scholarly journals Aldosterone Blockade in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Qiao Chen ◽  
Die Zhao ◽  
Jie Sun ◽  
Chengzhi Lu

Background. A comprehensive evaluation of the benefits of mineralocorticoid receptor antagonists (MRA) in acute myocardial infarction (AMI) patients is lacking. Objective. To summarize the evidence on the efficacy and safety of MRA in patients admitted for AMI. Methods. Articles were identified through PubMed, Embase, Cochrane Library, Ovid (Medline1946-2021), and ClinicalTrials.gov databases from their inception to December 31, 2020. Results. 15 articles with a total of 11,861 patients were included. MRA reduced the risk of all-cause mortality by 16% (relative ratio (RR): 0.84; 95% confidence interval (CI) (0.76, 0.94); P = 0.002 ) and the incidence of cardiovascular adverse events by 12% (RR: 0.88, 95% CI (0.83, 0.93), P < 0.00001 ) in post-AMI patients, and further analysis demonstrated that early administration of MRA within 7 days after AMI resulted in a greater reduction in all-cause mortality (RR: 0.72, 95% CI (0.61, 0.85), P < 0.0001 ). Subgroup analyses showed that post-STEMI patients without left ventricular systolic dysfunction (LVSD) treated with MRA had a 36% reduction in all-cause mortality (RR: 0.64, 95% CI (0.46, 0.89), P = 0.007 ) and a 22% reduction in cardiovascular adverse events (RR: 0.78, 95% CI (0.67, 0.91), P = 0.002 ). Meanwhile, post-STEMI patients without LVSD treated with MRA get significant improvements in left ventricular ejection fraction (mean difference (MD): 2.69, 95% CI (2.44, 2.93), P < 0.00001 ), left ventricular end-systolic index (MD: -4.52 ml/m2, 95% CI (-8.21, -0.83), P = 0.02 ), and left ventricular end-diastolic diameter (MD: -0.11 cm, 95% CI (-0.22, 0.00), P = 0.05 ). The corresponding RR were 1.72 (95% CI (1.43, 2.07), P < 0.00001 ) for considered common adverse events (hyperkalemia, gynecomastia, and renal dysfunction). Conclusions. Our findings suggest that MRA treatment reduces all-cause mortality and cardiovascular adverse events in post-AMI patients, which is more significant in patients after STEMI without LVSD. In addition, MRA treatment may exert beneficial effects on the reversal of cardiac remodeling in patients after STEMI without LVSD.

2021 ◽  
Author(s):  
Qiao Chen ◽  
Zhuqing Li ◽  
Die Zhao ◽  
Jie Sun ◽  
Yiling Wang ◽  
...  

Abstract Purpose: A comprehensive evaluation of the benefits of mineralocorticoid receptor antagonists (MRA) in acute myocardial infarction (AMI) patients is lacking. We aimed to summarize the evidence on the efficacy and safety of MRA in post-AMI patients.Methods: Articles were identified through PubMed, Embase, Cochrane Library, Ovid (Medline1946-2021) and ClinicalTrials.gov databases from their inception to Dec 31, 2020. Results: MRA reduced the risk of all-cause mortality by 16% (relative ratio(RR) 0.84, 95% confidence interval(CI) (0.76,0.94), P=.002), new or worsening heart failure (HF) 14% (RR 0.86, 95%CI (0.78,0.96), P=.007), death from HF by 22% (RR 0.78, 95%CI (0.62,0.99), P=.04), and cardiovascular death by 16% (RR 0.84, 95%CI (0.74,0.94), P=.003) in post-AMI patients. Meanwhile, all-cause mortality was reduced by 38% (RR 0.62, 95%CI (0.42,0.90), P=.01), 30% (RR 0.70, 95%CI (0.49,1.00), P=.05), and 29% (RR 0.71, 95%CI (0.59,0.86), P=.0004) in ST-elevation myocardial infarction (STEMI) patients and those who initiated MRA treatment within 3 days and (3,7) days, respectively. Post-AMI patients without left ventricular systolic dysfunction (LVSD) treated with MRA improved left ventricular ejection fraction (mean difference[MD] 2.74, 95%CI (2.49,2.99), P<.00001) and reduced left ventricular end-systolic and end-diastolic volume indices (MD -6.23, 95%CI (-10.93,-1.52), P=.009; MD -3.13, 95%CI (-5.79,-0.47), P=.02). The corresponding RR were 1.73 (95%CI (1.44,2.08), P<.00001) for considered common side effects (hyperkalemia and gynecomastia).Conclusion: Our findings suggest that all-cause mortality is lower in STEMI patients and in patients initiating MRA within 7 days, and that post-AMI patients without LVSD have improved left ventricular remodeling and cardiac function.


2021 ◽  
Author(s):  
Qiao Chen ◽  
Die Zhao ◽  
Jie Sun ◽  
Chengzhi Lu

Abstract We aimed to summarize the evidence on the efficacy and safety of mineralocorticoid receptor antagonists (MRA) in post acute myocardial infarction (AMI) patients. Articles were identified through PubMed, Embase, Cochrane Library, Ovid (Medline1946-2021) and ClinicalTrials.gov databases from their inception to December 31, 2020. MRA reduced the risk of all-cause mortality by 16% (relative ratio (RR) 0.84, 95% confidence interval (CI) (0.76, 0.94), P = 0.002). Meanwhile, all-cause mortality was reduced by 38% (RR 0.62, 95% CI (0.42, 0.90), P = 0.01), 30% (RR 0.70, 95% CI (0.49, 1.00), P = 0.05), and 29% (RR 0.71, 95% CI (0.59, 0.86), P = 0.0004) in ST-elevation myocardial infarction (STEMI) patients and those who initiated MRA treatment within 3 days and (3,7) days, respectively. Post-AMI patients without left ventricular systolic dysfunction (LVSD) treated with MRA improved left ventricular ejection fraction (mean difference [MD] 2.74, 95% CI (2.49, 2.99), P < 0.00001) and reduced left ventricular end-systolic and end-diastolic volume indices (MD -6.23, 95% CI (-10.93, -1.52), P = 0.009; MD -3.13, 95% CI (-5.79, -0.47), P = 0.02). The corresponding RR were 1.73 (95% CI (1.44, 2.08), P < 0.00001) for considered common side effects (hyperkalemia and gynecomastia). Our findings suggest that all-cause mortality is lower in STEMI patients and in patients initiating MRA within 7 days, and that post-AMI patients without LVSD have improved left ventricular remodeling and cardiac function.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Von Lewinski ◽  
B Merkely ◽  
I Buysschaert ◽  
R.A Schatz ◽  
G.G Nagy ◽  
...  

Abstract Background Regenerative therapies offer new approaches to improve cardiac function after acute ST-elevation myocardial infarction (STEMI). Mobilization of stem cells and homing within the infarcted area have been identified as the key mechanisms for successful treatment. Application of granulocyte-colony stimulating factor (G-CSF) is the least invasive way to mobilize stem cells while DDP4-inhibitor facilitates homing via stromal cell-derived factor 1 alpha (SDF-1α). Dutogliptin, a novel DPP4 inhibitor, combined with stem cell mobilization using G-CSF significantly improved survival and reduced infarct size in a murine model. Purpose We initiated a phase II, multicenter, randomized, placebo-controlled efficacy and safety study (N=140) analyzing the effect of combined application of G-CSF and dutogliptin, a small molecule DPP-IV-inhibitor for subcutaneous use after acute myocardial infarction. Methods The primary objective of the study is to evaluate the safety and tolerability of dutogliptin (14 days) in combination with filgrastim (5 days) in patients with STEMI (EF &lt;45%) following percutaneous coronary intervention (PCI). Preliminary efficacy will be analyzed using cardiac magnetic resonance imaging (cMRI) to detect &gt;3.8% improvement in left ventricular ejection fraction (LV-EF). 140 subjects will be randomized to filgrastim plus dutogliptin or matching placebos. Results Baseline characteristics of the first 26 patients randomized (24 treated) in this trial reveal a majority of male patients (70.8%) and a medium age of 58.4 years (37 to 84). During the 2-week active treatment period, 35 adverse events occurred in 13 patients, with 4 rated as serious (hospitalization due to pneumonia N=3, hospitalization due to acute myocardial infarction N=1), and 1 adverse event was rated as severe (fatal pneumonia), 9 moderate, and 25 as mild. 6 adverse events were considered possibly related to the study medication, including cases of increased hepatic enzymes (N=3), nausea (N=1), subcutaneous node/suffusion (N=1) and syncope (N=1). Conclusions Our data demonstrate that the combined application of dutogliptin and G-CSF appears to be safe on the short term and feasible after acute myocardial infarction and may represent a new therapeutic option in future. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This research is funded by the sponsor RECARDIO, Inc., 1 Market Street San Francisco, CA 94150, USA. RECARDIO Inc. is funding the complete study. The Scientific Board of RECARDIO designed the study. Data Collection is at the participating sites. Interpretation of the data by the Scientific Board and Manuscript written by the authors and approved by the Sponsor


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Thomsen ◽  
S Pedersen ◽  
P K Jacobsen ◽  
H V Huikuri ◽  
P E Bloch Thomsen ◽  
...  

Abstract Introduction The CARISMA trial was the first study to use continuous monitoring for documentation of long-term arrhythmias in post-infarction patients with left ventricular dysfunction. During the study duration (2000–2005), primary PCI (pPCI) as treatment of acute myocardial infarction was introduced approximately midway (2002) on the enrolling centres. Purpose The aim of this study was to describe the influence of mode of revascularization after myocardial infarction (AMI) on long-term risk of risk of new onset atrial fibrillation, ventricular tachyarrhythmias and brady arrhythmias. Methods The study is a sub-study on the CARISMA study population that consisted of patients with AMI and left ventricular ejection fraction ≤40%, which received an implantable loop recorder and was followed for 2 years. After exclusion of 15 patients who refused device implantation and 26 with pre-existing arrhythmias, 268 of the 312 patients were included. Choice of revascularization was made by the treating team independently of the trial and was retrospectively divided into primary percutaneous intervention (pPCI), subacute PCI (24 hours to 2 weeks after AMI), primary thrombolysis or no revascularization. Endpoints were new-onset of arrhythmias and major cardiovascular events (MACE). The Kaplan-Meier (figure 1) and Mantel-Byar methods were used for time to first event risk analysis. Results A total of 77 patients received no revascularization, whereas 49 received thrombolysis only and 142 received PCI. At two-years follow up patients treated with any PCI had a significant lower risk (0.40, n=63) of any arrhythmia compared to patients treated with trombolysis (0.60, n=30) or no revascularization (0.68, n=16) (p<0.001, unadjusted) (figure 1). Risk of MACE was significant higher in patients with any arrhythmia (0.25, n=76) compared to no arrhythmia (0.11, n=93) at two years follow-up (p=0.004, unadjusted). Figure 1 Conclusion(s) The long-term risk of new onset arrhythmias after AMI was significantly lower in patients treated with any PCI compared to patients not revascularized or treated with thrombolysis. Risk of MACE was significantly higher in patients with new onset arrhythmias compared to patients with no arrhythmias.


2020 ◽  
Vol 41 (38) ◽  
pp. 3702-3710 ◽  
Author(s):  
Anthony Mathur ◽  
Francisco Fernández-Avilés ◽  
Jozef Bartunek ◽  
Ann Belmans ◽  
Filippo Crea ◽  
...  

Abstract Aims  Bone marrow-derived mononuclear cell (BM-MNC) therapy may improve myocardial recovery in patients following acute myocardial infarction (AMI), though existing trial results are inconsistent. Methods and results  Originally an open-label, multicentre Phase III trial, BAMI was designed to demonstrate the safety and efficacy of intracoronary infusion of BM-MNCs in reducing the time to all-cause mortality in patients with reduced left ventricular ejection fraction (LVEF, ≤45%) after primary angioplasty (PPCI) for ST-elevation AMI. Unexpectedly low recruitment means the trial no longer qualifies as a hypothesis-testing trial, but is instead an observational study with no definitive conclusions possible from statistical analysis. In total, 375 patients were recruited: 185 patients were randomized to the treatment arm (intracoronary infusion of BM-MNCs 2–8 days after PPCI) and 190 patients to the control arm (optimal medical therapy). All-cause mortality at 2 years was 3.26% [6 deaths; 95% confidence interval (CI): 1.48–7.12%] in the BM-MNC group and 3.82% (7 deaths; 95% CI: 1.84–7.84%) in the control group. Five patients (2.7%, 95% CI: 1.0–5.9%) in the BM-MNC group and 15 patients (8.1%, CI : 4.7–12.5%) in the control group were hospitalized for heart failure during 2 years of follow-up. Neither adverse events nor serious adverse events differed between the two groups. There were no patients hospitalized for stroke in the control group and 4 (2.2%) patients hospitalized for stroke in the BM-MNC group. Conclusions  Although BAMI is the largest trial of autologous cell-based therapy in the treatment of AMI, unexpectedly low recruitment and event rates preclude any meaningful group comparisons and interpretation of the observed results.


Open Heart ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. e000987 ◽  
Author(s):  
Brunilda Alushi ◽  
Andel Douedari ◽  
Georg Froehlig ◽  
Wulf Knie ◽  
Thomas H Wurster ◽  
...  

ObjectiveWe investigated the benefit of Impella, a modern percutaneous mechanical support (pMCS) device, versus former standard intra-aortic balloon pump (IABP) in acute myocardial infarction complicated by cardiogenic shock (AMICS).MethodsThis single-centre, retrospective study included patients with AMICS receiving pMCS with either Impella or IABP. Disease severity at baseline was assessed with the IABP-SHOCK II score. The primary outcome was all-cause mortality at 30 days. Secondary outcomes were parameters of shock severity at the early postimplantation phase. Adjusted Cox proportional hazards models identified independent predictors of the primary outcome.ResultsOf 116 included patients, 62 (53%) received Impella and 54 (47%) IABP. Despite similar baseline mortality risk (IABP-SHOCK II high-risk score of 18 % vs 20 %; p = 0.76), Impella significantly reduced the inotropic score (p < 0.001), lactate levels (p < 0.001) and SAPS II (p =0.02) and improved left ventricular ejection fraction (p = 0.01). All-cause mortality at 30 days was similar with Impella and IABP (52 % and 67 %, respectively; p = 0.13), but bleeding complications were more frequent in the Impella group (3 vs 4 units of transfused erythrocytes concentrates due to bleeding complications, p = 0.03). Previous cardiopulmonary resuscitation (HR 3.22, 95% CI 1.76 to 5.89; p < 0.01) and an estimated intermediate (HR 2.77, 95% CI 1.42 to 5.40; p < 0.01) and high (HR 4.32 95% CI 2.03 to 9.24; p = 0.01) IABP-SHOCK II score were independent predictors of all-cause mortality.ConclusionsIn patients with AMICS, haemodynamic support with the Impella device had no significant effect on 30-day mortality as compared with IABP. In these patients, large randomised trials are warranted to ascertain the effect of Impella on the outcome.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Hirota ◽  
K Moriwaki ◽  
A Takasaki ◽  
T Takamura ◽  
T Kurita ◽  
...  

Abstract Introduction Early identification of high-risk patients is the cornerstone of managing patients with acute myocardial infarction (AMI). Age Shock index (ASI; age multiplied by the ratio of heart rate/systolic blood pressure) has been reported to be similar to Global Registry of Acute Coronary Events (GRACE) risk score for predicting mortality in patients with AMI. However, prognostic impacts of prehospital ASI (pre-ASI) in patients with AMI remain unknown. Methods We analyzed of 2578 AMI patients who underwent emergency primary percutaneous coronary intervention (PCI) from January 2013 to March 2018, using data from Mie ACS Registry, a prospective and multicenter registry in Japan. Pre-ASI was recorded by emergency medical services at the first contact with the patient before admission, and in-hospital ASI (in-ASI) was recorded prior to PCI at admission. The primary end point was defined as all-cause death. Results Median follow-up duration was 753 days (497–838 days). All-cause death was observed in 230 (8.9%) patients. The ROC-AUC (Receiver operating characteristic-area under the curve) of pre-ASI for all- cause death was 0.76 (p&lt;0.001), which was similar to that of in-ASI (0.78, p&lt;0.001) (p=0.25 for pre-ASI versus in-ASI). The cut-off value for pre-ASI and in-ASI was for the prediction of all-cause death was both 45 with a sensitivity of 0.66 and a specificity of 0.78, with a sensitivity of 0.68 and a specificity of 0.76 respectively. According to the Kaplan-Meier survival analysis by combination of pre-ASI≥45 and in-ASI≥45, the patients with pre-ASI≥45 and in-ASI≥45 showed significantly higher all-cause mortality compared to the patients with pre-ASI≥45 and in-ASI&lt;45, the patients with pre-ASI&lt;45 and in-ASI≥45, and the patients with pre-ASI&lt;45 and in-ASI&lt;45 (p&lt;0.001) (Figure). The addition of pre-ASI≥45 to in-ASI≥45 (global chi-squared score: 205) resulted in a significantly increased global chi-squared score, suggesting the incremental prognostic value of pre-ASI (267; p&lt;0.001). Multivariate cox proportional hazard regression analysis for all-cause mortality demonstrated pre-ASI≥45 was a significant independent predictor (HR: 4.86; 95% CI: 3.36 to 7.02, p&lt;0.001). It was strongest predictor compared to left ventricular ejection fraction&lt;40% (HR: 2.45; 95% CI 1.67 to 3.58, p&lt;0.001), hemodialysis (HR: 3.45; 95% CI 1.66 to 7.17, p=0.001), door to balloon time&gt;90 minutes (HR: 1.66; 95% CI 1.18 to 2.34, p=0.004). Conclusions High pre-ASI predict increase mortality and assessment of both high pre-ASI and high in-ASI enhance risk stratification in patients with AMI. Early recognizing high pre-ASI may help us make better strategies and improve prognosis for high-risk AMI patients. Figure 1 Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 7 ◽  
Author(s):  
Jinying Zhou ◽  
Shiqin Yu ◽  
Yu Tan ◽  
Peng Zhou ◽  
Chen Liu ◽  
...  

Objective: Left ventricular systolic dysfunction (LVSD) after ST-segment elevation myocardial infarction (STEMI) is associated with poor outcome. Trimethylamine N-oxide (TMAO), a gut metabolite, is linked to cardiovascular diseases but its relationship with LVSD after STEMI remains unclear. The present study therefore aimed to investigate the relationship between TMAO and LVSD at 30 days after a first anterior STEMI.Methods: This was a sub-study from the OCTAMI (Optical Coherence Tomography Examination in Acute Myocardial Infarction) registry. Eligible patients were included in current study if they: (1) presented with a first anterior STEMI; (2) had available baseline TMAO concentration; (3) completed a cardiovascular magnetic resonance examination at 30 days after STEMI. LVSD was defined as left ventricular ejection fraction &lt; 50%. Associations between TMAO and left ventricular ejection fraction, infarct size and left ventricular global strain were examined.Results: In total, 78 patients were included in final analysis. Overall, TMAO was moderately associated with peak cTnI (r = 0.27, p = 0.01), age (r = 0.34, p &lt; 0.01), and estimated glomerular filtration rate (r = −0.30, p &lt; 0.01). At 30-day follow-up, 41 patients were in the LVSD group and 37 in the non-LVSD group. Baseline TMAO levels were not significantly different between the two groups (LVSD vs. non-LVSD: median 1.9 μM, 25−75th percentiles 1.5–3.3 μM vs. median 1.9 μM, 25−75th percentiles 1.5–2.7 μM; p = 0.46). Linear regression analyses showed that TMAO was not associated with left ventricular ejection fraction, infarct size or left ventricular global strain at 30 days (all p &gt; 0.05).Conclusions: TMAO was not significantly correlated with 30-day LVSD in patients with a first anterior STEMI after primary revascularization.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03593928.


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