Major Adverse Cardiac Events Research Articles

Triggers of type 2 myocardial infarction: implications for long-term prognosis

Abstract Background Type 2 myocardial infarction (T2MI) is characterized by a mismatch between myocardial oxygen supply and demand, unrelated to acute coronary thrombosis. This discrepancy arises from triggers, which may or may not be of cardiac origin. Common cardiac triggers include coronary artery spasm, coronary embolism, and arrhythmias, whereas non-cardiac triggers encompass factors such as anemia, hypertension/hypotension, sepsis, renal damage, and respiratory failure. However, identifying these triggers isn't always straightforward. Aim Our study aimed to identify, whenever possible, the triggers contributing to the oxygen supply-demand mismatch in T2MI cases, as defined by the Fourth Universal Definition of Myocardial Infarction. Additionally, we sought to explore the correlation between these triggers and patient prognosis. Methods We enrolled all consecutive patients diagnosed with non-ST-segment elevation myocardial infarction (NSTEMI) who met the criteria for T2MI and underwent coronary angiography within 72 hours of diagnosis. Patients were categorized into three groups based on the trigger causing T2MI: cardiac, non-cardiac, and unidentified. The primary endpoint was the occurrence of major adverse cardiovascular events (MACEs), including all-cause mortality, new myocardial infarction, hospitalization for heart failure, and ischemic stroke, during long-term follow-up. We estimated MACE-free survival using Kaplan-Meier curves and compared it among the three groups using the log-rank test. Multivariable logistic regression analysis was performed to identify independent predictors of MACE. Results The final cohort comprised 598 T2MI patients, with 308 having a cardiac trigger, 147 having a non-cardiac trigger, and 143 with an unidentified trigger. The mean age of the overall population was 69.6±13.1 years, with a median follow-up time of 25 (13-49) months. Kaplan-Meier curves demonstrated statistically significant differences in MACEs based on the trigger causing T2MI (p<0.001). Specifically, patients with an unidentified trigger exhibited a better prognosis, while those with a non-cardiac trigger had a worse prognosis during long-term follow-up. Multivariable logistic regression analysis confirmed that not having an identified trigger is an independent protective factor for MACEs (HR 0.63, 95% CI 0.45-0.89, p=0.009, unidentified trigger vs cardiac + non-cardiac trigger). Conclusions T2MI is prevalent in clinical practice, yet reliable outcome predictors remain elusive. Our findings indicate a relationship between the type of trigger precipitating T2MI and patient prognosis, notably demonstrating that the absence of a specific identifiable trigger is linked to a more favorable long-term outcome. Further studies are needed to better define the prognostic stratification of these patients.MACE-free survival Kaplan Meier

Prognostic implication of computational angiography-derived fractional flow reserve in patients with non-obstructive coronary artery disease

Abstract Background Non-obstructive coronary artery disease (NOCAD) is proved to have high association with rate of major adverse cardiovascular events (MACE) in recent studies, yet risk stratification of symptomatic Non-Obstructive Coronary Artery Disease (NOCAD) patients remains uncertain. Objectives Our study assessed clinical value of single-vessel, multi-vessel, and three-vessel computational angiography-derived fractional flow reserve (caFFR) measurement in NOCAD patients. Methods We enrolled patients with ≤ 50% stenosis with a caFFR value ≥ 0.8 in all three coronary arteries on coronary angiography. The sum of caFFR values in the three vessels was computed for each patient. Patient stratification was based on median value of the following criteria: single vessel analysis, multi-vessel analysis, 3-vessel (3V) analysis. The primary endpoint of this study was major adverse cardiac events (MACE) at 5 years, defined as a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. Results A total of 490 patients were included (mean age 64.39 ± 11.16, 55.5% male). The 5-year MACE rates in single-vessel analysis were statistically insignificant between low and high caFFR groups (Left anterior descending artery (P=0.163); Left circumflex artery (P=0.797); Right coronary artery (P=0.127)). In multi-vessel analysis, patients in multiple-vessel low-caFFR group (with 2-3 vessels lower than median value of all coronary arteries) show an increased risk of 5-year MACE than patients in single-vessel low-caFFR group (0-1 vessel) (hazard ratio [HR] 2.648, 95% confidence interval [CI] 1.141 - 6.145, P = 0.023). In 3-vessel analysis, patients in the low 3V-caFFR group demonstrated a greater 5-year MACE risk than the high 3V-caFFR group ([HR] 2.43, 95% 95%[CI] 1.087 - 5.433, P = 0.031). Conclusion In patients with NOCAD, the higher count of vessels exhibiting with low caFFR values and the low 3V-caFFR values have been found to be associated with increased rate of MACE over a 5-year period. We demonstrated that both multiple-vessel and 3V-caFFR measurements serve as valuable prognostic indicators for risk assessment in NOCAD patients.

Association of HbA1C with mortality and cardiovascular outcome in patients with type 2 diabetes using drugs with different hypoglycemic risk

Abstract Background Previous clinical trials showed that intensive glucose control did not reduce macrovascular events and mortality. It was speculated that severe hypoglycaemia contributed to these adverse outcomes. More contemporary clinical trials using newer anti-diabetic agents with less hypoglycaemic potential showed a linear relationship between major adverse cardiovascular events (MACE) and HbA1c reduction according to a meta-regression analysis. Purpose The aim of this study was to examine the association between clinical outcomes and HbA1c under different treatment backgrounds in the real-world setting. We hypothesised that when using drugs with minimal hypoglycaemic risk, lower HbA1c would be associated with better outcomes. Methods This was a retrospective population-based cohort study using a multi-centre electronic medical record database. Eligible patients were those diagnosed with type 2 diabetes between 2009 and 2020 who received non-insulin antidiabetic drugs. Patients were stratified into two groups based on the drugs received: drugs with high hypoglycaemic risk (sulphonylurea, meglitinide) and drugs with low hypoglycaemic risk (thiazolidinediones, acarbose, DPP4 inhibitors, GLP1 agonists, SGLT-2 inhibitors). Patients were excluded if they had received these drugs for less than 180 days or had received both high and low hypoglycaemic risk oral drugs simultaneously. HbA1c levels were assessed from the index date to the date of the interested outcome or the end of the study period (31 December 2021), whichever came first. The relationship between HbA1c and clinical outcomes was examined using a Cox proportional hazards model. The outcomes of interest included all-cause mortality and MACE. Results The study population consisted of 6,923 patients, including 3,639 high hypoglycaemic risk drug users and 3,284 low hypoglycaemic risk drug users. Patients with lower HbA1c levels during the follow-up period were older and frailer. After adjusting for baseline covariates, the association between the risk of death and HbA1c presented a U-shaped pattern, and this U-shaped association was similar in the two treatment cohorts (Table 1). On the other hand, the association between the risk of MACE and HbA1c presented a J-shaped pattern. In the high hypoglycaemic risk drug cohort, patients with the highest HbA1c levels (mean HbA1c 9.6%) were associated with a higher risk of MACE compared to the group with a mean HbA1c of 7.2% (hazard ratio [HR] 4.16, 95% confidence interval [CI] 2.07-8.37); lower HbA1c levels were not associated with a lower risk of MACE (Table 2). In contrast, in the low hypoglycaemic risk drug cohort, lower HbA1c levels were associated with a higher risk of MACE (HR 3.82, 95% CI 1.29-11.28). Conclusion Lower HbA1c levels were not associated with a lower risk of all-cause mortality and MACE. Furthermore, this phenomenon was independent of the hypoglycaemic risk of anti-diabetic drugs.

Obesity paradox, weight-free anthropometric measures, and major adverse cardiovascular events in the elderly: Insight from the Northern Shanghai Study

Abstract Aims Many studies have investigated the obesity paradox in the elderly. However, besides body mass index (BMI), many other anthropometric measures, such as the waist-to-hip ratio (WHR), provide a better indication of body fat distribution and may be more useful in a geriatric population. Methods 3285 participants aged over 65 years old from the Northern Shanghai Study were included in this analysis. Eight anthropometric measures, including weight-related measures (BMI, weight-adjusted-waist index, body shape index and body surface area) and weight-free measures (WHR, waist-to-height ratio, body roundness index, relative fat mass) were measured and calculated with standard methods. Major adverse cardiovascular events (MACEs) included the non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Results Participants had an average age of 71.4 years and 1428 (43.47%) were men. The median follow-up was 5.4 years (IQR, 4.4-7.3 years) and 218 events occurred. Participants with obesity (BMI ≥ 28 kg/m2) were associated with a higher risk of MACEs compared with the normal (adjusted Hazard ratio = 1.54, 95% confidence interval (CI): 1.07-2.22, P=0.020). Restricted cubic splines also highlighted the robust correlation between high BMI and high MACEs risk (Pfor overall=0.025, Pfor nonlinear=0.339). Similarly, the aHR for the incidence of MACEs in WHR quartile 4 versus quartile 1 was 1.96 (95% CI: 1.26-3.05, P=0.003). When WHR was examined as a continuous variable, the result remained unaltered (Pfor overall=0.020, Pfor nonlinear=0.353). In adjusted model, all four weight-free measures were significantly associated with increased risk of MACEs (all P<0.05), while only two weight-related measures were related to the risk of MACEs. Conclusion In the elderly, BMI and alternative anthropometric measures showed no evidence of an "obesity paradox". Weight-free measures were more relevant to a risk of MACEs.Take home message

Twelve-month outcome of robotic assisted PCI

Abstract Background Robotics in interventional cardiology (R-PCI) is a technique with high potential for optimising the outcome of patients with coronary heart disease. In order to compare R-PCI with conventional, manual PCI (M-PCI), it is necessary to analyse both the index procedure during the initial hospital stay and, in particular, the long-term outcome. Methods We report twelve-month follow up data of our prospective FRiK registry, started in mid 2021. This registry focuses on success rates and safety, radiation dose of patients and personnel as well as long-term outcome (after 6 and 12 months). Moreover, R-PCI is compared with M-PCI in these categories. Results 73 patients received R-PCI. PCI success rate was 100%, with 17.8% requiring manual assistance. Rate of complications (MACE - major adverse cardiovascular events) was 0%. Compared with 152 M-PCI patients, treated by the same interventionalists, there was a higher median procedural time (diagnostic and intervention) 102.5 (82.8-123.5) min vs. 73 (51-101.5) (p<0.001) and fluoroscopy time 18.3 (14.4-26.6) min vs. 16.2 (9.8-23.4) min (p=0.037) in R-PCI patients. However, there was no significant difference between the dose-area product 4062 (2337-5990) cGycm² vs. 3747 (2238-5904) cGycm² (p=0.878) and contrast volume use 180 (140-250) ml vs. 180 (135-235) ml (p=0.370, figure 1). Twelve months after the intervention, all patients in both groups were alive. R-PCI and M-PCI had comparable rates of rehospitalisation (11.4% vs. 8.1%, p=0.903) and unscheduled PCI (4.3% vs. 2.7%, p=0.932, figure 2). Target vessel failure occurred in one vs. two patients in the R-PCI and M-PCI group, respectively (1.4% vs. 1.3%, p=0.932). Conclusion R-PCI showed a high success rate, low rates for need of manual assistance, and a very high safety profile without any complications. Also at 12-month follow-up, R-PCI was comparable to the M-PCI in all categories.Comparison of procedural characteristicsComparison of twelve-month outcome

The impact of discontinuing proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors on clinical outcomes

Abstract Background/Introduction Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors have demonstrated efficacy in lowering low-density lipoprotein cholesterol (LDL-C) levels and reducing the risk of cardiovascular events. Despite these advantages, some patients are unable to continue the use of PCSK9 inhibitors due to financial or other reasons. Limited clinical studies have been conducted to investigate the clinical outcomes of patients discontinuing PCSK9 inhibitors for various reasons. Purpose This study aims to specifically investigate patients who were unable to continue PCSK9 inhibitors, with a particular focus on those discontinuing due to financial or other reasons. The primary objective is to assess the impact of discontinuation on major adverse cardiovascular events (MACE). Methods This study focused on 205 Japanese patients who received PCSK9 inhibitors between July 2016 and December 2023. The clinical outcomes of patients who continued or discontinued PCSK9 inhibitors were comprehensively compared. The primary endpoint was major adverse cardiovascular events (MACE), encompassing cardiovascular death, coronary revascularization, target lesion revascularization (TLR), and fatal or non-fatal myocardial infarction (MI). Results Among 205 patients (median age: 69 years; interquartile range [IQR]: 60-76 years 68% male), the median follow-up was 413 days (IQR, 49-1148 days). At one year, the median LDL-C was 43mg/dL, and 158 patients (77%) achieved LDL-C <70 mg/dL. During the follow-up, 64% (131 patients) continued PCSK9 inhibitors, while 36% (74 patients) discontinued. Of the discontinuation group, 30% (22 patients) cited financial problems, 24% (18 patients) clinical stability, and 12% (9 patients) patient preference. Multivariate Cox regression analysis revealed that the group discontinuing PCSK9 inhibitors had a higher incidence of MACE than the group that continued (hazard ratio: 1.84; 95% confidence interval: 1.02 to 3.55; p=0.05). Conclusions This study suggests an increased risk of MACE when PCSK9 inhibitors are discontinued for financial or other reasons. This insight is vital for healthcare management and decision-making among medical practitioners.PCSK9: continuation vs discontinuation

Adverse cardiovascular outcomes due to potential drug-drug interactions in statin therapy: a population-based study

Abstract Background Statins have been proven to reduce morbidity and mortality in patients with known atherosclerotic cardiovascular disease (ASCVD) and in primary prevention. Given their unique role in ASCVD, concomitant use of statins and other medications are inevitable. Our clinicians’ duty is to identify clinically important drug-drug interactions (DDI) with statins and to minimize potential life-threatening adverse drug reactions. Purpose To understand the clinical relevance of statin related DDI, we aimed to analyse the prevalence and level of severity of potential statin DDI in a real-world territory-wide population-based study. Methods We retrospectively analysed 95278 patients (mean age 64.3±11.4, female 45.0%) prescribed simvastatin (N=56111, 59%), atorvastatin (N=33902, 36%), or rosuvastatin (N=5265, 5%) from 2013-2022 among 16 public hospitals. Covariates were balanced with 1:1 propensity score matching for patients with and without potential DDI, resulting in 35907 patients in each arm. A composite 4-point MACE (major adverse cardiovascular events) was used as the primary outcome, which included coronary revascularisation, stroke, myocardial infarction (MI), and cardiovascular-related death (CV death). Cox proportional-hazard model with competing risk regression was performed to estimate adjusted hazards ratio (aHR) with corresponding 95% confidence intervals (CI). Secondary analyses would be focusing on adverse drug reactions in these three different statin subgroups. Results At 1-year follow up, subjects with potential statin related DDI have higher propensities of deranged liver function (ALT>=3x ULN, 4.9% vs 3.4%; p<0.001), elevated creatine kinase (CK>=5x ULN, 0.9% vs 0.5%, p<0.001) and deranged renal function (creatinine level >=2X ULN, 0.3% vs 0.2%, p<0.001) than non-DDI group. At 5-year follow up, the statin DDI group had higher incidences of MI (2.9% vs 1.9%, p<0.01), stroke (4.0% vs 2.3%, p<0.001) and CV death (1.7 % vs 1.5%, p=0.038). Potential DDI had most significant effect seen on simvastatin compared to other statins. Simvastatin DDI cohort had strong association with subsequent coronary vascularization (aHR 1.41, 95% CI 1.21–1.64, p<0.005), MI (aHR 1.66, 95% CI 1.46–1.88, p<0.005), stroke (aHR 1.95, 95% CI 1.76–2.16, p<0.005), and CV-related death (aHR 1.18, 95% 1.00–1.38, p=0.05) as compared to control. Atorvastatin DDI cohort was associated with higher rates of MI (aHR 1.81, 95% CI 1.54–2.12, p<0.005) and stroke (aHR 1.64, 95% CI 0.39–1.94, p<0.005) than control. Rosuvastatin DDI cohort was weakly associated with higher rates of MI (aHR 1.75, 95% CI 1.02–3.01, p=0.04). Conclusion Potential statin related drug-drug interactions are prevalent and were associated with major adverse cardiovascular events. Our real-world data demonstrated that simvastatin related drug-drug interaction pose a significant threat to our patients with association with CV death, myocardial infarction, stroke and future coronary revascularization.4-point MACE

Comparison of the predicting value for incident cardiovascular events by vascular age based on brachial-ankle pulse wave velocity or carotid-femoral pulse wave velocity

Abstract Background There is a good correlation between brachial-ankle pulse wave velocity（baPWV）and carotid-femoral pulse wave velocity (cfPWV). Whether baPWV has the same predictability for cardiovascular risk as cfPWV in calculating vascular age remains to be clarified. Purpose This study examines which vascular age calculated by baPWV or cfPWV has a stronger association with the risk of cardiovascular events. Methods This prospective cohort study included 5725 participants from a community atherosclerosis cohort in Beijing, China. Vascular age was the predicted age in a multivariable regression model, including classical cardiovascular risk factors (sex, systolic and diastolic blood pressure, glycemia, triglyceride, low density lipoprotein cholesterol, waist, body mass index, heart rate, smoking) and treatment (anti-hypertensive agents, hypoglycemic agents, lipid-lowering agents) and pulse wave velocity. Residuals between chronological age and vascular age were defined as ∆-age, and the 10th and 90th percentiles of ∆-age were used as cutoffs to define supernormal vascular aging, normal vascular aging, and early vascular aging, respectively. The major adverse cardiovascular event was a composite of myocardial infarction, stroke, and cardiovascular death. The study used Cox proportional hazards regression to examine the association between vascular age and major adverse cardiovascular events. Results During the median 3-year follow-up period, 172 endpoint events were observed. After adjusting for age and sex, ∆-age as a continuous variable calculated by baPWV was significantly and increasingly associated with cardiovascular events (every 1-year increase led to a rise of 1.04% [95% confidence interval [CI]: 1.00%-1.08%; p=0.03] in cardiovascular events risk). After adjusting for age, sex, smoking, body mass index, hypertension, diabetes, dyslipidemia, anti-hypertensive agents, lipid-lowering agents, hypoglycemic agents, family history of atherosclerotic cardiovascular disease, and estimated glomerular filtration rate, early vascular aging group calculated by baPWV had an increased risk of cardiovascular events (hazard ratio: 1.76; 95% CI: 1.19-2.62 p=0.005), compared with the normal vascular aging group. In contrast, no significant results were observed in vascular age calculated by cfPWV. Conclusion(s) Vascular age calculated by baPWV has a stronger predictive ability for cardiovascular events than that calculated by cfPWV in the Chinese population. Considering baPWV is a simple and convenient method, it is recommended for vascular age calculation.

Association of a history of acute kidney injury with major adverse cardiovascular events in chronic kidney disease patients

Abstract Background/introduction Acute kidney injury (AKI) is strongly associated with major adverse cardiovascular events (MACE), particularly heart failure, in both general and critically ill populations. A recent study questioned whether this association holds true only for patients without chronic kidney disease (CKD). Purpose To evaluate the association of a history of AKI with MACE in a large real-world CKD population defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Methods A retrospective cohort study was conducted using Merative® Explorys electronic health records (>54 million patients) from Jan 2010 to Dec 2019. Six cohorts of CKD patients (diagnosed or not) were created, one for each stage (1-5). Patients were required to have two consecutive abnormal eGFR, uACR/uPCR results within 3-18 months to determine CKD stage, to have at least a 12-months lookback period, and no history of end-stage kidney disease. CKD classification was not mutually exclusive (individual patients could contribute to multiple stages). Index date was the date of the second abnormal test. History of AKI was defined using ICD diagnosis codes, not through biological changes. We followed each patient until the occurrence of a composite of MACE including death, coronary events [acute coronary syndrome + coronary revascularization], any stroke, hospitalization for heart failure, or loss to follow-up, or for up to 5 years. We used multivariable Cox proportional hazards regression to estimate associations between the history of AKI and the risk of MACE during follow-up, adjusted for the following confounders: age, sex, ethnicity, systolic blood pressure, eGFR, BMI, CV history, diabetes, and any CKD diagnosis at baseline. Results Most of the 969,394 patients included in at least one CKD stage cohort were in stage 3a (see table) and Caucasian. Mean ages were 57-75y and 42%-64% were females across the 5 CKD stages. The prevalence of pre-existing CV disease increased from 24% in stage 1 to 57% in stage 4. The proportion of patients with a history of AKI increased from 4% in stage 1 to 36% in stage 4, as well as, the proportion of patients with a ICD code for CKD diagnosis at baseline (3% to 44%). The 5-year incidence of the composite of MACE increased from 25.1% in stage 1 to 65.8% in stage 5. Death was the most frequent event across all stages. In multivariable analysis, a history of AKI was associated with increased risk of MACE (hazard ratios, HR 1.19 to 1.32), all-cause death (HR 1.12 to 1.86), and hospitalization for Heart Failure (HR 1.59 to 1.98) for all CKD stages, and coronary events for stage 2 to 5 (HR 1.14 to 1.22), but not stroke. Conclusion Patients with CKD and a history of AKI are at higher risk of adverse CV outcomes, especially hospitalization for heart failure. This study suggest that these patients should receive cardio -protective intervention.

Impact of chronic kidney disease on patients with Myocardial Infarction with Non Obstructive Coronary Arteries (MINOCA)

Abstract Background Chronic kidney disease (CKD) in patients with myocardial infarction (MI) is associated with more advanced disease, a higher risk of complications and poorer prognosis, as well as increased mortality. The aim of this study is to assess the impact of CKD in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) and its influence on the prognosis of these patients. Methods it was an observational, prospective and analytic study. We analyzed all consecutive patients with MI who underwent coronary angiography admitted to our Hospital between 2016 and 2023; MINOCA patients were classified following the 2023 ESC Guidelines definition. The patients were divided into two groups depending on whether they had CKD or not. Median follow-up was 43 months [20-71]. Results we included 136 patients with MINOCA, of whom 11 (8.1%) had CKD. Patients with impaired kidney function were older and mostly male. They also exhibited a higher prevalence of classic cardiovascular risk factors such as hypertension, diabetes, or dyslipidemia. However, there were fewer smokers in this group. We did not find significant differences in coronary artery anatomy (smooth or small plaques) between both groups. Additionally, the majority of patients in both groups had preserved left ventricular function. Despite that, patients with CKD typically had ST segment elevation in the ECG and higher myocardial injury biomarkers’ levels as well as NT-proBNP. During hospitalization, patients without renal dysfunction had more complications (11.2% vs 0%, p=0.062) such as inotropic requirements, stroke or cardiogenic shock, but overall there were very few. In terms of treatment, it was fairly similar in both groups, although patients with kidney disease received diuretics significantly more often. Throughout the follow up, there were no significant differences in MACE (major adverse cardiovascular events) between death (27.3% vs 7.4%, p=0.06), readmission (10% vs 10.8%, p=1) or MI (0% vs 3.4%, p=1), but patients with CKD suffered more frequently from stroke (40% vs 4.2%, p<0.01). Conclusions 1) Patients with MINOCA and CKD are typically older and predominantly male with a high prevalence of cardiovascular comorbidities (hypertension, diabetes, dyslipidaemia). 2) The severity of MI appears to be slightly higher in this group, as evidenced by more ST-segment elevation upon admission and higher hs Troponine T levels. However, they experience fewer cardiovascular complications and maintain normal left ventricular function. 3) Although we found no significant differences in major adverse cardiovascular events (MACE), patients with CKD were more likely to suffer from stroke.Table 1Table 1

Efficacy of diet with low glycemic index on coronary artery disease

Abstract Background Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide, with dietary factors playing a significant role in its pathogenesis. The glycemic index (GI) of foods has been implicated in cardiovascular health, with low GI diets hypothesized to reduce the risk of CAD and improve outcomes [1]. However, the efficacy of low glycemic index diets in patients with established CAD remains uncertain. Objective This study aimed to assess the efficacy of a low glycemic index diet on coronary artery disease by evaluating changes in cardiovascular biomarkers and major adverse cardiovascular events (MACE) using Kaplan-Meier analysis and Cox regression models. Material and Methods A randomized controlled trial was conducted involving 156 patients with established coronary artery disease (Aged 43-75 years, mean age 62.4±12.7 years, male=57%). Participants were randomized to either a low glycemic index diet group or a control group receiving standard dietary advice. Changes in cardiovascular biomarkers, including lipid profiles, inflammatory markers, and glycemic control parameters, were assessed at baseline and follow-up visits. Major adverse cardiovascular events, including myocardial infarction, stroke, and cardiovascular death, were recorded over a median follow-up period of 6.2±2.4 years. Kaplan-Meier analysis and Cox regression models were used to evaluate the association between adherence to a low glycemic index diet and MACE. Results Preliminary analysis demonstrated significant improvements in cardiovascular biomarkers, including reductions in LDL cholesterol, triglycerides, and inflammatory markers, in the low glycemic index diet group compared to the control group (p < 0.05). Kaplan-Meier analysis revealed a lower incidence of MACE in patients adherent to the low glycemic index diet compared to non-adherent patients (log-rank p < 0.05). Cox regression analysis confirmed the independent association between adherence to a low glycemic index diet and reduced risk of MACE after adjusting for confounding factors (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.60-0.95; p < 0.001). Conclusion Our findings suggest that a low glycemic index diet may be efficacious in reducing cardiovascular risk and improving outcomes in patients with coronary artery disease. Adherence to a low glycemic index diet was associated with favorable changes in cardiovascular biomarkers and a reduced risk of major adverse cardiovascular events. Further research is warranted to confirm these findings and elucidate the mechanisms underlying the cardioprotective effects of low glycemic index diets.

Altered clot formation and fibrinolysis in heart transplant recipients

Abstract Background Long-term survival after heart transplantation (HTx) is limited by cardiac allograft vasculopathy (CAV), a frequent accelerated form of coronary artery disease. The pathogenesis remains incompletely understood, but thrombosis may be involved. We aimed to investigate clot formation and fibrinolysis in HTx patients and relate the findings to prognosis. Methods This prospective cohort study included 69 patients (median 8.4 years after HTx) with angiographically documented CAV 0 (not significant, n=36), CAV 1 (mild, n=19), and CAV 2-3 (moderate to severe, n=14). Healthy individuals (n=69) served as age- and gender-matched controls. Using a plasma-based fibrin clot formation and lysis assay, we assessed the following clot properties off-aspirin: 1) clot formation reflected by peak absorbance, 2) fibrinolysis measured by clot lysis time, and 3) a combined measure of clot formation and lysis reflected by area under the curve (AUC). Major adverse cardiac events (MACE) included heart failure hospitalization, cardiovascular death, and significant CAV progression. Results Median follow-up time was 5.1 (2.1-5.9) years. Five CAV 2-3 patients were excluded as it was not considered safe to interrupt aspirin therapy. Five patients had missing values due to either lysis resistance or severely decreased fibrin formation, and four of these underwent MACE with CAV progression and/or heart failure during follow up. Peak absorbance was significantly higher in HTx patients compared with healthy controls (0.72 vs. 0.50 aggregation units (AU), p<0.0001). Further, a stepwise increment above reference range through CAV groups was seen; CAV 2-3 patients (0.85 ± 0.12 AU) versus CAV 1 patients (0.72 ± 0.17 AU, p<0.05) and CAV 0 patients (0.68 ± 0.27 AU, p=0.06). Clot lysis time was significantly longer in HTx patients compared with healthy controls (1275 vs. 733 seconds, p<0.0001). AUC was significantly increased compared with healthy controls (1399 vs. 547 AU x seconds, p<0.0001). Overall, clot formation and fibrinolysis was not related to MACE. Conclusion HTx-patients have increased clot formation and prolonged fibrinolysis compared with healthy controls. Further, HTx-patients have an increased combined measure of these parameters compared with healthy controls, suggesting imbalance between fibrin clot formation and fibrinolysis. None of the measured parameters were related to prognosis.Clot formation and fibrinolysis

The upfront lipid-lowering combination therapy of statins and ezetimibe vs statin monotherapy in the reduction of cardiovascular outcomes. A meta-analysis.

Abstract Background Despite some data in last few years, there is still some inconsistency concerning the effectiveness and safety of the upfront intensive lipid lowering combination therapy (LLT; of moderate to high intensity statin therapy and ezetimibe) in comparison to high intensity statin therapy and recommended by some guidelines stepwise therapy approach. Purpose We sought to evaluate the efficacy of combination LLT compared with statin monotherapy for cardiovascular outcomes, LDL-C reduction, and associated adverse events. Methods A systematic literature search was conducted using PubMed, Embase, and ClinicalTrial.gov to identify relevant articles published from inception until 29th December 2023. The outcomes were assessed using pooled odds ratio (OR) for categorical data and mean difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CI). Results A total of 11 studies (8 randomized controlled trials and 3 cohort studies) with 106,358 were involved in the analysis. The mean age of the patients in the combination LLT and statin monotherapy group was 65.3 and 65.7 years, respectively. Pooled analysis shows that combination LLT significantly reduces the LDL-C level from the baseline (MD, -12.13 mg/dl [0.31 mmol/l] (95%CI: -18.26 to -5.99 mg/dl), p<0.001), all-cause mortality (ACM) (OR, 0.75, 95%CI: 0.62 to 0.92, p=0.01), cardiovascular mortality (CVM) (OR 0.75, 95%CI: 0.66 to 0.84, p<0.001), major adverse cardiovascular events (MACE) (OR, 0.72 95%CI: 0.63 to 0.82, p<0.001), non-significant reduction in the incidence of stroke (OR 0.82, 95%CI: 0.66 to 1.01, p=0.06) when compared with statin monotherapy alone. Similarly, the therapy discontinuation rate was comparable between combination LLT and statin monotherapy groups (OR, 0.87 (95%CI: 0.53 to 1.40), p=0.56). The risk of adverse events related to the gastrointestinal tract (OR, 1.12 (95%CI: 0.93 to 1.36), p=0.23) and musculoskeletal system (OR, 0.88 (95%CI: 0.52 to 1.50), p=0.65) was comparable between both the groups of patients. Conclusion Combination LLT was associated with an overall greater reduction in LDL-C, a lower risk of ACM, MACE, and CVM compared to statin monotherapy alone.Forest Plot of desired outcomes.Central illustration with key findings.

Intravascular lithotripsy in the management of underexpanded stents

Abstract Introduction Stent underexpansion significantly heightens the risk of major adverse cardiac events (MACE), and available treatment options for this condition remain limited. Intravascular Lithotripsy (IVL) technology disrupts superficial and deep calcium by using localized pulsative sonic pressure waves, emerges as a promising tool for underexpanded stents. Methods Following PRISMA guidelines, we systematically explored PubMed, SCOPUS, and Cochrane databases up to September 3, 2023, for studies evaluating IVL's safety and efficacy in treating underexpanded stents. We gathered angiographic (QCA) and intracoronary imaging (OCT or IVUS) data, examining the stent's minimal diameter stenosis (MDS), minimal lumen diameter (MLD), minimal stent area (MSA), and minimal lumen area (MLA) pre- and post-IVL application. Procedural success constituted the efficacy endpoint, while peri-procedural complications, in-hospital-30-days and long-term mortality, and MACE were safety endpoints Results This meta-analysis comprised 21 studies including 669 patients and 673 treated lesions in underexpanded stent. The mean age was 73.2 ± 2.1 years, with an overall IVL procedural success rate of 93% [(95% Confidence Interval (CI): 88%-96%, I2=29%), while the in-hospital-30-days and long-term mortality incidence were 1% (95% CI: 1%-3%, I2=0%) and 3% (95% CI: 2%-6%, I2=0), respectively. The 30-days target lesion revascularization (TLR) was approximately 6% (95% CI: 3%-12%, I2=50%). There was a significant increase in the MDS [Standardized Mean Difference (SMD): +50.52%, 95% CI: 39.4-61.6, I2=94%)] and in MSA (SMD: +3.52, 95% CI: 2.47 to -4.58, I2=83%) immediately after IVL application. It was observed a significant increase in MLD (SMD: +1.54, 95% CI: 1.09 to 1.98, I2=95%) and in the MLA (SMD: +3.64, 95% CI: 2.62-4.66, I2=5%). Major procedural and device related complications were 3% (95% CI: 1%-6%, I2=0%) and 1% (95% CI: 0%-2%, I2=85%) respectively. Notably low rates were observed for stent thrombosis (0%, 95% CI: 0%-2%, I2=0%), dissections (1%, 95% CI: 1%-4%, I2=0%), perforations (1%, 95% CI: 1%-3%, I2=0%) and no-reflow (0%, 95% CI: 0%-1%, I2=0%). Conclusions IVL demonstrates promise as a safe and effective strategy for underexpanded stent treatment, characterized by low rates of periprocedural complications. Future prospective studies are now warranted to compare IVL to other lesion preparation strategies.30day All-Cause Mortality after IVL use.Minimum Stent Diameter after IVL use.

Efficacy and safety of P2Y12 inhibitors plus aspirin versus aspirin alone in ischemic stroke or high-risk transient ischemic attack: a meta-analysis of randomized controlled trials

Abstract Background Patients with mild ischemic stroke or transient ischemic attack (TIA) have an increased risk of recurrent stroke within 90 days after the onset of the initial thrombotic event. Antiplatelet therapy plays an essential role in reducing the risk of stroke recurrence. However, data regarding the efficacy and safety of dual antiplatelet therapy (DAPT) with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy is limited. Purpose We performed an updated systematic review and meta-analysis to evaluate the effectiveness of DAPT versus aspirin monotherapy in patients with mild ischemic stroke or TIA in the light of new published evidence. Moreover, we investigated whether antiplatelet therapy started within 72 hours is effective in reducing recurrent stroke as compared to the conventionally used 24-hour time window for initiating DAPT. Methods PubMed/MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared DAPT with aspirin plus clopidogrel to aspirin alone started within 24 hours or 72 hours in patients with acute mild ischemic stroke or high-risk TIA from inception to December 31st, 2023. A random-effects model was used to pool risk ratios (RRs) and 95% confidence intervals (CIs) for clinical endpoints. Results Five RCTs with 27,563 patients were included in this study. DAPT significantly reduced the risk of recurrent stroke by 23% (RR: 0.77; 95% CI: 0.70-0.83; p<0.00001), ischemic stroke by 26% (RR: 0.74; 95% CI: 0.68-0.81; p<0.00001), and major adverse cardiovascular events (MACE) by 23% (RR: 0.77; 95% CI: 0.71-0.84; p<0.00001). However, DAPT was associated with a significantly increased risk of moderate or severe bleeding (RR: 2.19; 95% CI: 1.38-3.48; p=0.0009) and hemorrhagic stroke (RR: 2.08; 95% CI: 1.13-3.82; p=0.02). No significant differences were observed for all-cause death (RR: 1.28; 95% CI: 0.95-1.71; p=0.10), cardiovascular death (RR: 1.38; 95% CI: 0.81-2.33; p=0.23), and myocardial infarction (RR: 1.63; 95% CI: 0.77-3.46; p=0.20). We performed sensitivity analysis based on the hazard ratio reported by RCTs which showed comparable results. Subgroup analysis based on treatment onset time (therapy initiation within 24 hours of thrombotic event vs therapy initiation within 72 hours of thrombotic event) showed that both strategies were effective in reducing the risk of recurrent stroke. Subgroup analysis based on the duration of DAPT (21 days vs. 90 days) showed that DAPT for 90 days was associated with an increased risk of moderate or severe bleeding as compared to therapy lasting for 21 days. Conclusion DAPT with P2Y12 inhibitors and aspirin reduces the risk of recurrent stroke and MACE but is associated with an increased risk of moderate or severe bleeding.

Safety and effectiveness of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: insights from the SPUM-ACS study

Abstract Aims Data on Glycoprotein IIb/IIIa inhibitors (GPI) use in real world ACS patients following the introduction of potent P2Y12 inhibitors and newer generation stents are scant. Here, we aimed to assess the utilization, effectiveness, and safety of GPI in a large prospective cohort of contemporary ACS patients. Methods SPUM-ACS is a prospective, multicentre study in which ACS patients between 2009 and 2017 were recruited. The primary endpoint of the present study was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction (MI) and non-fatal stroke at one year. Any bleeding events, BARC 3-5 bleeding, and net adverse cardiovascular events (NACE) comprised the secondary endpoints. Results A total of 4395 ACS patients were included in the analysis. GPI-treated patients had more total coronary artery occlusion (56% vs 35%, p<0.001) and thrombus (60% vs 35%, p<0.001) at angiography. Among the propensity score matched (PSM) population (1992 patients equally split into two groups), GPI-treated patients showed lower MACE risk (PSM adjusted HR 0.70, 95% CI 0.49-0.99) but a higher risk of any (PSM adj HR 1.46, 95% CI 1.06-1.99) and major bleedings (PSM adj HR 1.73, 95% CI 1.09-2.76), resulting in a neutral effect on NACE (PSM adj HR 0.87, 95% CI 0.65-1.17). These results remained consistent across all subgroups. When including only patients treated with potent P2Y12, the incidence of MACE was not different between the two groups, (log rank p=0.50 and PSM adjusted HR 0.94, 95% CI 0.60-1.48). In the PSM population, GPI use (HR 0.76, 95% CI 0.59-0.99, p=0.04), TIMI 3 at the end of the procedure (HR 0.16, 95% CI 0.08-0.30, p<0.001) and potent P2Y12 inhibitor use (HR 0.70, 95% CI 0.49-0.99, p=0.04) were protective independent predictors of MACE at follow-up, while oral anticoagulation at discharge (4.48, 95% CI 2.10-9.52, p<0.001), multivessel disease (HR 1.95, 95% CI 1.09-3.48, p=0.02) and KILLIP class ≥ 2 at admission (HR 1.98, 95% CI 0.99-3.95, p=0.05) were adverse independent predictors. Conclusion In ACS patients undergoing PCI and broadly treated with potent P2Y12 inhibitors, GPI use reduced the risk of MACE at 1 year, while increasing the risk of major bleedings, with a neutral effect on NACE. The routine use of these pharmacological agents should be discouraged, while in selected patients GPI use should be considered following personalized balancing between ischaemic and bleeding risk.Events in PSM populationEvents in PSM population

Long-term prognosis after ST-elevation myocardial infarction according to the Canadian Cardiovascular Society classification of tissue injury severity in acute myocardial infarction

Abstract Background The recently proposed Canadian Cardiovascular Society (CCS) classification of acute myocardial infarction (MI) describes 4 stages of tissue injury identified by cardiac magnetic resonance imaging (CMR); 1) oedema without late gadolinium enhancement (LGE); 2) LGE without microvascular obstruction (MVO); 3) MVO; and 4) intramyocardial haemorrhage (IMH). Prior studies examining the relationship between these characteristics and outcomes are limited by variations in imaging and measurement techniques, in particular the distinction between MVO and IMH. The relationship between the proposed CCS classification of MI and outcomes has not been described. Purpose To explore the prognostic significance of the CCS classification of MI tissue injury in patients with ST-elevation MI (STEMI). Methods The British Heart Foundation MR-MI study was a prospective single-centre CMR cohort study in patients with STEMI (July 2011-November 2012). CMR was performed on a single Siemens MAGNETOM Avanto 1.5-Tesla scanner at 2 days post-STEMI. The imaging protocol included LGE and T2* mapping, allowing for the identification of infarct, MVO, and IMH. Follow-up for the occurance of major adverse cardiovascular events (MACE) (recurrent MI, ischaemic stroke and cardiovascular death) and a composite outcome of heart failure hospitalization/ICD implantation (HFH) or all-cause death was performed via electronic case note review. Results 246 patients had complete data for this analysis. Of these, 6 (2%) were CCS Stage 1, 105 (43%) were Stage 2, 33 (13%) were Stage 3, and 102 (41%) were Stage 4. Due to the low number in CCS stage 1, these patients were pooled with Stage 2 for the purposes of this analysis (CCS Stage 1/2). Average age was 58 (SD 11) years and 188 (76%) were male. With higher CCS stage, more patients were Killip class III/IV at presentation, had the LAD as culprit artery and had TIMI flow 0/1 pre-PCI. Patients with higher CCS stage had higher peak troponin-I and NT-proBNP, lower left ventricular function, higher left ventricular volumes and larger infarct size (Table). Median follow-up was 11.8 years. HFH or all-cause death occurred in 80 (33%) patients (22 HFH and 58 all-cause deaths), and MACE occurred in 63 (26%) patients (41 recurrent MI, 11 ischaemic stroke events, and 11 cardiovascular deaths). There were no significant differences in outcomes between CCS Stage 3 and CCS Stage 1/2 (Figure). Patients with CCS Stage 4 had a higher risk of HFH or all-cause death (HR 1.73, 95%CI 1.08-2.77; p=0.022) and MACE (HR 1.88, 95%CI 1.10-3.20; p=0.021) as compared with those in CCS Stage 1/2 (Figure). Conclusion The novel CCS classification of MI tissue injury identifies patients at the highest risk of adverse outcomes following STEMI. The relationship between the presence of IMH (CCS Stage 4) and adverse outcomes highlights the importance of T2* imaging in post-MI CMR protocols in order to identify this prognostically important biomarker.

Incidence, characteristics, and prognostic impact of cancers in patients with atrial fibrillation: a report from the GLORIA-AF registry

Abstract Background Cancers and atrial fibrillation (AF) are all aging-related diseases. Coexistence of the two conditions makes management complex due to increased risk of both thromboembolism and bleeding. Purpose The aim of the present study was to analyze the incidence and prognostic impact of cancers in patients with AF in the GLORIA-AF registry. Methods GLORIA-AF registry is a prospective multi-centered international multi-centered AF cohort studies. We characterized these patients according to the presence or absence of a cancer diagnosis when enrolled. The primary endpoints were all-cause mortality, cardiovascular mortality, and major bleeding; the secondary endpoints were major adverse cardiovascular events (MACEs) including all-cause mortality, stroke, and major bleeding. Results The prevalence of cancers was 9.7%. The mean CHA2DS2-VASc and HAS-BLED scores in cancer patients were higher than in non-cancer patients (mean CHA2DS2-VASc 3.5 vs. 3.2, P<0.001; mean HAS-BLED score 1.6 vs. 1.3, P<0.001). Patients with cancers had higher oral anticoagulant use than non-cancer patients (84.4% vs. 81.0%, P<0.001) and were more likely to receive NOACs (58.4% vs. 54.0%, P<0.001). During a mean follow up period of 3 years, AF patients with cancers had significantly higher all-cause mortality (15.0% vs. 8.3%, P<0.001), major bleeding rate (5.3% vs. 3.1%, P<0.001), the composite of all-cause mortality, stroke, and major bleeding (20.0% vs. 12.0%, P<0.001), and composite of all-cause mortality, thromboembolism, and major bleeding than non-cancer patients (21.0% vs. 12.0%, P<0.001), but nonsignificant differences in cardiovascular mortality (3.6% vs. 3.1%, P=0.2), any stroke, transient ischemic attack, or non-central nervous system embolism (3.2% vs. 2.7%, P=0.1), and OAC discontinuation (29.0% vs. 28%, P=0.2). Among the cancers, hematological cancer was associated the highest risk of all-cause mortality (HR=3.7, 95%CI 2.69-5.0, P<0.001) while respiratory cancer was associated the highest risk of major bleeding (HR=2.62, 95%CI 1.24-5.5, P=0.011). After multivariable adjustment, cancer was independently associated with increased risk of all-cause mortality (HR=1.30, 95%CI 1.05-1.62, P=0.018), composite of all-cause mortality, stroke, and major bleeding (HR=1.32, 95%CI 1.04-1.68, P=0.022), and composite of all-cause mortality, thromboembolism, and major bleeding (HR=1.29, 95%CI 1.04-1.60, P=0.022), but the risk of major bleeding was nonsignificantly different (HR=1.16, 95%CI 0.71-1.87, P=0.6). Conclusions Cancer is a common comorbidity in patients with AF and is independently associated with increased risk of poor outcomes including all-cause mortality and MACEs. However, cancer did not increase the risk of cardiovascular mortality, major bleeding, and discontinuation of OAC. Cancer in patients with AF should receive appropriate treatments for the cancer itself and appropriate OAC, although strategies may vary between different cancers.Distribution of caners in GLORIA-AFKaplan-Meier curves for the outcomes

Enhancing guidewire efficacy for transradial access: the EAGER randomised controlled trial

Abstract Background and Purpose The standard J tip peripheral guidewire used to perform coronary angiography was originally designed for transfemoral access and large vascular interventions over 70 years ago. The 3mm J tip on the standard wire is larger than the typical radial artery diameter and has limited ability to navigate smaller tortuous peripheral arteries increasing the risk of vessel spasm, and potentially reducing procedural success. We compared the efficacy and safety of a hydrophilic 1.5mm J tip guidewire (intervention - ‘baby J wire’) upfront versus the standard fixed core 0.035" J wire (‘control wire’). Methods Investigator initiated, blinded multicentre randomised trial conducted in Australia. Patients undergoing clinically indicated transradial coronary angiography were randomized 1:1 to either control or baby J peripheral guidewire use upfront. The primary endpoint was technical success defined as gaining access to the aortic root with the randomised guidewire. Secondary endpoints included total procedural time, time to aorta and coronary intubation, crossover rates to alternate wire or access site, fluoroscopy times, radial artery spasm, haematoma (EASY criteria), bleeding complications (BARC criteria) and vascular complications (VARC 2 criteria). Major adverse cardiac events (MACE) and clinical endpoints were adjudicated by a blinded independent clinical events committee. Results 330 patients were enrolled over a 9-month period from October 2022 to June 2023. The median age was 69 years (36% female), BMI 29kg/m2. The primary efficacy endpoint of technical success was achieved more frequently in the intervention group (96% v 85%; ARR 10.9% (95% CI 4.6 -17.2); P <0.001). Women were significantly more likely to benefit from the intervention related to higher failure rates with the control wire (69% vs 93% in men; P = < 0.001). Overall procedure times were similar between the groups (median 1135 vs 1354 seconds; P=0.094) but fluoroscopy time was lower in the baby J wire group (median 344 vs 491 seconds; P = 0.024). Radial completion of procedures was high and did not differ between groups (100% v 98%; P=0.2). Clinically significant bleeding (BARC2+) was more common in the control wire group (3% v 0%; P=0.017). There were no differences in MACE or vascular complications. Conclusion The hydrophilic 1.5mm J tip Baby J peripheral guidewire leads to greater upfront technical success and reduced fluoroscopy time for transradial coronary angiography compared to the standard 3mm J tip guidewire. The baby J hydrophilic guidewire is safe and may have key incremental benefits for the transradial approach particularly in patients with smaller diameter radial arteries including women.Primary Outcome

Safety of beta-blocker discontinuation in patients after acute coronary syndromes and preserved left ventricular ejection fraction: long-term clinical outcomes from the SPUM-ACS cohort

Abstract Background While beta-blockers have been shown to improve outcomes after acute coronary syndromes (ACS), most trials predate the advent of reperfusion therapy and modern secondary prevention. Recent trial data in the reperfusion era found no all-cause or cardiovascular mortality benefit in patients with a left ventricular ejection fraction (LVEF) >40%, while myocardial infarction and angina were reduced. We hypothesized that, in patients who receive optimal contemporary treatment following ACS and who have an LVEF >40%, beta-blocker discontinuation within 1 year after ACS is safe and non-inferior to beta-blocker continuation in terms of the 5-year incidence of major adverse cardiovascular events (MACE). Purpose We assessed the safety of beta-blocker discontinuation within 12 months following ACS in patients with an LVEF >40% at discharge, compared to continued long-term beta-blocker therapy, with respect to the 5-year incidence of MACE. Methods Data was derived from the Swiss Special Program University Medicine – Inflammation in ACS (SPUM-ACS) cohort (N=3,762), a multicenter prospective cohort of patients hospitalized for invasive management of ACS between 2009-2017. We included patients with an LVEF >40%, beta-blockers at discharge, and who completed the 5-year follow-up. Patients who continued beta-blockers at one year were compared with those who discontinued beta-blockers at any time throughout the first year after ACS using a target trial emulation design. Adjusted hazard ratios (aHR) were obtained with a Cox model using an inverse probability weighting adjustment for baseline characteristics including demographic parameters, comorbidities, and concomitant medication. The primary endpoint was 5-year MACE (cardiovascular death, myocardial infarction, stroke or transient ischemic attack, unplanned coronary revascularization, and hospitalization for unstable angina). Results Of 2,077 patients with an LVEF >40% and beta-blockers at discharge, 1,758 (85%) continued beta-blockers and 319 (15%) had discontinued beta-blocker therapy at one year. The 5-year risk between the discontinuation and continuation group was similar for the primary endpoint (14.5% vs 14.3%, respectively, aHR 1.00, 95%CI 0.73-1.36, p=0.98). All-cause mortality (aHR 1.08, 95%CI, 0.64-1.81, p=0.79) did not differ between both groups. In a subgroup analysis, there was no effect modification by LVEF, but some evidence for a higher risk of primary endpoint with beta-blocker discontinuation in STEMI (aHR 1.50, 95%CI 1.02-2.21) compared with NSTEMI (aHR 0.69, 95%CI 0.40-1.19, P interaction = 0.022). Conclusion Beta-blocker discontinuation within 12 months following ACS in patients with an LVEF >40% was not associated with an increased risk of MACE at 5 years, compared to long-term continuation of beta-blocker therapy. In the absence of a dedicated randomized controlled trial, beta-blocker discontinuation may be safe, especially after NSTEMI.Kaplan-Meier plot: probability of MACE