Showing papers by "Remo H.M. Furtado published in 2020"

Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19.

Abstract: Background Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is...

Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus: Insights From the DECLARE-TIMI 58 Trial.

Abstract: Background: Atrial fibrillation (AF) and atrial flutter (AFL) are associated with both diabetes mellitus and its related comorbidities, including hypertension, obesity, and heart failure (HF). SGLT...

Dapagliflozin and Cardiac, Kidney, and Limb Outcomes in Patients With and Without Peripheral Artery Disease in DECLARE-TIMI 58.

Abstract: Background: Patients with peripheral artery disease (PAD) are at heightened risk of cardiovascular complications. The SGLT2 inhibitor (SGLT2i) dapagliflozin reduces the risk for hospitalization for...

Long-term ticagrelor for secondary prevention in patients with prior myocardial infarction and no history of coronary stenting: insights from PEGASUS-TIMI 54.

Abstract: Aims PEGASUS-TIMI 54 demonstrated that long-term dual antiplatelet therapy (DAPT) with aspirin and ticagrelor reduced the risk of major adverse cardiovascular events (MACE), with an acceptable increase in bleeding, in patients with prior myocardial infarction (MI). While much of the discussion around prolonged DAPT has been focused on stented patients, patients with prior MI without prior coronary stenting comprise a clinically important subgroup. Methods and results This was a pre-specified analysis from PEGASUS-TIMI 54, which randomized 21 162 patients with prior MI (1-3years) and additional high-risk features to ticagrelor 60 mg, 90 mg, or placebo twice daily in addition to aspirin. A total of 4199 patients had no history of coronary stenting at baseline. The primary efficacy outcome (MACE) was the composite of cardiovascular death, MI, or stroke. Patients without history of coronary stenting had higher baseline risk of MACE [13.2% vs. 8.0%, adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.15-1.73, in the placebo arm]. The relative risk reduction in MACE with ticagrelor (pooled doses) was similar in patients without (HR 0.82, 95% CI 0.68-0.99) and with prior stenting (HR 0.85, 95% CI 0.75-0.96; P for interaction = 0.76). Conclusion Long-term ticagrelor reduces thrombotic events in patients with prior MI regardless of whether they had prior coronary stenting. These data highlight the benefits of DAPT in prevention of spontaneous atherothrombotic events and indicate that long-term ticagrelor may be considered in high-risk patients with prior MI even if they have not been treated with stenting.

What Lessons Have We Learned and What Remains to be Clarified for PCSK9 Inhibitors? A Review of FOURIER and ODYSSEY Outcomes Trials

Abstract: For more than half a century, low-density lipoprotein cholesterol (LDL-C) has been recognized as a major risk factor for incident atherosclerotic cardiovascular disease. The discovery of proprotein convertase subtilisin-kexin type 9 (PCSK9) in 2003, which prevents LDL-C receptor recycling, identified a new target for drug intervention. Recently, two large-scale randomized clinical outcomes trials involving fully human anti-PCSK9 monoclonal antibodies tested the hypothesis that targeting this pathway would reduce cardiovascular events. Both the FOURIER (Further cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk) and ODYSSEY OUTCOMES trials met their primary efficacy endpoints, confirming findings reported earlier that major adverse cardiovascular events can be reduced by a further lowering of LDL-C beyond that achieved with statin therapy. In both trials, there were incremental reductions in LDL-C of > 50% from baseline, with no major safety concerns, over the trials’ median follow-up time (2.2 and 2.8 years, respectively). While there were differences in design, lipid management and overall results, key messages from both studies were similar. However, post-publication, additional questions have arisen, especially regarding drug effects over the long-term, including a potential mortality benefit.

Performance of acute coronary syndrome approaches in Brazil: a report from the BRACE (Brazilian Registry in Acute Coronary SyndromEs).

Abstract: AIMS Diagnostic and therapeutic tools have a significant impact on morbidity and mortality associated with acute coronary syndromes (ACS). Data about ACS performance measures are scarce in Brazil, and improving its collection is an objective of the Brazilian Registry in Acute Coronary syndromEs (BRACE). METHODS AND RESULTS The BRACE is a cross-sectional, observational epidemiological registry of ACS patients. Stratified 'cluster sampling' methodology was adopted to obtain a representative picture of ACS. A performance score (PS) varying from 0 to 100 was developed to compare studied parameters. Performance measures alone and the PS were compared between institutions, and the relationship between the PS and outcomes was evaluated. A total of 1150 patients, median age 63 years, 64% male, from 72 hospitals were included in the registry. The mean PS for the overall population was 65.9% ± 20.1%. Teaching institutions had a significantly higher PS (71.4% ± 16.9%) compared with non-teaching hospitals (63.4% ± 21%; P < 0.001). Overall in-hospital mortality was 5.2%, and the variables that correlated independently with in-hospital mortality included: PS-per point increase (OR = 0.97, 95% CI 0.95-0.98, P < 0.001), age-per year (OR = 1.06, 95% CI 1.03-1.09, P < 0.001), chronic kidney disease (OR = 3.12, 95% CI 1.08-9.00, P = 0.036), and prior angioplasty (OR = 0.25, 95% CI 0.07-0.84, P = 0.025). CONCLUSIONS In BRACE, the adoption of evidence-based therapies for ACS, as measured by the performance score, was independently associated with lower in-hospital mortality. The use of diagnostic tools and therapeutic approaches for the management of ACS is less than ideal in Brazil, with high variability especially among different regions of the country.

Hydroxychloroquine alone or in combination with azithromycin to prevent major clinical events in hospitalised patients with coronavirus infection (COVID-19): rationale and design of a randomised, controlled clinical trial

Abstract: Introduction Hydroxychloroquine and its combination with azithromycin have been suggested to improve viral clearance in patients with COVID-19, but its effect on clinical outcomes remains uncertain. Methods and analysis We describe the rationale and design of an open-label pragmatic multicentre randomised (concealed) clinical trial of 7 days of hydroxychloroquine (400 mg BID) plus azithromycin (500 mg once daily), hydroxychloroquine 400 mg BID, or standard of care for moderately severe hospitalised patients with suspected or confirmed COVID-19 (in-patients with up to 4L/minute oxygen supply through nasal catheter). Patients are randomised in around 50 recruiting sites and we plan to enrol 630 patients with COVID-19. The primary endpoint is a 7-level ordinal scale measured at 15-days: 1)not hospitalised, without limitations on activities; 2)not hospitalised, with limitations on activities; 3)hospitalised, not using supplementary oxygen; 4)hospitalised, using supplementary oxygen; 5)hospitalised, using high-flow nasal cannula or non-invasive ventilation; 6)hospitalised, on mechanical ventilation; 7)death. Secondary endpoints are the ordinal scale at 7 days, need for mechanical ventilation and rescue therapies during 15 days, need of high-flow nasal cannula or non-invasive ventilation during 15 days, length of hospital stay, in-hospital mortality, thromboembolic events, occurrence of acute kidney injury, and number of days free of respiratory support at 15 days. Secondary safety outcomes include prolongation of QT interval on electrocardiogram, ventricular arrhythmias, and liver toxicity. The main analysis will consider all patients with confirmed COVID-19 in the groups they were randomly assigned. Ethics and dissemination This study has been approved by Brazil’s National Ethic Committee (CONEP) and National Health Surveillance Agency (ANVISA). An independent data monitoring committee will perform interim analyses and evaluate adverse events throughout the trial. Results will be submitted for publication after enrolment and follow-up are complete, as well as presented and reported to local health agencies. ClinicalTrials.gov identifier NCT04322123 Strengths and limitations of this study Pragmatic randomised controlled trial of 7 days of hydroxychloroquine plus azithromycin, hydroxychloroquine or standard of care for moderately severe in-patients with suspected or confirmed COVID-19 Multicentre: around 50 recruiting sites in Brazil with planned enrolment of 630 patients (1:1:1) The primary endpoint is a 7-level ordinal scale ([1] not hospitalised, without limitations on activities; [2] not hospitalised, with limitations on activities; [3] hospitalised, not using supplementary oxygen; [4] hospitalised, using supplementary oxygen; [5] hospitalised, using high-flow nasal cannula or non-invasive ventilation; [6] hospitalised, on mechanical ventilation; [7] death) measured at 15 days. Open label design (no placebo)

Relation of High Lipoprotein ( a ) Concentrations to Platelet Reactivity in Individuals with and Without Coronary Artery Disease

Abstract: Lipoprotein (a) [Lp(a)] is a risk factor for coronary artery disease (CAD). To the best of our knowledge, this is the first study addressing the relationship between Lp(a) and platelet reactivity in primary and secondary prevention. Lp(a) was evaluated in 396 individuals with (82.3%) and without (17.7%) obstructive CAD. The population was divided into two groups according to Lp(a) concentrations with a cutoff value of 50 mg/dL. The primary objective was to evaluate the association between Lp(a) and adenosine diphosphate (ADP)-induced platelet reactivity using the VerifyNow™ P2Y12 assay. Platelet reactivity was also induced by arachidonic acid and collagen–epinephrine (C-EPI) and assessed by Multiplate™, platelet function analyzer™ 100 (PFA-100), and light transmission aggregometry (LTA) assays. Secondary objectives included the assessment of the primary endpoint in individuals with or without CAD. Overall, 294 (74.2%) individuals had Lp(a) 0.05). Finally, multivariable analysis did not show a significant association between ADP-induced platelet reactivity and Lp(a) ≥ 50 mg/dL [adjusted OR = 1.00 [(95% CI 0.99–1.01), P = 0.590]. In individuals with or without CAD, Lp(a) ≥ 50 mg/dL was not associated with higher platelet reactivity.

Caffeinated Beverage Intake, Dyspnea With Ticagrelor, and Cardiovascular Outcomes: Insights From the PEGASUS-TIMI 54 Trial.

Abstract: Background A proposed cause of dyspnea induced by ticagrelor is an increase in adenosine blood levels. Because caffeine is an adenosine antagonist, it can potentially improve drug tolerability with...

Influence of Direct Thrombin Inhibitor and Low Molecular Weight Heparin on Platelet Function in Patients with Coronary Artery Disease: A Prospective Interventional Trial.

Abstract: The interaction between anticoagulants and platelet function is complex. Previous publications showed mixed results regarding the role of heparins in platelet aggregation. On the other hand, the direct thrombin inhibitor (DTI) dabigatran might enhance the risk of myocardial infarction in patients with atrial fibrillation, which could be related to increased platelet aggregability. This was a prospective, interventional study of patients with chronic coronary artery disease (CAD) taking low-dose aspirin. The objective of the current study was to compare the effects of dabigatran versus enoxaparin on platelet aggregability. Subjects initially were on orally administered dabigatran for 5 days followed by subcutaneously administered enoxaparin after a 30-day washout period. Platelet function was assessed at baseline and after each intervention by multiple electrode aggregometry (MEA-ASPI) (primary endpoint), serum thromboxane B2 (TXB2), VerifyNow Aspirin™, and coagulation tests (secondary endpoints). Compared to baseline MEA-ASPI values, dabigatran increased platelet aggregation while enoxaparin decreased platelet aggregation (+ 5 U ± 24.1 vs − 6 U ± 22.2, respectively, p = 0.012). The TXB2 assay showed the same pattern (+ 2 pg/ml for dabigatran vs − 13 pg/ml for enoxaparin, p = 0.011). None of the additional tests showed significant differences between the groups. Individually, compared to baseline TXB2 results, enoxaparin significantly decreased platelet activation [33 (16.5–95) pg/mL vs 20 (10–52) pg/mL, respectively, p = 0.026], but no significant differences were observed with dabigatran. DTI and anti-Xa drugs exert opposite effects on platelet function. A significant decrease in platelet activation through COX1 (also known as prostaglandin G/H synthase 1) was observed with enoxaparin, but no significant differences in platelet function were observed with dabigatran. ClinicalTrials.gov identifier, NCT02389582.

Diabetes association with self-reported health, resource utilization, and prognosis post-myocardial infarction.

Abstract: BACKGROUND Diabetes mellitus (DM) is associated with increased cardiovascular (CV) risk. We compared health-related quality of life (HRQoL), healthcare resource utilization (HRU), and clinical outcomes of stable post-myocardial infarction (MI) patients with and without DM. HYPOTHESIS In post-MI patients, DM is associated with worse HRQoL, increased HRU, and worse clinical outcomes. METHODS The prospective, observational long-term risk, clinical management, and healthcare Resource utilization of stable coronary artery disease study obtained data from 8968 patients aged ≥50 years 1 to 3 years post-MI (369 centers; 25 countries). Patients with ≥1 of the following risk factors were included: age ≥65 years, history of a second MI >1 year before enrollment, multivessel coronary artery disease, creatinine clearance ≥15 and <60 mL/min, and DM treated with medication. Self-reported health status was assessed at baseline, 1 and 2 years and converted to EQ-5D scores. The main outcome measures were baseline HRQoL and HRU during follow-up. RESULTS DM at enrollment was 33% (2959 patients, 869 insulin treated). Mean baseline EQ-5D score (0.86 vs 0.82; P < .0001) was higher; mean number of hospitalizations (0.38 vs 0.50, P < .0001) and mean length of stay (LoS; 9.3 vs 11.5; P = .001) were lower in patients without vs with DM. All-cause death and the composite of CV death, MI, and stroke were significantly higher in DM patients, with adjusted 2-year rate ratios of 1.43 (P < .01) and 1.55 (P < .001), respectively. CONCLUSIONS Stable post-MI patients with DM (especially insulin treated) had poorer EQ-5D scores, higher hospitalization rates and LoS, and worse clinical outcomes vs those without DM. Strategies focusing specifically on this high-risk population should be developed to improve outcomes. TRIAL REGISTRATION ClinicalTrials.gov: NCT01866904 (https://clinicaltrials.gov).

Ejection fraction versus B-type natriuretic peptide for revascularization strategy in left main disease: two sides of the same coin or a wooden nickel?

Abstract: The fraction of blood ejected from the left ventricle with each cardiac systole was recognized as a physiologically important variable in the earliest days of modern cardiology when the first measurements of left ventricular ejection fraction (LVEF) were performed via interatrial septal puncture and injection of a radioisotope.1 Since that time, a strong association has been observed between LVEF and mortality rates across numerous disease states, particularly atherosclerotic coronary artery disease (CAD).2 Coronary revascularization has proven mortality reduction for patients with reduced LVEF and severe CAD. Landmark trials performed mainly in the 1970s and 1980s, when the use of renin–angiotensin–aldosterone system inhibitors and beta-blockers was not yet established as the standard of care for reducing mortality in patients with heart failure (HF), suggested that patients with stable CAD and left ventricular (LV) dysfunction derived a robust mortality reduction with coronary artery bypass graft (CABG) surgery compared to medical management alone.3 In the contemporary era of standard medical therapy for both LV dysfunction and atherosclerosis, patients with CAD and LVEF≤ 35% also derived a survival advantage with CABG compared to medical management alone in the long term.4 Surgical revascularization has also demonstrated an important survival benefit vs. medical management alone for patients with left main coronary artery (LMCA) disease.5 International guidelines recommend revascularization for patients with CAD who have significant LMCA disease or reduced LVEF.6,7