Effect of antihypertensive agents on sleep apnea and ambulatory blood pressure in patients with hypertension: A randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) and hypertension are common conditions that may be linked through sympathetic activation and water retention. We hypothesized that diuretics, which reduce the body water content, may be more effective than amlodipine, a blood pressure (BP)-lowering agent implicated with edema, in controlling OSA in patients with hypertension. We also aimed to compare the effects of these treatments on ambulatory blood pressure monitoring (ABPM). METHODS: In a randomized, double-blind clinical trial, we compared the effects of chlorthalidone/amiloride 25/5 mg with amlodipine 10 mg on OSA measured by portable sleep monitor and BP measured by ABPM. The study included participants older than 40 who had moderate OSA (10-40 apneas/hour of sleep) and BP within the systolic range of 140-159 mmHg or diastolic range of 90-99 mmHg. RESULTS: The individuals in the experimental groups were comparable in age, gender, and other relevant characteristics. Neither the combination of diuretics nor amlodipine alone reduced the AHI after 8 weeks of treatment (AHI 26.3 with diuretics and 25.0 with amlodipine. P = 0.713). Both treatments significantly lowered office, 24-h, and nighttime ABP, but the two groups had no significant difference. CONCLUSION: Chlorthalidone associated with amiloride and amlodipine are ineffective in decreasing the frequency of sleep apnea episodes in patients with moderate OSA and hypertension. Both treatments have comparable effects in lowering both office and ambulatory blood pressure. The notion that treatments could offer benefits for both OSA and hypertension remains to be demonstrated. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT01896661.

Effects of Antihypertensive Treatment on Left and Right Ventricular Global Longitudinal Strain and Diastolic Parameters in Patients with Hypertension and Obstructive Sleep Apnea: Randomized Clinical Trial of Chlorthalidone plus Amiloride vs. Amlodipine.

Hypertension is highly prevalent in patients with obstructive sleep apnea (OSA), and fluid retention with its nighttime rostral distribution is one potential mechanism. We tested whether or not diuretics differ from amlodipine in their impact on echocardiographic parameters. Patients with moderate OSA and hypertension were randomized to receive diuretics (chlorthalidone plus amiloride) or amlodipine daily for 8 weeks. We compared their effects on left and right ventricular global longitudinal strain (LV-GLS and RV-GLS, respectively), on LV diastolic parameters, and on LV remodeling. In the 55 participants who had echocardiographic images feasible for strain analysis, all echocardiographic parameters were within normal ranges. After 8 weeks, the 24 h blood pressure (BP) reduction values were similar, while most echocardiographic metrics were kept unchanged, except for LV-GLS and LV mass. In conclusion, the use of diuretics or amlodipine had small and similar effects on echocardiographic parameters in patients with moderate OSA and hypertension, suggesting that they do not have important effects on mediating the interaction between OSA and hypertension.

Secondary Pharmacological Prevention of Coronary Artery Disease among Patients Submitted to Clinical Management, Percutaneous Coronary Intervention, or Coronary Artery Bypass Graft Surgery. / Prevenção Farmacológica Secundária da Doença Arterial Coronariana em Pacientes Submetidos ao Manejo Clínico, Intervenção Coronária Percutânea ou Cirurgia de Revascularização Miocárdica.

BACKGROUND: Secondary prevention is recommended for patients with evidence of coronary artery disease (CAD) regardless of the indication for treatment by coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI). OBJECTIVES: This study evaluated whether clinical treatment, PCI or CABG had an influence on adherence to the pharmacological secondary prevention in patients with stable CAD. METHODS: This cohort included patients aged ≥40 years with stable CAD confirmed by coronary angiography. The decision for medical treatment alone, or additionally with PCI or CABG, was made by the attending physicians. Adherence to the prescribed drugs recommended by the guidelines for secondary prevention (optimal pharmacological treatment), including antiplatelet agents, lipid-lowering drugs, beta-blockers, and renin-angiotensin-aldosterone system blockers, was assessed at follow-up. Differences were considered significant for p values <0.05. RESULTS: From 928 patients enrolled at baseline, 415 had mild CAD and 66 moderate to severe CAD. The average follow-up was 5.2 ± 1.5 years. Patients submitted to CABG were more likely to receive the optimal pharmacological treatment than those submitted to PCI or treated clinically (63.5% versus 39.1% versus 45.7% respectively, p=0.003). Baseline factors independently associated with greater probability of having a prescription of optimal treatment at follow-up were CABG [39% higher (6% - 83%, p=0.017) and diabetes [25% higher (1% - 56%), p=0.042] than their counterparts treated by other methods and participants without diabetes, respectively. CONCLUSIONS: Patients with CAD submitted to CABG are more commonly treated with optimal pharmacological secondary prevention than patients treated by PCI or exclusively with medical therapy.

FUNDAMENTO: A prevenção secundária é recomendada a pacientes com evidência de doença arterial coronariana (DAC) independentemente da indicação de tratamento por cirurgia de bypass da artéria coronária (CABG) ou intervenção coronária percutânea (ICP). OBJETIVOS: Este estudo avaliou se o tratamento clínico, a ICP ou o CABG teve influência na adesão à prevenção secundária farmacológica em pacientes com DAC estável. MÉTODOS: Esta coorte incluiu pacientes com idade ≥40 anos com DAC estável confirmada por angiografia coronária estável. A decisão por tratamento clínico isolado, ou combinado com ICP ou CABG foi feita por médicos assistentes. A adesão às drogas prescritas recomendadas pelas diretrizes de prevenção secundária (tratamento farmacológico ótimo), incluindo agentes antiplaquetários, drogas hipolipemianetes, betabloqueadores, e bloqueadores do sistema angiotensina aldosterona, foi avaliada no acompanhamento. Diferenças com valores de p < 0,05 foram consideradas estatisticamente significativas. RESULTADOS: Dos 928 pacientes incluídos inicialmente, 415 apresentaram DAC leve e 66 apresentaram DAC leve a moderada. O período médio de seguimento foi 5,2 ± 1,5 anos. Os pacientes submetidos ao CABG apresentaram maior probabilidade de receberem tratamento farmacológico ótimo que aqueles submetidos à ICP ou tratamento clínico (63,5% versus 39,1% versus 45,7% respectivamente, p=0,003). Fatores basais independentemente associados com maior probabilidade de prescrição de tratamento ótimo foram CABG [39% maior (6% - 83%, p=0,017)] em comparação a outros tratamentos e diabetes [25% maior (1% - 56%), p=0,042] em comparação à ausência de diabetes. CONCLUSÕES: Pacientes com DAC submetidos ao CABG são mais frequentemente tratados com prevenção secundária farmacológica ótima que pacientes tratados com ICP ou exclusivamente com tratamento clínico.

Prevenção Farmacológica Secundária da Doença Arterial Coronariana em Pacientes Submetidos ao Manejo Clínico, Intervenção Coronária Percutânea ou Cirurgia de Revascularização Miocárdica / Secondary Pharmacological Prevention of Coronary Artery Disease among Patients Submitted to Clinical Management, Percutaneous Coronary Intervention, or Coronary Artery Bypass Graft Surgery

Resumo Fundamento A prevenção secundária é recomendada a pacientes com evidência de doença arterial coronariana (DAC) independentemente da indicação de tratamento por cirurgia de bypass da artéria coronária (CABG) ou intervenção coronária percutânea (ICP). Objetivos Este estudo avaliou se o tratamento clínico, a ICP ou o CABG teve influência na adesão à prevenção secundária farmacológica em pacientes com DAC estável. Métodos Esta coorte incluiu pacientes com idade ≥40 anos com DAC estável confirmada por angiografia coronária estável. A decisão por tratamento clínico isolado, ou combinado com ICP ou CABG foi feita por médicos assistentes. A adesão às drogas prescritas recomendadas pelas diretrizes de prevenção secundária (tratamento farmacológico ótimo), incluindo agentes antiplaquetários, drogas hipolipemianetes, betabloqueadores, e bloqueadores do sistema angiotensina aldosterona, foi avaliada no acompanhamento. Diferenças com valores de p < 0,05 foram consideradas estatisticamente significativas. Resultados Dos 928 pacientes incluídos inicialmente, 415 apresentaram DAC leve e 66 apresentaram DAC leve a moderada. O período médio de seguimento foi 5,2 ± 1,5 anos. Os pacientes submetidos ao CABG apresentaram maior probabilidade de receberem tratamento farmacológico ótimo que aqueles submetidos à ICP ou tratamento clínico (63,5% versus 39,1% versus 45,7% respectivamente, p=0,003). Fatores basais independentemente associados com maior probabilidade de prescrição de tratamento ótimo foram CABG [39% maior (6% - 83%, p=0,017)] em comparação a outros tratamentos e diabetes [25% maior (1% - 56%), p=0,042] em comparação à ausência de diabetes. Conclusões Pacientes com DAC submetidos ao CABG são mais frequentemente tratados com prevenção secundária farmacológica ótima que pacientes tratados com ICP ou exclusivamente com tratamento clínico.

Abstract Background Secondary prevention is recommended for patients with evidence of coronary artery disease (CAD) regardless of the indication for treatment by coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI). Objectives This study evaluated whether clinical treatment, PCI or CABG had an influence on adherence to the pharmacological secondary prevention in patients with stable CAD. Methods This cohort included patients aged ≥40 years with stable CAD confirmed by coronary angiography. The decision for medical treatment alone, or additionally with PCI or CABG, was made by the attending physicians. Adherence to the prescribed drugs recommended by the guidelines for secondary prevention (optimal pharmacological treatment), including antiplatelet agents, lipid-lowering drugs, beta-blockers, and renin-angiotensin-aldosterone system blockers, was assessed at follow-up. Differences were considered significant for p values <0.05. Results From 928 patients enrolled at baseline, 415 had mild CAD and 66 moderate to severe CAD. The average follow-up was 5.2 ± 1.5 years. Patients submitted to CABG were more likely to receive the optimal pharmacological treatment than those submitted to PCI or treated clinically (63.5% versus 39.1% versus 45.7% respectively, p=0.003). Baseline factors independently associated with greater probability of having a prescription of optimal treatment at follow-up were CABG [39% higher (6% - 83%, p=0.017) and diabetes [25% higher (1% - 56%), p=0.042] than their counterparts treated by other methods and participants without diabetes, respectively. Conclusions Patients with CAD submitted to CABG are more commonly treated with optimal pharmacological secondary prevention than patients treated by PCI or exclusively with medical therapy.

The performance of SYNTAX score versus the coronary angiogram standard evaluation in the prediction of cardiovascular events in a cohort of patients with stable coronary heart disease.

Background: Scores for prediction of cardiovascular events in patients with stable coronary artery disease (CAD) submitted to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) or medical-therapy (MT), such as the SYNTAX score (SXscore), have been proposed, but there is no comparative assessment of their performance with the coronary angiogram standard evaluation (CASE). This study aimed to evaluate the performance of the SXscore versus the CASE in the prediction of major cardiovascular outcomes (MACCE) in patients with chronic CAD who were treated with MT or additionally submitted to CABG or PCI. Methods: Prospective cohort study of 454 patients with CAD referred for elective diagnostic coronary angiography in Hospital de Clínicas de Porto Alegre, Brazil, with 40 years of age or over, which were followed on average for 6±2.0 years. Patients with acute coronary syndromes, valvular heart disease, aortic diseases, previous coronary revascularization, heart failure, chronic renal disease, history of cancer, or severe psychiatric illness were excluded. Agreement between the scores was evaluated by Kappa statistics. The performance of the scores to predict MACCE was evaluated by Cox proportional hazard models. Areas under the ROC curves were compared by the DeLong test. Results: Patients with moderate to high SXscores or with left main or multivessel CAD (LMMCAD) in the CASE evaluation had higher rates of all-cause death and MACCE than those with low SXscore or without LMMCAD. After adjusting for confounding, only LMMCAD remained associated with the incidence of all-cause death in the total sample (HR =2.81;95% CI: 1.17-6.74) and for MACCE in patients undergoing MT (HR =8.72; 95% CI: 1.73-44.10). The ROC curves for all treatments were similar. Kappa statistics was not significant in patients submitted to MT, poor for patients treated by PCI and fair for the whole sample and patients treated with CABG. Conclusions: The severity of CAD defined by CASE or the SXscore provides similar prediction of the occurrence of cardiovascular events in patients submitted to clinical, PCI or CABG therapies. CASE is easier to do and may be the preferential method in the stratification of risk of patients with stable CAD.

Thiazide diuretics alone or in combination with a potassium-sparing diuretic on blood pressure-lowering in patients with primary hypertension: protocol for a systematic review and network meta-analysis.

BACKGROUND: The use of thiazide (T) diuretics for the treatment of hypertension may be associated with adverse metabolic effects, which can be minimized by combining thiazides with potassium-sparing (PS) diuretics. The additional blood pressure (BP)-lowering effect provided by the addition of a PS diuretic is unclear. Due to a large number of drugs in the T diuretics class, and the possible difference between them, there is a need to identify the best available evidence for health decision-making. This systematic review with network meta-analysis aims to compare the antihypertensive efficacy of T diuretics alone or in combination with a PS diuretic in patients with primary hypertension, as well as the safety of such drugs through the measurement of drug-related adverse events. METHODS: A comprehensive electronic search will be conducted in six electronic bibliographic databases (PubMed/MEDLINE, Cochrane Library, Embase, Web of Science, Scopus, Lilacs), a registration database ( ClinicalTrials.gov ), and Educational Resources Information Center (ERIC [ProQuest]), published from inception to the date of the search. The search will be updated towards the end of the review. A hand search of the reference sections of the included studies and cited studies will also be performed. In case of missing data, authors will be contacted by e-mail or academic social networking sites whenever possible. To be included in the review, studies must be double-blind randomized controlled trials evaluating T diuretics alone or in combination with PS diuretics in patients with primary hypertension. The primary outcome measure will be office BP. Ambulatory BP monitoring (ABPM), non-melanoma skin cancer, major adverse cardiovascular events, laboratory parameters, and the number of withdrawals will be included as secondary outcomes. The results will be quantitatively summarized using differences between the mean change from baseline or differences between means for quantitative outcomes and relative risk for dichotomous outcomes. Results will be presented as mean or relative risk with credible intervals through a league table. The treatments will also be ranked using the surface under the cumulative ranking curve method. The risk of bias will be assessed through the RoB 1.0 tool. DISCUSSION: To the best of our knowledge, this review will be the first to synthesize currently available evidence on the antihypertensive efficacy of different T diuretics alone or in combination with PS diuretics in adults with hypertension. The goals of hypertension treatment are to control high BP and to reduce associated cardiovascular morbidity and mortality, using the most appropriate therapy. Thiazides are widely used for pharmacological treatment due to their demonstrated effectiveness in reducing BP, favorable safety profile, and low cost. The results of this study will provide evidence regarding the best therapeutic strategies with T and PS diuretics, evidencing interventions with better antihypertensive efficacy and safety profile. TRIAL REGISTRATION: This systematic review and network meta-analysis was prospectively registered at the PROSPERO database ( CRD42018118492 ).