Acute Coronary Syndrome Guidelines Research Articles

Sub-Saharan Africa's contribution to clinical trials in international acute coronary syndromes and heart failure guidelines

Abstract Introduction There is a growing burden of acute coronary syndrome (ACS) and heart failure (HF) in sub-Saharan Africa (SSA), yet outcomes remain poor compared to high-income countries (HICs). Global clinical guidelines are pivotal to the delivery of evidence based cardiovascular care, however their applicability to populations in SSA remains unclear. Purpose To evaluate the extent to which populations from SSA contribute to pharmacotherapeutic randomised clinical trials informing international ACS and HF clinical guidelines. Methods We extracted details on pharmacotherapeutic randomised control trials (RCTs) contributing to Class I or II guideline recommendations from the 2023 European Society of Cardiology (ESC) guidelines for ACS and the 2021 ESC guidelines for HF. Data on RCTs contributing to these guidelines were extracted from the ClinicalTrials.gov or published articles. We analysed the proportion of RCTs which had a contribution from countries in each World Bank income group. Then we specifically assessed the contribution of SSA countries to clinical trials and analysed temporal trends. Results Of 119 RCTs from the ESC HF guidelines and the 343 pharmacotherapy RCTs from the ESC ASC guidelines 75.9% were exclusively conducted in high-income countries, 22.2% of the trials included at least one site from a middle-income country and none included sites from a low-income country (figure 1). The global distribution of HF (figure 2a) and ACS (figure 2b) pharmacotherapy guidelines is demonstrated in figure 2. The only country represented from SSA was South Africa which is an upper middle-income country. A site from South Africa was included in 17 (14.2%) HF RCTs and 28 (8.2%) ACS RCTs. There has been a significant increase in the proportion HF RCTs conducted in SSA, increasing from 2.6% between 1990 and 1999 to 50% since 2020 (OR 28.8, 95% CI 2.6 – 983.4, p-value for trend< 0.0001). For ACS RCTs, the proportion of trials conducted in SSA increased from 1.8% pre 1990 to 23.4% during 2000-2009 (OR 15.9, 95% CI 4.2 - 112.9, p value for trend = 0.003) then declined to 11.3% from 2010-2019. Conclusions There is a marked under-representation of SSA countries in ACS and HF pharmacotherapy RCTs, despite the region's escalating cardiovascular disease burden. South Africa is the sole contributor from the region, with all other SSA countries absent. This finding could potentially affect the applicability and generalisability of global guidelines to populations in SSA with distinct clinical presentations and healthcare challenges.Figure 1 Figure 2

Undiagnosed Diabetes Mellitus is an important risk factor in secondary prevention after an acute coronary syndrome and warrants active screening

Abstract Background/Introduction Previous studies have shown that patients with Diabetes Mellitus (DM) undergoing percutaneous coronary intervention (PCI) for an acute coronary syndrome (ACS) have an increased ischemic risk compared to non-diabetics. This has led to the recommendation to take DM into account when considering extended dual antiplatelet therapy (DAPT) to prevent ischemic events. Although screening for DM can simply be conducted by measuring HbA1c values, the ACS guidelines do not yet recommend to screen for DM de novo. This may lead to undertreatment. Purpose We aimed to determine the ischemic risk of previously diagnosed DM and of DM de novo compared to patients without DM in a real world ACS population. Methods We included patients from the South East (Zuid Oost) Netherlands Heart Registry (ZON-HR) undergoing PCI for ACS without using oral anticoagulants and compared outcomes between DM and non-DM patients. In a subgroup of patients without previously diagnosed DM with available HbA1c measurements at baseline, we compared outcomes between patients with or without DM de novo (HbA1c ≥48 mmol/mol). All analyses were performed using Cox regression analysis. We used multivariate analysis to adjust for known ischemic risk factors. Results Of the 2406 patients included, 426 were previously diagnosed with DM. Additional ischemic risk factors, such as a history of myocardial infarction (MI), multivessel disease and kidney disease, were significantly more often present in patients with DM. Patients with DM showed numerically more major adverse cardiac and cerebral events (MACCE). However, this was not significant (HR: 1.24, 95% CI: 0.92-1.66). All-cause mortality was higher in patients with DM at 30 days (HR: 1.51, 95% CI 1.00-2.29) and 1 year (HR: 1.55, 95% CI 1.10-2.18), which remained significant at 1 year when corrected for additional risk factors. The HbA1c values at baseline were available in 387 patients without previously diagnosed DM. In this subgroup, 69 (18%) patients showed an elevated HbA1c level of ≥48 mmol/mol. Outcomes within this subgroup are presented in table 1. Patients with de novo DM showed significant more ischemic events after one month and one year follow-up compared to patients without DM de novo. Figure 1 depicts the survival from MACCE over time in these subgroups. Conclusion In our real world population of ACS patients undergoing PCI, we found no significant difference in ischemic risk between patients with previously diagnosed DM compared to non-DM. However, all-cause mortality was significant higher in DM patients. Active screening for DM resulted in a large proportion of patients with DM de novo who showed a major increase in ischemic risk. These results demonstrate the importance of screening for DM in ACS patients undergoing PCI.

Analyzing the economic ramifications of the broad implementation of generic prasugrel

Abstract Introduction The 2023 European Acute Coronary Syndrome (ACS) guidelines state that prasugrel (PRG) should be considered in preference to ticagrelor (TCG) in patients (pts) who proceed to percutaneous coronary angioplasty (PCI). In Portugal, PRG is less available due to earlier evidence considering pretreatment and contraindications for each drug. PRG (10mg) is currently a generic drug, while TCG is not. We aimed to evaluate the proportion of pts that could be switched from TCG to PRG, and the economic impact of a widespread national adoption. Methods To determine eligibility for generic PRG 10mg, we examined a single center prospective database of consecutive ACS pts undergoing PCI in a full year. Eligibility for TCG and PRG was based on drug specific contraindications, previous stroke for PRG and chronic liver disease (CLD) for TCG, and indication for PRG dose reduction (≤60 kg and ≥75 years). To estimate hospital costs we used the price per pill indicated by the pharmacy (0.98€ TCG, 0.67€ PRG). To obtain post-discharge and NHS savings we used the INFARMED public information. We estimated 3500 PCIs per year on a national level, based on published data. Results A total of 780 pts were included, median age 68±10.4years, 523 (67.1%) were male, 51.9% (n=406) had non-ST elevation ACS. Mean admission time was 8.36 days. Considering PRG and TCG contraindications, 157 pts (20.3%) had a previous history of stroke and 20pts (2.6%) had CLD. 150 pts (19.2%) had PRG dose reduction criteria. Eligible for PRG 10mg and TCG 90mg were 434 pts (57.8% of total PCI pts). Cost per admission would be 33 697.35€ for TCG and 17 617.28€ for PRG. At a national level, hospital costs can be reduced by 16080.07€. Considering the 1-year outpatient setting and a widespread generic PRG 10mg adoption, NHS savings are estimated in 898 323.59€, and patient savings in 401248.25€ (198.38€ per patient). Conclusions ACS pts in real-world scenarios exhibit both eligibility for PRG and TCG. Considering the lower cost, the NHS can potentially save 914 403,66€ (figure 1) annually through the widespread adoption of generic PRG 10mg.

Beta-Blockers for Secondary Prevention following Myocardial Infarction in Patients Without Reduced Ejection Fraction or Heart Failure: An Updated Meta-Analysis.

The 2023 ESC guidelines for acute coronary syndrome note that contemporary data are heterogenous regarding beta-blockers (BB) use post-myocardial infarction (MI) in patients without reduced ejection fraction (EF) or heart failure (HF). We aimed to address the heterogeneity in contemporary data around BB post-MI in this population. We searched 6 databases from Jan 1, 2000 to Sep 1, 2024 to identify contemporary studies enrolling MI patients without reduced EF (≤40%) or history of HF receiving BB at index MI, and comparing outcomes between BB users and non-users. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiac and cerebrovascular events (MACCE) and cardiovascular (CV) mortality. Random-effects meta-analysis was conducted using the restricted maximum likelihood method. There were 24 studies including 290,349 patients enrolled in the contemporary era. Overall, BB use was associated with a significant 11% reduction in all-cause mortality (HR, 0.89; 95% CI, 0.81 to 0.97; I2 = 40%; Figure 1), however with moderate-to-high statistical heterogeneity. Prespecified subgroup analyses demonstrate comparable all-cause mortality (HR, 0.99; 95% CI, 0.94 to 1.06; I2 = 0%), CV mortality (HR, 0.99; 95% CI, 0.85 to 1.15; I2 = 0%), and MACCE (HR, 1.24; 95% CI, 1.01 to 1.52; I2 = 0%) in patients with a 1-year event-free period, defined as no death, recurrent MI, or HF while on BB following index MI. In patients with no event-free period, meta-regression revealed that BB mortality benefits were modified by the study inclusion period (P = 0.01), reflecting a temporal trend of decreasing BB mortality benefits over time. Based on the temporal trend, in patients with preserved EF post-2010, BB exhibited no reduction in all-cause mortality (HR, 0.97; 95% CI, 0.90 to 1.04; I2 = 0%), but a non-significant trend towards increased CV mortality (HR, 1.29; 95% CI, 0.96 to 1.72; I2 = 0%) and a significant increase in MACCE (HR, 1.24; 95% CI, 1.01 to 1.52; I2 = 0%). In the contemporary reperfusion era, BB may not confer additional mortality benefits beyond a 1-year event-free period post-MI in patients without reduced EF. Moreover, post-MI BB use was associated with detrimental effects in patients with preserved EF.

Post-procedural Anticoagulation With Unfractionated Heparin in Acute Coronary Syndrome: Insight from the STOPDAPT-3 Trial

The current guidelines for acute coronary syndrome (ACS) discourage the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation is not well supported by evidence. In this post hoc analysis of the ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3 (STOPDAPT-3) trial, 30-day outcomes were compared between the 2 groups with and without post-PCI heparin administration among patients with ACS who did not receive mechanical support devices. The co-primary end points were the bleeding end point, defined as the Bleeding Academic Research Consortium type 3 or 5 bleeding, and the cardiovascular end point, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4,088 patients with ACS, 2,339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher among those with ST-elevation myocardial infarction compared with others (72.3% and 38.8%, p <0.001), and among patients with intraprocedural adverse angiographic findings compared with those without (67.6% and 47.5%, p <0.001). Post-PCI heparin compared with no post-PCI heparin was associated with a significantly increased risk of the bleeding end point (4.75% and 2.52%, adjusted hazard ratio 1.69, 95% confidence interval 1.15 to 2.46, p = 0.007) and a numerically increased risk of the cardiovascular end point (3.16% and 1.72%, adjusted hazard ratio 1.56, 95% confidence interval 0.98 to 2.46, p = 0.06). Higher hourly dose or total doses of heparin were also associated with higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in patients with ACS. Post-PCI heparin use was associated with harm in terms of increased bleeding without the benefit of reducing cardiovascular events. Trial identifier: STOPDAPT-3 ClinicalTrials.gov number, NCT04609111.

Updated Guidelines for Acute Coronary Syndrome

Despite medical and invasive advancements, cardiovascular mortality attributable to ischemic heart disease, including acute coronary syndrome (ACS), persists at a substantial level. Clinical guidelines have been issued by the European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association to support clinicians in making appropriate decisions and improving the prognosis of ACS patients. ESC recently introduced a new ACS guideline in August 2023. This review discusses the recent modification in the diagnosis and management of early-phase ACS in the 2023 ESC guideline.

Prescription of lipid-lowering therapy, LDLc control, and risk of MACE in patients after ST-elevation myocardial infarction in Mexico

Abstract Funding Acknowledgements None. Background/Introduction Optimal control of low-density lipoprotein cholesterol (LDLc) has been demonstrated to reduce cardiovascular event rates after ST-elevation myocardial infarction (STEMI). However, real-world data shows that a low proportion of patients achieve LDLc targets. Furthermore, the association of LDLc levels and major cardiovascular adverse events (MACE) in post-STEMI patients is limited in developing countries. Purpose In this study, we aimed to assess the prescription patterns of lipid-lowering therapies, LDLc control, and their impact on the risk of MACE after STEMI in Mexico. Methods We conducted a prospective observational study of patients with STEMI. LDLc levels and prescriptions of lipid-lowering therapy were assessed during the first scheduled visit following STEMI hospital discharge. LDLc control was determined in accordance with the 2023 European Society of Cardiology Acute Coronary Syndrome Guidelines, which recommend achieving LDLc levels below 55 mg/dL for secondary prevention. Patients were categorized as controlled (if LDLc &amp;lt;55 mg/dL) and not controlled (if LDLc &amp;gt;55 mg/dL) and were followed for a median of 4.5 years to evaluate the rate of MACE, including cardiovascular death, cardiogenic shock, recurrent MI, and heart failure. Results We included 447 patients with a mean age of 57.87 (± 10.5 years), predominantly male (84.5%). Hypertension (43.8%), smoking (41.1%), type 2 diabetes mellitus (33.5%), obesity (26.6%), and dyslipidemia (21.4%) were highly prevalent. The median LDLc level in the total population was 65.4 mg/dL (IQR 49.2- 87.7). Among these, 34% (152) were considered controlled, while 66% (295) were not. Baseline clinical characteristics did not significantly differ among the groups. Prescription of high-intensity statins reached 94.7%, and ezetimibe and PCSK-9i were used in 1.8% and 0.4% of cases, respectively. We observed no statistically significant difference (Hazard ratio: 1.03, 95% confidence interval 0.74-1.73) in the rate of MACE based on LDLc control (Fig.1). The risk of MACE was also not different based on the use of high-intensity statins. Conclusions In this real-world study of patients post-STEMI, LDLc control was achieved in just one-third of the population. While the prescription of high-intensity statins was high, combination therapy was low. We did not observe a statistically significant association with an increased long-term risk of MACE; however, we noted a higher rate of events compared with other series.

Influence of Clinician-Related Factors on Adherence to the American Heart Association Guidelines for Acute Coronary Syndrome among Clinicians at Kenya Ports Authority Clinics in Mombasa, Kenya

Purpose: The aim of the study was to assess influence of clinician-related factors on adherence to the American heart association guidelines for acute coronary syndrome among clinicians at Kenya Ports Authority clinics in Mombasa, Kenya. Methodology: A descriptive cross-sectional study involving quantitative methods of data collection was adopted. An interviewer administered questionnaire was used for data collection. The study was carried out in Kenya Ports Authority clinics in Mombasa, Kenya. The target population was 106 clinicians attending to patients who present with Acute Coronary Syndrome at the KPA clinics in Mombasa. A census method was used to determine the study participants. The sample size was made up of a hundred and six participants. The clinicians who consented to participate in the study were included while those who were on sick off, leave or who recently joined the clinic were excluded. Pretesting of the study tool was done at the Kenya Pipeline Clinic Mombasa. Data analysis was done using Statistical Package for Social Sciences version 25 and presented via tables. Findings: The study results showed that at 95% level of confidence (ρ-value = 0.05%), there was a significant association between gender (ᾳ=0.025), work experience (ᾳ=0.016), job cadre (ᾳ=0.014) and training received (ᾳ=0.022) on adherence to the American Heart Association Guidelines for Acute Coronary Syndrome among clinicians at Kenya Ports Authority clinics in Mombasa, Kenya. The association was insignificant between age (ᾳ=0.178), education level (ᾳ=0.439) and specialization (ᾳ=0.489) on adherence to the AHA guidelines. Unique Contribution to Theory, Practice and Policy: The study recommends that the KPA management should increase the medical budget to ensure availability of adequate resources for ACS patient management. These resources include adequate staffing, medication, equipment, and staff training costs. The clinic management should ensure that medications such as aspirin, morphine and nitroglycerine are readily available and accessible at patients care points. The KPA clinic management to formulate a simple algorithm that outlines the steps to be taken when managing ACS patients. The study recommends that the clinics should assess their equipment reqularly for maintenance controls to ensure efficiency. The study further recommends random assessments and post care audits to assess the adherence to ACS guidelines among clinicians. Training associated with adherence to the AHA guidelines and as such, KPA should continue offering training and education on the latest AHA guidelines for ACS to ensure updated guidelines for practice.

The new ESC acute coronary syndrome guideline and its impact in the CPU and emergency department setting.

The new guideline on acute coronary syndrome (ACS) of the European Society of Cardiology (ESC) replaces two separate guidelines on ST-elevation myocardial infarction (STEMI) and non-ST-elevation (NSTE) ACS. This change of paradigm reflects the experts view that the ACS is acontinuum, starting with unstable angina and ending in cardiogenic shock or cardiac arrest due to severe myocardial ischemia. Secondary, partly non-atherosclerotic-caused myocardial infarctions ("type2") are not integrated in this concept.With respect to acute care in the setting of emergency medicine and the chest pain unit structures, the following new aspects have to be taken into account:1.New procedural approach as "think A.C.S." meaning "abnormal ECG," "clinical context," and "stable patient"2.New recommendation regarding aholistic approach for frail patients3.Revised recommendations regarding imaging and timing of invasive strategy in suspected NSTE-ACS4.Revised recommendations for antiplatelet and anticoagulant therapy in STEMI5.Revised recommendations for cardiac arrest and out-of-hospital cardiac arrest6.Revised recommendations for in-hospital management (starting in the CPU/ED) and ACS comorbid conditionsIn summary, the changes are mostly gradual and are not based on extensive new evidence, but more on focused and healthcare process-related considerations.

2024 Korean Society of Myocardial Infarction/National Evidence-Based Healthcare Collaborating Agency Guideline for the Pharmacotherapy of Acute Coronary Syndromes.

Many countries have published clinical practice guidelines for appropriate clinical decisions, optimal treatment, and improved clinical outcomes in patients with acute coronary syndrome. Developing guidelines that are specifically tailored to the Korean environment is crucial, considering the treatment system, available medications and medical devices, racial differences, and level of language communication. In 2017, the Korean Society of Myocardial Infarction established a guideline development committee. However, at that time, it was not feasible to develop guidelines, owing to the lack of knowledge and experience in guideline development and the absence of methodology experts. In 2022, the National Evidence-Based Healthcare Collaborating Agency collaborated with a relevant academic association to develop internationally reliable guidelines, with strict adherence to the methodology for evidence-based guideline development. The first Korean acute coronary syndrome guideline starts from the 9 key questions for pharmacotherapy.

Adherence to Clinical Practice Guidelines for Non-ST Elevation Acute Coronary Syndrome in the Emergency Department: Exploring the Role of Social, Healthcare-system, and Clinical Determinants.

The aim of this study was to assess adherence to the European Society of Cardiology 2020 non-ST elevation acute coronary syndrome (NST-ACS) guidelines, identify factors affecting this compliance, and explore the link between adherence and adverse cardiac outcomes. This prospective cohort study was conducted in a tertiary-level academic hospital between January 2022 and January 2023. Patients diagnosed with NST-ACS in the emergency department (ED) were included. The primary outcome measured was the rate of adherence to the guidelines, and secondary outcomes were factors affecting this adherence in the ED and its association with 28-day adverse cardiac outcomes. Of the 298 patients included, guideline adherence was achieved in 32.2% in the ED. The highest compliance was observed in performing a 12-lead electrocardiogram (ECG) within 10 minutes (99.7%), while the lowest was found for obtaining additional right and posterior ECG leads when ongoing ischemia was suspected (42.3%). Factors associated with better adherence included the experience level of the treating physician, the presence of cardiac-quality chest pain, initial ischemic ECG findings, higher initial troponin levels, and advanced history, electrocardiogram, age, risk factors, and troponin score and Charlson comorbidity index. Complete guideline adherence over 28 days was achieved in 19.1% of patients and was found to be significantly associated with lower rates of adverse cardiac outcomes. Adherence to NST-ACS guidelines was generally low but was associated with improved patient outcomes. This study highlighted the importance of various factors associated with guideline adherence. Future research should explore further barriers to guideline adherence and develop targeted interventions.

Type of evidence supporting ACC/AHA and ESC clinical practice guidelines for acute coronary syndrome.

The aim of clinical practice guidelines for ST elevation myocardial infarction (STEMI) and non-ST elevation acute coronary syndrome (NSTE-ACS) is to assist healthcare professionals in clinical decision-making. We evaluated the type of studies supporting these guidelines and their recommendations. All references and recommendations in the 2013 and 2014 ACC/AHA and 2017 and 2020 (ESC clinical guidelines for STEMI and NSTE-ACS were reviewed. References were classified into meta-analyses, randomised, non-randomised, and other types (e.g., position papers, reviews). Recommendations were classified according to class and their level of evidence (LOE). We retrieved 2128 non-duplicated references: 8.4% were meta-analyses, 26.2% randomised studies, 44.7% non-randomised studies, and 20.7% 'other' papers. Meta-analyses were based on randomised data in 78% of cases and used individual-patient data in 20.2%. Compared to non-randomised studies, randomised studies were more frequently multicentre (85.5% vs. 65.5%) and international (58.2% vs. 28.5%). The type of studies supporting recommendations varied as per the LOE of the recommendation. For LOE-A recommendations, the breakdown of supporting recommendations was: 18.5% meta-analyses, 56.6% randomised studies, 16.6% non-randomised studies and 8.3% 'other' papers; for LOE-B this breakdown was 9%, 39.8%, 38.2%, and 12.9%; and for LOE-C; 4.6%, 19.3%, 30.3%, and 45.9%. The references supporting the ACC/AHA and ESC guidelines on STEMI and NSTE-ACS consisted of non-randomised studies in ~ 45% of cases, with less than a third of the references consisting of meta-analyses and randomised studies. The type of studies supporting guideline recommendations varied widely by the LOE of the recommendation.

A systematic assessment of the characteristics of randomized controlled trials cited by acute coronary syndrome clinical practice guidelines.

The aim of this study was to describe the methodological features of the randomized controlled trials (RCTs) cited in American and European clinical practice guidelines (CPGs) for ST elevation myocardial infarction (STEMI) and non-ST elevation acute coronary syndrome (NSTE-ACS). Out of 2128 non-duplicated references cited in the 2013 and 2014 American College of Cardiology/American Heart Association and 2017 and 2020 European Society of Cardiology CPGs for STEMI and NSTE-ACS, we extracted data for 407 RCTs (19.1% of total references). The majority were multicenter studies (81.8%), evaluated pharmacological interventions (63.1%), had a 2-arm (82.6%), and superiority (90.4%) design. Most RCTs (60.2%) had an active comparator, and 46.2% were funded by industry. The median observed sample size was 1001 patients (84.2% of RCTs achieved≥80% of the intended sample size). Most RCTs had a single primary outcome (90.9%), which was a composite in just over half (51.9%). Among the RCTs testing for superiority, 44.0% reported a P-value of≥0.05 for the primary outcome and 61.9% observed a risk reduction of>15%. The observed treatment effect was lower-than-expected in 67.6% of RCTs, with 34.4% having at least a 20% lower-than-expected treatment effect. The calculated post hoc statistical power was≥80% for 33.9% of cited RCTs. This analysis demonstrates that RCTs cited by CPGs can still have significant methodological issues and limitations, highlighting that a better understanding of the methodological aspects of RCTs is crucial in order to formulate recommendations relevant to clinical practice.

Improving prioritization processes for clinical practice guidelines: new methods and an evaluation from the National Heart Foundation of Australia

BackgroundReleasing timely and relevant clinical guidelines is challenging for organizations globally. Priority-setting is crucial, as guideline development is resource-intensive. Our aim, as a national organization responsible for developing cardiovascular clinical guidelines, was to develop a method for generating and prioritizing topics for future clinical guideline development in areas where guidance was most needed.MethodsSeveral novel processes were developed, adopted and evaluated, including (1) initial public consultation for health professionals and the general public to generate topics; (2) thematic and qualitative analysis, according to the International Classification of Diseases (ICD-11), to aggregate topics; (3) adapting a criteria-based matrix tool to prioritize topics; (4) achieving consensus through a modified-nominal group technique and voting on priorities; and (5) process evaluation via survey of end-users. The latter comprised the organization’s Expert Committee of 12 members with expertise across cardiology and public health, including two citizen representatives.ResultsTopics (n = 405; reduced to n = 278 when duplicates removed) were identified from public consultation responses (n = 107 respondents). Thematic analysis synthesized 127 topics that were then categorized into 37 themes using ICD-11 codes. Exclusion criteria were applied (n = 32 themes omitted), resulting in five short-listed topics: (1) congenital heart disease, (2) valvular heart disease, (3) hypercholesterolaemia, (4) hypertension and (5) ischaemic heart diseases and diseases of the coronary artery. The Expert Committee applied the prioritization matrix to all five short-listed topics during a consensus meeting and voted to prioritize topics. Unanimous consensus was reached for the topic voted the highest priority: ischaemic heart disease and diseases of the coronary arteries, resulting in the decision to update the organization’s 2016 clinical guidelines for acute coronary syndromes. Evaluation indicated that initial public consultation was highly valued by the Expert Committee, and the matrix tool was easy to use and improved transparency in priority-setting.ConclusionDeveloping a multistage, systematic process, incorporating public consultation and an international classification system led to improved transparency in our clinical guideline priority-setting processes and that topics chosen would have the greatest impact on health outcomes. These methods are potentially applicable to other national and international organizations responsible for developing clinical guidelines.

The Fragility Index in randomised clinical trials supporting clinical practice guidelines for acute coronary syndrome: measuring robustness from a different perspective.

In randomised clinical trials (RCTs) rejecting the null hypothesis, the fragility index (FI) yields the minimum number of participants who would need to have had a different outcome for the results of the trial to become non-significant. We evaluated the robustness of RCTs supporting ACC/AHA and ESC clinical practice guidelines (CPGs) for ST elevation myocardial infarction (STEMI) and non-ST elevation acute coronary syndrome (NSTE-ACS) using the FI. There were 407 RCTs among the 2128 studies cited in the 2013 and 2014 ACC/AHA and 2017 and 2020 ESC CPGs for STEMI and NSTE-ACS, respectively. The FI could be calculated in 132 RCTs (32.4%) meeting the needed criteria for its estimation (2-arm RCT, 1:1 allocation, binary outcome, p < 0.05). The median FI was 12 (interquartile range: 4-29). Hence, a change in the outcome status of 12 patients would be needed to reverse the statistical significance of the primary endpoint in 50% of the RCTs. The FI was ≤1% than their sample size in 55.7% RCTs, whereas in 47% of RCTs, the FI was lower than the number of patients lost to follow-up. Some study design features were associated with higher FI (international, multicentre, private funding; all p < 0.05), whilst baseline patient characteristics were not substantially different by FI (e.g., age, female sex, white study participants; all p > 0.05), except for geographic enrolment (p = 0.042). FI might be useful to evaluate the robustness of those RCTs with statistically significant findings for the primary endpoint that have an impact on key guideline recommendations.

Pretreatment with a P2Y12 receptor inhibitor and delay to coronary artery bypass surgery in patients with non-ST segment elevation acute coronary syndrome.

2020 ESC guidelines for non-ST elevation acute coronary syndromes (NSTE-ACS) recommend against the pretreatment with P2Y12 receptor inhibitors (P2Y12i) in patients undergoing early invasive management (<24 h). The rationale is, in part, to prevent bleeding complications and the delay of coronary artery bypass graft surgery (CABG) in patients with suitable coronary anatomy. This study aimed to analyze the theoretical impact of pretreatment with a P2Y12i on delay to CABG surgery in a real-world population with NSTE-ACS. Single-center retrospective cohort of consecutive patients with NSTE-ACS undergoing invasive evaluation in 2019. Those with previous CABG or nonobstructive coronary disease were excluded. The total cohort included 262 patients (mean age 68±12 years, 69% male, 15% with unstable angina and mean GRACE score 134±35). Median time from FMC to angiography was 2 (1-4) days. Overall, 168 (64%) patients underwent percutaneous coronary intervention, 47 (18%) were proposed for CABG and the remainder received conservative management. All patients considered for CABG received pretreatment with P2Y12i (clopidogrel or ticagrelor). The median time from angiography to CABG was 12 (7-15) days. Six patients experienced recurrent angina (13%) and 2 (4%) died before surgery due to refractory ventricular fibrillation. Those who underwent CABG under P2Y12i effect were more likely to receive blood and platelets transfusions (64.7% vs. 28.6%, P=0.017 and 82.4% vs. 21.4%, P<0.001, respectively), although there were no differences regarding major bleeding. Pretreatment with P2Y12i was a potential but not the sole driver of CABG delay in our cohort. Adopting the new recommendations of withholding pretreatment might decrease this delay, but other factors must be considered.

Prehospital Administration of Aspirin and Nitroglycerin for Patients With Suspected Acute Coronary Syndrome - A Systematic Review.

Background: Recent guidelines for acute coronary syndrome (ACS) recommend prehospital administration of aspirin and nitroglycerin for ACS patients. However, there is no clear evidence to support this. We investigated the benefits and harms of prehospital administration of aspirin and nitroglycerin by non-physician healthcare professionals in patients with suspected ACS.Methods and Results: We searched the PubMed database and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Three retrospective studies for aspirin and 1 for nitroglycerin administered in the prehospital setting to patients with acute myocardial infarction were included. Prehospital aspirin administration was associated with significantly lower 30-day and 1-year mortality compared with aspirin administration after arrival at hospital, with odds ratios (OR) of 0.59 (95% confidence interval [CI] 0.35–0.99) and 0.47 (95% CI 0.36–0.62), respectively. Prehospital nitroglycerin administration was also associated with significantly lower 30-day and 1-year mortality compared with no prehospital administration (OR 0.34 [95% CI 0.24–0.50] and 0.38 [95% CI 0.29–0.50], respectively). The certainty of evidence was very low in both systematic reviews.Conclusions: Our systematic reviews suggest that prehospital administration of aspirin and nitroglycerin by non-physician healthcare professionals is beneficial for patients with suspected ACS, although the certainty of evidence is very low. Further investigation is needed to determine the benefit of the prehospital administration of these agents.

Myocardial infarction with non-obstructive coronary arteries (MINOCA): predictors of long-term outcome

Abstract Introduction Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous clinical entity. There is still limited knowledge about long-term prognosis of MINOCA patients. The aim of this study was to assess the incidence, time-to-event and predictors of mayor adverse cardiovascular events (MACE) in the long-term follow-up. Methods We carried out an analytical and observational study including all consecutive patients admitted to our hospital with acute myocardial infarction. Patients were classified as obstructive coronary artery disease (MICAD) or MINOCA using the definition of 2020 ESC acute coronary syndrome guidelines. Cardiovascular death, myocardial infarction, stroke and cardiovascular readmission were considered MACE. To determine MINOCA independent predictors, a multivariate analysis with cox regression was carried out in those variables with clinical or statistical relevance. Results During the studied period, 805 patients were included and 81 (10.1%) of them were diagnosed with MINOCA. Baselines characteristics of MINOCA patients: 53% were men, the mean age was 65±15 years, 67% suffered hypertension, 48% dyslipidemia, 21% mellitus diabetes and 43% were smokers. Follow-up (middle [interquartile range] 38 [19–57] months) was completed in 80 (99%) MINOCA patients and 18 (23%) of them had MACE (8 deaths, 6 myocardial infarctions, 2 strokes and 14 readmissions). The mean time to MACE was 53±2.9 months (Figure 1). Comparing MICAD vs. MINOCA, the 6 years rates of MACE (29% vs. 23%), mortality (12.7% vs. 10.0%), myocardial infarctions (6.5% vs. 7.5%), strokes (2.8% vs. 2.5%) and readmissions (17.5% vs. 24.2%) were similar with no statistically significant differences between MICAD and MINOCA patients. In the multivariate analysis (Table 1) chronic heart failure (HR=18.89; 95% CI 4.94–72.20) and peripheral vascular disease (HR=4.86; 95% CI 1.29–18.36) were independent predictors of MACE in MINOCA patients. The predictive model has a R2 of Nagelkerke of 0.07. Conclusion This study shows that chronic heart failure and peripheral vascular disease are associated with adverse outcomes in MINOCA patients and appears to be independent predictors of MACE in the long-term follow-up. Those predictors seem to be similar to factors previously shown to predict MACE in MICAD patients. Funding Acknowledgement Type of funding sources: None.

Acute myocardial infarction (AMI) in a patient with Human Immunodeficiency Virus infection

Introduction: Recent studies have shown that in HIV patients, the incidence of acute myocardial infarction is up to two times higher than in people who are not infected with HIV. HIV patients presenting with the first episode of the acute coronary syndrome are, on average, a decade younger than the general population, more frequently in men and current smokers. Case Report: We report a case report of a 33-year-old man with a diagnosis of anteroseptal STEMI and recent HIV on first-line ART, a combination of zidovudine 300 mg and lamivudine 150 mg, plus efavirenz 600 mg. The patient had typical angina complaints and had risk factors, namely smoking and a history of dyslipidemia. Patients were treated according to acute coronary syndrome guidelines, given DAPT, heparinization for five days, statins, anti-ischemia, ACE-I, and DCA-PCI. The DCA-PCI result in this patient was CAD 1 VD with 1 DES installed in the proximal LAD (complete revascularization). The patient was discharged from the hospital after seven days of treatment. Prognosis in these patients is still quite good, but preventing recurrent myocardial infarction needs risk factors and control for successful myocardial infarction therapy and ART. Conclusion: Special attention should be given to the risk of myocardial in HIV patients. Early diagnosis and prompt treatment could significantly lower mortality and improve patients' quality of life.

Outcomes of patients admitted with high-sensitive cardiac troponin T levels meeting the new rule out criteria for myocardial infarction

Abstract Background The 2020 ESC non-ST-elevation (NSTE) acute coronary syndromes (ACS) guidelines have adopted the paradigm that patients presenting with suspected NSTE-ACS and high-sensitive cardiac troponin T (hs-cTnT) values &amp;lt;99th percentile in a single test or small increment within 1/2 hours have a high negative predictive value for myocardial infarction (MI). Their management remains controversial. Purpose We examined the clinical outcomes and resource utilization of suspected NSTE-ACS patients who presented with hs-cTnT values meeting the early rule out criteria, but were nevertheless admitted. Methods Our single center retrospective cohort study included 4,263 visits for suspected NSTE-ACS triaged in the Emergency Room (ER), had hs-cTnT values that met the early rule-out criteria, and were admitted (Figure 1). Routine quality control and dedicated tests proved a coefficient of variance of &amp;lt;10% for hs-cTnT values &amp;lt;99th percentile (14 ng/L). Results There were no deaths in-hospital and at 30 days. Discharge diagnosis of MI was documented in 10 patients (∼0.2%). Median ER stay and hospital stay were 6 hours and 3 days, respectively. In hospital evaluation included 844 gated cardiac CT angiography (CTA), 580 SPECT heart scans, 101 ECG-exercise tests, and 178 coronary angiography, of which 70 (∼1.6% of cohort) culminated in percutaneous/surgical intervention. Conclusion Our findings highlight the high negative predictive value for MI applying the early rule out algorithm and supports a policy of ER discharge for further evaluation, sparing unnecessary and resource-consuming hospital admissions. Funding Acknowledgement Type of funding sources: None. Figure 1