Randomized Controlled Trial

IJCS

Case Report

A Fixed-Dose Triple-Combination Therapy for the Initial Steps of Hypertension Treatment: Protocol for the NEXT Randomized Clinical Trial

Rogerio Orlow et al. Caroline Consuelo de Sousa Sayuri Inuzuka Audes Feitosa … Andréa Araujo Brandão Marco Mota Gomes Vanildo da Silva Guimarães Neto Elizabeth do Espírito Santo Cestario Eduardo Costa Duarte Barbosa Rodrigo Bezerra Mayara Cedrim Santos Ana Luiza Lima Sousa Sandro Rodrigues Batista Priscila Valverde de Oliveira Vitorino Weimar Kunz Sebba Barroso

Introduction

Complications from arterial hypertension account for an estimated 18 deaths per minute worldwide, establishing it as the second leading risk factor for global mortality. Between 1990 and 2019, the number of adults with arterial hypertension doubled from 650 million to 1.3 billion. Of these, only 54% are diagnosed, 42% are treated, and a mere 21% of those treated achieve adequate blood pressure (BP) control.

Although effective BP control often requires the use of multiple drugs, monotherapy remains a predominant initial approach to arterial hypertension management globally, which limits the timely achievement of therapeutic goals. This is significant because even modest reductions in systolic BP of 5 mmHg are associated with an approximate 10% reduction in the risk of major cardiovascular events, irrespective of pre-existing cardiovascular disease.

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Editorial

Stress Reduction, Meditation and Mindfulness Program for Heart Failure Patients: Some Light in the Darkness

Luís Beck-da-Silva

The study entitled “Impact of a Stress Reduction, Meditation, and Mindfulness Program in Patients with Chronic Heart Failure: A Randomized Controlled Trial” has raised a very important subject to be addressed in patients with heart failure and aimed to do so by conducting a randomized clinical trial. The impact of patients’ stress, depression, lack of life purpose, and psychological changes imposed by a chronic and debilitating disease definitely contributes to worsening quality of life and possibly to worse prognosis.^, To assess this impact and to research possible therapies is deeply needed. The authors should be recognized for their interest and huge effort in conducting such a laborious trial.

The study, however, has some deficiencies. Although the authors claim to be a heart failure with reduced ejection fraction (HFrEF) trial, the study included approximately half of the patients with HFrEF. Despite the heterogeneity of the sample, one-third of patients in the intervention group were lost to follow-up, while no patients were lost in the control group. Therefore, even having screened more than two hundred individuals, only 13 patients were actually submitted to intervention. The authors do not inform us of how these patients were pharmacologically treated, but given that the study was conducted four years ago, one can assume patients’ treatment was outdated.

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Original Article

Rationale and Design of the COVID-19 Outpatient Prevention Evaluation (COPE – Coalition V) Randomized Clinical Trial: Hydroxychloroquine vs. Placebo in Non-Hospitalized Patients

Haliton Alves de Oliveira Junior et al. Cleusa P. Ferri Icaro Boszczowski Gustavo B. F. Oliveira … Alexandre B. Cavalcanti Regis G. Rosa Renato D. Lopes Luciano C. P. Azevedo Viviane C. Veiga Otavio Berwanger Álvaro Avezum

Abstract

Background

Despite the need for targeting specific therapeutic options for coronavirus disease 2019 (COVID-19), there has been no evidence of effectiveness of any specific treatment for the outpatient clinical setting. There are few randomized studies evaluating hydroxychloroquine (HCQ) in non-hospitalized patients. These studies indicate no benefit from the use of HCQ, but they assessed different primary outcomes and presented important biases for outcome evaluation.

Objective

To evaluate if HCQ may prevent hospitalization due to COVID-19 compared to a matching placebo.

Methods

The COVID-19 Outpatient Prevention Evaluation (COPE) study is a pragmatic, randomized, double-blind, placebo-controlled clinical trial evaluating the use of HCQ (800 mg on day 1 and 400 mg from day 2 to day 7) or matching placebo for the prevention of hospitalization due to COVID-19 in early non-hospitalized confirmed or suspected cases. Inclusion criteria are adults (≥ 18 years) seeking medical care with mild symptoms of COVID-19, with randomization ≤ 7 days after symptom onset, without indication of hospitalization at study screening, and with at least one risk factor for complication (> 65 years; hypertension; diabetes mellitus; asthma; chronic obstructive pulmonary disease or other chronic lung diseases; smoking; immunosuppression; or obesity). All hypothesis tests will be two-sided. A p-value < 0.05 will be considered statistically significant in all analyses. Clinicaltrials.gov: NCT04466540.

Results

Clinical outcomes will be centrally adjudicated by an independent clinical event committee blinded to the assigned treatment groups. The primary efficacy endpoint will be assessed following the intention-to-treat principle.

Conclusion

This study has the potential to reliably answer the scientific question of HCQ use in outpatients with COVID-19. To our knowledge, this is the largest trial evaluating HCQ in non-hospitalized individuals with COVID-19.

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Original Article

Effects of Anti-TNF alpha Therapy on Blood Pressure in Resistant Hypertensive Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

Ana Paula de Faria et al. Alessandra M. V. Ritter Arthur Santa-Catharina Débora P. Souza … Estephania P. Naseri Manoel B. Bertolo Mariana Rodrigues Pioli Caio C. Carvalho Rodrigo Modolo Heitor Moreno

Abstract

Background:

The cytokine tumor necrosis factor-alpha (TNF-α) is elevated in resistant hypertension (RH), but the effects of a TNF-α inhibitor in this population is unknown.

Objective:

The aim of this trial was to evaluate whether a single dose of infliximab controlled by placebo acutely reduces blood pressure (BP) in RH subjects.

Methods:

A double-blind, placebo-controlled, crossover trial was conducted, and randomized RH subjects received either infliximab or placebo. The primary endpoint was the change in mean BP levels relative to the baseline immediately after the infusion obtained by continuously beat-to-beat non-invasive hemodynamic assessment. Secondary endpoints included changes in office, ambulatory and central BP measurements; endothelial function; and inflammatory biomarkers after 7 days. The level of significance accepted was alpha=0.05.

Results:

Ten RH subjects were enrolled. The primary endpoint analysis showed an acute decrease in mean BP values (mean of differences ± standard deviation = -6.3 ± 7.2 mmHg, p=0.02) from baseline, after the application of infliximab compared with placebo. Diastolic BP levels (-4.9 ± 5.5 mmHg, p=0.02), but not systolic BP levels (-9.4 ± 19.7 mmHg, p=0.16), lowered after infliximab infusion. No further significant differences were identified in either the other hemodynamic parameters or in secondary endpoints, except for TNF-α levels, which increased continuously after infliximab infusion. No adverse events were reported during the protocol.

Conclusions:

A single-dose of infliximab decreased the mean and diastolic BP levels immediately after its infusion, when compared to the placebo in RH. The anti-TNF-α therapy was found to be safe and well-tolerated. The results of this proof-of-concept are hypothesis-generating and need to be further investigated. (Arq Bras Cardiol. 2021; 116(3):443-451)

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Original Article

Stent versus Coronary Artery Bypass Surgery in Multi-Vessel and Left Main Coronary Artery Disease: A Meta-Analysis of Randomized Trials with Subgroups Evaluation

Pedro José Negreiros de Andrade et al. João Luiz de Alencar Araripe Falcão Breno de Alencar Araripe Falcão Hermano Alexandre Lima Rocha

Abstract

Background:

Comparison between percutaneous coronary intervention (PCI) using stents and Coronary Artery Bypass Grafting (CABG) remains controversial.

Objective:

To conduct a systematic review with meta-analysis of PCI using Stents versus CABG in randomized controlled trials.

Methods:

Electronic databases were searched to identify randomized trials comparing PCI using Stents versus CABG for multi-vessel and unprotected left main coronary artery disease (LMCAD). 15 trials were found and their results were pooled. Differences between trials were considered significant if p < 0.05.

Results:

In the pooled data (n = 12,781), 30 days mortality and stroke were lower with PCI (1% versus 1.7%, p = 0.01 and 0.6% versus 1.7% p < 0.0001); There was no difference in one and two year mortality (3.3% versus 3.7%, p = 0.25; 6.3% versus 6.0%, p = 0.5). Long term mortality favored CABG (10.6% versus 9.4%, p = 0.04), particularly in trials of DES era (10.1% versus 8.5%, p = 0.01). In diabetics (n = 3,274) long term mortality favored CABG (13.7% versus 10.3%; p < 0.0001). In six trials of LMCAD (n = 4,700) there was no difference in 30 day mortality (0.6%versus 1.1%, p = 0.15), one year mortality (3% versus 3.7%, p = 0.18), and long term mortality (8.1% versus 8.1%) between PCI and CABG; the incidence of stroke was lower with PCI (0.3% versus 1.5%; p < 0.001). Diabetes and a high SYNTAX score were the subgroups that influenced more adversely the results of PCI.

Conclusion:

Compared with CABG, PCI using Stents showed lower 30 days mortality, higher late mortality and lower incidence of stroke. Diabetes and a high SYNTAX were the subgroups that influenced more adversely the results of PCI.

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Original Article

Improving Post-Discharge Medication Adherence in Patients with CVD: A Pilot Randomized Trial

Alfredo D. Oliveira-Filho et al. Donald E. Morisky Francisco A. Costa Sara T. Pacheco … Sabrina F. Neves Divaldo P. Lyra-Jr

Background:

Effective interventions to improve medication adherence are usually complex and expensive.

Objective:

To assess the impact of a low-cost intervention designed to improve medication adherence and clinical outcomes in post-discharge patients with CVD.

Method:

A pilot RCT was conducted at a teaching hospital. Intervention was based on the four-item Morisky Medication Adherence Scale (MMAS-4). The primary outcome measure was medication adherence assessed using the eight-item MMAS at baseline, at 1 month post hospital discharge and re-assessed 1 year after hospital discharge. Other outcomes included readmission and mortality rates.

Results:

61 patients were randomized to intervention (n = 30) and control (n = 31) groups. The mean age of the patients was 61 years (SD 12.73), 52.5% were males, and 57.4% were married or living with a partner. Mean number of prescribed medications per patient was 4.5 (SD 3.3). Medication adherence was correlated to intervention (p = 0.04) and after 1 month, 48.4% of patients in the control group and 83.3% in the intervention group were considered adherent. However, this difference decreased after 1 year, when adherence was 34.8% and 60.9%, respectively. Readmission and mortality rates were related to low adherence in both groups.

Conclusion:

The intervention based on a validated patient self-report instrument for assessing adherence is a potentially effective method to improve adherent behavior and can be successfully used as a tool to guide adherence counseling in the clinical visit. However, a larger study is required to assess the real impact of intervention on these outcomes.

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Artigo Original

Miniaturized self-expanding drug-eluting stent in small coronary arteries: late effectiveness

Flavio Roberto Azevedo de Oliveira et al. Luiz Alberto Piva e Mattos Alexandre Abizaid Andrea S. Abizaid … J. Ribamar Costa Ricardo Costa Rodolfo Staico Roberto Botelho J. Eduardo Sousa Amanda Sousa

BACKGROUND: Small vessels represent a risk factor for restenosis in percutaneous coronary angioplasty (PCA). The Sparrow® self-expanding drug-eluting stent, which has a lower profile than the current systems, has never been tested in this scenario. OBJECTIVES: To evaluate the late effectiveness of the Sparrow® drug-eluting stent, regarding in-stent late lumen loss (LLL). METHODS: Patients with ischemia, symptomatic or documented, were submitted to PCA in vessels with reference diameter < 2.75 mm, divided into two groups regarding Sparrow® stent type: group 1: Sparrow® drug-eluting stent (DES), group 2: Sparrow® bare metal stent (BMS). Clinical follow-up duration was 12 months. Evaluation using quantitative coronary angiography (QCA) was performed immediately and at 8 months. A decrease of over 65% of in-stent LLL with DES was estimated to calculate sample size. IBM® SPSS software, release 19 (Chicago, Illinois, USA) was used for the statistical analysis. RESULTS: A total of 24 patients were randomized, 12 in each group. The DES and BMS groups were similar in age (63.25 ± 10.01 vs. 64.58 ± 11.54, p = 0.765), male gender (58.3% vs. 33.3%, p = 0.412), risk factors and all angiographs aspects. Immediate results were satisfactory in both groups. At 8 months in-stent late lumen loss was significantly lower in DES than in BMS group (DES vs. BMS 0.25 ± 0.16 0.97 ± 0.76, p = 0.008). CONCLUSION: In small-vessel PCA, the Sparrow® DES determined significant reduction in in-stent LLL, when compared to Sparrow® BMS.

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