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Background: Despite advances in coronary revascularization and in heart failure management, myocardial infarction survivors remain at substantially increased mortality risk. Precise risk assessment and risk-adapted follow-up care are crucial to improve their outcomes. Recently, the fragmented QRS complex, i.e. the presence of additional spikes within the QRS complexes on a 12-lead electrocardiogram, has been discussed as a potential non-invasive risk predictor in cardiac patients., Hypothesis: The aim of this study was to evaluate the prognostic meaning of the fragmented QRS complex in myocardial infarction survivors., Methods: 609 patients with narrow QRS complexes <120 ms were included in a prospective cohort study while hospitalized for myocardial infarction and followed for 5 years., Results: The prevalence of the fragmented QRS complex in these patients amounted to 46.8% (285 patients). These patients had no increased hazard of all-cause death (HR 0.84, 95%-CI 0.45-1.57, p = 0.582) with a mortality rate of 6.0% compared to 7.1% in patients without QRS fragmentations. Furthermore, the risks of cardiac death (HR 1.28, 95%-CI 0.49-3.31, p = 0.613) and of non-cardiac death (HR 0.6, 95%-CI 0.26-1.43, p = 0.25) were not significantly different in patients with QRS fragmentations. However, patients with QRS fragmentations had increased serum creatine kinase concentrations (1438U/l vs. 1160U/l, p = 0.039) and reduced left ventricular ejection fractions (52% vs. 54%, p = 0.011)., Conclusions: The hypothesis that QRS fragmentation might be a prognostic parameter in survivors of myocardial infarction was not confirmed. But those with QRS fragmentation had larger myocardial infarctions, as measured by creatine kinase and left ventricular ejection fraction., (© 2024 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Aims: The effect of a prasugrel vs. a ticagrelor based strategy on total (including both first and recurrent) ischaemic and bleeding events in patients with acute coronary syndromes (ACS) has not been evaluated. The aim of this analysis was to investigate the treatment effect of a prasugrel vs. a ticagrelor based strategy in patients with ACS undergoing an invasive management strategy when both first and recurrent non-fatal ischaemic and bleeding events are taken into account., Methods and Results: This is a post-hoc analysis of the ISAR-REACT 5 randomized control trial, including all 4018 patients in the trial. The main clinical endpoints of interest included ischaemic events [myocardial infarction (MI) and stroke] and bleeding events [Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding]. An additional endpoint of interest was definite/probable stent thrombosis. The effect of the prasugrel vs. ticagrelor based strategies on these endpoints was evaluated on both time-to-first event and total events analyses. Patients in the prasugrel group had a lower risk of MI in comparison to the ticagrelor group on both time-to-first event [hazard ratio (HR) = 0.61; 95% confidence interval 0.44-0.85] and total events [HR = 0.62 (0.45-0.86)] analysis. The risk of BARC type 3 to 5 bleeding was comparable between the prasugrel and ticagrelor groups on both time-to-first event [HR = 0.96 (0.75-1.25)] and total events [HR = 0.99 (0.76-1.31)] analysis., Conclusion: A prasugrel based strategy was associated with a reduction in total MI events in comparison to a ticagrelor based strategy in patients with ACS undergoing invasive assessment. Total BARC type 3 to 5 bleeding events were comparable between the two groups. Given the importance of this topic, future studies to confirm these findings would be welcome. ClinicalTrials.gov identifier: NCT01944800., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: To assess the efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome (ACS) presenting during off- and on-hours., Background: The efficacy and safety of ticagrelor versus prasugrel in patients with ACS according to time of hospital presentation remain unknown., Methods: This post hoc analysis of the ISAR-REACT 5 trial included 1565 patients with ACS presenting off-hours and 2453 patients presenting on-hours, randomized to ticagrelor or prasugrel. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium (BARC) type 3-5 bleeding, both at 12 months., Results: The primary endpoint occurred in 80 patients (10.4%) in the ticagrelor group and 57 patients (7.3%) in the prasugrel group in patients presenting off-hours (hazard ratio [HR] = 1.45; 95% confidence interval [CI] 1.03-2.03; P = 0.033), and 104 patients (8.5%) in the ticagrelor group and 80 patients (6.7%) in the prasugrel group in patients presenting on-hours (HR = 1.29 [0.97-1.73]; P = 0.085), without significant treatment arm-by-presentation time interaction (P int  = 0.62). BARC type 3 to 5 bleeding occurred in 35 patients (5.1%) in the ticagrelor group and 37 patients (5.3%) in the prasugrel group (P = 0.84) in patients presenting off-hours, and 60 patients (5.9%) in the ticagrelor group and 43 patients (4.6%) in the prasugrel group in patients presenting on-hours (P = 0.17)., Conclusions: In patients with ACS planned to undergo an invasive treatment strategy, time of presentation (off-hours vs. on-hours) does not interact significantly with the relative efficacy and safety of ticagrelor vs. prasugrel., Clinical Trial Registration: NCT01944800., (© 2022. The Author(s).)

Background The efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome and prior myocardial infarction (MI) remain unstudied. We aimed to assess the treatment effect of ticagrelor versus prasugrel according to prior MI status in patients with ACS. Methods and Results Patients with acute coronary syndrome planned for an invasive strategy and randomized to ticagrelor or prasugrel in the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial were included. The primary end point was the composite of 1-year all-cause death, MI, or stroke; the secondary safety end point was the composite of 1-year Bleeding Academic Research Consortium type 3 to 5 bleeding. The study included 4015 patients (prior MI=631 patients; no prior MI=3384 patients). As compared with patients without prior MI, the primary end point occurred more frequently in patients with prior MI (12.6% versus 7.2%; hazard ratio [HR], 1.78 [95% CI, 1.38-2.29]); the secondary safety end point appears to differ little between patients with and without prior MI (5.8% versus 5.7%, respectively; HR, 1.02 [95% CI, 0.71-1.45]). With regard to the primary end point, ticagrelor versus prasugrel was associated with an HR of 1.62 (95% CI, 1.03-2.55) in patients with prior MI and an HR of 1.28 (95% CI, 0.99-1.65) in patients without prior MI ( P int =0.37). With regard to the secondary safety end point, ticagrelor versus prasugrel was associated with an HR of 1.28 (95% CI, 0.56-2.91) in patients with prior MI and an HR of 1.13 (95% CI, 0.82-1.55) in patients without prior MI ( P int =0.79). Conclusions Patients with acute coronary syndrome and prior MI are at higher risk for recurrent ischemic but not bleeding events. Prasugrel is superior to ticagrelor in reducing the risk of ischemic events without a tradeoff in bleeding regardless of prior MI status. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

Background: Whether the access site influences the comparative efficacy and safety of ticagrelor and prasugrel in patients with acute coronary syndrome (ACS) undergoing invasive treatment strategy remains unstudied., Methods: This post-hoc analysis included ACS patients undergoing invasive treatment via radial or femoral access and randomized to either ticagrelor or prasugrel in the ISAR-REACT 5 trial. The primary efficacy endpoint was the composite of death, myocardial infarction (MI) or stroke, safety endpoint was BARC 3 to 5 bleeding. Outcomes were assessed out to 12 months after randomization., Results: Out of 4018 patients, 3984 underwent invasive treatment via radial or femoral access. 1479 had coronary angiography via radial access (ticagrelor, N = 748; prasugrel, N = 731) and 2505 via femoral access (ticagrelor, N = 1245; prasugrel, N = 1260). There was no interaction between access route and assignment to either ticagrelor or prasugrel regarding the primary efficacy or safety endpoints (P for interaction≥0.616). In the radial group, the primary efficacy endpoint (7.6% versus 5.8%, HR: 1.32 [0.88-1.97], P = 0.151) and the safety endpoint (4.3% versus 3.0%, HR: 1.36, [0.73-1.31], P = 0.300) were not statistically different in patients receiving either ticagrelor or prasugrel. In the femoral group, the primary efficacy endpoint occurred more frequently in patients assigned to ticagrelor as compared to prasugrel (10.3% versus 7.3%, HR: 1.44 [1.10-1.88], P = 0.006) without significant difference in terms of safety endpoint (6.4% versus 5.8%, HR: 1.14, [0.81-1.60], P = 0.470)., Conclusions: In patients with ACS undergoing an invasive treatment strategy, the access route does not influence the comparative efficacy and safety of ticagrelor and prasugrel., Clinical Trial Registration: NCT01944800., (Copyright © 2021. Published by Elsevier Inc.)

Background: Whether bleeding and myocardial infarction (MI) improve the performance of risk prediction models for mortality in patients with acute coronary syndromes (ACS) treated with percutaneous coronary intervention (PCI) remains unknown., Methods: This study included 3377 patients with ACS who underwent PCI in the setting of the ISAR-REACT 5 trial. Patients with bleeding, MI or those dying at 1 year after PCI were characterized in terms of baseline characteristics, risk estimates and C-statistic of the risk prediction models for these outcomes., Results: Major bleeding (Bleeding Academic Research Consortium types 3-5), MI and mortality occurred in 195 patients (5.8%), 143 patients (4.3%) and 143 patients (4.3%), respectively. After adjustment, bleeding [hazard ratio = 5.08; 95% confidence interval (CI), 3.03-8.53; P < 0.001] and MI [hazard ratio = 5.90; 95% CI, (3.00-11.65); P < 0.001) remained independently associated with the risk for 1-year mortality. The C-statistic (with 95% CI) of the model for bleeding, MI and mortality was, 0.755 (0.722-0.786), 0.752 (0.717-0.789) and 0.868 (0.837-0.896), respectively. The inclusion of bleeding [C-statistic: 0.892 (0.867-0.913); delta C-statistic 0.024 (-0.014 to 0.065); P = 0.200] or MI [C-statistic: 0.878 (0.851-0.903); delta C-statistic 0.011 (-0.030 to 0.053); P = 0.635] in the risk prediction models for mortality alongside baseline demographical and clinical variables did not improve prediction for mortality., Conclusions: In patients with ACS treated with PCI, mortality is the most accurately predicted outcome. Bleeding and MI did not improve risk discrimination for mortality when added in the risk prediction models for mortality suggesting that these outcomes do not provide incremental prognostic information on top of baseline demographical and clinical data., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Survivors of an acute myocardial infarction with diabetes mellitus retain an increased mortality risk. Reliable assessment of individual risk is required for effective and cost-efficient medical care in these patients. The Polyscore is a previously established risk predictor consisting of seven autonomic tests derived from electrocardiogram, blood pressure, and respiration. The Polyscore allows classification of survivors of myocardial infarction in groups at low, intermediate and high mortality risk. The aim of this study was to investigate the prognostic value of the Polyscore in diabetic survivors of acute myocardial infarction, which may be impaired by the presence of diabetic autonomic neuropathy. Survivors of an acute myocardial infarction were included in a prospective cohort study during hospitalisation due to the index event at two university hospitals in Munich, Germany. The Polyscore was determined from simultaneous non-invasive 30-min recordings of electrocardiogram, continuous arterial blood pressure, and respiration which were performed in all participants. Patients were followed for 5 years. The primary and secondary outcomes were all-cause mortality and cardiac mortality. 184 of 941 enrolled patients (19.6%) suffered from diabetes mellitus. 5-year-mortality was higher in diabetic patients (15.2%) compared to non-diabetic patients (5.8%). A multivariable Cox regression model confirmed the Polyscore as a strong predictor of mortality in diabetic post-MI patients (intermediate risk: HR 6.56, 95% CI 1.61-26.78, p = 0.004, mortality 22.8%; high risk: HR 18.76, 95% CI 4.35-80.98, p < 0.001, mortality 68.8%). There was no interaction between diabetes mellitus and the Polyscore regarding mortality prediction (p = 0.775). Interestingly, in contrast to the groups at intermediate and high risk (73 patients, 39.7%), the Polyscore identified a majority of diabetic patients (111, 60.3%) with a low mortality risk, comparable to that of low-risk non-diabetic patients (3.6% and 2.1%, respectively, p = 0.339). Consistent results were observed for cardiac mortality. This analysis shows that the Polyscore predicts all-cause and cardiac mortality in diabetic survivors of acute myocardial infarction. Within these patients it identifies a large population not affected by the excess mortality associated with diabetes in this setting. Thus, the Polyscore may facilitate risk-adapted follow-up strategies in diabetic survivors of myocardial infarction., (© 2022. The Author(s).)

Aims: Present society is constantly ageing and elderly frequently suffer from conditions that are difficult and/or costly to treat if detected late. Effective screening of the elderly is therefore needed so that those requiring detailed clinical work-up are identified early. We present a prospective validation of a screening strategy based on a Polyscore of seven predominantly autonomic, non-invasive risk markers., Methods and Results: Within a population-based survey in Germany (INVADE study), participants aged ≥60 years were enrolled between August 2013 and February 2015. Seven prospectively defined Polyscore components were obtained during 30-min continuous recordings of electrocardiogram, blood pressure, and respiration. Out of 1956 subjects, 168 were excluded due to atrial fibrillation, implanted pacemaker, or unsuitable recordings. All-cause mortality over a median 4-year follow-up was prospectively defined as the primary endpoint. The Polyscore divided the investigated population (n = 1788, median age: 72 years, females: 58%) into three predefined groups with low (n = 1405, 78.6%), intermediate (n = 326, 18.2%), and high risk (n = 57, 3.2%). During the follow-up, 82 (4.6%) participants died. Mortality in the Polyscore-defined risk groups was 3.4%, 7.4%, and 17.5%, respectively (P < 0.0001). The Polyscore-based mortality prediction was independent of Framingham score, diabetes, chronic kidney disease, and major stroke and/or myocardial infarction history. It was particularly effective in those aged <75 years (n = 1145)., Conclusion: The Polyscore-based mortality risk assessment from short-term non-invasive recordings is effective in the elderly general population, especially those aged 60-74 years. Implementation of a comprehensive Polyscore screening of this age group is proposed to advance preventive medical care., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To investigate whether immune cell composition and content of neutrophil extracellular traps (NETs) in relation to clinical outcome are different between acute ischemic stroke (AIS) and acute myocardial infarction (AMI), we performed histologic analysis and correlated results with clinical and procedural parameters., Methods: We retrieved thrombi from patients with AIS (n = 71) and AMI (n = 72) during endovascular arterial recanalization and analyzed their immune cell composition and NET content by immunohistology. We then associated thrombus composition with procedural parameters and outcome in AIS and with cardiac function in patients with AMI. Furthermore, we compared AIS thrombi with AMI thrombi and differentiated Trial of Org 10172 in Acute Stroke Treatment classifications to address potential differences in thrombus pathogenesis., Results: Amounts of leukocytes ( p = 0.133) and neutrophils ( p = 0.56) were similar between AIS and AMI thrombi. Monocytes ( p = 0.0052), eosinophils ( p < 0.0001), B cells ( p < 0.0001), and T cells ( p < 0.0001) were more abundant in stroke compared with AMI thrombi. NETs were present in 100% of patients with AIS and 20.8% of patients with AMI. Their abundance in thrombi was associated with poor outcome scores in patients with AIS and with reduced ejection fraction in patients with AMI., Conclusion: In our detailed histologic analysis of arterial thrombi, thrombus composition and especially abundance of leukocyte subsets differed between patients with AIS and AMI. The presence and amount of NETs were associated with patients' outcome after AIS and AMI, supporting a critical impact of NETs on thrombus stability in both conditions., (© 2020 American Academy of Neurology.)

Objectives: The aim of this study was to compare the contrast-to-noise ratio (CNR) values of infarct and remote myocardium as well as infarct and blood after application of 0.1 mmol/kg gadobutrol and 0.1 mmol/kg gadobenate dimeglumine on late gadolinium enhancement magnetic resonance (MR) images., Material and Methods: The study was a prospective randomized controlled clinical study. After informed consent was obtained, 20 patients (12 men, 8 women; mean age, 67 ± 11 years) with known chronic myocardial infarction were included for an intraindividual comparison of a single-dose gadobutrol and a single-dose gadobenate dimeglumine. Two MR imaging examinations were performed within a period of 28 days in a crossover design. Late gadolinium enhancement imaging was performed 10 minutes after gadolinium administration using a 2-dimensional phase-sensitive inversion recovery gradient echo sequence at 3 T. Infarct size, signal intensities (SIs), signal-to-noise ratio, and CNR were determined on phase-sensitive MR images. Values for CNR were calculated as CNRinfarct/myocardium = (SIinfarct - SImyocardium)/SDnoise and CNRinfarct/blood = (SIinfarct - SIblood)/SDnoise. In addition, the areas of myocardial infarction were determined on single slices. The entire infarct volumes were calculated by adding the areas with hyperenhancement multiplied by the slice thickness., Results: Late gadolinium enhancement was present in all patients. Median values of the infarct area, infarct volume, and transmurality for gadobutrol and gadobenate dimeglumine showed good to excellent concordance (rc = 0.85, rc = 0.95, and rc = 0.71, respectively). The mean signal-to-noise ratio values for infarct, remote myocardium, and ventricular blood were 18.6 ± 6.5, 4.1 ± 3.7, and 14.6 ± 7.5, respectively, for gadobutrol and 18.8 ± 8.9, 4.9 ± 4.5, and 17.8 ± 10.1, respectively, for gadobenate dimeglumine (P = 0.93, P = 0.48, and P = 0.149, respectively). The mean values of CNRinfarct/myocardium and CNRinfarct/blood were 14.5 ± 5.9 and 4.0 ± 4.6, respectively, for gadobutrol and 13.9 ± 6.1 and 0.9 ± 4.5, respectively, for gadobenate dimeglumine (P = 0.69 and P = 0.02, respectively)., Conclusion: Both gadobutrol and gadobenate dimeglumine allow for successful late gadolinium enhancement imaging of chronic myocardial infarction after a single-dose application (0.1 mmol/kg) at 3 T. Gadobutrol provides a higher CNR between infarct and blood. The CNRs between infarct and normal myocardium, infarct size, and transmural extent were similar for both contrast agents.

Background: Women have unfavorable prognosis after myocardial infarction (MI). This text describes sex differences in mortality and in the power of risk predictors in contemporarily-treated MI patients., Methods: A population of 4141 MI patients (26.5% females) was followed up for 5years. Effects of sex and age on total mortality were investigated by multivariable Cox analysis. Mortality predictors were investigated by receiver-operator characteristics analysis. Stepwise multivariable Cox regression was used to create sex-specific predictive models., Results: Thirty-day mortality was 1.5-fold higher in women. However, sex was not a significant mortality predictor in a model adjusted for age. Predictors for 5-year mortality performed differently in male and female patients. In women, a sex-specific model provided better risk stratification than a sex-neutral model., Conclusion: The unfavorable prognosis of female MI patients can be explained by advanced age. Sex-specific predictive models might improve risk stratification in female survivors of acute MI., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We recently reported that nocturnal respiratory rate (NRR) predicts non-sudden cardiac death in survivors of myocardial infarction (MI). Here, we present the details of the technique deriving NRR from ECG recordings., Methods: Continuous ECG and respiratory chest excursions were simultaneously recorded in 941 MI survivors who were followed-up for 5-years. Mean respiratory rate was derived from the ECG based on RR intervals, QRS amplitudes, and QRS vectors and compared to chest belt measurements. NRR was calculated from Holter-ECGs accordingly using the same ECG processing., Results: Directly-measured and ECG-derived respiratory rates were in good agreement. Areas under the ROC curve for 10-min-ECG- and Holter-derived respiratory rate were well in the confidence intervals of that of the chest belt measurement. The optimum dichotomy of NRR for the prediction of mortality was ≥18.6 breaths per minute., Conclusions: The mean respiratory rate can be precisely derived from continuous ECGs., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Postextrasystolic blood pressure potentiation (PESP), the pulse wave augmentation after an extrasystolic beat, is typically enhanced in heart failure (HF) patients. This study prospectively tested the association of PESP and mortality in cardiac patients., Methods and Results: Consecutive patients (n=941; mean age, 61 years; 19% female) presenting with acute myocardial infarction were enrolled between May 2000 and March 2005 and followed up until August 2010. The main study outcome was 5-year all-cause mortality. Patients underwent noninvasive 30-minute recordings of ECG and continuous blood pressure. PESP presence was based on the ratio between the first postectopic pulse wave amplitude and the mean of the subsequent 9 pulse wave amplitudes. A ratio above 1 was prospectively defined as PESP present. Ventricular premature complexes (VPCs) suitable for PESP quantification were present in recordings of 220 patients. PESP was present in 62 of these patients. Patients without suitable VPCs were classified as PESP absent.During the follow-up, 72 patients died. Among the 220 patients in whom PESP was measurable, 27 died. Under univariable analysis, PESP was a significant predictor of death (P<0.001) as were GRACE score (P<0.001), left ventricular ejection fraction (LVEF) (P<0.001), and the number of recorded VPCs (P<0.001). Under multivariable analysis, PESP (P<0.001), GRACE score (P<0.001), and LVEF (P=0.001) were independently associated with outcome. The combination of PESP presence and LVEF ≤ 35% identified a subgroup of patients with a particularly high mortality of 46.7%. Separate validation reproduced the finding in an unrelated population of 146 HF patients., Conclusions: PESP, which likely reflects abnormalities of myocardial calcium cycling, predicts the mortality risk in postinfarction patients., Clinical Trial Registration Url: ClinicalTrials.gov. Unique identifier: NCT00196274., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Aims: Present society is constantly ageing and elderly frequently suffer from conditions that are difficult and/or costly to treat if detected late. Effective screening of the elderly is therefore needed so that those requiring detailed clinical work-up are identified early. We present a prospective validation of a screening strategy based on a Polyscore of seven predominantly autonomic, non-invasive risk markers.Methods and Results: Within a population-based survey in Germany (INVADE study), participants aged ≥60 years were enrolled between August 2013 and February 2015. Seven prospectively defined Polyscore components were obtained during 30-min continuous recordings of electrocardiogram, blood pressure, and respiration. Out of 1956 subjects, 168 were excluded due to atrial fibrillation, implanted pacemaker, or unsuitable recordings. All-cause mortality over a median 4-year follow-up was prospectively defined as the primary endpoint. The Polyscore divided the investigated population (n = 1788, median age: 72 years, females: 58%) into three predefined groups with low (n = 1405, 78.6%), intermediate (n = 326, 18.2%), and high risk (n = 57, 3.2%). During the follow-up, 82 (4.6%) participants died. Mortality in the Polyscore-defined risk groups was 3.4%, 7.4%, and 17.5%, respectively (P < 0.0001). The Polyscore-based mortality prediction was independent of Framingham score, diabetes, chronic kidney disease, and major stroke and/or myocardial infarction history. It was particularly effective in those aged <75 years (n = 1145).Conclusion: The Polyscore-based mortality risk assessment from short-term non-invasive recordings is effective in the elderly general population, especially those aged 60-74 years. Implementation of a comprehensive Polyscore screening of this age group is proposed to advance preventive medical care. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of a reduced dose of prasugrel versus a standard dose of ticagrelor in elderly patients or those with a low body weight presenting with an acute coronary syndrome (ACS) are unknown.Objective: To investigate the effect of an age- and weight-adapted dose of prasugrel versus a standard dose of ticagrelor in patients with ACS. (ClinicalTrials.gov: NCT01944800).Design: Prespecified analysis of the multicenter, randomized ISAR-REACT 5 trial.Setting: 23 centers in Germany and Italy.Patients: 3997 patients with ACS planned for invasive management.Intervention: Participants were randomly assigned to receive a standard dose of ticagrelor or prasugrel (reduced dose in the elderly or low-weight group and standard dose in the neither elderly nor low-weight group).Measurements: The efficacy end point was a composite of death, myocardial infarction, or stroke, and the safety end point was bleeding, both at 12 months.Results: In the elderly or low-weight group, the efficacy end point occurred in 12.7% of patients assigned to receive prasugrel and 14.6% of those assigned to receive ticagrelor (hazard ratio [HR], 0.82 [95% CI, 0.60 to 1.14]); in the neither elderly nor low-weight group, the efficacy end point occurred in 4.8% of patients assigned to receive prasugrel and 7.3% of those assigned to receive ticagrelor (HR, 0.65 [CI, 0.48 to 0.88]; P for interaction > 0.2). In the elderly or low-weight group, Bleeding Academic Research Consortium type 3 to 5 bleeding occurred in 8.1% of patients assigned to receive prasugrel and 10.6% of those assigned to receive ticagrelor (HR, 0.72 [0.46 to 1.12]), and in 3.7% and 3.8%, respectively, of patients in the neither elderly nor low-weight group (HR, 0.98 [CI, 0.65 to 1.47]; P for interaction > 0.2).Limitation: The study is a subgroup analysis.Conclusion: In elderly or low-weight patients with ACS, a reduced dose of prasugrel compared with the standard dose of ticagrelor is associated with maintained anti-ischemic efficacy while protecting these patients against the excess risk for bleeding.Primary Funding Source: German Center for Cardiovascular Research and Deutsches Herzzentrum München. [ABSTRACT FROM AUTHOR]

Background: The relative efficacy and safety of more potent P2Y12 inhibitors in patients with acute coronary syndrome and high bleeding risk (HBR) undergoing percutaneous coronary intervention remains unclear. We aimed to study the treatment effect of ticagrelor and prasugrel in percutaneous coronary intervention patients presenting with acute coronary syndrome and HBR. Methods: This post hoc analysis of the ISAR-REACT 5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5) included patients with acute coronary syndrome undergoing percutaneous coronary intervention, randomized to ticagrelor or prasugrel, in whom HBR was defined as per Academic Research Consortium criteria. The primary (efficacy) end point was the composite of all-cause death, myocardial infarction, or stroke. The secondary (safety) end point was Bleeding Academic Research Consortium type 3 to 5 bleeding. Outcomes were assessed 12 months after randomization. Results: Out of the 3239 patients included in this analysis, 486 fulfilled the criteria for Academic Research Consortium-HBR definition (HBR group; ticagrelor, n=230 and prasugrel, n=256), while 2753 did not (non-HBR group; ticagrelor, n=1375 and prasugrel, n=1378). Compared with the non-HBR group, the HBR group had a higher risk for the primary (hazard ratio [HR]=3.57 [95% CI, 2.79–4.57]; P <0.001) and secondary end point (HR=2.94 [2.17–3.99]; P <0.001). In the HBR group, the primary (HR=1.09 [0.73–1.62]) and secondary (HR=1.18 [0.67–2.08]) end points were not significantly different between patients assigned to ticagrelor and prasugrel. In the non-HBR group, the primary end point (HR=1.62 [1.19–2.20]) occurred more frequently in patients assigned to ticagrelor as compared to patients assigned to prasugrel, without difference in safety (HR=1.08 [0.74–1.58]). There was no significant treatment allocation-by-HBR status interaction with respect to the primary (P for interaction=0.12) or secondary (P for interaction=0.80) end points. Conclusions: In patients with acute coronary syndrome undergoing percutaneous coronary intervention, HBR status increased both ischemic and bleeding risk without significant impact on the relative efficacy and safety of either ticagrelor or prasugrel. These results warrant confirmation in larger cohorts. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800. [ABSTRACT FROM AUTHOR]

Background: Data on the comparative efficacy and safety of ticagrelor versus prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention are limited. We assessed the efficacy and safety of ticagrelor versus prasugrel in a head-to-head comparison in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention.Methods: In this prespecified subgroup analysis, we included 1653 patients with ST-segment-elevation myocardial infarction randomized to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5). The primary end point was the incidence of death, myocardial infarction, or stroke at 1 year after randomization. The secondary end point was the incidence of bleeding defined as BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 1 year after randomization.Results: The primary end point occurred in 83 patients (10.1%) in the ticagrelor group and in 64 patients (7.9%) in the prasugrel group (hazard ratio, 1.31 [95% CI, 0.95-1.82]; P=0.10). One-year incidence of all-cause death (4.9% versus 4.7%; P=0.83), stroke (1.3% versus 1.0%; P=0.46), and definite stent thrombosis (1.8% versus 1.0%; P=0.15) did not differ significantly in patients assigned to ticagrelor or prasugrel. One-year incidence of myocardial infarction (5.3% versus 2.8%; hazard ratio, 1.95 [95% CI, 1.18-3.23]; P=0.010) was higher with ticagrelor than with prasugrel. BARC type 3 to 5 bleeding occurred in 46 patients (6.1%) in the ticagrelor group and in 39 patients (5.1%) in the prasugrel group (hazard ratio, 1.22 [95% CI, 0.80-1.87]; P=0.36).Conclusions: In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, there was no significant difference in the primary end point between prasugrel and ticagrelor. Ticagrelor was associated with a significant increase in the risk for recurrent myocardial infarction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800. [ABSTRACT FROM AUTHOR]