Sodium Thiosulfate in Acute Myocardial Infarction: A Randomized Clinical Trial.
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SUBMITTER: de Koning MLY
PROVIDER: S-EPMC10714171 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
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Sodium Thiosulfate in Acute Myocardial Infarction: A Randomized Clinical Trial.
de Koning Marie-Sophie L Y MLY van Dorp Paulien P Assa Solmaz S Pundziute-Do Prado Gabija G Voskuil Michiel M Anthonio Rutger L RL Veen Duco D Leiner Tim T Sibeijn-Kuiper Anita J AJ van Goor Harry H van Veldhuisen Dirk J DJ van der Meer Peter P Nijveldt Robin R Lipšic Erik E van der Harst Pim P
JACC. Basic to translational science 20230823 10
In this proof-of-principle trial, the hypothesis was investigated that sodium thiosulfate (STS), a potent antioxidant and hydrogen sulfide donor, reduces reperfusion injury. A total of 373 patients presenting with a first ST-segment elevation myocardial infarction received either 12.5 g STS intravenously or matching placebo at arrival at the hospital and 6 hours later. The primary outcome, infarct size, measured by cardiac magnetic resonance at 4 months after randomization, did not differ betwee ...[more]
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Project description:AimDespite prompt revascularization of acute myocardial infarction (AMI), substantial myocardial injury may occur, in part a consequence of ischaemia reperfusion injury (IRI). There has been considerable interest in therapies that may reduce IRI. In experimental models of AMI, sodium nitrite substantially reduces IRI. In this double-blind randomized placebo controlled parallel-group trial, we investigated the effects of sodium nitrite administered immediately prior to reperfusion in patients with acute ST-elevation myocardial infarction (STEMI).Methods and resultsA total of 229 patients presenting with acute STEMI were randomized to receive either an i.v. infusion of 70 μmol sodium nitrite (n = 118) or matching placebo (n = 111) over 5 min immediately before primary percutaneous intervention (PPCI). Patients underwent cardiac magnetic resonance imaging (CMR) at 6-8 days and at 6 months and serial blood sampling was performed over 72 h for the measurement of plasma creatine kinase (CK) and Troponin I. Myocardial infarct size (extent of late gadolinium enhancement at 6-8 days by CMR-the primary endpoint) did not differ between nitrite and placebo groups after adjustment for area at risk, diabetes status, and centre (effect size -0.7% 95% CI: -2.2%, +0.7%; P = 0.34). There were no significant differences in any of the secondary endpoints, including plasma troponin I and CK area under the curve, left ventricular volumes (LV), and ejection fraction (EF) measured at 6-8 days and at 6 months and final infarct size (FIS) measured at 6 months.ConclusionsSodium nitrite administered intravenously immediately prior to reperfusion in patients with acute STEMI does not reduce infarct size.
| S-EPMC4019912 | biostudies-literature
Project description:The acute myocardial infarction (AMI) present high mortality rate that may be reduced with cardiac rehabilitation. Despite its good establishment in outpatient care, few studies analyzed cardiac rehabilitation during hospitalization. Thus, this study aims to clarify the safety and efficacy of early cardiac rehabilitation after AMI. This will be a clinical, controlled, randomized trial with blind outcome evaluation and a superiority hypothesis. Twenty-four patients with AMI will be divided into two groups (1:1 allocation ratio). The intervention group will receive an individualized exercise-based cardiac rehabilitation protocol during hospitalization and a semi-supervised protocol after hospital discharge; the control group will receive conventional care. The primary outcomes will be the cardiac remodeling assessed by cardiac magnetic resonance imaging, functional capacity assessed by maximal oxygen consumption, and cardiac autonomic balance examined via heart rate variability. Secondary outcomes will include safety and the total exercise dose provided during the protocol. Statistical analysis will consider the intent-to-treat analysis. Trial registration. Trial registration number: Brazilian Registry of Clinical Trials (ReBEC) (RBR- 9nyx8hb).
| S-EPMC10781044 | biostudies-literature
Project description:RationalePreclinical evidence demonstrates that inorganic nitrite, after its in situ conversion to nitric oxide, attenuates consequent myocardial reperfusion injury.ObjectiveWe investigated whether intracoronary injection of nitrite during primary percutaneous coronary intervention might improve infarct size in ST-elevated myocardial infarction.Methods and resultsPatients undergoing primary percutaneous coronary intervention (n=80) were randomized to receive intracoronary (10 mL) sodium nitrite (1.8 μmol) or NaCl (placebo) before balloon inflation. The primary end point was infarct size assessed by measuring creatine kinase release. Secondary outcomes included infarct size assessed by troponin T release and by cardiac MRI on day 2. Baseline characteristics were similar between the groups. No evidence of differences in creatine kinase release (P=0.92), troponin T (P=0.85), or cardiac MRI-assessed infarct size (P=0.254) were evident. In contrast, there was an improvement [corrected] in myocardial salvage index (P=0.05) and reduction in [corrected] major adverse cardiac event at 1 year (2.6% versus 15.8%; P=0.04) in the nitrite group. In a 66-patient subgroup with thrombolysis in myocardial infarction ≤1 flow, there was reduced serum creatine kinase (P=0.030) and a 19% reduction in cardiac MRI-determined infarct size (P=0.034) with nitrite. No adverse effects of nitrite were detected.ConclusionsIn this phase II study, intracoronary nitrite infusion did not alter infarct size, although a trend to improved myocardial salvage index and a significant reduction in major adverse cardiac event was evident. In a subgroup of patients with thrombolysis in myocardial infarction flow ≤1, nitrite reduced infarct size and major adverse cardiac event and improved myocardial salvage index, indicating that a phase III clinical trial assessing intracoronary nitrite administration as an adjunct to percutaneous coronary intervention in ST-elevated myocardial infarction patients is warranted.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT01584453.
| S-EPMC4340586 | biostudies-literature
Project description:BackgroundGiven the shortage of cardiac rehabilitation (CR) programs in India and poor uptake worldwide, there is an urgent need to find alternative models of CR that are inexpensive and may offer choice to subgroups with poor uptake (e.g., women and elderly).ObjectivesThis study sought to evaluate the effects of yoga-based CR (Yoga-CaRe) on major cardiovascular events and self-rated health in a multicenter randomized controlled trial.MethodsThe trial was conducted in 24 medical centers across India. This study recruited 3,959 patients with acute myocardial infarction with a median and minimum follow-up of 22 and 6 months. Patients were individually randomized to receive either a Yoga-CaRe program (n = 1,970) or enhanced standard care involving educational advice (n = 1,989). The co-primary outcomes were: 1) first occurrence of major adverse cardiovascular events (MACE) (composite of all-cause mortality, myocardial infarction, stroke, or emergency cardiovascular hospitalization); and 2) self-rated health on the European Quality of Life-5 Dimensions-5 Level visual analogue scale at 12 weeks.ResultsMACE occurred in 131 (6.7%) patients in the Yoga-CaRe group and 146 (7.4%) patients in the enhanced standard care group (hazard ratio with Yoga-CaRe: 0.90; 95% confidence interval [CI]: 0.71 to 1.15; p = 0.41). Self-rated health was 77 in Yoga-CaRe and 75.7 in the enhanced standard care group (baseline-adjusted mean difference in favor of Yoga-CaRe: 1.5; 95% CI: 0.5 to 2.5; p = 0.002). The Yoga-CaRe group had greater return to pre-infarct activities, but there was no difference in tobacco cessation or medication adherence between the treatment groups (secondary outcomes).ConclusionsYoga-CaRe improved self-rated health and return to pre-infarct activities after acute myocardial infarction, but the trial lacked statistical power to show a difference in MACE. Yoga-CaRe may be an option when conventional CR is unavailable or unacceptable to individuals. (A study on effectiveness of YOGA based cardiac rehabilitation programme in India and United Kingdom; CTRI/2012/02/002408).
| S-EPMC7132532 | biostudies-literature
Project description:ContextThe acute phase of the nonthyroidal illness syndrome (NTIS) is characterized by low T3 and high rT3 levels, affecting up to 75% of critically ill patients. Oxidative stress has been implicated as a causative factor of the disturbed peripheral thyroid hormone metabolism.ObjectiveThe objective of the study was to investigate whether N-acetylcysteine (NAC), a potent intracellular antioxidant, can prevent NTIS in patients with acute myocardial infarction.DesignThis was a randomized, multicenter clinical trial.SettingsConsecutive patients admitted to the emergency and intensive care units of two tertiary hospitals in southern Brazil were recruited. Patients and intervention included 67 patients were randomized to receive NAC or placebo during 48 hours. Baseline characteristics and blood samples for thyroid hormones and oxidative parameters were collected.Main outcomeVariation of serum T3 and rT3 levels was measured.ResultsBaseline characteristics were similar between groups (all P > .05). T3 levels decreased in the placebo group at 12 hours of follow-up (P = .002) but not in NAC-treated patients (P = .10). Baseline rT3 levels were elevated in both groups and decreased over the initial 48 hours in the NAC-treated patients (P = .003) but not in the control group (P = .75). The free T4 and TSH levels were virtually identical between the groups throughout the study period (P > .05). Measurement of total antioxidant status and total carbonyl content demonstrated that oxidative balance was deranged in acute myocardial infarction patients, whereas NAC corrected these alterations (P < .001).ConclusionsNAC administration prevents the derangement in thyroid hormone concentrations commonly occurring in the acute phase of acute myocardial infarction, indicating that oxidative stress is involved in the NTIS pathophysiology.
| S-EPMC4255112 | biostudies-literature
Project description:ImportanceIn 2013, the Trial to Assess Chelation Therapy (TACT) reported that in 1708 patients with stable coronary disease and prior myocardial infarction (MI), oral multivitamins and multiminerals (OMVMs), in a factorial design with edetate disodium (EDTA) chelation therapy, did not reduce cardiovascular events relative to placebo OMVMs, but active EDTA combined with active OMVMs was superior to placebo OMVM/placebo EDTA.ObjectiveTo compare OMVM vs placebo in terms of efficacy for reducing major adverse cardiovascular events in patients with diabetes and prior MI.Design, setting, and participantsThe TACT2 randomized, multicenter double-masked 2 × 2 factorial clinical trial took place across 88 sites in the US and Canada. Participants were 50 years or older, had diabetes, and had an MI 6 weeks ago or more. TACT2 participants were enrolled between September 2016 and December 2020. Data were collected between October 2016 and June 2023.InterventionsSix caplets daily of a 28 component OMVM or matching OMVM placebo, and 40 weekly infusions of an EDTA-based chelation solution or matching placebo, in a 1:1:1:1 allocation ratio.Main outcomes and measuresThe primary end point was the composite of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina.ResultsA total of 1000 participants were randomized (500 in the active OMVM group and 500 in the placebo group). The median (IQR) age was 67 (60-72) years, and 730 (73%) were male. Median (IQR) follow-up was 48 (34-58) months. The primary end point occurred in 175 participants (35%) in the active OMVM group and 175 (35%) in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.80-1.22]; P = .92). The 5-year event rate for the primary end point in the EDTA chelation + active OMVM group was 34.0%; in the EDTA chelation + placebo OMVM group, 35.7%; in the placebo infusion + active OMVM group, 36.0%; and in the placebo infusion + placebo OMVM group, 34.3%. The comparison of the active infusion + active OMVM with the placebo infusion + placebo OMVM was not significant (HR, 0.91 [95% CI, 0.67-1.23]; P = .54). Although nonsignificant, there was a numerically higher event rate of MI, stroke, mortality from cardiovascular causes in the active OMVM compared to placebo OMVM group.Conclusions and relevanceThe results of this randomized clinical trial demonstrated that, for participants with chronic coronary disease, diabetes, and a previous MI, high-dose OMVM alone or in conjunction with EDTA-based chelation did not reduce cardiovascular events.Trial registrationClinicalTrials.gov Identifier: NCT02733185.
| S-EPMC11877407 | biostudies-literature
Project description:Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 inhibitor (SGLT2i), is a new type of oral antidiabetic agent. Here, we examined the effects of DAPA on AMI and investigated the potential mechanisms.Heart tissue specimens were collected from C57BL/6J mice induced by ligation of the left anterior descending coronary artery and treated with DAPA at 1 mg/kg/day dose for 4 weeks after surgery. Echocardiography, histological staining, and RNA sequencing (RNA-seq) of these specimens were performed. The differentially expressed genes of interest were confirmed by qualitative RT-PCR (RT-qPCR) and western blotting (WB). In vitro experiments were performed to evaluate the effect of DAPA on myosin light-chain 4 (Myl4) upregulation and reduction of autophagy following hypoxic treatment. As a result, DAPA could improve cardiac function post MI by upregulating Myl4 and reducing autophagy; this finding suggests that the molecular regulation associated with Myl4 might be an important mechanism of AMI treatment by SGLT2i.
2024-03-01 | GSE248442 | GEO
Project description:BackgroundThe role of a drug-coated balloon (DCB) in the treatment of acute myocardial infarction (AMI) is not well established.MethodsFive databases were searched for randomized controlled trials that compared DCB with stents in the treatment of AMI from their inception to 30 July 2021. The primary clinical endpoint was major adverse cardiac events (MACEs). Summary estimations were conducted using fixed-effects analysis complemented by several subgroups. The protocol was registered with PROSPERO (https://clinicaltrials.gov/ct2/show/CRD42021272886).ResultsA total of 4 randomized controlled trials with 485 patients were included. On routine clinical follow-up, DCB was associated with no difference in the incidence of MACEs compared with control (risk ratio [RR] 0.59 [0.31 to 1.13]; P=0.11). DCB was associated with similar MACEs compared with drug-eluting stent and lower MACEs compared with bare-metal stent. There was no difference between DCB and control in terms of all-cause mortality, cardiovascular mortality, stent thrombosis, target lesion revascularization, and minimal lumen diameter during follow-up. However, DCB was associated with a lower incidence of myocardial infarction (RR 0.16 [0.03 to 0.90]; P=0.04) and lower late lumen loss (mean difference -0.20 [-0.27 to -0.13]; P < 0.00001).ConclusionsIn treatment of patients with AMI, DCB might be a feasible interventional strategy versus control as it associated with comparable clinical outcomes. Future large-volume, well-designed randomized controlled trials to evaluating the role of the DCB in this setting are warranted.
| S-EPMC9810407 | biostudies-literature
Project description:Abstract Aims To investigate the additional prognostic value of myocardial work (MW) parameters following acute myocardial infarction (AMI). Methods and results Between 2018 and 2020, 244 patients admitted in the cardiac intensive care unit in Lille University Hospital for AMI were included. One-month following AMI, comprehensive transthoracic echocardiography (TTE) was performed to assess parameters of myocardial function. Patients were then followed for major events (ME): cardiovascular death, heart failure, and unplanned coronary revascularization. At 1-month, half of the population was symptomatic (NYHA ≥ II), and medical therapy was almost optimized (angiotensin-converting enzyme inhibitor/angiotensin 2 receptor blocker in 95.5%, beta-blockers in 96.3%, DAPT in 94.7%, and statins in 97.1%). After a median follow-up of 681 (interquartile range: 538–840) days, ME occurred in 26 patients (10.7%). Patients presenting ME were older (65.5 ± 14.2 vs. 58.1 ± 12.1years, P = 0.005) with a higher prevalence of hypertension (65.4 vs. 36.2%, P = 0.004), more impaired left ventricular (LV) function as assessed by LV ejection fraction (P = 0.07), global longitudinal strain (P = 0.03), or MW parameters [P = 0.01 for global work efficiency (GWE)], and greater LV and left atrium dilatations (P = 0.06 for left ventricular end-diastolic volume index and P = 0.03 for left atrial volume index). After adjustment, GWE was the only TTE parameter independently associated with long-term occurrence of ME (P = 0.02). A GWE value <91% was selected to identify patients at higher ME risk (hazard ratio: 95% confidence interval) = 2.94 (1.36–6.35), P = 0.0041). Conclusion Lower GWE at 1 month after AMI is independently associated with higher ME rates. A GWE <91% can improve the post-AMI patient risk stratification. Graphical Abstract Graphical abstract Flow chart summarizing the prognostic value of global work efficiency (GWE) 1-month after myocardial infarction (MI). GWE <91% was independently associated with adverse events.
| S-EPMC9242079 | biostudies-literature
Project description:AimsSodium-glucose co-transporter 2 inhibition reduces the risk of hospitalization for heart failure and for death in patients with symptomatic heart failure. However, trials investigating the effects of this drug class in patients following acute myocardial infarction are lacking.Methods and resultsIn this academic, multicentre, double-blind trial, patients (n = 476) with acute myocardial infarction accompanied by a large creatine kinase elevation (>800 IU/L) were randomly assigned to empagliflozin 10 mg or matching placebo once daily within 72 h of percutaneous coronary intervention. The primary outcome was the N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) change over 26 weeks. Secondary outcomes included changes in echocardiographic parameters. Baseline median (interquartile range) NT-proBNP was 1294 (757-2246) pg/mL. NT-proBNP reduction was significantly greater in the empagliflozin group, compared with placebo, being 15% lower [95% confidence interval (CI) -4.4% to -23.6%] after adjusting for baseline NT-proBNP, sex, and diabetes status (P = 0.026). Absolute left-ventricular ejection fraction improvement was significantly greater (1.5%, 95% CI 0.2-2.9%, P = 0.029), mean E/e' reduction was 6.8% (95% CI 1.3-11.3%, P = 0.015) greater, and left-ventricular end-systolic and end-diastolic volumes were lower by 7.5 mL (95% CI 3.4-11.5 mL, P = 0.0003) and 9.7 mL (95% CI 3.7-15.7 mL, P = 0.0015), respectively, in the empagliflozin group, compared with placebo. Seven patients were hospitalized for heart failure (three in the empagliflozin group). Other predefined serious adverse events were rare and did not differ significantly between groups.ConclusionIn patients with a recent myocardial infarction, empagliflozin was associated with a significantly greater NT-proBNP reduction over 26 weeks, accompanied by a significant improvement in echocardiographic functional and structural parameters.Clinicaltrials.gov registrationNCT03087773.
| S-EPMC9622301 | biostudies-literature