REMO HOLANDA DE MENDONCA FURTADO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
35 resultados
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- The Use of Oral Beta-Blockers and Clinical Outcomes in Patients with Non-ST-Segment Elevation Acute Coronary Syndromes: a Long-Term Follow-Up Study(2018) NICOLAU, Jose C.; FURTADO, Remo H. M.; BARACIOLI, Luciano M.; LARA, Livia M.; DALCOQUIO, Talia F.; SCANAVINI JUNIOR, Marco A.; PEREIRA, Cesar A. C.; LIMA, Viviane M.; GONCALVES, Talita M.; COLODETTI, Raiza; FERRARI, Aline G.; LOPES, Renato D.; GIUGLIANO, Robert P.BackgroundThe role of beta-blockers in patients with acute coronary syndromes is mainly derived from studies including patients with ST-segment elevation myocardial infarction. Little is known about the use of beta-blockers and associated long-term clinical outcomes in patients with non-ST-elevation acute coronary syndromes (NSTEACS).MethodsWe analyzed short- and long-term clinical outcomes of 2921 patients with NSTEACS using or not oral beta-blockers in the first 24h of the acute coronary syndromes (ACS) presentation. The association between beta-blocker use and mortality was assessed using a propensity score adjusted analysis (N=1378).ResultsPatients starting oral beta-blockers in the first 24h of hospitalization, compared with patients who did not, had lower rates of in-hospital mortality (OR=0.52, 95% CI 0.33 to 0.74, P=0.002) and higher mean survival times in the long-term follow-up (11.860.4years vs. 9.92 +/- 0.39years, P<0.001).Conclusion The use of beta-blockers in the first 24h of patients presenting with NSTEACS was associated with better in-hospital and long-term mortality outcomes.
- Does prior coronary angioplasty affect outcomes of surgical coronary revascularization? Insights from the STICH trial(2019) NICOLAU, Jose C.; STEVENS, Susanna R.; AL-KHALIDI, Hussein R.; JATENE, Fabio B.; FURTADO, Remo H. M.; DALLAN, Luis A. O.; LISBOA, Luiz A. F.; DESVIGNE-NICKENS, Patrice; HADDAD, Haissam; JOLICOEUR, E. Marc; PETRIE, Mark C.; DOENST, Torsten; MICHLER, Robert E.; OHMAN, E. Magnus; MADDURY, Jyotsna; ALI, Imtiaz; DEJA, Marek A.; ROULEAU, Jean L.; VELAZQUEZ, Eric J.; HILL, James A.Background: The STICH trial showed superiority of coronary artery bypass plus medical treatment (CABG) over medical treatment alone (MED) in patients with left ventricular ejection fraction (LVEF) <= 35%. In previous publications, percutaneous coronary intervention (PCI) prior to CABG was associated with worse prognosis. Objectives: The main purpose of this study was to analyse if prior PCI influenced outcomes in STICH. Methods and results: Patients in the STICH trial (n=1212), followed for a median time of 9.8 years, were included in the present analyses. In the total population, 156 had a prior PCI (74 and 82, respectively, in the MED and CABG groups). In those with vs. without prior PCI, the adjusted hazard-ratios (aHRs) were 0.92 (95% CI=0.74-1.15) for all-cause mortality, 0.85 (95% CI=0.64-1.11) for CV mortality, and 1.43 (95% CI=1.15-1.77) for CV hospitalization. In the group randomized to CABG without prior PCI, the aHRs were 0.82 (95% CI=0.70-0.95) for all-cause mortality, 0.75 (95% CI=0.62-0.90) for CV mortality and 0.67 (95% CI=0.56-0.80) for CV hospitalization. In the group randomized to CABG with prior PCI, the aHRs were 0.76 (95% CI=0.50-1.15) for all-cause mortality, 0.81 (95% CI=0.49-1.36) for CV mortality and 0.61 (95% CI=0.41-0.90) for CV hospitalization. There was no evidence of interaction between randomized treatment and prior PCI for any endpoint (all adjusted p > 0.05). Conclusion: In the STICH trial, prior PCI did not affect the outcomes of patients whether they were treated medically or surgically, and the superiority of CABG over MED remained unchanged regardless of prior PCI.
- Long-term ticagrelor for secondary prevention in patients with prior myocardial infarction and no history of coronary stenting: insights from PEGASUS-TIMI 54(2020) FURTADO, Remo H. M.; NICOLAU, Jose C.; MAGNANI, Giulia; IM, Kyungah; BHATT, Deepak L.; STOREY, Robert F.; STEG, P. Gabriel; SPINAR, Jindrich; BUDAJ, Andrzej; KONTNY, Frederic; CORBALAN, Ramon; KISS, Robert G.; ABOLA, Maria Teresa; JOHANSON, Per; JENSEN, Eva C.; BRAUNWALD, Eugene; SABATINE, Marc S.; BONACA, Marc P.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.
- Morphine and Cardiovascular Outcomes Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Undergoing Coronary Angiography(2020) FURTADO, Remo H. M.; NICOLAU, Jose C.; GUO, Jianping; IM, Kyungah; WHITE, Jennifer A.; SABATINE, Marc S.; NEWBY, L. Kristin; GIUGLIANO, Robert P.BACKGROUND Mechanistic studies have shown that morphine blunts the antiplatelet effects of oral adenosine diphosphate receptor blockers. However, the clinical relevance of this interaction is controversial. OBJECTIVES This study sought to explore the association between morphine and ischemic events in 5,438 patients treated with concomitant clopidogrel presenting with non-ST-segment elevation acute coronary syndromes (NSTEACS) in the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome) trial. Patients not treated with clopidogrel (n = 3,462) were used as negative controls. METHODS Endpoints were the composite of death, myocardial infarction (MI), recurrent ischemia, or thrombotic bailout at 96 h (4-way endpoint) and the composite of death or MI at 30 days. RESULTS In patients treated with clopidogrel, morphine use was associated with higher rates of the 4-way endpoint at 96 h (adjusted odds ratio [OR]: 1.40; 95% confidence interval [CI]: 1.04 to 1.87; p = 0.026). There was a trend for higher rates of death or MI at 30 days (adjusted OR: 1.29; 95% CI: 0.98 to 1.70; p = 0.072), driven by events in the first 48 h (adjusted hazard ratio: 1.54; 95% CI: 1.07 to 2.23; p = 0.021). In patients not treated with clopidogrel, morphine was not associated with either the 4-way endpoint at 96 h (adjusted OR: 1.05; 95% CI: 0.74 to 1.49; p = 0.79; p(interaction) = 0.36) or death or MI at 30 days (adjusted OR: 1.07; 95% CI: 0.77 to 1.48; p = 0.70; p(interaction) = 0.46). CONCLUSIONS When used concomitantly with clopidogrel pre-treatment, morphine was associated with higher rates of ischemic events in patients with NSTEACS. (C) 2020 by the American College of Cardiology Foundation.
- What Lessons Have We Learned and What Remains to be Clarified for PCSK9 Inhibitors? A Review of FOURIER and ODYSSEY Outcomes Trials(2020) FURTADO, Remo H. M.; GIUGLIANO, Robert P.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.
- Relation of High Lipoprotein (a) Concentrations to Platelet Reactivity in Individuals with and Without Coronary Artery Disease(2020) SALSOSO, Rocio; DALCOQUIO, Talia F.; FURTADO, Remo H. M.; FRANCI, Andre; BARBOSA, Carlos J. D. G.; GENESTRETI, Paulo R. R.; STRUNZ, Celia M. C.; LIMA, Viviane; BARACIOLI, Luciano M.; GIUGLIANO, Robert P.; GOODMAN, Shaun G.; GURBEL, Paul A.; MARANHAO, Raul C.; NICOLAU, Jose C.Introduction 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. Methods 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 (TM) P2Y(12)assay. Platelet reactivity was also induced by arachidonic acid and collagen-epinephrine (C-EPI) and assessed by Multiplate (TM), platelet function analyzer (TM) 100 (PFA-100), and light transmission aggregometry (LTA) assays. Secondary objectives included the assessment of the primary endpoint in individuals with or without CAD. Results Overall, 294 (74.2%) individuals had Lp(a) < 50 mg/dL [median (IQR) 13.2 (5.8-27.9) mg/dL] and 102 (25.8%) had Lp(a) >= 50 mg/dL [82.5 (67.6-114.5) mg/dL],P < 0.001. Univariate analysis in the entire population revealed no differences in ADP-induced platelet reactivity between individuals with Lp(a) >= 50 mg/dL (249.4 +/- 43.8 PRU) versus Lp(a) < 50 mg/dL (243.1 +/- 52.2 PRU),P = 0.277. Similar findings were present in individuals with (P = 0.228) and without (P = 0.669) CAD, and regardless of the agonist used or method of analysis (allP > 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]. Conclusion 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(2020) FURTADO, Remo H. M.; VENKATESWARAN, Ramkumar V.; NICOLAU, Jose C.; GURMU, Yared; BHATT, Deepak L.; STOREY, Robert F.; STEG, P. Gabriel; MAGNANI, Giuglia; GOTO, Shinya; DELLBORG, Mikael; KAMENSKY, Gabriel; ISAZA, Daniel; AYLWARD, Philip; JOHANSON, Per; BONACA, Marc P.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 regard to dyspnea. Furthermore, association between caffeine and cardiovascular events is of clinical interest. METHODS AND RESULTS: This prespecified analysis used data from the PEGASUS TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial, which randomized 21 162 patients with prior myocardial infarction to ticagrelor 60 mg or 90 mg or matching placebo (twice daily). Baseline caffeine intake in cups per week was prospectively collected for 9694 patients. Outcomes of interest included dyspnea, major adverse cardiovascular events (ie, the composite of cardiovascular death, myocardial infarction, or stroke), and arrhythmias. Dyspnea analyses considered the pooled ticagrelor group, whereas cardiovascular outcome analyses included patients from the 3 randomized arms. After adjustment, caffeine intake, compared with no intake, was not associated with lower rates of dyspnea in patients taking ticagrelor (adjusted hazard ratio (HR), 0.91; 95% CI, 0.76-1.10; P= 0.34). There was no excess risk with caffeine for major adverse cardiovascular events (adjusted HR, 0.78; 95% CI, 0.63-0.98; P=0.031), sudden cardiac death (adjusted HR, 0.98; 95% CI, 0.57-1.70; P=0.95), or atrial fibrillation (adjusted odds ratio, 1.07; 95% CI, 0.56-2.04; P=0.84). CONCLUSIONS: In patients taking ticagrelor for secondary prevention after myocardial infarction, caffeine intake at baseline was not associated with lower rates of dyspnea compared with no intake. Otherwise, caffeine appeared to be safe in this population, with no apparent increase in atherothrombotic events or clinically significant arrhythmias.
- Drug Interaction Between Clopidogrel and Ranitidine or Omeprazole in Stable Coronary Artery Disease: A Double-Blind, Double Dummy, Randomized Study(2016) FURTADO, Remo Holanda de Mendonca; GIUGLIANO, Robert Patrick; STRUNZ, Celia Maria Cassaro; CAVALHEIRO FILHO, Cyrillo; RAMIRES, Jose Antonio Franchini; KALIL FILHO, Roberto; LEMOS NETO, Pedro Alves; PEREIRA, Alexandre Costa; ROCHA, Tania Rubia; FREIRE, Beatriz Tonon; D'AMICO, Elbio Antonio; NICOLAU, Jose CarlosBackground Proton-pump inhibitors (PPIs) are often prescribed to patients receiving dual antiplatelet therapy (DAPT). However, this class of medication, especially omeprazole, has been associated with a reduction in clopidogrel efficacy, leading many clinicians to substitute omeprazole with ranitidine. Objectives Our objective was to compare the antiplatelet effect of clopidogrel before and after the addition of omeprazole or ranitidine. Methods We measured platelet aggregability at baseline and after 1 week of clopidogrel 75 mg daily. Subjects were then randomized in a double-blinded, double-dummy fashion to omeprazole 20 mg twice daily (bid) or ranitidine 150 mg bid. We repeated aggregability tests after 1 additional week, using VerifyNow P2Y12 (TM) (Accumetrics; San Diego, CA, USA), depicting aggregability as percent inhibition of platelet aggregation (IPA). Results We enrolled 41 patients in the omeprazole group and 44 in the ranitidine group. IPA was significantly decreased after the addition of omeprazole to clopidogrel (from 26.3 +/- 32.9 to 17.4 +/- 33.1 %; p = 0.025), with no statistical significant changes observed in the ranitidine group (from 32.6 +/- 28.9 to 30.1 +/- 31.3 %; p = 0.310). The comparison of IPA in both groups at the end of the follow-up showed a trend toward significance (p = 0.07, 95 % confidence interval [CI] -1.19 to 26.59); after excluding homozygous patients for 2C19*2 genotype, the comparison of IPA between the groups reached statistical significance (32.7 +/- 30.8 vs. 17.7 +/- 33.4 %, respectively, for ranitidine and omeprazole groups; p = 0.04). Conclusions Unlike omeprazole, ranitidine did not influence platelet aggregability response to clopidogrel.
conferenceObject Platelet aggregability evaluation in patients with acute coronary syndromes scheduled for coronary artery bypass graft. The PLAT-CABG study(2019) NAKASHIMA, C. A. K.; DALLAN, L. A. O.; LISBOA, L. A. F.; HAJJAR, L. A.; SOEIRO, A. M.; SILVA, B. A.; COSTA, M. S. S.; DORNAS, C. J. C. B.; DALCOQUIO, T. F.; FURTADO, R. H. M.; BARACIOLI, L. M.; FUKUSHIMA, J. T.; GURBEL, P. A.; GIUGLIANO, R. P.; NICOLAU, J. C.- Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus Insights From the DECLARE-TIMI 58 Trial(2020) ZELNIKER, Thomas A.; BONACA, Marc P.; FURTADO, Remo H. M.; MOSENZON, Ofri; KUDER, Julia F.; MURPHY, Sabina A.; BHATT, Deepak L.; LEITER, Lawrence A.; MCGUIRE, Darren K.; WILDING, John P. H.; BUDAJ, Andrzej; KISS, Robert G.; PADILLA, Francisco; GAUSE-NILSSON, Ingrid; LANGKILDE, Anna Maria; RAZ, Itamar; SABATINE, Marc S.; WIVIOTT, Stephen D.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). SGLT2 (sodium-glucose cotransporter 2) inhibitors have been shown to lower blood pressure, reduce weight, have salutary effects on left ventricular remodeling, and reduce hospitalization for HF and cardiovascular death in patients with type 2 diabetes mellitus. We therefore investigated whether SGLT2 inhibitors could also reduce the risk of AF/AFL. Methods: DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) studied the efficacy and safety of the SGLT2 inhibitor dapagliflozin versus placebo in 17 160 patients with type 2 diabetes mellitus and either multiple risk factors for atherosclerotic cardiovascular disease (n=10 186) or known atherosclerotic cardiovascular disease (n=6974). We explored the effect of dapagliflozin on the first and total number of AF/AFL events in patients with (n=1116) and without prevalent AF/AFL using Cox and negative binomial models, respectively. AF/AFL events were identified by search of the safety database using MedDRA preferred terms (""atrial fibrillation,"" ""atrial flutter""). Results: Dapagliflozin reduced the risk of AF/AFL events by 19% (264 versus 325 events; 7.8 versus 9.6 events per 1000 patient-years; hazard ratio [HR], 0.81 [95% CI, 0.68-0.95]; P=0.009). The reduction in AF/AFL events was consistent regardless of presence or absence of a history of AF/AFL at baseline (previous AF/AFL: HR, 0.79 [95% CI, 0.58-1.09]; no AF/AFL: HR, 0.81 [95% CI, 0.67-0.98]; P for interaction 0.89). Similarly, presence of atherosclerotic cardiovascular disease (HR, 0.83 [95% CI, 0.66-1.04]) versus multiple risk factors (HR, 0.78 [95% CI, 0.62-0.99]; P for interaction 0.72) or a history of HF (HF: HR, 0.78 [95% CI, 0.55-1.11]; No HF: HR, 0.81 [95% CI, 0.68-0.97]; P for interaction 0.88) did not modify the reduction in AF/AFL events observed with dapagliflozin. Moreover, there was no effect modification by sex, history of ischemic stroke, glycated hemoglobin A(1c), body mass index, blood pressure, or estimated glomerular filtration rate (all P for interaction >0.20). Dapagliflozin also reduced the total number (first and recurrent) of AF/AFL events (337 versus 432; incidence rate ratio, 0.77 [95% CI, 0.64-0.92]; P=0.005). Conclusions: Dapagliflozin decreased the incidence of reported episodes of AF/AFL adverse events in high-risk patients with type 2 diabetes mellitus. This effect was consistent regardless of the patient's previous history of AF, atherosclerotic cardiovascular disease, or HF. Registration: URL: ; Unique identifier: NCT01730534.