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IMPORTANCE: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol management guidelines identified 2 distinct groups of patients with atherosclerotic cardiovascular disease (ASCVD) prompting different treatment recommendations. OBJECTIVE: To investigate whether the addition of high-sensitivity troponin (hsTn) testing to guideline-derived ASCVD risk can improve risk classification and downstream treatment recommendations. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort biomarker substudy was performed that included 8635 patients enrolled in the Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial. Patients were assigned to risk groups of either very high-risk ASCVD or lower-risk ASCVD based on their cardiovascular history and comorbidities, in line with the 2018 AHA/ACC cholesterol management guidelines criteria. Patients were also classified on the basis of hsTnI level (ARCHITECT assay; Abbott) using cut points of 2 ng/L (limit of detection) and 6 ng/L (risk threshold), followed by joint classification on the basis of clinical features and hsTnI level. The setting was a nested prospective cohort study in a completed multinational trial. Participants were all patients who had a myocardial infarction 1 to 3 years before enrollment, were at least 50 years of age, and had at least 1 high-risk feature. The study dates were October 2010 to December 2014. The dates of analysis were June 2019 to January 2020. MAIN OUTCOMES AND MEASURES: The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. RESULTS: Among 8635 patients enrolled in the PEGASUS-TIMI 54 trial, the median age was 65 years (interquartile range, 58-71 years), and 6614 (76.6%) were men; 8340 (96.6%) were White individuals and 176 (2.0%) were Black individuals. Patients meeting clinical criteria for the very high-risk ASCVD group had a primary end point 3-year event rate of 8.8% compared with 5.0% in the lower-risk ASCVD group (hazard ratio, 2.01; 95% CI, 1.58-2.57; P < .001). When patients in the very high-risk ASCVD group were further risk stratified by hsTnI level, 614 of 6789 patients (9.0%) with an undetectable hsTnI level had a 3-year event rate of 2.7% (<1% per year), which was less than the overall rate in the lower-risk ASCVD group. Analogously, in the lower-risk ASCVD group, 417 of 1846 patients (22.6%) with an hsTnI level exceeding 6 ng/L had an event rate of 9.1%, comparable to the overall rate in the very high-risk ASCVD group. The addition of hsTnI to guideline-derived ASCVD risk led to a net reclassification index at event rate of 0.15 (95% CI, 0.10-0.21). Overall, use of hsTnI reclassified 1031 of 8635 patients (11.9%) (1 in 11 with very high-risk ASCVD and 1 in 4 with lower-risk ASCVD). CONCLUSIONS AND RELEVANCE: The findings of this cohort substudy suggest that a strategy incorporating hsTn into a guideline-derived ASCVD risk algorithm provides enhanced risk stratification and reclassifies 11.9% of patients into a more appropriate risk group. This application of hsTn testing might be used to optimize the care of patients with ASCVD.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment.

Supplemental Digital Content is available in the text.

Background Bone impaction grafting is a biologically and mechanically appealing option in acetabular revision surgery, allowing restitution of the bone stock and restoration of the biomechanics. We analysed differences in proximal migration of the revision acetabular components when bone impaction grafting is used together with a cemented or an uncemented cup.Patients and Methods 43 patients (47 hips), revised due to acetabular loosening and judged to have less than 50% host bone-implant contact were included. The hips were randomised to either an uncemented (n = 20) or a cemented (n = 27) revision cup. Radiostereometry and radiography was performed postoperatively, at 3 and 6 months, 1, 2, 3, 5, 7, 10 and 13 and 17 years postoperatively. Clinical follow-up was performed at 1, 2 and 5 years postoperatively and thereafter at the same interval as in the radiographic follow-up.Results here were no differences in the base line demographic data between the 2 groups. At the last follow-up (17 years) 14 hips (10 cemented, 4 uncemented) had been re-revised due to loosening. 3 additional cups (1 uncemented and 2 cemented) were radiographically loose. There was a higher early proximal migration in the cemented cups.Discussion Cups operated on with cement showed a higher early migration measured with RSA and also a higher number of late revisions. The reason for this is not known, but factors such as inclusion of cases with severe bone defects, use of smaller bone chips and issues related to the impaction technique might have had various degrees of influence.

Introduction:Elevated blood levels of lipoprotein(a) [Lp(a)] are an independent causal risk factor for atherosclerotic cardiovascular disease. Lp(a) particles are formed by a lipid domain and an apolipoprotein B (apoB) protein that is bound to apolipoprotein(a). Standard low-density lipoprotein cholesterol (LDL-C) and ApoB lowering treatments have minimal Lp(a)-lowering efficacy. We have previously shown that AZD8233 inhibits hepatic PCSK9 synthesis and causes substantial reductions in LDL-C. Here we report the significant effects of AZD8233 on Lp(a) and ApoB.Methods:ETESIAN was a multicenter phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study (NCT04641299). Eligible participants were 18-75 years old, on statin therapy, with LDL-C of ≥ 70 to < 190 mg/dL, and with fasting triglycerides of < 400 mg/dL. Participants were randomized 1:1:1:1 to subcutaneous injections (days 1, 8, 29, and 57) of either 15, 50, or 90 mg AZD8233, or placebo. The primary objective was to evaluate the effect of AZD8233 versus placebo on LDL-C at week 12. Secondary objectives were to assess Lp(a) levels and other lipid parameters.Results:A total of 119 patients were enrolled in ETESIAN. AZD8233 was well tolerated and demonstrated dose-dependent and clinically meaningful reductions in LDL-C, Lp(a), and ApoB (Table). The relative distribution of these effects across participant subgroups and the interaction of effects on Lp(a), ApoB, and LDL-C will be presented.Conclusion:In patients with dyslipidemia on statins, AZD8233 caused substantial reductions in LDL-C and Lp(a), two independent risk factors for major adverse cardiovascular events. The broad lipid-modifying effect of AZD8233 may, hence, provide an opportunity to reduce cardiovascular risk in patients with ASCVD beyond currently available medications.

Maximal utility of accessible data is attractive to all partners in clinical research, whether it directly improves patient care or more accurately allows identification of the safety and efficacy of a new drug or procedure. The Food and Drug Administration (FDA) has presented a guideline draft addressing digitization of electrocardiogram (ECG) data in clinical trials to improve the standards for collection, analysis, and storage of safety information on new medical therapies. This FDA initiative has led to discussions and collaboration among the FDA, the pharmaceutical industry, the electrocardiography manufacturers, and the academic as well as the nonacademic ECG core labs. In this article, we present a broad-based viewpoint from two groups of academic ECG core labs, the Alliance of Academic ECG Core Labs and the Virtual Electronic ECG Corelab International Consortium. We have chosen to widen the perspective from using digitized ECG data in safety trials only, as addressed by the FDA guideline draft, to a discussion on the possibilities and the potential problems when using digitized ECG data also in large clinical trials focusing on efficacy measurements. We conclude that the benefit of digital data mining is probably well worth an initial incremental effort and expense.

Maximal utility of accessible data is attractive to all partners in clinical research, whether it directly improves patient care or more accurately allows identification of the safety and efficacy of a new drug or procedure. The Food and Drug Administration (FDA) has presented a guideline draft addressing digitization of electrocardiogram (ECG) data in clinical trials to improve the standards for collection, analysis, and storage of safety information on new medical therapies. This FDA initiative has led to discussions and collaboration among the FDA, the pharmaceutical industry, the electrocardiography manufacturers, and the academic as well as the nonacademic ECG core labs. In this article, we present a broad-based viewpoint from two groups of academic ECG core labs, the Alliance of Academic ECG Core Labs and the Virtual Electronic ECG Corelab International Consortium. We have chosen to widen the perspective from using digitized ECG data in safety trials only, as addressed by the FDA guideline draft, to a discussion on the possibilities and the potential problems when using digitized ECG data also in large clinical trials focusing on efficacy measurements. We conclude that the benefit of digital data mining is probably well worth an initial incremental effort and expense.

Background: Early and complete myocardial reperfusion is the goal when treating a patient with acute myocardial infarction. To achieve this in each individual, an on‐line, accurate, easily handled and preferably noninvasive technique to monitor flow alterations is needed. Recurrent ST‐segment elevation has been shown to reflect cyclic disturbances in perfusion.