Natural History and Clinical Outcomes After ST-Segment Elevation Myocardial Infarction Without Stent Insertion.

After restoration of coronary perfusion in patients presenting with ST-segment elevation myocardial infarction (STEMI), discrete severe stenotic coronary lesions are not always apparent. There remains ambiguity whether drug-eluting stent (DES) insertion or initial medical management is best practice. We sought to assess short-term clinical outcomes in patients presenting with STEMI without initial stent insertion. Patients who underwent percutaneous coronary intervention for STEMI between 2014 and 2020 were prospectively enrolled and assessed for inclusion. Patients presenting with in-stent restenosis or stent thrombosis, or who did not survive to hospital discharge were excluded. Of 13,871 patients presenting, 456 (3.3%) were treated without initial stenting. These patients were older than those treated with DES (66.1 ± 13.6 vs 62.3 ± 12.4 years, p <0.001), had higher rates of diabetes (23.5% vs 16.0%, p <0.001) and previous revascularization with either percutaneous coronary intervention (14.0% vs 7.3%, p <0.001) or coronary artery bypass graft (3.5% vs 1.8%, p = 0.008). Thirty-day mortality was elevated in patients treated without stenting compared to those receiving DES (4.2% vs 0.9%, p <0.001), as were rates of myocardial infarction (1.3% vs 0.5%, p = 0.026) and major adverse cardiac events (10.5% vs 2.4%, p <0.001). After propensity matching, a trend toward increased mortality remained (4.2% vs 2.0%, p = 0.055). In conclusion, a no-stenting initial strategy, compared with DES insertion, is associated with increased 30-day mortality in those presenting with STEMI without severe stenosis. These data suggest when appropriate, current-generation DES insertion should be undertaken.

When and why are employees willing to engage in voice behavior: a power cognition perspective.

Previous studies have found that sense of power is an important predictor of employee voice; however, the mechanism underlying the relationship between these factors remains unclear. To explore this mechanism, 642 valid questionnaires from 45 enterprises were used to conduct an empirical test based on the approach-inhibition theory of power. The results showed that sense of power can affect error risk taking positively, error risk taking mediates the relationship between sense of power and employee voice; and power congruence moderates both the direct relationship between sense of power and employee voice and their indirect relationship via error risk taking. This study thus provides a useful reference for improving employees' enthusiasm for voice behavior and can help enhance the competitiveness of enterprises.

A non-canonical Hippo pathway represses the expression of ΔNp63.

The p63 transcription factor, a member of the p53 family, plays an oncogenic role in squamous cancers, while in breast cancers its expression is often repressed. In the canonical conserved Hippo pathway, known to play a complex role in regulating growth of cancer cells, the protein kinases MST1/2 and LATS1/2 act sequentially to phosphorylate and inhibit the YAP/TAZ transcription factors. We found that in the MCF10A mammary epithelial cell line as well as in squamous and breast cancer cell lines, expression of ΔNp63 RNA and protein is strongly repressed by inhibition of the Hippo pathway protein kinases in a manner that is independent of p53. While MST1/2 and LATS1 are required for p63 expression, the next step of the pathway, namely phosphorylation and degradation of the YAP/TAZ transcriptional activators is not required for repression of p63. This suggests that regulation of p63 expression occurs by a non-canonical version of the Hippo pathway. We additionally identified additional genes that were similarly regulated suggesting the broader importance of this pathway. Interestingly, we observed that experimentally lowering p63 expression leads to increased YAP protein levels, thereby constituting a feedback loop. These results, which reveal the intersection of the Hippo and p63 pathways, may prove useful for the control of their activities in cancer cells. One Sentence Summary: Regulation of p63 expression occurs by a non-canonical version of the Hippo pathway in mammary epithelial, breast carcinoma and head and neck squamous carcinoma cells.

Colchicine in the Management of Acute Coronary Syndrome: A Meta-analysis.

INTRODUCTION: Colchicine, thought to exert its effect via reduction of inflammation, has recently been studied in patients following acute coronary syndromes (ACS). We performed a meta-analysis of all available randomized controlled trials (RCTs) in this high-risk cohort, evaluating efficacy and safety. METHODS: MEDLINE, PubMed, EMBASE, clinical trial registries, and select conference proceedings were searched for RCTs comparing colchicine to placebo in patients following ACS. The primary outcome was trial-defined major adverse cardiovascular events (MACE). Secondary endpoints included stroke, myocardial infarction (MI), all-cause and cardiovascular death, and urgent revascularization. Analysis was performed at the longest available clinical follow-up. RESULTS: Two RCTs with a pooled sample size of 5540 patients with 2778 (50.1%) receiving colchicine and 2762 (49.9%) placebo were included. In order to maximize consistency, composite efficacy endpoints between trials were modified. Compared to placebo, patients receiving colchicine had reduction in study-defined composite endpoint (5.5% vs. 7.6%) OR 0.67 (95% CI 0.46-0.98, p = 0.04, I2 = 46%). Similarly, there was a significant reduction in cerebrovascular accidents (OR 0.31, 95% CI 0.14-0.69, p = 0.004, I2 = 0%) and repeat revascularization OR 0.36 (95% CI 0.14-0.90, p = 0.03, I2 = 54%). There was no difference between cardiovascular death (OR 0.92, 95% CI 0.52-1.62, p = 0.78, I2 = 0%), non-cardiovascular death OR 1.27 (95% CI 0.72-2.24, p = 0.41, I2 = 0%), MI at longest available follow-up OR 0.89 (95% CI 0.67-1.17, p = 0.39, I2 = 0%) or resuscitated cardiac arrest OR 0.88 (95% CI 0.32-2.43, p = 0.81, I2 = 0%) in those receiving colchicine. CONCLUSIONS: These data suggest colchicine, in addition to guideline-directed medical therapy following acute coronary syndrome reduces MACE, cerebrovascular accidents, and rates of urgent revascularization at 2 years of follow-up.

Performance of Modified ALMS and BLISS Criteria with Standard of Care Treatment in Two US Health Care Systems.

OBJECTIVE: A retrospective cohort study was undertaken in a predominantly Black population undergoing standard treatment for lupus nephritis (LN) to estimate the incidence of, and risk factors for, complete response (CR) according to modified Aspreva Lupus Management Study (mALMS) and modified Belimumab International Study in Lupus Nephritis (mBLISS) criteria by 12 months. METHODS: Patients with biopsy-proven LN class III or IV ± V, urine protein-to-creatinine ratio of ≥1gm/gm and estimated glomerular filtration rate of >50 ml/minute/1.73 m2 at the time of the incident LN flare were included. The clinical, treatment, and laboratory factors associated with CR were identified using multivariable Cox regression. RESULTS: Of 173 patients, 86.1% were women, 77.5% were Black, and over half (59.5%) had non-commercial insurance. By 12 months, 20.6% (95% confidence interval (95% CI) 14.6-28.6%) achieved mALMS CR and 33.7% (95% CI 26.4-42.4%) achieved mBLISS CR. Factors associated with mBLISS CR were commercial insurance (adjusted CR ratio = 3.5 [95% CI 1.9-6.7]; P < 0.001), albumin (adjusted CR ratio = 1.8 per 1 gm/dl increase in albumin; P = 0.02), and low C4 (adjusted CR ratio = 2.6; P = 0.03). Cumulative incidence of end-stage renal disease (ESRD) at 3 years was 23.1% (95% CI 15.7-31.3%) and 6.1% (95% CI 2.8-11.1%) for death. Patients with non-commercial insurance were more likely to develop ESRD, with cumulative incidence of 30.4% (95% CI 19.6-41.9%) compared to 12.7% (95% CI 5.0-24.2%) for patients with commercial insurance (P = 0.024). CONCLUSION: In a primarily Black, uninsured LN population, despite achieving similar CR rates at 12 months, the incidence of ESRD and death exceeded those observed in controlled clinical trials with placebo arms.

Colchicine and Quality of Life in Patients With Acute Coronary Syndromes: Results From the COPS Randomized Trial.

BACKGROUND: Recent data suggest that colchicine may reduce cardiovascular events among patients presenting with acute coronary syndromes. This sub-study of the Australian COPS trial aimed to assess whether colchicine affects health status outcomes. METHODS: Health status was assessed at baseline and 12-months using the EuroQol-5 Dimension 5-level (EQ-5D-5L) score and the full 19-question Seattle Angina Questionnaire (SAQ). Data were available for 786 patients (388 randomized to colchicine, 398 to placebo). RESULTS: Baseline characteristics were well matched between groups; mean age was 60.1 (SD 14.8) years, and 20 % were female. Baseline health status scores were impaired, and most parameters demonstrated significant improvement from baseline to 12-months (EQ-5D-5L Visual Analogue Score [VAS] 69.3 to 77.7; SAQ angina frequency score 83.0 to 95.3, both p < 0.001). No significant differences in adjusted mean score change among any of the EQ-5D-5L or SAQ dimensions were observed between treatment groups in either intention-to-treat or per-protocol analysis. There were borderline interactions in EQ-5D-5L scores for those with previous MI vs not, and in SAQ scores for those with obesity vs not. In categorical analysis using observed data, patients treated with colchicine were more likely to have clinically significant improvement in physical limitation score over the period (36 % improved vs. 28 %, p < 0.05). Baseline health status scores were not associated with the primary endpoint at 12 months. CONCLUSIONS: Treatment with colchicine did not appear to affect change in measures of health status following acute coronary syndromes, but it did lead to a greater likelihood of improvement in physical limitation scores. TRIAL REGISTRATION: ACTRN, ACTRN12615000861550. Registered 18/08/2015, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368973.

Contemporary device management of cardiogenic shock following acute myocardial infarction.

Despite advances in the overall management of acute myocardial infarction (AMI), cardiogenic shock in the setting of AMI (CS-AMI) continues to be associated with poor patient outcomes. There are multiple devices that can be used in CS-AMI to support the failing circulation, although their utility in improving outcomes as compared with conventional pharmacotherapy of vasopressors and inotropes remains to be established. This contemporary review provides an update on the evidence base for each of these techniques. In CS-AMI, acute thrombotic occlusion of a major epicardial artery leads to hypoxia and myocardial ischaemia in the territory subtended by that vessel. The resultant regional dysfunction in myocardial contractility can severely compromise stroke volume and result in acute circulatory failure, systemic hypoperfusion, lactic acidosis, multi-organ failure and ultimately death.

MDM2, MDMX, and p73 regulate cell-cycle progression in the absence of wild-type p53.

The p53 tumor suppressor protein, known to be critically important in several processes including cell-cycle arrest and apoptosis, is highly regulated by multiple mechanisms, most certifiably the Murine Double Minute 2-Murine Double Minute X (MDM2-MDMX) heterodimer. The role of MDM2-MDMX in cell-cycle regulation through inhibition of p53 has been well established. Here we report that in cells either lacking p53 or expressing certain tumor-derived mutant forms of p53, loss of endogenous MDM2 or MDMX, or inhibition of E3 ligase activity of the heterocomplex, causes cell-cycle arrest. This arrest is correlated with a reduction in E2F1, E2F3, and p73 levels. Remarkably, direct ablation of endogenous p73 produces a similar effect on the cell cycle and the expression of certain E2F family members at both protein and messenger RNA levels. These data suggest that MDM2 and MDMX, working at least in part as a heterocomplex, may play a p53-independent role in maintaining cell-cycle progression by promoting the activity of E2F family members as well as p73, making them a potential target of interest in cancers lacking wild-type p53.

p53 Frameshift Mutations Couple Loss-of-Function with Unique Neomorphic Activities.

p53 mutations that result in loss of transcriptional activity are commonly found in numerous types of cancer. While the majority of these are missense mutations that map within the central DNA-binding domain, truncations and/or frameshift mutations can also occur due to various nucleotide substitutions, insertions, or deletions. These changes result in mRNAs containing premature stop codons that are translated into a diverse group of C-terminally truncated proteins. Here we characterized three p53 frameshift mutant proteins expressed from the endogenous TP53 locus in U2OS osteosarcoma and HCT116 colorectal cancer cell lines. These mutants retain intact DNA-binding domains but display altered oligomerization properties. Despite their abnormally high expression levels, they are mostly transcriptionally inactive and unable to initiate a stimuli-induced transcriptional program characteristic of wild-type p53. However, one of these variant p53 proteins, I332fs*14, which resembles naturally expressed TAp53 isoforms ß and γ, retains some residual antiproliferative activity and can induce cellular senescence in HCT116 cells. Cells expressing this mutant also display decreased motility in migration assays. Hence, this p53 variant exhibits a combination of loss-of-gain and gain-of-function characteristics, distinguishing it from both wild type p53 and p53 loss. IMPLICATIONS: p53 frameshift mutants display a mixture of residual antiproliferative and neomorphic functions that may be differentially exploited for targeted therapy.

Epidemiology of COVID-19 Infection in Hospitalized End-Stage Kidney Disease Patients in a Predominantly African-American Population.

BACKGROUND: End-stage kidney disease patients on dialysis are particularly susceptible to COVID-19 infection due to comorbidities, age, and logistic constraints of dialysis making social distancing difficult. We describe our experience with hospitalized dialysis patients with COVID-19 and factors associated with mortality. METHODS: From March 1, 2020, to May 31, 2020, all dialysis patients admitted to 4 Emory Hospitals and tested for COVID-19 were identified. Sociodemographic information and clinical and laboratory data were obtained from the medical record. Death was defined as an in-hospital death or transfer to hospice for end-of-life care. Patients were followed until discharge or death. RESULTS: Sixty-four dialysis patients with COVID-19 were identified. Eighty-four percent were African-American. The median age was 64 years, and 59% were males. Four patients were on peritoneal dialysis, and 60 were on hemodialysis for a median time of 3.8 years, while 31% were obese. Fever (72%), cough (61%), and diarrhea (22%) were the most common symptoms at presentation. Thirty-three percent required admission to intensive care unit, and 23% required mechanical ventilation. The median length of stay was 10 days, while 11 patients (17%) died during hospitalization and 17% were discharged to a temporary rehabilitation facility. Age >65 years (RR 13.7, CI: 1.9-100.7), C-reactive protein >100 mg/dL (RR 8.3, CI: 1.1-60.4), peak D-dimer >3,000 ng/mL (RR 4.3, CI: 1.03-18.2), bilirubin >1 mg/dL (RR 3.9, CI: 1.5-10.4), and history of peripheral vascular disease (RR 3.2, CI: 1.2-9.1) were associated with mortality. Dialysis COVID-19-infected patients were more likely to develop thromboembolic complications than those without COVID-19 (RR 3.7, CI: 1.3-10.1). CONCLUSION: In a predominantly African-American population, the mortality of end-stage kidney disease patients admitted with COVID-19 infection was 17%. Age, C-reactive protein, D-dimer, bilirubin, and history of peripheral vascular disease were associated with worse survival.

Use of a Telemedicine Risk Assessment Tool to Predict the Risk of Hospitalization of 496 Outpatients With COVID-19: Retrospective Analysis.

BACKGROUND: Risk assessment of patients with acute COVID-19 in a telemedicine context is not well described. In settings of large numbers of patients, a risk assessment tool may guide resource allocation not only for patient care but also for maximum health care and public health benefit. OBJECTIVE: The goal of this study was to determine whether a COVID-19 telemedicine risk assessment tool accurately predicts hospitalizations. METHODS: We conducted a retrospective study of a COVID-19 telemedicine home monitoring program serving health care workers and the community in Atlanta, Georgia, with enrollment from March 24 to May 26, 2020; the final call range was from March 27 to June 19, 2020. All patients were assessed by medical providers using an institutional COVID-19 risk assessment tool designating patients as Tier 1 (low risk for hospitalization), Tier 2 (intermediate risk for hospitalization), or Tier 3 (high risk for hospitalization). Patients were followed with regular telephone calls to an endpoint of improvement or hospitalization. Using survival analysis by Cox regression with days to hospitalization as the metric, we analyzed the performance of the risk tiers and explored individual patient factors associated with risk of hospitalization. RESULTS: Providers using the risk assessment rubric assigned 496 outpatients to tiers: Tier 1, 237 out of 496 (47.8%); Tier 2, 185 out of 496 (37.3%); and Tier 3, 74 out of 496 (14.9%). Subsequent hospitalizations numbered 3 out of 237 (1.3%) for Tier 1, 15 out of 185 (8.1%) for Tier 2, and 17 out of 74 (23%) for Tier 3. From a Cox regression model with age of 60 years or older, gender, and reported obesity as covariates, the adjusted hazard ratios for hospitalization using Tier 1 as reference were 3.74 (95% CI 1.06-13.27; P=.04) for Tier 2 and 10.87 (95% CI 3.09-38.27; P<.001) for Tier 3. CONCLUSIONS: A telemedicine risk assessment tool prospectively applied to an outpatient population with COVID-19 identified populations with low, intermediate, and high risk of hospitalization.

Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials.

AIMS: Recent randomized trials demonstrated a benefit of low-dose colchicine added to guideline-based treatment in patients with recent myocardial infarction or chronic coronary disease. We performed a systematic review and meta-analysis to obtain best estimates of the effects of colchicine on major adverse cardiovascular events (MACE). METHODS AND RESULTS: We searched the literature for randomized clinical trials of long-term colchicine in patients with atherosclerosis published up to 1 September 2020. The primary efficacy endpoint was MACE, the composite of myocardial infarction, stroke, or cardiovascular death. We combined the results of five trials that included 11 816 patients. The primary endpoint occurred in 578 patients. Colchicine reduced the risk for the primary endpoint by 25% [relative risk (RR) 0.75, 95% confidence interval (CI) 0.61-0.92; P = 0.005], myocardial infarction by 22% (RR 0.78, 95% CI 0.64-0.94; P = 0.010), stroke by 46% (RR 0.54, 95% CI 0.34-0.86; P = 0.009), and coronary revascularization by 23% (RR 0.77, 95% CI 0.66-0.90; P < 0.001). We observed no difference in all-cause death (RR 1.08, 95% CI 0.71-1.62; P = 0.73), with a lower incidence of cardiovascular death (RR 0.82, 95% CI 0.55-1.23; P = 0.34) counterbalanced by a higher incidence of non-cardiovascular death (RR 1.38, 95% CI 0.99-1.92; P = 0.060). CONCLUSION: Our meta-analysis indicates that low-dose colchicine reduced the risk of MACE as well as that of myocardial infarction, stroke, and the need for coronary revascularization in a broad spectrum of patients with coronary disease. There was no difference in all-cause mortality and fewer cardiovascular deaths were counterbalanced by more non-cardiovascular deaths.

Description of symptom course in a telemedicine monitoring clinic for acute symptomatic COVID-19: a retrospective cohort study.

OBJECTIVE: Describe the disease course in a cohort of outpatients with COVID-19 and evaluate factors predicting duration of symptoms. DESIGN: Retrospective cohort study. SETTING: Telemedicine clinic at a large medical system in Atlanta, Georgia. PARTICIPANTS: 337 patients with acute COVID-19. Exclusion criteria included intake visit more than 10 days after symptom onset and hospitalisation prior to intake visit. MAIN OUTCOME MEASURES: Symptom duration in days. RESULTS: Common symptoms at intake visit are upper respiratory (73% cough, 55% loss of smell or taste, 57% sinus congestion, 32% sore throat) and systemic (66% headache, 64% body aches, 53% chills, 30% dizziness, 36% fever). Day of symptom onset was earliest for systemic and upper respiratory symptoms (median onset day 1 for both), followed by lower respiratory symptoms (day 3, 95% CI 2 to 4), with later onset of gastrointestinal symptoms (day 4, 95% CI 3 to 5), when present. Cough had the longest duration when present with median 17 days (95% CI 15 to 21), with 42% not resolved at final visit. Loss of smell or taste had the second longest duration with 14 days (95% CI 12 to 17), with 38% not resolved at final visit. Initial symptom severity is a significant predictor of symptom duration (p<0.01 for multiple symptoms). CONCLUSIONS: COVID-19 illness in outpatients follows a pattern of progression from systemic symptoms to lower respiratory symptoms and persistent symptoms are common across categories. Initial symptom severity is a significant predictor of disease duration for most considered symptoms.

Clinical course and outcomes of COVID-19 in rheumatic disease patients: a case cohort study with a diverse population.

OBJECTIVE: To determine clinical course and outcomes in rheumatic disease patients with coronavirus disease 2019 (COVID-19) and compare results to uninfected patients. METHODS: We conducted a case cohort study of autoimmune disease patients with COVID-19 (confirmed by severe acute respiratory syndrome coronavirus 2 PCR) from February 1, 2020, to July 31, 2020, and compared them in a 1:3 ratio with uninfected patients who were matched based on race, age, sex, and comorbidity index. Patient demographics, clinical course, and outcomes were compared among these patient groups. RESULTS: A total of 70 rheumatic disease patients with COVID-19 (mean age, 56.6 years; 64% African American) were identified. The 34 (49%) patients who were hospitalized used oral glucocorticoids more frequently than those treated as outpatients (p < 0.01). All 10 patients using anti-TNFα medications were treated as outpatients (p < 0.01). Those hospitalized with COVID-19 more often required ICU admission (17 (50%) vs 27 (26%), p = 0.01) and intubation (10 (29%) vs 6 (6%), p < 0.01) than uninfected patients and had higher mortality rates (6 (18%) vs 3 (3%), p < 0.01). Of the six COVID-19 patients who died, only one was of African ancestry (p = 0.03). CONCLUSION: Rheumatic disease patients infected with COVID-19 were more likely to require ICU admission, ventilation, and died more frequently versus uninfected patients with autoimmune disease. Patients on anti-TNFα medications were hospitalized less frequently, while those on chronic glucocorticoids were hospitalized more frequently. These findings have important implications for medication choice in rheumatic disease patients during the ongoing spread of COVID-19. Key Points • We show that hospitalized rheumatic disease patients with COVID-19 have poorer outcomes including ICU admission, ventilation, and death compared to hospitalized rheumatic disease patients not infected with COVID-19. • This study adds further support regarding protective effects of anti-TNFα medications in COVID-19 disease course, with 0 of 10 of these patients required hospitalization.

Breaking the deadlock of calcified coronary artery lesions: A contemporary review.

Percutaneous coronary intervention (PCI) of severely calcified lesions is known to result in lower procedural success rates, higher complication rates, and worse long-term clinical outcomes compared to noncalcified lesions. Adequate lesion preparation through calcium modification is crucial in ensuring procedural success and reducing adverse cardiovascular outcomes. There are numerous calcium modification devices currently available whose usefulness depends on the nature of the calcific disease and its anatomical distribution. It can be challenging for the interventionists to decide which device is best suited for their patient. There is also emerging evidence for intravascular imaging in guiding selection of calcium modification devices using parameters such as calcium distribution and depth that directly impact on procedural success and clinical outcomes. In this review we aim to discuss the pathophysiology of coronary calcification, evaluate strategies and technologies of calcium modification and propose an A-M-A-S-A algorithm in managing calcified coronary lesions.

Utility of Zwolle Risk Score in Guiding Low-Risk STEMI Discharge.

BACKGROUND: Despite emerging evidence suggesting that selected patients presenting with ST-segment elevation myocardial infarction (STEMI) treated successfully with primary percutaneous coronary intervention (PPCI) may be considered for early discharge, STEMI patients are typically hospitalised longer to monitor for serious complications. METHODS: We assessed the feasibility of identifying low-risk STEMI patients in our institution for early discharge using the Zwolle risk score (ZRS). We evaluated consecutive STEMI patients who underwent successful PPCI within the period 1 January 2016 to 31 December 2017. Low-risk was defined as ZRS≤3. Demographic, angiographic characteristics, length of stay (LOS), and 30-day major adverse cardiovascular events (MACE) defined as cardiac death, stroke, congestive cardiac failure, and non-fatal myocardial infarction, were recorded. RESULTS: There were 183 STEMI patients in our study cohort (mean age 62.0±12.2 years, 77.0% male). The median ZRS was 2 (interquartile range 1-4) with 132 (72.1%) patients classified as low-risk. The overall 30-day MACE and mortality rates were 10.4% and 3.3% respectively. None of the 35 (26.5%) low-risk patients who were discharged within 72 hours experienced MACE at 30 days. Low-risk STEMI patients had significantly shorter median LOS (86.3 vs. 93.2 hours, p=0.002), lower 30-day MACE (4.5% vs. 25.5%, p<0.0001) and mortality (0% vs. 11.8%, p<0.0001) compared to high-risk group (ZRS>3). Receiver operating characteristic (ROC) curve analyses for ZRS in predicting 30-day MACE and mortality yielded C-statistics of 0.79 (95%CI 0.68-0.90, p<0.0001) and 0.98 (95%CI 0.95-1.00, p<0.0001) respectively. CONCLUSION: Low-risk STEMI patients stratified by Zwolle risk score, who were treated successfully with PPCI, experienced low 30-day MACE and mortality rates, indicating that early discharge may be safe in these patients. Larger studies are warranted to evaluate the safety of ZRS-guided early discharge of STEMI patients, as well as the economic and psychological impacts.

Colchicine in Patients With Acute Coronary Syndrome: The Australian COPS Randomized Clinical Trial.

BACKGROUND: Inflammation plays a crucial role in clinical manifestations and complications of acute coronary syndromes (ACS). Colchicine, a commonly used treatment for gout, has recently emerged as a novel therapeutic option in cardiovascular medicine owing to its anti-inflammatory properties. We sought to determine the potential usefulness of colchicine treatment in patients with ACS. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial involving 17 hospitals in Australia that provide acute cardiac care service. Eligible participants were adults (18-85 years) who presented with ACS and had evidence of coronary artery disease on coronary angiography managed with either percutaneous coronary intervention or medical therapy. Patients were assigned to receive either colchicine (0.5 mg twice daily for the first month, then 0.5 mg daily for 11 months) or placebo, in addition to standard secondary prevention pharmacotherapy, and were followed up for a minimum of 12 months. The primary outcome was a composite of all-cause mortality, ACS, ischemia-driven (unplanned) urgent revascularization, and noncardioembolic ischemic stroke in a time to event analysis. RESULTS: A total of 795 patients were recruited between December 2015 and September 2018 (mean age, 59.8±10.3 years; 21% female), with 396 assigned to the colchicine group and 399 to the placebo group. Over the 12-month follow-up, there were 24 events in the colchicine group compared with 38 events in the placebo group (P=0.09, log-rank). There was a higher rate of total death (8 versus 1; P=0.017, log-rank) and, in particular, noncardiovascular death in the colchicine group (5 versus 0; P=0.024, log-rank). The rates of reported adverse effects were not different (colchicine 23.0% versus placebo 24.3%), and they were predominantly gastrointestinal symptoms (colchicine, 23.0% versus placebo, 20.8%). CONCLUSIONS: The addition of colchicine to standard medical therapy did not significantly affect cardiovascular outcomes at 12 months in patients with ACS and was associated with a higher rate of mortality. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12615000861550.