The Experts below are selected from a list of 33069 Experts worldwide ranked by ideXlab platform
Gervasio A. Lamas - One of the best experts on this subject based on the ideXlab platform.
-
differential outcomes with edetate disodium based treatment among stable post anterior vs non anterior myocardial infarction patients
Cardiovascular Revascularization Medicine, 2020Co-Authors: Eldrin F. Lewis, Gervasio A. Lamas, Christine Goertz, Daniel B. Mark, Richard L. Nahin, Francisco Ujueta, Rhonda S Roberts, Mario StylianouAbstract:Abstract Background The Trial to Assess Chelation Therapy (TACT) found that Chelation therapy significantly reduced clinical events in patients with a history of myocardial infarction (MI). The initial report of TACT included the observation of an interaction between edetate disodium infusions and MI location, as well as diabetes. Thus, we examined in greater detail the effect of edetate disodium Chelation therapy as a function of MI location and diabetes. Methods Patients (n = 1708) at least 6 weeks post-MI and age ≥ 50 were randomized to receive 40 infusions of a 500 mL Chelation solution or placebo (median follow-up 55 months). The effect of edetate disodium on the primary outcome (all-cause mortality, MI, stroke, hospitalization for angina, or coronary revascularization) was assessed as a function of MI location using log-rank test and Cox regression model, adjusting for other prognostic variables. Results Among patients with post anterior MI (n = 674), Chelation was associated with a lower risk of the primary endpoint (HR 0.63, 95% CI 0.47–0.86, p = 0.003) among anterior MI patients, but not in post non-anterior MI (n = 1034) patients (HR 0.96, 95% CI 0.77–1.20, p = 0.702) (p-for-interaction = 0.032). The point estimates for each component of the primary endpoint favored Chelation therapy. The differing treatment effect in patients with post anterior vs. non-anterior MI was consistent among patients with or without diabetes and remained significant after adjusting for other prognostic variables (p Conclusions Edetate disodium infusions reduced the risk of cardiovascular events among patients with a prior anterior MI. Future studies should focus on replicating these results and understanding the mechanisms of benefit.
-
Chelation therapy to prevent diabetes-associated cardiovascular events.
Current opinion in endocrinology diabetes and obesity, 2018Co-Authors: Denisse Diaz, Vivian Fonseca, Yamil W Aude, Gervasio A. LamasAbstract:Purpose of reviewFor over 60 years, Chelation therapy with disodium ethylene diamine tetraacetic acid (EDTA, edetate) had been used for the treatment of cardiovascular disease (CVD) despite lack of scientific evidence for efficacy and safety. The Trial to Assess Chelation Therapy (TACT) was develope
-
chronic toxic metal exposure and cardiovascular disease mechanisms of risk and emerging role of Chelation therapy
Current Atherosclerosis Reports, 2016Co-Authors: Ehimen Aneni, Gervasio A. Lamas, Esteban EscolarAbstract:Over the last few decades, there has been a growing body of epidemiologic evidence linking chronic toxic metal exposure to cardiovascular disease-related morbidity and mortality. The recent and unexpectedly positive findings from a randomized, double-blind, multicenter trial of metal Chelation for the secondary prevention of atherosclerotic cardiovascular disease (Trial to Assess Chelation Therapy (TACT)) have focused the discussion on the role of chronic exposure to toxic metals in the development and propagation of cardiovascular disease and the role of toxic metal Chelation therapy in the secondary prevention of cardiovascular disease. This review summarizes the most recent evidence linking chronic toxic metal exposure to cardiovascular disease and examines the findings of TACT.
-
Chelation therapy to treat atherosclerosis, particularly in diabetes: is it time to reconsider?
Expert review of cardiovascular therapy, 2016Co-Authors: Gervasio A. Lamas, Ian ErguiAbstract:ABSTRACTIntroduction: Case reports and case series have suggested a possible beneficial effect of Chelation therapy in patients with atherosclerotic disease. Small randomized trials conducted in patients with angina or peripheral artery disease, however, were not sufficiently powered to provide conclusive evidence on clinical outcomes.Areas covered: The Trial to Assess Chelation Therapy (TACT) was the first randomized trial adequately powered to detect the effects of Chelation therapy on clinical endpoints. We discuss results and future research.Expert commentary: Chelation reduced adverse cardiovascular events in a post myocardial infarction (MI) population. Patients with diabetes demonstrated even greater benefit, with a number needed to treat of 6.5 patients to prevent a cardiac event over 5 years, with a 41% relative reduction in risk of a cardiac event (p = 0.0002). These results led to the revision of the ACC/AHA guideline recommendations for Chelation therapy, changing its classification from class...
-
abstract 16630 clinical benefit of Chelation therapy in post mi patients with diabetes and peripheral artery disease
Circulation, 2014Co-Authors: Gervasio A. Lamas, Christine Goertz, Robin Boineau, Daniel B. Mark, Richard L. Nahin, Esteban Escolar, Patrick Golden, Dorothy Merritt, Yves Rosenberg, Lauren LindbladAbstract:Introduction: The NIH-funded Trial to Assess Chelation Therapy (TACT) reported a clinical benefit of ethylene diamine tetraacetic acid (EDTA)-based Chelation on cardiovascular (CV) outcomes in post-MI patients with diabetes (DM). Post-MI diabetic patients with peripheral artery disease (PAD) have particularly high risk. Methods: TACT, a multi-center, double-blind, placebo-controlled, trial of EDTA Chelation, enrolled patients (pts) age > 50 years with an MI at least 6 weeks prior and creatinine Results: TACT enrolled 1708 pts, of which 303 (18%) had PAD. EDTA Chelation reduced the primary endpoint by a similar extent in pts with (hazard ratio (HR) 0.7) and without PAD (HR 0.87, p for interaction 0.38). Among the 633 (37%) of patients with DM, 153 (24%) had PAD. There were 81 assigned to EDTA and 72 to placebo. Baseline characteristics including obesity, hypertension, hypercholesterolemia, heart failure, stroke and prior CABG were similar between treatment groups. Creatinine was higher in the placebo group (median 1.2 v 1.0; p=0.003). There were 80% on statins, 92% on antiplatelet or antithrombotic therapy, and 32% treated with insulin. EDTA Chelation led to a reduction in the primary endpoint (46% vs. 22%; p=0.002, Figure), and total mortality (25% v. 11%, p=0.032). HR point estimates comparing Chelation vs. placebo for each component of the composite endpoint were all Conclusions: In post-MI pts with DM and PAD treated with standard therapies, EDTA-based Chelation therapy markedly reduced cardiovascular events.
Guillermo Sanz - One of the best experts on this subject based on the ideXlab platform.
-
impact of treatment with iron Chelation therapy in patients with lower risk myelodysplastic syndromes participating in the european mds registry
Haematologica, 2020Co-Authors: Marlijn Hoeks, Saskia Langemeijer, Simon Crouch, Louise De Swart, Pierre Fenaux, Argiris Symeonidis, Jaroslav Cermak, Eva Hellstromlindberg, Guillermo SanzAbstract:Iron overload due to red blood cell (RBC) transfusions is associated with morbidity and mortality in lower-risk myelodysplastic syndrome (MDS) patients. Many studies have suggested improved survival after iron Chelation therapy (ICT), but valid data are limited. The aim of this study was to assess the effect of ICT on overall survival and hematologic improvement in lower-risk MDS patients in the European MDS registry. We compared chelated patients with a contemporary, non-chelated control group within the European MDS registry, that met the eligibility criteria for starting iron Chelation. A Cox proportional hazards model was used to assess overall survival (OS), treating receipt of Chelation as a time-varying variable. Additionally, chelated and non-chelated patients were compared using a propensity-score matched model. Of 2,200 patients, 224 received iron Chelation. The hazard ratio and 95% confidence interval for OS for chelated patients, adjusted for age, sex, comorbidity, performance status, cumulative RBC transfusions, Revised-International Prognostic Scoring System (IPSS-R), and presence of ringed sideroblasts was 0.50 (0.34-0.74). The propensity-score analysis, matched for age, sex, country, RBC transfusion intensity, ferritin level, comorbidity, performance status, and IPSS-R, and, in addition, corrected for cumulative RBC transfusions and presence of ringed sideroblasts, demonstrated a significantly improved OS for chelated patients with a hazard ratio of 0.42 (0.27-0.63) compared to non-chelated patients. Up to 39% of chelated patients reached an erythroid response. In conclusion, our results suggest that iron Chelation may improve OS and hematopoiesis in transfused lower-risk MDS patients. This trial was registered at clinicaltrials.gov identifier: 00600860.
-
evolution of iron overload in patients with low risk myelodysplastic syndrome iron Chelation therapy and organ complications
Annals of Hematology, 2015Co-Authors: Angel F Remacha, Beatriz Arrizabalaga, A Villegas, Maria Soledad Duran, Lourdes Hermosin, Raquel De Paz, M A Garcia, Maria Diez Campelo, Guillermo SanzAbstract:This study aimed to evaluate the evolution of iron overload, assessed by serum ferritin (SF), in transfusion-dependent lower risk patients with myelodysplastic syndrome (MDS), as well as to describe the occurrence of organ complications, and to analyze its relationship with iron Chelation therapy. This observational retrospective study was conducted from March 2010 to March 2011 in 47 Spanish hospitals. A total of 263 patients with lower risk MDS (International Prognostic Scoring System [IPSS] low/intermediate-1 risk or Spanish Prognostic Index [SPI] 0–1 risk), transfusion-dependent, and who had received ≥10 packed red blood cells (PRBC) were included. At MDS diagnosis, patients received a mean of 2.8 ± 3.9 PRBC/month, and 8.7 % of patients showed SF ≥1000 μg/L. Over the course of the disease, patients received a mean of 83.4 ± 83.3 PRBC, and 36.1 % of patients presented SF ≥2500 μg/L. Cardiac, hepatic, endocrine, or arthropathy complications appeared/worsened in 20.2, 11.4, 9.9, and 3.8 % of patients, respectively. According to investigator, iron overload was a main cause of hepatic (70.0 %) and endocrine (26.9 %) complications. A total of 96 (36.5 %) patients received iron Chelation therapy for ≥6 months, being deferasirox the most frequent first Chelation treatment (71.9 %). Chelation-treated patients showed longer overall survival (p < 0.001), leukemia-free survival (p = 0.007), and cardiac event-free survival (p = 0.017) than non-chelated patients. In multivariable analyses, age (p = 0.011), IPSS (p < 0.001), and Chelation treatment (p = 0.015) were predictors for overall survival; IPSS (p = 0.014) and transfusion frequency (p = 0.001) for leukemia-free survival; and Chelation treatment (p = 0.040) and Sorror comorbidity index (p = 0.039) for cardiac event-free survival. In conclusion, these results confirm the potential survival benefit of iron Chelation therapy and provide additional evidence on the deleterious effect of iron overload in lower risk MDS patients.
Patrick J Walsh - One of the best experts on this subject based on the ideXlab platform.
-
highly diastereoselective Chelation controlled additions to α silyloxy ketones
Journal of the American Chemical Society, 2011Co-Authors: Gretchen R Stanton, Gamze Koz, Patrick J WalshAbstract:The polar Felkin–Anh, Cornforth−Evans, and Cram-Chelation models predict that the addition of organometallic reagents to silyl-protected α-hydroxy ketones proceeds via a nonChelation pathway to give anti-diol addition products. This prediction has held true for the vast majority of additions reported in the literature, and few methods for Chelation-controlled additions of organometallic reagents to silyl-protected α-hydroxy ketones have been introduced. Herein, we present a general and highly diastereoselective method for the addition of dialkylzincs and (E)-di-, (E)-tri-, and (Z)-disubstituted vinylzinc reagents to α-silyloxy ketones using alkyl zinc halide Lewis acids, RZnX, to give Chelation-controlled products (dr ≥18:1). The compatibility of organozinc reagents with other functional groups makes this method potentially very useful in complex molecule synthesis.
-
overriding felkin control a general method for highly diastereoselective Chelation controlled additions to α silyloxy aldehydes
Journal of the American Chemical Society, 2010Co-Authors: Gretchen R Stanton, Corinne N Johnson, Patrick J WalshAbstract:According to the Felkin−Anh and Cram-Chelation models, nucleophilic additions to α-silyloxy aldehydes proceed through a nonChelation pathway due to the steric and electronic properties of the silyl group, giving rise to Felkin addition products. Herein we describe a general method to promote Chelation-control in additions to α-silyloxy aldehydes. Dialkylzincs, functionalized dialkylzincs, and (E)-disubstituted, (E)-trisubstituted, and (Z)-disubstituted vinylzinc reagents add to silyl-protected α-hydroxy aldehydes with high selectivity for Chelation-controlled products (dr of 10:1 to >20:1) in the presence of alkylzinc halides or triflates, RZnX. With the high functional group tolerance of organozinc reagents, the mild Lewis acidity of RZnX, and the excellent diastereoselectivities favoring the Chelation-controlled products, this method will be useful in the synthesis of natural products. A mechanism involving Chelation is supported by (1) NMR studies of a model substrate, (2) a dramatic increase in reacti...
John B. Porter - One of the best experts on this subject based on the ideXlab platform.
-
The challenges of adherence and persistence with iron Chelation therapy
International journal of hematology, 2011Co-Authors: John B. Porter, Michael Evangeli, Amal El-beshlawyAbstract:Due to advances in medical sciences, many chronic diseases that formerly resulted in early death can now be effectively managed with long-term treatment regimens. Patients with potentially fatal anemias, for example, can be treated with ongoing blood transfusions and iron Chelation therapy. Ensuring adherence and persistence is challenging, as the benefits of therapy are not perceived immediately. Poor adherence severely compromises the effectiveness of treatment and, therefore, improving compliance in terms of quality of life and health economics is critical. Although adherence to Chelation therapy is generally poor, the availability of oral iron chelators may help to improve patient compliance. For chronic conditions such as thalassemia major, even when oral Chelation therapy is available, support by an integrated team including a clinical psychologist and nurse specialist working with the treatment center is recommended to achieve optimal results.
-
iron overload in thalassemia and related conditions therapeutic goals and assessment of response to Chelation therapies
Hematology-oncology Clinics of North America, 2010Co-Authors: John B. Porter, Farrukh ShahAbstract:Transfusional iron loading inevitably results in hepatic iron accumulation, with variable extrahepatic distribution that is typically less pronounced in sickle cell disease than in thalassemia disorders. Iron Chelation therapy has the goal of preventing iron-mediated tissue damage through controlling tissue iron levels, without incurring chelator-mediated toxicity. Historically, target levels for tissue iron control have been limited by the increased frequency of deferoxamine-mediated toxicity and low levels of iron loading. With newer Chelation regimes, these limitations are less evident. The reporting of responses to Chelation therapies has typically focused on average changes in serum ferritin in patient populations. This approach has three limitations. First, changes in serum ferritin may not reflect trends in iron balance equally in all patients or for all Chelation regimens. Second, this provides no information about the proportion of patients likely respond. Third, this gives insufficient information about iron trends in tissues such as the heart. Monitoring of iron overload has advanced with the increasing use of MRI techniques to estimate iron balance (changes in liver iron concentration) and extrahepatic iron distribution (myocardial T2*). The term nonresponder has been increasingly used to describe individuals who fail to show a downward trend in one or more of these variables. Lack of a response of an individual may result from inadequate dosing, high transfusion requirement, poor treatment adherence, or unfavorable pharmacology of the Chelation regime. This article scrutinizes evidence for response rates to deferoxamine, deferiprone (and combinations), and deferasirox.
-
mechanisms for the shuttling of plasma non transferrin bound iron ntbi onto deferoxamine by deferiprone
Translational Research, 2010Co-Authors: Patricia Evans, Reem Kayyali, Robert C Hider, John F Eccleston, John B. PorterAbstract:In iron overload conditions, plasma contains non-transferrin bound iron species, collectively referred to as plasma NTBI. These include iron citrate species, some of which are protein bound. Because NTBI is taken into tissues susceptible to iron loading, its removal by Chelation is desirable but only partial using standard deferoxamine (DFO) therapy. Speciation plots suggest that, at clinically achievable concentrations, deferiprone (DFP) will shuttle iron onto DFO to form feroxamine (FO), but whether NTBI Chelation by DFO is enhanced to therapeutically relevant rates by DFP is unknown. As FO is highly stable, kinetic measurements of FO formation by high-performance liquid chromatography or by stopped-flow spectrometry are achievable. In serum from thalassemia major patients supplemented with 10 μM DFO, FO formation paralleled NTBI removal but never exceeded 50% of potentially available NTBI; approximately one third of NTBI was chelated rapidly but only 15% of the remainder at 20 h. Addition of DFP increased the magnitude of the slower component, with increments in FO formation equivalent to complete NTBI removal by 8 h. This shuttling effect was absent in serum from healthy control subjects, indicating no transferrin iron removal. Studies with iron citrate solutions also showed biphasic Chelation by DFO, the slow component being accelerated by the addition of DFP, with optimal enhancement at 30 μM. Physiological concentrations of albumin also enhanced DFO Chelation from iron citrate, and the co-addition of DFP further accelerated this effect. We conclude that at clinically relevant concentrations, DFP enhances plasma NTBI Chelation with DFO by rapidly accessing and shuttling NTBI fractions that are otherwise only slowly available to DFO.
-
optimizing iron Chelation strategies in β thalassaemia major
Blood Reviews, 2009Co-Authors: John B. PorterAbstract:beta-thalassaemia has served as a paradigm for Chelation management for over three decades, both in terms of defining the complications of transfusional iron overload, and demonstrating the benefits of Chelation therapy. Iron Chelation therapy can be used to reduce unacceptably high tissue iron levels, or to maintain current levels if these are deemed safe, by matching the rate of transfused iron. Chelation therapy should be tailored to the individual patient, based on the transfusional iron loading rate and the current level of iron load both intra- and extra-hepatically, for example in the myocardium. In general, it is preferable to prevent extra-hepatic complications by controlling the body iron load rather than attempting to rescue patients once extra-hepatic complications have developed. Deferoxamine, which has been available since the late 1970s and is given parenterally, has been shown to prolong life and decrease morbidity from iron overload in patients who comply with therapy. Deferiprone may control body iron as oral monotherapy in a variable proportion of patients but is now more frequently used in combinations with deferoxamine, either to control total levels of body iron or to reduce increased levels of myocardial iron. In this article, recent advances in the use of deferasirox, a once-daily oral iron chelator, are reviewed. Large-scale prospective trials show efficacy with an acceptable safety profile in adults and children with up to 5 years follow-up. Recent evidence suggests that deferasirox up to 30 mg/kg/day can be safely administered to patients with serum ferritin levels between 500 and 1000 mg/L, while doses above 30 mg/kg/day can be given to patients with substantial iron overload or with high transfusion rates. Further, prospective data show that myocardial iron can be effectively decreased with this Chelation treatment.
Esteban Escolar - One of the best experts on this subject based on the ideXlab platform.
-
chronic toxic metal exposure and cardiovascular disease mechanisms of risk and emerging role of Chelation therapy
Current Atherosclerosis Reports, 2016Co-Authors: Ehimen Aneni, Gervasio A. Lamas, Esteban EscolarAbstract:Over the last few decades, there has been a growing body of epidemiologic evidence linking chronic toxic metal exposure to cardiovascular disease-related morbidity and mortality. The recent and unexpectedly positive findings from a randomized, double-blind, multicenter trial of metal Chelation for the secondary prevention of atherosclerotic cardiovascular disease (Trial to Assess Chelation Therapy (TACT)) have focused the discussion on the role of chronic exposure to toxic metals in the development and propagation of cardiovascular disease and the role of toxic metal Chelation therapy in the secondary prevention of cardiovascular disease. This review summarizes the most recent evidence linking chronic toxic metal exposure to cardiovascular disease and examines the findings of TACT.
-
abstract 16630 clinical benefit of Chelation therapy in post mi patients with diabetes and peripheral artery disease
Circulation, 2014Co-Authors: Gervasio A. Lamas, Christine Goertz, Robin Boineau, Daniel B. Mark, Richard L. Nahin, Esteban Escolar, Patrick Golden, Dorothy Merritt, Yves Rosenberg, Lauren LindbladAbstract:Introduction: The NIH-funded Trial to Assess Chelation Therapy (TACT) reported a clinical benefit of ethylene diamine tetraacetic acid (EDTA)-based Chelation on cardiovascular (CV) outcomes in post-MI patients with diabetes (DM). Post-MI diabetic patients with peripheral artery disease (PAD) have particularly high risk. Methods: TACT, a multi-center, double-blind, placebo-controlled, trial of EDTA Chelation, enrolled patients (pts) age > 50 years with an MI at least 6 weeks prior and creatinine Results: TACT enrolled 1708 pts, of which 303 (18%) had PAD. EDTA Chelation reduced the primary endpoint by a similar extent in pts with (hazard ratio (HR) 0.7) and without PAD (HR 0.87, p for interaction 0.38). Among the 633 (37%) of patients with DM, 153 (24%) had PAD. There were 81 assigned to EDTA and 72 to placebo. Baseline characteristics including obesity, hypertension, hypercholesterolemia, heart failure, stroke and prior CABG were similar between treatment groups. Creatinine was higher in the placebo group (median 1.2 v 1.0; p=0.003). There were 80% on statins, 92% on antiplatelet or antithrombotic therapy, and 32% treated with insulin. EDTA Chelation led to a reduction in the primary endpoint (46% vs. 22%; p=0.002, Figure), and total mortality (25% v. 11%, p=0.032). HR point estimates comparing Chelation vs. placebo for each component of the composite endpoint were all Conclusions: In post-MI pts with DM and PAD treated with standard therapies, EDTA-based Chelation therapy markedly reduced cardiovascular events.
-
Chelation therapy after the trial to assess Chelation therapy: results of a unique trial.
Current opinion in cardiology, 2014Co-Authors: Maria D. Avila, Esteban Escolar, Gervasio A. LamasAbstract:Purpose of reviewEDTA Chelation therapy has been in off-label use for the treatment of atherosclerosis. We review the results of the first large-scale randomized trial of this treatment.Recent findingsThe trial to assess Chelation therapy was a $30 million National Institutes of Health-funded study
-
the effect of an edta based Chelation regimen on patients with diabetes mellitus and prior myocardial infarction in the trial to assess Chelation therapy tact
Circulation-cardiovascular Quality and Outcomes, 2014Co-Authors: Esteban Escolar, Gervasio A. Lamas, Christine Goertz, Robin Boineau, Daniel B. Mark, Theodore Rozema, Richard L. Nahin, Pamela Ouyang, Yves Rosenberg, Allan MagazinerAbstract:Background—The Trial to Assess Chelation Therapy (TACT) showed clinical benefit of an EDTA-based infusion regimen in patients aged ≥50 years with prior myocardial infarction. Diabetes mellitus before enrollment was a prespecified subgroup. Methods and Results—Patients received 40 infusions of EDTA Chelation or placebo. A total of 633 (37%) patients had diabetes mellitus (322 EDTA and 311 placebo). EDTA reduced the primary end point (death, reinfarction, stroke, coronary revascularization, or hospitalization for angina; 25% versus 38%; hazard ratio, 0.59; 95% confidence interval [CI], 0.44–0.79; P<0.001) over 5 years. The result remained significant after Bonferroni adjustment for multiple subgroups (99.4% CI, 0.39–0.88; adjusted P=0.002). All-cause mortality was reduced by EDTA Chelation (10% versus 16%; hazard ratio, 0.57; 95% CI, 0.36–0.88; P=0.011), as was the secondary end point (cardiovascular death, reinfarction, or stroke; 11% versus 17%; hazard ratio, 0.60; 95% CI, 0.39–0.91; P=0.017). However, af...