mota Gomes

Estudo `LOTHAR`: avaliação de eficácia e tolerabilidade da combinação fixa de anlodipino e losartana no tratamento da hipertensão arterial primária

OBJETIVO: O estudo LOTHAR avaliou a eficacia, tolerabilidade e os efeitos metabolicos em medio e longo prazo (um ano) da combinacao fixa de anlodipino e losartana versus anlodipino e losartana isoladamente. METODOS: Estudo multicentrico brasileiro, randomizado, duplo-cego e comparativo realizado com 198 pacientes com hipertensao arterial primaria em estagios 1 e 2. RESULTADOS: A combinacao fixa apresenta alta eficacia anti-hipertensiva que se mantem em longo prazo com percentual reduzido de escape do controle pressorico, inferior a dos dois regimes monoterapicos de comparacao. Em longo prazo, mais de 60% dos pacientes tratados com a combinacao fixa permaneceram com niveis da PAD < 85 mmHg e o efeito anti-hipertensivo quando avaliado pela MAPA persistiu nas 24 horas com relacao vale-pico de 76,7%. A frequencia de eventos adversos foi bastante reduzida neste grupo sendo a incidencia em longo prazo de edema de membros inferiores cerca de quatro vezes menor que a observada com o anlodipino isolado. A combinacao fixa nao alterou os metabolismos da glicose e dos lipides tanto em medio quanto em longo prazos. CONCLUSAO: Estes resultados nos permitem afirmar que a combinacao de anlodipino e losartana, a primeira combinacao fixa de um antagonista dos canais de calcio e um bloqueador do receptor da angiotensina II disponivel no mercado farmaceutico constitui-se em excelente opcao para o tratamento da hipertensao arterial em larga gama de pacientes hipertensos.

Effectiveness of Chlorthalidone Plus Amiloride for the Prevention of Hypertension: The PREVER‐Prevention Randomized Clinical Trial

Background Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension (PREVER‐Prevention) trial aimed to evaluate the efficacy and safety of a low‐dose diuretic for the prevention of hypertension and end‐organ damage. Methods and Results This randomized, parallel, double‐blind, placebo‐controlled trial was conducted in 21 Brazilian academic medical centers. Participants with prehypertension who were aged 30 to 70 years and who did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new‐onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms. The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with 358 allocated to placebo (hazard ratio 0.56, 95% CI 0.38–0.82), resulting in a cumulative incidence of 11.7% in the diuretic arm versus 19.5% in the placebo arm (P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow‐Lyon voltage and voltage‐duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02). Conclusions A combination of low‐dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension. Clinical Trial Registration URL: http://www.ClinicalTrials.gov, www.ensaiosclinicos.gov. Unique identifiers: NCT00970931, RBR‐74rr6s.

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.

Amlodipine 2.5 mg once daily in older hypertensives: a brazilian multi-centre study

ObjectivesThe use of low-dose amlodipine has not yet been well established in the elderly. This study therefore aimed to evaluate the efficacy and tolerability of low-dose amlodipine in elderly patients with Joint National Committee VI stage I or II hypertension. Patients and methodsSixty-five hypertensive individuals (aged 66.3±5.3 years) received amlodipine 2.5 mg per day for 12 weeks before and after two periods of 4 weeks of placebo. At weeks 0, 12 and 16, patients were submitted to office, 24 h ambulatory blood pressure monitoring and home blood pressure measurement. ResultsOffice systolic and diastolic blood pressure showed decreases at weeks 8 (153±17, 90±9 mmHg) and 12 (152±16, 90±9 mmHg) compared with weeks 0 (164±16, 99±6 mmHg) and 16 (162±19, 95±9 mmHg). During ambulatory monitoring, a decrease was observed in the average 24 h systolic and diastolic pressure at week 12 (143±13, 86±7 mmHg) compared with weeks 0 (155±15, 93±6 mmHg) and 16 (152±16, 92±8 mmHg). A daytime and night-time reduction in systolic and diastolic pressure was observed on home blood pressure monitoring at week 12 (146±16/88±8, 144±16/93±8 mmHg) compared with weeks 0 (159±17/94±8, 161±19/93±8 mmHg) and 16 (153±16/93±8, 154±17/92±8 mmHg). Adverse reactions were infrequent. ConclusionsAmlodipine at a dose of 2.5 mg per day showed efficacy and good tolerability in elderly hypertensives.

The effect of siesta in parameters of cardiac structure and in interpretation of ambulatory arterial blood pressure monitoring

OBJECTIVE To evaluate the influence of the siesta in ambulatory blood pressure (BP) monitoring and in cardiac structure parameters. METHODS 1940 ambulatory arterial blood pressure monitoring tests were analyzed (Spacelabs 90207, 15/15 minutes from 7:00 to 22:00 hours and 20/20 minutes from 22:01 to 6.59hours) and 21% of the records indicated that the person had taken a siesta (263 woman, 52+/-14 years). The average duration of the siesta was 118+/-58 minutes. RESULTS (average +/- standard deviation) The average of systolic/diastolic pressures during wakefulness, including the napping period, was less than the average for the period not including the siesta (138+/-16/85+/-11 vs 139+/-16/86+/-11 mmHg, p<0. 05); 2) pressure loads during wakefulness including the siesta, were less than those observed without the siesta); 3) the averages of nocturnal sleep blood pressures were similar to those of the siesta, 4) nocturnal sleep pressure drops were similar to those in the siesta including wakefulness with and without the siesta; 5) the averages of BP in men were higher (p<0.05) during wakefulness with and without the siesta, during the siesta and nocturnal sleep in relation to the average obtained in women; 6) patients with a reduction of 0- 5% during the siesta had thickening of the interventricular septum and a larger posterior wall than those with a reduction during the siesta >5%. CONCLUSION The siesta influenced the heart structure parameters and from a statistical point of view the average of systolic and diastolic pressures and the respective pressure loads of the wakeful period.

Monitorização residencial da pressão arterial e monitorização ambulatorial da pressão arterial versus medida de pressão arterial no consultório

PURPOSE To compare both home blood pressure measurement (HBPM) and ambulatory blood pressure monitoring (ABPM) with office blood pressure measurement (OBP); and also to compare the correlation between HBPM and OBP with LVMI (left ventricular mass index). METHODS Protocol 1--68 hypertensive patients (58 +/- 12 years, 37 females): a) self recorded blood pressure at home in the 7 days; b) recorded the ABPM during 24 hours; and c) the physician recorded blood pressure in the office. Protocol 2-41 hypertensive patients underwent the HBPM, OBP, and BI-dimensional echocardiogram. RESULTS Protocol 1--OBP (153 +/- 24/96 +/- 13 mmHg) was higher (p < 0.05) than HBPM (133 +/- 18/84 +/- 12 mmHg) and ABPM (137 +/- 17/87 +/- 12 mmHg); Protocol 2--LVMI correlated better with HBPM (r = 0.39/0.49, p < 0.05, systolic and diastolic, respectively) than OBP (r = 0.02/ 0.22, p > 0.05, systolic and diastolic, respectively). CONCLUSION This study showed that HBPM has a better correlation with LVMI than OBP.

Guidelines on the management of arterial hypertension and related comorbidities in Latin America

Univ Hosp, Hypertens & Metab Unit, Fdn Favaloro, Belgrano 1782 P 4, RA-1093 Buenos Aires, DF, Argentina

Fatores associados ao aumento no índice de incremento de pressão radial em indivíduos hipertensos

BACKGROUND Arterial stiffness is a variable predictor of morbidity and mortality and a possible marker of vascular injury. Its non-invasive assessment by radial tonometry and analysis of the augmentation index (r-AI) allows identifying patients exposed to higher cardiovascular risk. OBJECTIVE To analyze the influence of r-AI on clinical-biochemical variables and its influence on the prevalence of target-organ damage in hypertensive patients. METHODS 140 consecutive hypertensive patients, followed-up in an outpatient clinic, were analyzed in a cross-sectional study. Blood pressure (BP) levels and r-AI were obtained by applanation tonometry of the radial artery (HEM-9000AI, Onrom). The patients were allocated into r-AI tertiles (r-AI < 85%; 85< r-AI < 97%; r-AI > 97%). RESULTS The sample was predominantly composed of women (56.4%), mean age of 61.7 ± 11.7 years and body mass index 29.6 ± 6.1 Kg/m². The highest tertile showed higher proportion of women (p = 0.001), higher systolic BP (p = 0.001) and pulse pressure (p = 0.014), and lower weight (p = 0.044), height (p < 0.001) and heart rate (p < 0.001). Multivariate analysis demonstrated that weight (β = -0.001, p = 0.017), heart rate (β = -0.001, p = 0.007) and central pressure (β = 0.015, p < 0.001) correlated independently with r-AI. In logistic regression analyses, the 3rd r-AI tertile was associated to lower levels of diabetes (DM) (OR = 0.41; 95% CI 0.17-0.97; p = 0.042). CONCLUSION This study demonstrated that weight, heart rate and central BP were independently related to r-AI.

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).

Effectiveness of low-dose diuretics for blood pressure reduction to optimal values in prehypertension: a randomized clinical trial

Background: To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood pressure (BP) in adults with prehypertension. Methods: The PREVER-prevention trial was a randomized, parallel, double-blinded, placebo-controlled trial, with 18 months of follow-up, conducted at 21 academic medical centers in Brazil. Of 1772 individuals evaluated for eligibility, 730 volunteers with prehypertension who were aged 30–70 years, and who did not reach optimal blood pressure after 3 months of lifestyle intervention, were randomized to a fixed association of chlorthalidone 12.5 mg and amiloride 2.5 mg or placebo once a day. The main outcomes were the percentage of participants who achieved an optimal level of BP. Results: A total of 372 participants were randomly allocated to diuretics and 358 to placebo. After 18 months of treatment, optimal BP was noted in 25.6% of the diuretic group and 19.3% in the placebo group (P < 0.05). The mean net reduction in SBP and DBP for the diuretic group compared with placebo was 2.8 mmHg (95% CI 1.1 to 4.5) and 1.1 mmHg (95% CI −0.09 to 2.4), respectively. Most participants in the active treatment group (74.5%) and in the placebo group (80.7%) continued to have BP in the prehypertension range or progressed to hypertension. Conclusion: Low-dose diuretic therapy increased the probability of individuals with prehypertension to achieve optimal BP but most of those treated continued to have a BP in the prehypertension range or progressed to having overt hypertension.