Abstract
Aims
To evaluate whether a strategy of double-dose influenza vaccination during hospitalization for an acute coronary syndrome (ACS) compared with standard-dose outpatient vaccination (as ...recommended by current guidelines) would further reduce the risk of major cardiopulmonary events.
Methods and results
Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) was a pragmatic, randomized, multicentre, active-comparator, open-label trial with blinded outcome adjudication comparing two strategies of influenza vaccination following an ACS: double-dose quadrivalent inactivated vaccine before hospital discharge vs. standard-dose quadrivalent inactivated vaccine administered in the outpatient setting 30 days after randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analysed by the win ratio method. Patients were followed for 12 months. During two influenza seasons, 1801 participants were included at 25 centres in Brazil. The primary outcome was not different between groups, with 12.7% wins in-hospital double-dose vaccine group and 12.3% wins in the standard-dose vaccine group {win ratio: 1.02 95% confidence interval (CI): 0.79–1.32, P = 0.84}. Results were consistent for the key secondary outcome, a hierarchical composite of cardiovascular death, myocardial infarction and stroke win ratio: 0.94 (95% CI: 0.66–1.33), P = 0.72. Time-to-first event analysis for the primary outcome showed results similar to those of the main analysis hazard ratio 0.97 (95% CI: 0.75–1.24), P = 0.79. Adverse events were infrequent and did not differ between groups.
Conclusion
Among patients hospitalized with an ACS, double-dose influenza vaccination before discharge did not reduce cardiopulmonary outcomes compared with standard-dose vaccination in the outpatient setting.
Clinical Trial Registration
ClinicalTrials.gov number: NCT04001504
Study design, and results of the primary efficacy hierarchical endpoints.
The win ratio was calculated using an unmatched non-parametric pairwise comparison for each endpoint. The win ratio given as ...the total number of winner pairs by the total number of the loser pairs. In the present study, a win ratio > 1 indicates benefit of double-dose in-hospital influenza vaccination.
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•The first 45 days after an ACS is the period with the more risk for CV events.•Double-dose influenza vaccination following an ACS did not reduce cardiorespiratory.•Similar results were found for only to hierarchical cardiovascular endpoints.•COVID-19 hospitalizations and death did not impact hierarchical endpoints.
Influenza vaccination prevents major cardiovascular events in individuals presenting a recent acute coronary syndrome (ACS), however the early effect of an in-hospital double-dose vaccination strategy remains uncertain.
The VIP-ACS was a randomized, pragmatic, multicenter, open-label trial with a blinded-adjudication endpoint. Patients with ACS ≤ 7 days of hospitalization were randomized to an in-hospital double-dose quadrivalent inactivated influenza vaccine (double-dose) or a standard-dose influenza vaccine at 30 days post-randomization. The primary endpoint was a hierarchical composite of death, myocardial infarction, stroke, hospitalization for unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory infections, analyzed with the win ratio (WR) method in short-term follow-up (45-days after randomization).
The trial enrolled 1,801 patients (≥18 years old). Median participant age was 57 years, 70 % were male. There were no significant differences between groups on the primary hierarchical endpoint: there were 5.7 % wins in the double-dose in-hospital group and 5.5 % wins in the standard-dose delayed vaccination group (WR: 1.03; 95 % CI: 0.70–––1.53; P = 0.85). In a sensitivity analysis including COVID-19 infection in the hospitalizations for respiratory infections endpoint, overall results were maintained (WR: 1.03; 95 % CI 0.71–––1.51; P = 0.87). Results were consistent for major cardiovascular events only (WR: 0.82; 95 % CI: 0.48–––1.39; P = 0.46). No serious adverse events were observed.
In patients with recent ACS, in-hospital double-dose influenza vaccination did not significantly reduce cardiorespiratory events at 45 days compared with standard-dose vaccination at 30 days post-randomization.
IntroductionDaily multidisciplinary rounds (DMRs) consist of systematic patient-centred discussions aiming to establish joint therapeutic goals for the next 24 hours of intensive care unit (ICU) ...care. The aim of the present study protocol is to evaluate whether an intervention consisting of guided DMRs, supported by a remote specialist and audit/feedback on care performance will reduce ICU length of stay compared with a control group.Methods and analysisA multicentre, controlled, cluster-randomised superiority trial including 30 ICUs in Brazil (15 intervention and 15 control), from August 2019 to June 2021. In a parallel assignment, ICUs are randomised to a complex-intervention composed by daily rounds carried out through Tele-ICU by a remote ICU physician; development of local quality indicators dashboards coupled with monthly meetings with local leadership; and dissemination of evidence-based clinical protocols versus usual care. Primary outcome is ICU length of stay. Secondary outcomes include classification of the unit according to the profiles defined by the standardised resource use and the standardised mortality rate, hospital mortality, incidence of healthcare-associated infections, ventilator-free days at 28 days, patient-days receiving oral or enteral feeding, patient-days under light sedation or alert and calm, rate of patients under normoxaemia. All adult patients admitted after the beginning of the study in each participant ICU will be enrolled. Inclusion criteria (clusters): public Brazilian ICUs with a minimum of 8 ICU beds interested/committed to participating in the study. Exclusion criteria (clusters): units with fully established DMRs by an intensivist, specialised or step-down units.Ethics and disseminationThe study protocol was approved by the institutional review board (IRB) of the coordinator centre, and by IRBs of each enrolled hospital/ICU. Statistical analysis protocol is being prepared for submission before the end of patient’s enrolment. Results will be disseminated through conferences, peer-reviewed journals and to each participating unit.Trial registration numberNCT03920501; Pre-results.
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.
Aims
To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of JNC 7 Stage I hypertension in patients with type 2 ...diabetes mellitus.
Methods
In an a priori subgroup analysis of a randomized, double-blind, controlled trial, volunteers aged 30–70 years, with stage I hypertension and diabetes
mellitus
, were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (
N
= 47) or 50 mg of losartan (
N
= 50), and followed for 18 months in 21 clinical centers. If BP remained uncontrolled after three months, study medication dose was doubled, and if uncontrolled after six months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg BID) were added as open label drugs in a progressive fashion.
Results
Systolic BP decreased to a greater extent in participants allocated to diuretics compared to losartan (
P
< 0.001). After 18 months of follow-up, systolic BP was 128.4 ± 10.3 mmHg in the diuretic group versus 133.5 ± 8.0 in the losartan group (
P
< 0.01). In the diuretic group, 36 out of 43 participants (83.7%) had a JNC 7 normal BP, compared to 31/47 (66%) in the losartan group (
P
= 0.089). Serum cholesterol was higher in the diuretic arm at the end of the trial. Other biochemical parameters and reports of adverse events did not differ by treatment.
Conclusions
Treatment of hypertension based on a combination of chlorthalidone and amiloride is more effective for BP lowering compared to losartan in patients with diabetes
mellitus
and hypertension.
Trial registration
Clinical trials registration number: NCT00971165
Background:
Studies have shown significant benefits of exercise therapy in heart failure (HF) with a reduced ejection fraction (HFrEF) and HF with a preserved ejection fraction (HFpEF). The ...mechanisms responsible for the beneficial effect of exercise in HFrEF and HFpEF are still unclear. We hypothesized that the effect of exercise on myocardial remodeling may explain its beneficial effect.
Methods:
IMAGING-REHAB-HF is a single-center, randomized, controlled clinical trial using cardiac magnetic resonance imaging, vasomotor endothelial function, cardiac sympathetic activity imaging and serum biomarkers to compare the effect of exercise therapy in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%). Subjects will be assessed at baseline and after 4 months. The exercise program will consist of three 60-min exercise sessions/week. The primary endpoints are the effect of exercise on myocardial extracellular volume (ECV), left ventricular (LV) systolic function, LV mass, LV mass-to-volume and LV cardiomyocyte volume. Secondary endpoints include the effect of exercise on vasomotor endothelial function, cardiac sympathetic activity and plasmatic biomarkers. Patients will be allocated in a 2:1 fashion to supervised exercise program or usual care. A total sample size of 90 patients, divided into two groups according to LVEF:HFpEF group (45 patients:30 in the intervention arm and 15 in the control arm) and HFrEF group (45 patients:30 in the intervention arm and 15 in the control arm) – will be necessary to achieve adequate power.
Conclusion:
This will be the first study to evaluate the benefits of a rehabilitation program on cardiac remodeling in HF patients. The unique design of our study may provide unique data to further elucidate the mechanisms involved in reverse cardiac remodeling after exercise in HFpEF and HFrEF patients.
Resumo Fundamento Estudos anteriores revelaram alto risco de eventos tromboembólicos arteriais e venosos como consequência de danos virais diretos do SARS-CoV-2 em células endoteliais e um meio ...procoagulante devido ao aumento de biomarcadores como o D-dímero, fibrinogênio, fator VIII. Foram realizados ensaios controlados randomizados de terapias antitrombóticas em pacientes internados, no entanto, poucos estudos avaliaram o papel da tromboprofilaxia no ambiente ambulatorial. Objetivo Avaliar se a profilaxia antitrombótica com rivaroxabana reduz o risco de eventos trombóticos venosos ou arteriais, suporte ventilatório invasivo e morte em pacientes ambulatoriais com COVID-19. Métodos O estudo CARE é um ensaio randomizado, aberto, multicêntrico e controlado por rivaroxabana 10 mg uma vez por dia durante 14 dias ou tratamento local padrão isolado, para a prevenção de resultados adversos, registrado no Clinicaltrials.gov (NCT04757857). Os critérios de inclusão são adultos com infecção confirmada ou suspeita do SARS-CoV-2, com sintomas leves ou moderados, sem indicação de hospitalização, no prazo de 7 dias após o início dos sintomas e um fator de risco de complicação da COVID-19 (>65 anos, hipertensão, diabetes, asma, doença pulmonar obstrutiva crônica ou outras doenças pulmonares crônicas, tabagismo, imunossupressão ou obesidade). O desfecho primário composto inclui tromboembolismo venoso, necessidade de ventilação mecânica invasiva, eventos cardiovasculares agudos maiores e mortalidade no prazo de 30 dias após a randomização, sendo avaliado segundo o princípio da intenção de tratar. Todos os pacientes assinaram termo de consentimento. Foi estabelecido um nível de significância de 5% para todos os testes estatísticos. Resultados Os principais desfechos trombóticos e hemorrágicos, hospitalizações e mortes serão avaliados centralmente por um comitê de eventos clínicos independente, sob a condição cega para a alocação dos grupos de tratamento. Conclusão O estudo CARE fornecerá informação relevante e contemporânea sobre o possível papel da tromboprofilaxia em pacientes ambulatoriais com COVID-19.
Patients with type 2 diabetes (T2DM) have a substantial risk of developing cardiovascular disease. The strong connection between the severity of hyperglycaemia, metabolic changes secondary to T2DM ...and vascular damage increases the risk of macrovascular complications. There is a challenging demand for the development of drugs that control hyperglycaemia and influence other metabolic risk factors to improve cardiovascular outcomes such as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina and heart failure (major adverse cardiovascular events). In recent years, introduction of the new drug class of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has changed the treatment landscape as GLP-1RAs have become well-established therapies in T2DM. The benefits of GLP-1RAs are derived from their pleiotropic effects, which include appetite control, glucose-dependent secretion of insulin and inhibition of glucagon secretion. Importantly, their beneficial effects extend to the cardiovascular system. Large clinical trials have evaluated the cardiovascular effects of GLP-1RAs in patients with T2DM and elevated risk of cardiovascular disease and the results are very promising. However, important aspects still require elucidation, such as the specific mechanisms involved in the cardioprotective effects of these drugs. Careful interpretation is necessary because of the heterogeneity across the trials concerning the definition of cardiovascular risk or cardiovascular disease, baseline characteristics, routine care and event rates. The aim of this review is to describe the main clinical aspects of the GLP-1RAs, compare them using data from both the mechanistic and randomized controlled trials and discuss potential reasons for improved cardiovascular outcomes observed in these trials. This review may help clinicians to decide which treatment is most appropriate in reducing cardiovascular risk in patients with T2DM.
Following publication of the original article 1, based on the authors review, the GLP1 receptor agonists in type 2 diabetes published in Cardiovascular Diabetology, a meta-analysis of GLP-1 and ...non-GLP-1 based therapies was performed on cardiovascular outcomes.
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