Angiotensin Receptor Blockers Evaluated by Office and Home Blood Pressure Measurements. TeleHBPM Study. / Bloqueadores do Receptor de Angiotensina Avaliados por Medida de Consultório e Residencial da Pressão Arterial. Estudo TeleMRPA.

BACKGROUND: Adequate treatment of arterial hypertension and achieving arterial hypertension goals in are important in reducing cardiovascular outcomes. OBJECTIVES: To describe angiotensin receptor blockers in monotherapy or double combination therapy and the rate of arterial hypertension control. METHODS: This cross-sectional study evaluated patients who were using angiotensin receptor blockers between 2017 and 2020. Those using three or more antihypertensive drugs were excluded. The analyzed variables included sex, age, body mass index, valid home blood pressure monitoring (HBPM) measurements, casual and HBPM systolic and diastolic blood pressure measurements, blood pressure variability, and antihypertensive and angiotensin receptor blocker class. Paired t, chi-square, and Fisher's exact tests were used, as well as overlapping 95% confidence intervals and a significance level of 5% (p < 0.05). RESULTS: Of 17,013 patients, 12,813 met the inclusion criteria, 62.1% of whom were female. The mean number of valid measurements was 23.3 (SD, 2.0). The mean HBPM and casual measurements for systolic blood pressure were 126.8 (SD, 15.8) mmHg and 133.5 (SD, 20.1) mmHg (p <0.001), respectively, while those for diastolic blood pressure were 79.1 (SD, 9.7 mmHg) and 83.6 (SD, 11.9) mmHg (p <0.001), respectively. Losartan was the most common angiotensin receptor blocker and resulted in the highest blood pressure values. Combinations of angiotensin receptor blockers with diuretics or calcium channel antagonists resulted in lower blood pressure values. CONCLUSIONS: More than half of the patients used losartan, although it was the least efficient drug for reducing and controlling blood pressure.

FUNDAMENTO: O tratamento adequado e a obtenção das metas na hipertensão arterial são importantes na redução dos desfechos cardiovasculares. OBJETIVOS: Descrever os bloqueadores do receptor de angiotensina (BRA) em monoterapia ou combinação dupla e a taxa de controle da hipertensão arterial. MÉTODOS: Estudo transversal que avaliou pacientes em uso de BRA entre 2017 e 2020. Foram excluídos aqueles em uso de três ou mais anti-hipertensivos. As variáveis analisadas foram: sexo, idade, índice de massa corporal, medidas válidas da medida residencial da pressão arterial (MRPA); pressão arterial sistólica (PAS) e diastólica (PAD) obtidas pela MRPA e de forma casual; variabilidade pressórica; classe dos anti-hipertensivos e dos BRAs. Foram utilizados testes de t pareado, qui-quadrado e Fisher, além de sobreposição dos intervalos de confiança de 95% com nível de significância de 5% (p < 0,05). RESULTADOS: Foram selecionados 17.013 pacientes; destes, 12.813 preencheram os critérios, dos quais 62,1% eram do sexo feminino. O número médio de medidas válidas foi de 23,3 (±2,0), com médias para a PAS de 126,8±15,8 mmHg e 133,5±20,1 mmHg (p < 0,001) e para a PAD de 79,1±9,7 mmHg e 83,6±11,9 mmHg (p < 0,001) pela MRPA e medida casual, respectivamente. Losartana foi o BRA mais utilizado e o que apresentou comportamentos mais elevados da pressão arterial. As combinações de BRA com diuréticos ou com antagonistas de canal de cálcio tiveram menores valores de pressão arterial. CONCLUSÕES: Losartana foi utilizada em mais da metade dos pacientes, apesar de ser a menos eficiente na redução e no controle da pressão arterial.

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 physician's 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.

Bloqueadores do Receptor de Angiotensina Avaliados por Medida de Consultório e Residencial da Pressão Arterial. Estudo TeleMRPA / Angiotensin Receptor Blockers Evaluated by Office and Home Blood Pressure Measurements. TeleHBPM Study

Resumo Fundamento O tratamento adequado e a obtenção das metas na hipertensão arterial são importantes na redução dos desfechos cardiovasculares. Objetivos Descrever os bloqueadores do receptor de angiotensina (BRA) em monoterapia ou combinação dupla e a taxa de controle da hipertensão arterial. Métodos Estudo transversal que avaliou pacientes em uso de BRA entre 2017 e 2020. Foram excluídos aqueles em uso de três ou mais anti-hipertensivos. As variáveis analisadas foram: sexo, idade, índice de massa corporal, medidas válidas da medida residencial da pressão arterial (MRPA); pressão arterial sistólica (PAS) e diastólica (PAD) obtidas pela MRPA e de forma casual; variabilidade pressórica; classe dos anti-hipertensivos e dos BRAs. Foram utilizados testes de t pareado, qui-quadrado e Fisher, além de sobreposição dos intervalos de confiança de 95% com nível de significância de 5% (p < 0,05). Resultados Foram selecionados 17.013 pacientes; destes, 12.813 preencheram os critérios, dos quais 62,1% eram do sexo feminino. O número médio de medidas válidas foi de 23,3 (±2,0), com médias para a PAS de 126,8±15,8 mmHg e 133,5±20,1 mmHg (p < 0,001) e para a PAD de 79,1±9,7 mmHg e 83,6±11,9 mmHg (p < 0,001) pela MRPA e medida casual, respectivamente. Losartana foi o BRA mais utilizado e o que apresentou comportamentos mais elevados da pressão arterial. As combinações de BRA com diuréticos ou com antagonistas de canal de cálcio tiveram menores valores de pressão arterial. Conclusões Losartana foi utilizada em mais da metade dos pacientes, apesar de ser a menos eficiente na redução e no controle da pressão arterial.

Abstract Background Adequate treatment of arterial hypertension and achieving arterial hypertension goals in are important in reducing cardiovascular outcomes. Objectives To describe angiotensin receptor blockers in monotherapy or double combination therapy and the rate of arterial hypertension control. Methods This cross-sectional study evaluated patients who were using angiotensin receptor blockers between 2017 and 2020. Those using three or more antihypertensive drugs were excluded. The analyzed variables included sex, age, body mass index, valid home blood pressure monitoring (HBPM) measurements, casual and HBPM systolic and diastolic blood pressure measurements, blood pressure variability, and antihypertensive and angiotensin receptor blocker class. Paired t, chi-square, and Fisher's exact tests were used, as well as overlapping 95% confidence intervals and a significance level of 5% (p < 0.05). Results Of 17,013 patients, 12,813 met the inclusion criteria, 62.1% of whom were female. The mean number of valid measurements was 23.3 (SD, 2.0). The mean HBPM and casual measurements for systolic blood pressure were 126.8 (SD, 15.8) mmHg and 133.5 (SD, 20.1) mmHg (p <0.001), respectively, while those for diastolic blood pressure were 79.1 (SD, 9.7 mmHg) and 83.6 (SD, 11.9) mmHg (p <0.001), respectively. Losartan was the most common angiotensin receptor blocker and resulted in the highest blood pressure values. Combinations of angiotensin receptor blockers with diuretics or calcium channel antagonists resulted in lower blood pressure values. Conclusions More than half of the patients used losartan, although it was the least efficient drug for reducing and controlling blood pressure.

[The "LOTHAR" study: evaluation of efficacy and tolerability of the fixed combination of amlodipine and losartan in the treatment of essential hypertension]. / Estudo "LOTHAR": avaliação de eficácia e tolerabilidade da combinação fixa de anlodipino e losartana no tratamento da hipertensão arterial primária.

OBJECTIVE: The LOTHAR study evaluated medium and long term (one year) efficacy, tolerability and metabolic effects of the fixed combination of amlodipine and losartan compared to amlodipine or losartan alone. METHODS: Brazilian multicenter, randomized, double-blind and comparative trial performed with 198 patients in stage 1 and 2 essential hypertension. RESULTS: The fixed combination has a high antihypertensive efficacy that is sustained in the long term with very low percentage of loss of blood pressure control. This percentage is incidentally lower than that of the two monotherapy comparative regimens. In the long term, more than 60% of the patients treated with the fixed combination remained with DBP < or = 85 mmHg, and the antihypertensive effect, when assessed by ABPM persisted for 24 hours with a trough-to-peak ratio of 76.7%. The frequency of adverse events was quite low in this group, and the long-term incidence of leg edema was approximately four-fold lower than that observed with amlodipine alone. The fixed combination did not change glucose and lipid metabolism in the medium or in the long term. CONCLUSION: Based on these results, we can say that the combination of amlodipine and losartan--the first fixed combination of a calcium channel blocker and an angiotensin II receptor blocker available in the pharmaceutical market, is an excellent option for the treatment of a wide range of hypertensive patients.

A importância da mapa na doença hipertensiva / The importance of ABPM in hypertensive disease

A Monitorização Ambulatorial da Pressão Arterial (MAPA) já é uma ferramenta devidamente incorporada à prática clínica e referendada por muitas publicações principalmente pelo seu valor na detecção de situações especiais denominadas de hipertensão e efeito do avental branco; e, hipertensão mascarada e efeito mascarado da hipertensão. No Brasil, a MAPA já foi referendada por seis Diretrizes, sendo a última publicada recentemente. O objetivo desse artigo é colocar em discussão determinados aspectos que fortalecem a utilização da MAPA na prática clínica, colaborando para melhor diagnosticar e tratar os indivíduos hipertensos. Além disso, demonstrar as novas perspectivas da MAPA com a disponibilização de dispositivos capazes de avaliar a pressão periférica de 24 horas e, também, os parâmetros centrais de rigidez e hemodinâmicos que podem acrescentar muito ao tratamento da doença hipertensiva.

Ambulatory Blood Pressure Monitoring (ABPM) is already a tool duly incorporated into clinical practice and endorsed by many publications mainly for its value in the detection of special situations called hypertension and white coat effect; and, masked hypertension and masked hypertension effect. In Brazil, ABPM has already been endorsed by six Guidelines, the latter being published recently. The purpose of this article is to discuss certain aspects that strengthen the use of ABPM in clinical practice, collaborating to better diagnose and treat hypertensive individuals. In addition, to demonstrate the new perspectives of ABPM with the availability of devices capable of evaluating the 24-hour peripheral pressure and also the central parameters of stiffness and hemodynamics that can add much to the treatment of hypertensive disease.

Efficacy and safety of two ramipril and hydrochlorothiazide fixed-dose combination formulations in adults with stage 1 or stage 2 arterial hypertension evaluated by using ABPM.

BACKGROUND: Fixed-dose combinations of antihypertensive agents demonstrate advantages in terms of efficacy, tolerability, and treatment adherence. OBJECTIVE: This study was designed to compare the efficacy and safety of 2 ramipril and hydrochlorothiazide (HCTZ) fixed-dose combinations in patients with hypertension stage 1 or 2. Patients' blood pressure (BP) profiles were evaluated by using 24-hour ambulatory BP monitoring (ABPM). METHODS: This was a multicenter, prospective, randomized, open-label, parallel-group, noninferiority trial of adult patients (age ≥18 years) with hypertension stage 1 or 2 and systolic blood pressure (SBP) within 140 to 179 mm Hg or diastolic blood pressure (DBP) 90 to 109 mm Hg. After a 2-week washout period, eligible patients were randomized to receive 1 of 2 ramipril/HCTZ fixed-dose combination formulations (5/25 mg/d) for 8 weeks. The primary end point was the difference in 24-hour ABPM SBP/DBP mean reductions between groups after 8 weeks of treatment. The secondary end points were the changes in daytime and nighttime ABPM and in office BP. Safety profile and tolerability assessments included monitoring of adverse events. RESULTS: A total of 102 patients with hypertension (54 in group A [test formulation] and 48 in group B [reference formulation]), aged 27 to 85 years, completed the 8-week treatment period. The decreases in SBP and DBP according to 24-hour ABPM from baseline to week 8 were significant and similar in both groups. SBP decreased from 149.1 to 133.0 mm Hg (-16.1 mm Hg) in group A and from 146.2 to 130.6 mm Hg in group B (-15.6 mm Hg) (P = 0.8537); DBP was reduced by 8.8 mm Hg in group A and by 8.5 mm Hg in group B (P = 0.8748). Because the lower 95% CI limit for the difference between groups A and B of 3.96 mm Hg in SBP and 3.54 mm Hg in DBP was lower than that preestablished by the trial protocol (4 mm Hg), noninferiority of the test formulation was demonstrated compared with the reference formulation. For the secondary end points, there was no significant difference between groups in SBP and DBP during daytime or nighttime at the end of week 8. Office BP was significantly reduced in both treatment groups, with no significant differences between groups. The incidence of adverse events was 23.7% in group A and 21.7% in group B. CONCLUSIONS: Both treatment options were well tolerated and equally reduced BP. The results support the conclusion that group A (new fixed-dose combination of ramipril/HCTZ) was noninferior to group B (reference medication in Brazil). ISRCTN Register: ISRCTN05051235.

Factors associated with increased radial augmentation index in hypertensive individuals.

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 (ß = -0.001, p = 0.017), heart rate (ß = -0.001, p = 0.007) and central pressure (ß = 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.

Avaliação de rigidez arterial correlacionando dois marcadores distintos: Augmentation Index versus Índice Ambulatorial de rigidez Arterial / Evaluation of arterial stiffness correlating two different markers: Augmentation Index versus Ambulatory Arterial Stiffness Index

A prevenção e o tratamento da hipertensão arterial são medidas importantes na redução do risco cardiovascular. Entretanto, o comportamento da pressão arterial periférica não parece suficiente para se entender e agir sobre essa doença. Assim, a avaliação da pressão sistólica central (PSc) torna-se fundamental. A medida estimada da PSc pode ser obtida por meio da tonometria de aplanação. O aumento da PSc pode ser determinado pelo índice derivado da análise da curva da pressão central da aorta, o Augmentation Index (AI). Esse índice pode ser correlacionado com o Índice Ambulatorial de Rigidez Arterial (IARA), obtido através da Monitorização Ambulatorial da Pressão Arterial (MAPA). Objetivou-se avaliar a rigidez arterial correlacionando dois marcadores distintos: AI e IARA. Trata-se de estudo observacional transversal, e os pacientes incluídos foram submetidos à tonometria de aplanação através do Tonômetro HEM9000-AI, da OMRON. A análise do IARA foi definida após a MAPA de 24 horas, utilizando-se o software da MICROMED. O ponto de corte foi de R2 >0,36,sendoesteolimitedesensibilidadequemelhora a estratificação de risco cardiovascular. Utilizou-se a correlação de Spearman com auxílio de gráficos de dispersão. Adotou-se um valor de significância p < 0,05. A amostra estudada foi de 72 pacientes, sendo 55 (76%) do sexo feminino e 17 (24%) do sexo masculino, com idade média de 56 ± 15 anos. O AI médio encontrado foi de 86,4±11,4% e o IARA médio foi de 0,49 ± 0,18. Foi observada uma correlação positiva e significativa entre AI e IARA (rspearman=0,306 p=0,009). Quando essa correlação foi estratificada pelo sexo, manteve-se marginalmente significativa apenas no grupo de mulheres (rspearman= 0,265; p = 0,05). Existe correlação positiva entre IARA e AI na avaliação da rigidez arterial. Ambos os métodos se mostram válidos na prevenção das doenças cardiovasculares.

The prevention and treatment of hypertension are important measures in reducing cardiovascular risk. However, the behavior of peripheral arterial pressure seems not enough for one to understand and act on this disease. Thus, the assessment of central systolic pressure (PSc) becomes critical. as the estimated PSc measure can be obtained by applanation tonometry. The increase of PSc can be determined by the derived index of the assessment of the central aortic pressure curve, the Augmentation Index (AI). This index can be correlated with the Ambulatory Arterial Stiffness Index (AASI), obtained by Ambulatory Blood Pressure Monitoring (ABPM). The aim was to assess arterial stiffness correlating two different markers: AI and AASI. This is a cross-sectional observational study and the patients included underwent applanation tonometry through HEM9000-AI Tonometer, OMRON. The AASI analysis was defined after ABPM of 24 hours, using MICROMED software. The cutoff point was R2>0.36,beingthesensitivitylimitthatimproves cardiovascular risk stratification. We used the Spearman correlation with the aid of scatter plots. We adopted a significance value of p < 0.05. The sample was composed of 72 patients: 55 (76%) women and 17 (24%) men, with a mean age of 56 ± 15 years. The mean AI was found to be 86.4 ± 11.4% and the average AASI was 0.49 ± 0.18. A positive and significant correlation between AI and AASI (rspearman= 0.306; p = 0.009) was observed. When this correlation was stratified by gender, it remained marginally significant only in the group of women (rspearman = 0.265; p = 0.05). There is a positive correlation between AASI and AI in the evaluation of arterial stiffness. Both methods proved to be valid in the prevention of cardiovascular diseases.

Based treatment algorithm for essencial hypertension with olmesartan medoxomil.

BACKGROUND: The national and international guidelines emphasize the importance of the effective treatment of arterial hypertension. Nevertheless, low levels of control are observed, as well as low attainment of the recommended goals, indicating that it is important to plan and implement better treatment strategies. OBJECTIVE: To evaluate the efficacy of a based treatment algorithm with olmesartan medoxomil. METHODS: This is an open, national, multicentric and prospective study of 144 patients with primary arterial hypertension, stages 1 and 2, naïve to treatment or after a 2-to-3 week washout period for those in whom treatment was ineffective. The use of olmesartan medoxomil was assessed in a treatment algorithm divided into 4 phases: (i) monotherapy (20 mg), (ii-iii) associated to à hydrochlorothiazide (20/12.5 mg and 40/25 mg) and (iv) addition of amlodipine besylate (40/25 mg + 5 mg). RESULTS: At the end of the phased-treatment, 86% of the study subjects attained the goal of BP < 130/85 mmHg. Maximum reductions in SAP and DAP were -44.4 mmHg and -20.0 mmHg, respectively. The rate of systolic responders (SAP >or= 20 mmHg) and of diastolic responders (DAP >or= 10 mmHg) was 87.5% and 92.4%, respectively. CONCLUSION: The study was based on a treatment regimen that was similar to the therapeutic approach in daily clinical practice and showed that the use of olmesartan medoxomil in monotherapy or in association with hydrochlorothiazide and amlodipine was effective in the attainment of the recommended goals for hypertension stage 1 and 2 hypertensive individuals.

An evaluation of the Rastreometro, a new device for populational screening for high blood pressure in developing countries.

OBJECTIVE: To test a simplified blood pressure device called Rastreometro that could be used by the Health Agents. METHODS: The Rastreometro has been developed from an ordinary aneroid sphygmomanometer, in which the numeric display is covered by an adhesive with a red zone, indicating pressures equal or above 140 mmHg and a yellow zone indicating pressures below 140 mmHg. The onset of oscillations of the aneroid needle is taken as an indication of the systolic pressure value. The measurements made by the Rastreometro were compared with those made by the auscultatory method, and were carried out in 268 patients, by two operators. The influence on the results of confounding variables such as age, gender, BMI, arm length, upper arm circumference, skin colour and antihypertensive treatment were taken into consideration, as well as intra and interobserver variation. RESULTS: In the whole group, sensitivity was 95.1%, specificity was 63.1%, positive predictive value was 62.4% and negative predictive value was 95.3%. Hypertensive treatment significantly affected specificity, 32.7% as compared to 77.8% for the non-treated group. Both operators improved their results over time. CONCLUSION: This study suggests that the Rastreometro technique, as a screener for hypertension, has good sensitivity. Concerning specificity, it is acceptable, provided the patient is not on regular antihypertensive treatment. In this latter situation, it can be improved by a proper standardization of the method to read the systolic pressure by needle oscillations. Furthermore, the use of this technique requires well trained operators.