Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE - Coalition V): A double-blind, multicentre, randomised, controlled trial.

Background: Previous Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in non-hospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers. Methods: We conducted a multicenter, double-blind, RCT in 56 Brazilian sites. Adults with suspected or confirmed COVID-19 presenting with mild or moderate symptoms with ≤ 07 days prior to enrollment and at least one risk factor for clinical deterioration were randomised (1:1) to receive hydroxychloroquine 400 mg twice a day (BID) in the first day, 400 mg once daily (OD) thereafter for a total of seven days, or matching placebo. The primary outcome was hospitalisation due to COVID-19 at 30 days, which was assessed by an adjudication committee masked to treatment allocation and following the intention-to-treat (ITT) principle. An additional analysis was performed only in participants with SARS-CoV-2 infection confirmed by molecular or serology testing (modified ITT [mITT] analysis). This trial was registered at ClinicalTrials.gov, NCT04466540. Findings: From May 12, 2020 to July 07, 2021, 1372 patients were randomly allocated to hydroxychloroquine or placebo. There was no significant difference in the risk of hospitalisation between hydroxychloroquine and placebo groups (44/689 [6·4%] and 57/683 [8·3%], RR 0·77 [95% CI 0·52-1·12], respectively, p=0·16), and similar results were found in the mITT analysis with 43/478 [9·0%] and 55/471 [11·7%] events, RR 0·77 [95% CI 0·53-1·12)], respectively, p=0·17. To further complement our data, we conducted a meta-analysis which suggested no significant benefit of hydroxychloroquine in reducing hospitalisation among patients with positive testing (69/1222 [5·6%], and 88/1186 [7·4%]; RR 0·77 [95% CI 0·57-1·04]). Interpretation: In outpatients with mild or moderate forms of COVID-19, the use of hydroxychloroquine did not reduce the risk of hospitalisation compared to the placebo control. Our findings do not support the routine use of hydroxychloroquine for treatment of COVID-19 in the outpatient setting. Funding: COALITION COVID-19 Brazil and EMS.

Prevalence of masked hypertension evaluated by home blood pressure monitoring in a large sample of patients with office blood pressure <140/90 mmHg.

AIM: Patients with masked hypertension have a higher incidence of target organ damage, including increased left ventricular mass and carotid atherosclerosis and cardiovascular events when compared with normotensive patients. The adverse cardiovascular risks are even greater in patients already taking antihypertensive medication. OBJECTIVE: To identify the prevalence and clinical characteristics of masked hypertension in a large multicenter Brazilian sample that underwent office and home blood pressure monitoring. METHODS: This was an observational cross-sectional analytical study based on secondary data from the teleMRPA online platform, which included 32 cities from 15 states in the five regions of Brazil. The database included 3704 outpatient participants with office blood pressure <140/90 mmHg who performed home blood pressure monitoring for diagnostic investigation (diagnosis group; n = 1819) or treatment (treatment group; n = 1885) of hypertension in 2018. RESULTS: The prevalence of masked hypertension was 18.0% in the whole studied population and 15.4% and 20.4% in the diagnostic and treatment group, respectively. Masked hypertension was more frequently detected in patients with office blood pressure classified as high normal [systolic blood pressure (SBP) = 130-139 mmHg or diastolic blood pressure (DBP) = 85-89 mmHg], followed by those classified as normal (SBP = 120-129 mmHg or DBP = 80-84 mmHg) and optimal (SBP < 120 mmHg and DBP < 80 mmHg), with respective prevalence of 28.3, 13.4 and 4.4% in the diagnostic group and 30.8, 18.8 and 7.1% in the treatment group. CONCLUSION: Masked hypertension has a significant prevalence among individuals with office blood pressure <140/90 mmHg, which is greater with patients with high normal office blood pressure and even higher in patients already using antihypertensive medication.

Avaliação da segurança e eficácia da combinação ramipril/ anlodipino versus anlodipino em monoterapia no tratamento da hipertensão arterial pela monitorização ambulatorial da pressão arterial: estudo ATAR-MAPA / Evaluation of security and efficiency of the combination ramipril/amlopidine versus amlopidine in monotherapy for the treatment of arterial hypertension by the outpatient monitoring of blood pressure: study ATAR-ABPM

O objetivo do estudo é comparar a eficácia e a tolerabilidade da combinação fixa ramipril/anlodipino e do anlodipino em monoterapia para o tratamento de hipertensão arterial. Após um período de duas semanas de retirada de anti-hipertensivos e uso de placebo (washout), 265 pacientes hipertensos com idades entre 40 e 79 anos foram randomizados para iniciar tratamento com 2,5/2,5 mg de ramipril/anlodipino em combinação fixa ou 2,5 mg de anlodipino, que foram titulados para 5/5 mg e 10/10 mg de ramipril/anlodipino, ou 5 e 10 mg de anlodipino, se necessário. No total, 131 pacientes foram randomizados para terapia combinada e 134 para monoterapia sem diferenças significativas entre os grupos nas características basais e nos níveis de pressão arterial (PA) inicial. A redução média da PA sistólica nos períodos do dia (20,36 ± 13,42 versus 15,86 ± 12,71 mmHg; p = 0,003) e da noite (17,6 ± 17,61 versus 14,09 ± 14,32 mmHg; p = 0,051), avaliada pela monitorização ambulatorial de pressão arterial (MAPA), foi significativamente maior no grupo tratamento com combinação fixa. A redução média da PA diastólica durante o dia à MAPA (11,28 ± 8,29 versus 8,96 ± 8,16 versus mmHg; p = 0,009) foi maior no grupo terapia combinada, mas não durante a noite (8,42 ± 11,16 mmHg versus 7,70 ± 8,63; p = 0,567). A redução média da PA sistólica e diastólica em 24 horas à MAPA também foi maior no grupo tratamento combinado. Ambas as opções terapêuticas promoveram redução significativa da PA sistólica e diastólica; porém, os resultados observados foram melhores no grupo de combinação fixa ramipril/anlodipino

This study aims to compare the efficacy and tolerability of a fixed-dose ramipril/amlodipine combination and amlodipine monotherapy for the treatment of hypertension. After a 2-week placebo washout, 265 hypertensive patients aged 40 to 79 years were randomized for 2.5/2.5 mg ramipril/amlodipine or 2.5 mg amlodipine, titrated to ramipril/amlodipine 5/5 mg and 10/10 mg , or amlodipine 5 and 10 mg, if necessary. A total of 131 patients were assigned to combination therapy, and 134 to monotherapy with no significant differences among them in basal characteristics and blood pressure (BP) levels at the ambulatory blood pressure monitoring (ABPM). Mean reduction in daytime (20.36 ± 13.42 versus 15.86 ± 12.71 mmHg; p = 0.003) and night-time systolic BP on ABPM (17.6 ± 17.61 versus 14.09 ± 14.32 mmHg; p = 0.051) were significantly higher in the combination therapy. Mean daytime diastolic BP reduction on ABPM (11.28 ± 8.29 versus 8.96 ± 8.16 versus mmHg; p = 0.009) was greater in the combination group, but not at night-time (8.42 ± 11.16 mmHg versus 7.70 ± 8.63; p = 0.567). Mean change in 24-h systolic and diastolic BP on ABPM were also greater in the combination treatment. Both treatments promoted a marked reduction in systolic and diastolic BP, and the results observed were better in the ramipril/amlodipine combination group.

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

OBJECTIVES: The 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 METHODS: Sixty-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. RESULTS: Office 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. CONCLUSIONS: Amlodipine at a dose of 2.5 mg per day showed efficacy and good tolerability in elderly hypertensives.

Monitorizaçäo residencial da pressäo arterial e monitorizaçäo ambulatorial da pressäo arterial versus medida de pressäo arterial no consultório / Home blood pressure measurement and ambulatory blood pressure measurement versus office blood pressure measurement

Objetivos - Comparar a monitorização residencial da pressão arterial (MRPA) e monitorização ambulatorial da pressão arterial (MAPA) com os registros de consultório e correlacionar o índice de massa de ventrículo esquerdo (IMVE) com a MRPA e medida de consultório. Métodos - Protocolo 1 - Sessenta e oito hipertensos (58+12 anos, 37 mulheres) realizaram: a) MRPA durante 7 dias; b) MAPA de 24h; e c) medida da pressão arterial no consultório, pelo médico. Protocolo 2 - 41 hipertensos (48+14 anos, 25 mulheres) além de MRPA e medida no consultório, realizaram ecocardiograma bi-dimensional. Resultados - Protocolo 1 - a medida de consultório (153+24/96+13mmHg) foi maior (p<0,05) do que a obtida pela MRPA (133+18/84+12mmHg). Protocolo 2 - o IMVE mostrou correlação com as médias de pressão sistólica/diastólica da MRPA (r=0,02/0,22, p>0,05). Conclusão - A MRPA apresentou menores do que a medida de consultório e semelhantes aos da MAPA, além de melhor correlação com IMVE do que a medida de consultório.