Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk.

BACKGROUND: The appropriate duration of dual antiplatelet therapy in patients at high risk for bleeding after the implantation of a drug-eluting coronary stent remains unclear. METHODS: One month after they had undergone implantation of a biodegradable-polymer sirolimus-eluting coronary stent, we randomly assigned patients at high bleeding risk to discontinue dual antiplatelet therapy immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy). The three ranked primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding; cumulative incidences were assessed at 335 days. The first two outcomes were assessed for noninferiority in the per-protocol population, and the third outcome for superiority in the intention-to-treat population. RESULTS: Among the 4434 patients in the per-protocol population, net adverse clinical events occurred in 165 patients (7.5%) in the abbreviated-therapy group and in 172 (7.7%) in the standard-therapy group (difference, -0.23 percentage points; 95% confidence interval [CI], -1.80 to 1.33; P<0.001 for noninferiority). A total of 133 patients (6.1%) in the abbreviated-therapy group and 132 patients (5.9%) in the standard-therapy group had a major adverse cardiac or cerebral event (difference, 0.11 percentage points; 95% CI, -1.29 to 1.51; P = 0.001 for noninferiority). Among the 4579 patients in the intention-to-treat population, major or clinically relevant nonmajor bleeding occurred in 148 patients (6.5%) in the abbreviated-therapy group and in 211 (9.4%) in the standard-therapy group (difference, -2.82 percentage points; 95% CI, -4.40 to -1.24; P<0.001 for superiority). CONCLUSIONS: One month of dual antiplatelet therapy was noninferior to the continuation of therapy for at least 2 additional months with regard to the occurrence of net adverse clinical events and major adverse cardiac or cerebral events; abbreviated therapy also resulted in a lower incidence of major or clinically relevant nonmajor bleeding. (Funded by Terumo; MASTER DAPT ClinicalTrials.gov number, NCT03023020.).

Prevalence, Characteristics, and Outcomes of COVID-19-Associated Acute Myocarditis.

BACKGROUND: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19-associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. METHODS: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19-associated AM. RESULTS: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19-associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P<0.0001) similarly in patients with or without pneumonia. Corticosteroids were frequently administered (55.5%). CONCLUSIONS: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

Rationale and design of the PARTHENOPE trial: A two-by-two factorial comparison of polymer-free vs biodegradable-polymer drug-eluting stents and personalized vs standard duration of dual antiplatelet therapy in all-comers undergoing PCI.

BACKGROUND: Over the past few decades, percutaneous coronary intervention (PCI) has undergone significant advancements as a result of the combination of device-based and drug-based therapies. These iterations have led to the development of polymer-free drug-eluting stents. However, there is a scarcity of data regarding their clinical performance. Furthermore, while various risk scores have been proposed to determine the optimal duration of dual antiplatelet therapy (DAPT), none of them have undergone prospective validation within the context of randomized trials. DESIGN: The PARTHENOPE trial is a phase IV, prospective, randomized, multicenter, investigator-initiated, assessor-blind study being conducted at 14 centers in Italy (NCT04135989). It includes 2,107 all-comers patients with minimal exclusion criteria, randomly assigned in a 2-by-2 design to receive either the Cre8 amphilimus-eluting stent or the SYNERGY everolimus-eluting stent, along with either a personalized or standard duration of DAPT. Personalized DAPT duration is determined by the DAPT score, which accounts for both bleeding and ischemic risks. Patients with a DAPT score <2 (indicating higher bleeding than ischemic risk) receive DAPT for 3 or 6 months for chronic or acute coronary syndrome, respectively, while patients with a DAPT score ≥2 (indicating higher ischemic than bleeding risk) receive DAPT for 24 months. Patients in the standard DAPT group receive DAPT for 12 months. The trial aims to establish the noninferiority between stents with respect to a device-oriented composite end point of cardiovascular death, target-vessel myocardial infarction, or clinically-driven target-lesion revascularization at 12 months after PCI. Additionally, the trial aims to demonstrate the superiority of personalized DAPT compared to a standard approach with respect to a net clinical composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or type 2 to 5 bleeding according to the Bleeding Academic Research Consortium criteria at 24-months after PCI. SUMMARY: The PARTHENOPE trial is the largest randomized trial investigating the efficacy and safety of a polymer-free DES with a reservoir technology for drug-release and the first trial evaluating a personalized duration of DAPT based on the DAPT score. The study results will provide novel insights into the optimizing the use of drug-eluting stents and DAPT in patients undergoing PCI.

A comprehensive and easy-to-use ECG algorithm to predict the coronary occlusion site in ST-segment elevation myocardial infarction.

BACKGROUND: Several electrocardiogram (ECG) criteria have been proposed to predict the location of the culprit occlusion in specific subsets of patients presenting with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to develop, through an independent validation of currently available criteria, a comprehensive and easy-to-use ECG algorithm, and to test its diagnostic performance in real-world clinical practice. METHODS: We analyzed ECG and angiographic data from 419 consecutive STEMI patients submitted to primary percutaneous coronary intervention over a one-year period, dividing the overall population into derivation (314 patients) and validation (105 patients) cohorts. In the derivation cohort, we tested >60 previously published ECG criteria, using the decision-tree analysis to develop the algorithm that would best predict the infarct-related artery (IRA) and its occlusion level. We further assessed the new algorithm diagnostic performance in the validation cohort. RESULTS: In the derivation cohort, the algorithm correctly predicted the IRA in 88% of cases and both the IRA and its occlusion level (proximal vs mid-distal) in 71% of cases. When applied to the validation cohort, the algorithm resulted in 88% and 67% diagnostic accuracies, respectively. In a real-world comparative test, the algorithm performed significantly better than expert physicians in identifying the site of the culprit occlusion (P = .026 vs best cardiologist and P < .001 vs best emergency medicine doctor). CONCLUSIONS: Derived from an extensive literature review, this comprehensive and easy-to-use ECG algorithm can accurately predict the IRA and its occlusion level in all-comers STEMI patients.

Beneficial Effects of IABP in Anterior Myocardial Infarction Complicated by Cardiogenic Shock.

Background and Objectives. Recent guidelines have downgraded the routine use of the intra-aortic balloon pump (IABP) in patients with cardiogenic shock (CS) due to ST-elevation myocardial infarction (STEMI). Despite this, its use in clinical practice remains high. The aim of this study was to evaluate the prognostic impact of the IABP in patients with STEMI complicated by CS undergoing primary PCI (pPCI), focusing on patients with anterior MI in whom a major benefit has been previously hypothesized. Materials and Methods. We enrolled 2958 consecutive patients undergoing pPCI for STEMI in our department from 2005 to 2018. Propensity score matching and mortality analysis were performed. Results. CS occurred in 246 patients (8.3%); among these patients, 145 (60%) had anterior AMI. In the propensity-matched analysis, the use of the IABP was associated with a lower 30-day mortality (39.3% vs. 60.9%, p = 0.032) in the subgroup of patients with anterior STEMI. Conversely, in the whole group of CS patients and in the subgroup of patients with non-anterior STEMI, IABP use did not have a significant impact on mortality. Conclusions. The use of the IABP in cases of STEMI complicated by CS was found to improve survival in patients with anterior infarction. Prospective studies are needed before abandoning or markedly limiting the use of the IABP in this clinical setting.

The Intersection Between Heart Failure and Critical Care Cardiology: An International Perspective on Structure, Staffing, and Design Considerations.

The overall patient population in contemporary cardiac intensive care units (CICUs) has only increased with respect to patient acuity, complexity, and illness severity. The current population has more cardiac and noncardiac comorbidities, a higher prevalence of multiorgan injury, and consumes more critical care resources than previously. Patients with heart failure (HF) now occupy a large portion of contemporary tertiary or quaternary care CICU beds around the world. In this review, we discuss the core issues that relate to the care of critically ill patients with HF, including global perspectives on the organization, designation, and collaboration of CICUs regionally and across institutions, as well as unique models for provisioning care for patients with HF within a health care setting. The latter includes a discussion of traditional and emerging models, specialized HF units, the makeup and implementation of multidisciplinary team-based decision-making, and cardiac critical care admission and triage practices. This article illustrates the ways in which critically ill patients with HF have helped to shape contemporary CICUs throughout the world and explores how these very patients will similarly help to inform the future maturation of these specialized critical care units. Finally, we will critically examine broad, contemporary, international models of HF and cardiac critical care delivery in North America, Europe, South America, and Asia, and conclude with opportunities for the further investigation and generation of evidence for care delivery.

ANMCO position paper on antithrombotic treatment of patients with atrial fibrillation undergoing intracoronary stenting and/or acute coronary syndromes.

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with or without acute coronary syndromes (ACS) represent a subgroup with a challenging pharmacological management. Indeed, if on the one hand, antithrombotic therapy should reduce the risk related to recurrent ischaemic events and/or stent thrombosis; on the other hand, care must be taken to avoid major bleeding events. In recent years, several trials, which overall included more than 12 000 patients, have been conducted demonstrating the safety of different therapeutic combinations of oral antiplatelet and anticoagulant agents. In the present ANMCO position paper, we propose a decision-making algorithm on antithrombotic strategies based on scientific evidence and expert consensus to be adopted in the periprocedural phase, at the time of hospital discharge, and in the long-term follow-up of patients with AF undergoing PCI with/without ACS.

Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment-Elevation Myocardial Infarction: Primary Results of the FABOLUS-FASTER Trial.

BACKGROUND: Standard administration of newer oral P2Y12 inhibitors, including prasugrel or ticagrelor, provides suboptimal early inhibition of platelet aggregation (IPA) in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. We aimed to investigate the effects of cangrelor, tirofiban, and prasugrel, administered as chewed or integral loading dose, on IPA in patients undergoing primary percutaneous coronary intervention. METHODS: The FABOLUS-FASTER trial (Facilitation Through Aggrastat or Cangrelor Bolus and Infusion Over Prasugrel: A Multicenter Randomized Open-Label Trial in Patients with ST-Elevation Myocardial Infarction Referred for Primary Percutaneous Intervention) is an investigator-initiated, multicenter, open-label, randomized study. A total of 122 P2Y12-naive patients with ST-segment-elevation myocardial infarction were randomly allocated (1:1:1) to cangrelor (n=40), tirofiban (n=40) (both administered as bolus and 2-hour infusion followed by 60 mg of prasugrel), or 60-mg loading dose of prasugrel (n=42). The latter group underwent an immediate 1:1 subrandomization to chewed (n=21) or integral (n=21) tablets administration. The trial was powered to test 3 hypotheses (noninferiority of cangrelor compared with tirofiban using a noninferiority margin of 9%, superiority of both tirofiban and cangrelor compared with chewed prasugrel, and superiority of chewed prasugrel as compared with integral prasugrel, each with α=0.016 for the primary end point, which was 30-minute IPA at light transmittance aggregometry in response to 20 µmol/L adenosine diphosphate. RESULTS: At 30 minutes, cangrelor did not satisfy noninferiority compared with tirofiban, which yielded superior IPA over cangrelor (95.0±8.9 versus 34.1±22.5; P<0.001). Cangrelor or tirofiban were both superior to chewed prasugrel (IPA, 10.5±11.0; P<0.001 for both comparisons), which did not provide higher IPA over integral prasugrel (6.3±11.4; P=0.47), despite yielding higher prasugrel active metabolite concentration (ng/mL; 62.3±82.6 versus 17.1±43.5; P=0.016). CONCLUSIONS: Cangrelor provided inferior IPA compared with tirofiban; both treatments yielded greater IPA compared with chewed prasugrel, which led to higher active metabolite concentration but not greater IPA compared with integral prasugrel. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02978040; URL: https://www.clinicaltrialsregister.eu; EudraCT 2017-001065-24.

Early intra-aortic balloon pump in acute decompensated heart failure complicated by cardiogenic shock: Rationale and design of the randomized Altshock-2 trial.

BACKGROUND: Cardiogenic shock (CS) is a systemic disorder associated with dismal short-term prognosis. Given its time-dependent nature, mechanical circulatory support may improve survival. Intra-aortic balloon pump (IABP) had gained widespread use because of the easiness to implant and the low rate of complications; however, a randomized trial failed to demonstrate benefit on mortality in the setting of acute myocardial infarction. Acute decompensated heart failure with cardiogenic shock (ADHF-CS) represents a growing resource-intensive scenario with scant data and indications on the best management. However, a few data suggest a potential benefit of IABP in this setting. We present the design of a study aimed at addressing this research gap. METHODS AND DESIGN: The Altshock-2 trial is a prospective, randomized, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients with ADHF-CS will be randomized to early IABP implantation or to vasoactive treatments. The primary end point will be 60 days patients' survival or successful bridge to heart replacement therapy. The key secondary end point will be 60-day overall survival; 60-day need for renal replacement therapy; in-hospital maximum inotropic score, maximum duration of inotropic/vasopressor therapy, and maximum sequential organ failure assessment score. Safety end points will be in-hospital occurrence of bleeding events (Bleeding Academic Research Consortium >3), vascular access complications and systemic (noncerebral) embolism. The sample size for the study is 200 patients. IMPLICATIONS: The Altshock-2 trial will provide evidence on whether IABP should be implanted early in ADHF-CS patients to improve their clinical outcomes.

Antithrombotic strategies in patients needing oral anticoagulation undergoing percutaneous coronary intervention: A network meta-analysis.

BACKGROUND: The optimal antithrombotic regimen in patients with a concomitant indication for oral anticoagulation (OAT) presenting with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) remains unclear. OBJECTIVES: To perform a network meta-analysis of all randomized controlled trials (RCTs) evaluating different antithrombotic regimens among patients with ACS or undergoing PCI requiring OAT. METHODS: Network meta-analysis was performed in a frequentist framework. Antithrombotic regimens were categorized by OAC type (vitamin K antagonist-based [VKA]; non-VKA OAT [NOAC]) and antiplatelet agents (P2Y inhibitor only: dual therapy [DAT]; P2Y plus aspirin: triple therapy [TAT]). Safety outcomes were Thrombolysis in Myocardial Infarction (TIMI) major bleeding and intracranial hemorrhage (ICH). Efficacy outcomes were cardiovascular death, myocardial infarction, stroke and stent-thrombosis (ST). RESULTS: Five RCTs were included, encompassing 10,797 patients (atrial fibrillation 69-100%, ACS 28-62%, PCI 77-100%). Both VKA and NOAC-based DAT regimens reduced the occurrence of TIMI major bleeding compared to VKA TAT (VKA DAT: RR 0.62, 95% CI 0.39-0.98; NOAC DAT: RR 0.52, 95% CI 0.39-0.70). Nevertheless, only NOAC DAT significantly reduced the occurrence of ICH compared to VKA TAT (RR 0.33, 95% CI 0.17-0.64). Ischemic outcomes were similar among the four treatment regimens. However, numerical, potentially clinically important, higher ST occurrence was observed for NOAC DAT as compared to both VKA TAT (1.50, 95% confidence interval [CI] 0.96-2.33) and NOAC TAT (1.86, 95% CI 0.93-3.73). CONCLUSION: DAT regimens present the highest safety profile among antithrombotic strategies, with a NOAC-specific impact on ICH reduction. NOAC DAT might entail clinically important higher ST occurrence, warranting a case-by-case comprehensive evaluation that integrates patient- and procedure-related residual ischemic risk with the patient-specific bleeding risk.

Implications of atrial fibrillation on the clinical course and outcomes of hospitalized COVID-19 patients: results of the Cardio-COVID-Italy multicentre study.

AIMS: To assess the clinical relevance of a history of atrial fibrillation (AF) in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: We enrolled 696 consecutive patients (mean age 67.4 ± 13.2 years, 69.7% males) admitted for COVID-19 in 13 Italian cardiology centres between 1 March and 9 April 2020. One hundred and six patients (15%) had a history of AF and the median hospitalization length was 14 days (interquartile range 9-24). Patients with a history of AF were older and with a higher burden of cardiovascular risk factors. Compared to patients without AF, they showed a higher rate of in-hospital death (38.7% vs. 20.8%; P < 0.001). History of AF was associated with an increased risk of death after adjustment for clinical confounders related to COVID-19 severity and cardiovascular comorbidities, including history of heart failure (HF) and increased plasma troponin [adjusted hazard ratio (HR): 1.73; 95% confidence interval (CI) 1.06-2.84; P = 0.029]. Patients with a history of AF also had more in-hospital clinical events including new-onset AF (36.8% vs. 7.9%; P < 0.001), acute HF (25.3% vs. 6.3%; P < 0.001), and multiorgan failure (13.9% vs. 5.8%; P = 0.010). The association between AF and worse outcome was not modified by previous or concomitant use of anticoagulants or steroid therapy (P for interaction >0.05 for both) and was not related to stroke or bleeding events. CONCLUSION: Among hospitalized patients with COVID-19, a history of AF contributes to worse clinical course with a higher mortality and in-hospital events including new-onset AF, acute HF, and multiorgan failure. The mortality risk remains significant after adjustment for variables associated with COVID-19 severity and comorbidities.

Comparison of antithrombotic strategies in patients with cryptogenic stroke and patent foramen ovale: an updated meta-analysis.

PURPOSE: Patients with patent foramen ovale (PFO) and cryptogenic ischemic stroke (CS) are at risk for stroke recurrence. The optimal antithrombotic strategy in patients who undergo medical management is still debated. METHODS: We systematically searched the literature for studies that reported on cerebrovascular event recurrences and/or death in patients with PFO treated with oral anticoagulation (OAC) or antiplatelet therapy (APT) for secondary prevention of CS. The efficacy endpoints were stroke recurrence and the composite of stroke, transient ischemic attack or all-cause death. Major bleedings represented the safety endpoint. RESULTS: A total of 16 studies with 3953 patients (OAC = 1527, APT = 2426) were included. Weighted mean follow-up was 2.9 years. OAC was associated with a significant reduction in the risk of stroke compared with APT (RR 0.65; 95% CI 0.44-0.95; ARR 2%, NNT 49), while no difference was found regarding the composite outcome (RR 0.78; 95% CI 0.57-1.07) and the safety outcome (RR 1.57; 95% CI 0.85-2.90; p = 0.15). CONCLUSIONS: OAC was more effective than APT in reducing the risk of stroke recurrence in patients with PFO and CS, without a significant increase in the risk of major bleedings. Our findings support the need for further randomized data focused on the comparison of antithrombotic strategies in this setting.

Low-density lipoprotein cholesterol treatment and outcomes in patients with type 2 diabetes and established cardiovascular disease: Insights from TECOS.

BACKGROUND: Type 2 diabetes (T2D) patients are at increased risk for cardiovascular (CV) events. Most guidelines recommend treating low-density lipoprotein cholesterol (LDL-C) levels to ≤70 mg/dL (1.8 mM) for patients with T2D and established atherosclerotic CV disease, and some a more aggressive target of ≤55 mg/dL (1.4 mM). Our objective was to assess the degree to which these LDL-C targets are achieved in routine practice. METHODS: Using data from TECOS, an international pragmatic CV outcomes trial of sitagliptin vs placebo, we assessed lipid-lowering treatment among patients with T2D and CV disease, baseline lipid values, and the association between baseline LDL-C and 5-year risk for major adverse cardiac events (MACE; ie, CV death, nonfatal myocardial infarction, or nonfatal stroke). RESULTS: Overall, 11,066 of 14,671 TECOS participants (75.4%) had LDL-C measured at baseline. Median age was 65 years, 72% were male, and median T2D duration was 10 years. Overall, 82.5% of patients were on statins; only 5.8% were on ezetimibe. At baseline, 14.3% had LDL-C ≤55 mg/dL, 18.4% between 55.1 and 70 mg/dL, 35% between 70.1 and 100 mg/dL, and 32.3% >100 mg/dL. Each 10 mg/dL higher LDL-C value was associated with a higher risk of MACE (HR 1.05, 95% CI 1.03-1.07) or CV death (HR 1.06, 95% CI 1.04-1.09). CONCLUSIONS: Although most high-risk patients with T2D and CV disease were on lipid-lowering therapy, only 1:3 had LDL-C <70 mg/dL and 1:6 had LDL-C <55 mg/dL. Each 10 mg/dL higher LDL-C value was associated with a 5% and 6% higher 5-year incidence of MACE and CV death, respectively. (TECOS, NCT00790205).

Cangrelor use in a 6-year-old patient undergoing complex percutaneous coronary intervention after post-surgical myocardial infarction.

Cangrelor is an intravenously administered P2Y12 receptor antagonist, which has been approved for adult patients undergoing percutaneous coronary intervention and, due to its unique pharmacokinetics, it allows effective and controllable peri-procedural platelet inhibition. We report the case of a 6-year-old child with anomalous origin of right coronary artery from aortic left coronary sinus, who underwent elective surgical replacement of stenotic and calcified conduit between the right ventricle and the main pulmonary artery. The surgery was complicated by acute myocardial infarction secondary to coronary extrinsic compression. The patient was successfully treated with urgent percutaneous coronary intervention (simultaneous V-stenting) and cangrelor infusion, subsequently switched to clopidogrel therapy.

Acute myocardial infarction complicating ischemic stroke: is there room for cangrelor?

Acute myocardial infarction (AMI) complicating ischemic stroke is a well known and undertreated event. A conservative management is not infrequent in these settings, due to the fear of hemorrhagic complications related to antithrombotic therapy. Notably, an invasive approach with a primary percutaneous coronary intervention (PCI) has been shown to be associated with a lower in-hospital mortality in patients with concomitant ischemic stroke and AMI. The optimal antiplatelet regimen in these cases has been not clearly defined, yet. We report two cases of patients with AMI complicating ischemic stroke, successfully treated with cangrelor infusion, which was started during PCI and maintained up to 48 h at bridge therapy dosage (0.75 mcg/kg/min). Both patients underwent successful PCI in the acute phase, and neither ischemic nor hemorrhagic complications occurred during in-hospital stay.

Lack of implementation of guidelines recommendations for coronary revascularization in stable patients with complex disease is associated with high rates of incomplete revascularization : Analysis from the Apache study.

The objective of this study is to evaluate completeness of coronary revascularization in patients with complex stable coronary artery disease (SCAD) who underwent percutaneous coronary interventions (PCI), but a surgical revascularization indicated according to 2018 European Society of Cardiology guidelines. The optimal mode of revascularization for SCAD should take into account clinical, anatomic, and procedural characteristics-including anticipated completeness of revascularization-and modality of treatment should be discussed by a Heart Team. Among patients enrolled in the APpropriAteness of percutaneous Coronary interventions in patients with ischemic heart disease study, we identified patients with complex SCAD. Rates of ad-hoc PCI and documented heart team discussion were reported stratified by guideline recommended mode of revascularization. Completeness of revascularization was assessed by an angiographic core laboratory using residual SS (rSS) ≤ 8 and SYNTAX Revascularization Index (SRI) ≥ 70%. Among 336 PCI patients with SCAD, 182 (54.2%) had complex coronary disease and 152 underwent ad-hoc PCI (83.5%). Patients for whom surgery was the recommended revascularization option (9.3%) had a significantly and substantial higher rate of incomplete revascularization than patients for whom either mode of revascularization or PCI was recommended (61.3% vs 23.6% with rSS > 8, p < 0.001 and 77.4% vs 44.6% with SRI < 70%, p < 0.001). Patients with complex SCAD receiving percutaneous myocardial revascularization when surgery was recommended have substantially incomplete myocardial revascularization. These data support multidisciplinary decision-making in these patients and suggest considering anticipated completeness when deciding mode of coronary revascularization.

Association of acute kidney injury and bleeding events with mortality after radial or femoral access in patients with acute coronary syndrome undergoing invasive management: secondary analysis of a randomized clinical trial.

AIMS: In the Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX (MATRIX) trial, adults with acute coronary syndrome undergoing coronary intervention who were allocated to radial access had a lower risk of bleeding, acute kidney injury (AKI), and all-cause mortality, as compared with those allocated to femoral access. The mechanism of the mortality benefit of radial access remained unclear. METHODS AND RESULTS: We used multistate and competing risk models to determine the effects of radial and femoral access on bleeding, AKI and all-cause mortality in the MATRIX trial and to disentangle the relationship between these different types of events. There were large relative risk reductions in mortality for radial compared with femoral access for the transition from AKI to death [hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.31-0.97] and for the pathway from coronary intervention to AKI to death (HR 0.49, 95% CI 0.26-0.92). Conversely, there was little evidence for a difference between radial and femoral groups for the transition from bleeding to death (HR 1.05, 95% CI 0.42-2.64) and the pathway from coronary intervention to bleeding to death (HR 0.84, 95% CI 0.28-2.49). CONCLUSION: The prevention of AKI appeared predominantly responsible for the mortality benefit of radial as compared with femoral access in the MATRIX trial. There was little evidence for an equally important, independent role of bleeding.

Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation.

BACKGROUND: Atrial fibrillation is associated with an increased risk of death. High-sensitivity troponin T, growth differentiation factor-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and interleukin-6 levels are predictive of cardiovascular events and total cardiovascular death in anticoagulated patients with atrial fibrillation. The prognostic utility of these biomarkers for cause-specific death is unknown. METHODS: The ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients (1.9 years median follow-up). Cox models were used to identify clinical variables and biomarkers independently associated with each specific cause of death. RESULTS: In total, 1272 patients died: 652 (51%) cardiovascular, 32 (3%) bleeding, and 588 (46%) noncardiovascular/nonbleeding deaths. Among cardiovascular deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure deaths, and 106 (16%) stroke/systemic embolism deaths. Biomarkers were the strongest predictors of cause-specific death: a doubling of troponin T was most strongly associated with sudden death (hazard ratio [HR], 1.48; P<0.001), NT-proBNP with heart failure death (HR, 1.62; P<0.001), and growth differentiation factor-15 with bleeding death (HR, 1.72; P=0.028). Prior stroke/systemic embolism (HR, 2.58; P>0.001) followed by troponin T (HR, 1.45; P<0.0029) were the most predictive for stroke/ systemic embolism death. Adding all biomarkers to clinical variables improved discrimination for each cause-specific death. CONCLUSIONS: Biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients' risks for different causes of death. These data suggest a potential role of biomarkers for the identification of patients at risk for different causes of death in patients anticoagulated for atrial fibrillation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00412984.

Radial versus femoral access and bivalirudin versus unfractionated heparin in invasively managed patients with acute coronary syndrome (MATRIX): final 1-year results of a multicentre, randomised controlled trial.

BACKGROUND: The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox (MATRIX) programme was designed to assess the comparative safety and effectiveness of radial versus femoral access and of bivalirudin versus unfractionated heparin with optional glycoprotein IIb/IIIa inhibitors in patients with the whole spectrum of acute coronary syndrome undergoing invasive management. Here we describe the prespecified final 1-year outcomes of the entire programme. METHODS: MATRIX was a programme of three nested, randomised, multicentre, open-label, superiority trials in patients with acute coronary syndrome in 78 hospitals in Italy, the Netherlands, Spain, and Sweden. Patients with ST-elevation myocardial infarction were simultaneously randomly assigned (1:1) before coronary angiography to radial or femoral access and to bivalirudin, with or without post-percutaneous coronary intervention infusion or unfractionated heparin (one-step inclusion). Patients with non-ST-elevation acute coronary syndrome were randomly assigned (1:1) before coronary angiography to radial or femoral access and, only if deemed eligible to percutaneous coronary intervention after angiography (two-step inclusion), entered the antithrombin type and treatment duration programmes. Randomisation sequences were computer generated, blocked, and stratified by intended new or current use of P2Y12 inhibitor (clopidogrel vs ticagrelor or prasugrel), and acute coronary syndrome type (ST-elevation myocardial infarction, troponin-positive, or troponin-negative non-ST-elevation acute coronary syndrome). Bivalirudin was given as a bolus of 0·75 mg/kg, followed immediately by an infusion of 1·75 mg/kg per h until completion of percutaneous coronary intervention. Heparin was given at 70-100 units per kg in patients not receiving glycoprotein IIb/IIIa inhibitors, and at 50-70 units per kg in patients receiving glycoprotein IIb/IIIa inhibitors. Clinical follow-up was done at 30 days and 1 year. Co-primary outcomes for MATRIX access and MATRIX antithrombin type were major adverse cardiovascular events, defined as the composite of all-cause mortality, myocardial infarction, or stroke up to 30 days; and net adverse clinical events, defined as the composite of non-coronary artery bypass graft-related major bleeding, or major adverse cardiovascular events up to 30 days. The primary outcome for MATRIX treatment duration was the composite of urgent target vessel revascularisation, definite stent thrombosis, or net adverse clinical events up to 30 days. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01433627. FINDINGS: Between Oct 11, 2011, and Nov 7, 2014, we randomly assigned 8404 patients to receive radial (4197 patients) or femoral (4207 patients) access. Of these 8404 patients, 7213 were included in the MATRIX antithrombin type study and were randomly assigned to bivalirudin (3610 patients) or heparin (3603 patients). Patients assigned to bivalirudin were included in the MATRIX treatment duration study, and were randomly assigned to post-procedure infusion (1799 patients) or no post-procedure infusion (1811 patients). At 1 year, major adverse cardiovascular events did not differ between patients assigned to radial access compared with those assigned to femoral access (14·2% vs 15·7%; rate ratio 0·89, 95% CI 0·80-1·00; p=0·0526), but net adverse clinical events were fewer with radial than with femoral access (15·2% vs 17·2%; 0·87, 0·78-0·97; p=0·0128). Compared with heparin, bivalirudin was not associated with fewer major adverse cardiovascular (15·8% vs 16·8%; 0·94, 0·83-1·05; p=0·28) or net adverse clinical events (17·0% vs 18·4%; 0·91, 0·81-1·02; p=0·10). The composite of urgent target vessel revascularisation, stent thrombosis, or net adverse clinical events did not differ with or without post-procedure bivalirudin infusion (17·4% vs 17·4%; 0·99, 0·84-1·16; p=0·90). INTERPRETATION: In patients with acute coronary syndrome, radial access was associated with lower rates of net adverse clinical events compared with femoral access, but not major adverse cardiovascular events at 1 year. Bivalirudin with or without post-procedure infusion was not associated with lower rates of major adverse cardiovascular events or net adverse clinical events. Radial access should become the default approach in acute coronary syndrome patients undergoing invasive management. FUNDING: Italian Society of Invasive Cardiology, The Medicines Company, Terumo, amd Canada Research Chairs Programme.

Design and rationale of the Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Standard DAPT Regimen (MASTER DAPT) Study.

BACKGROUND: The optimal duration of antiplatelet therapy in high-bleeding risk (HBR) patients with coronary artery disease treated with newer-generation drug-eluting bioresorbable polymer-coated stents remains unclear. DESIGN: MASTER DAPT (clinicaltrial.govNCT03023020) is an investigator-initiated, open-label, multicenter, randomized controlled trial comparing an abbreviated versus a standard duration of antiplatelet therapy after bioresorbable polymer-coated Ultimaster (TANSEI) sirolimus-eluting stent implantation in approximately 4,300 HBR patients recruited from ≥100 interventional cardiology centers globally. After a mandatory 30-day dual-antiplatelet therapy (DAPT) run-in phase, patients are randomized to (a) a single antiplatelet regimen until study completion or up to 5 months in patients with clinically indicated oral anticoagulation (experimental 1-month DAPT group) or (b) continue DAPT for at least 5 months in patients without or 2 in patients with concomitant indication to oral anticoagulation, followed by a single antiplatelet regimen (standard antiplatelet regimen). With a final sample size of 4,300 patients, this study is powered to assess the noninferiority of the abbreviated antiplatelet regimen with respect to the net adverse clinical and major adverse cardiac and cerebral events composite end points and if satisfied for the superiority of abbreviated as compared to standard antiplatelet therapy duration in terms of major or clinically relevant nonmajor bleeding. Study end points will be adjudicated by a blinded Clinical Events Committee. CONCLUSIONS: The MASTER DAPT study is the first randomized controlled trial aiming at ascertaining the optimal duration of antiplatelet therapy in HBR patients treated with sirolimus-eluting bioresorbable polymer-coated stent implantation.