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Background: The ISAR-REACT 5 trial compared the efficacy and safety of ticagrelor and prasugrel in patients with ACS managed invasively. The present study sought to investigate the impact of ticagrelor and prasugrel on the incidence and pattern of urgent revascularization in acute coronary syndromes (ACS) patients undergoing percutaneous coronary intervention (PCI)., Methods and Results: This post-hoc analysis of the ISAR-REACT 5 trial included all ACS patients who underwent PCI. The primary endpoint for this analysis was the incidence of urgent revascularization at 12-month follow-up. Secondary outcome was the pattern of urgent revascularization procedures (namely, urgent target vessel/non-target vessel revascularization - TVR/NTVR). Among 3,377 ACS patients who underwent PCI, 1,676 were assigned to ticagrelor and 1,701 to prasugrel before PCI. After 12 months, the incidence of urgent revascularization was higher among patients assigned to ticagrelor as compared to prasugrel (6.8% vs. 5.2%; hazard ratio [HR] = 1.32, 95% confidence interval [CI] 1.00-1.75; p = 0.051), mostly attributable to significantly more urgent NTVR in the ticagrelor group (3.8% vs. 2.4%; HR = 1.62 [1.09-2.41]; p = 0.017). The risk of urgent TVR did not differ between treatment groups (3.3% vs. 3.0%; HR = 1.13 [0.77-1.65]; p = 0.546)., Conclusions: In ACS patients treated with PCI, the cumulative rate of urgent revascularizations after 12 months is higher with ticagrelor compared to prasugrel, due to a significant increase in urgent revascularizations involving remote coronary vessels., (© 2024. The Author(s).)

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.)

Importance: It is unclear whether ticagrelor or prasugrel hydrochloride is superior for patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI)., Objective: To assess the safety and efficacy of ticagrelor vs prasugrel for patients with ACS treated with PCI., Design, Setting, and Participants: A prespecified analysis was performed of a postrandomization subgroup of 3377 patients who presented with ACS and were treated with PCI in the investigator-initiated, multicenter, phase 4, open-label Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5 randomized clinical trial, conducted from September 1, 2013, to February 28, 2018. Statistical analysis was performed from September 1, 2020, to January 30, 2021. Analysis was performed according to the intention-to-treat principle., Interventions: Patients were randomly assigned to a ticagrelor-based or prasugrel-based strategy. This analysis focuses on the subgroup of patients who underwent PCI that was formed after randomization., Main Outcomes and Measures: The primary end point was a composite consisting of all-cause death, myocardial infarction, or stroke at 12 months. The safety end point was Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding., Results: The ticagrelor group comprised 1676 patients (1323 men [78.9%]; mean [SD] age, 64.4 [12.0] years), and the prasugrel group comprised 1701 patients (1341 men [78.8%]; mean [SD] age, 64.7 [12.0] years). The primary end point occurred for 162 patients (9.8%) in the ticagrelor group and 120 patients (7.1%) in the prasugrel group (hazard ratio [HR], 1.41; 95% CI, 1.11-1.78; P = .005). Myocardial infarction occurred in 88 patients (5.3%) in the ticagrelor group compared with 55 patients (3.8%) in the prasugrel group (HR, 1.67; 95% CI, 1.19-2.34; P = .003). The safety end point, BARC type 3 to 5 bleeding, occurred in 84 of 1672 patients (5.3%) in the ticagrelor group and 78 of 1680 patients (4.9%) in the prasugrel group (HR; 1.10; 95% CI, 0.81-1.50; P = .54)., Conclusions and Relevance: Among patients presenting with ACS who were treated with PCI, the incidence of the primary composite end point occurred less frequently for patients who received prasugrel compared with those who received ticagrelor. The incidence of bleeding events was comparable between the 2 groups. These results suggest that, for patients presenting with ACS who undergo PCI, a prasugrel-based strategy is superior to a ticagrelor-based strategy. However, because these observations are based on a postrandomization subgroup, these findings should be regarded as hypothesis generating and dedicated randomized clinical trials may be warranted to confirm these findings., Trial Registration: ClinicalTrials.gov Identifier: NCT01944800.

Objectives: The aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their estimated glomerular filtration rates (eGFRs)., Background: The outcomes of ticagrelor versus prasugrel in patients with ACS according to eGFR have not been defined., Methods: Patients (n = 4,012) were categorized into 3 groups: low eGFR (<60 mL/min/1.73 m 2 ), intermediate eGFR (≥60 and <90 mL/min/1.73 m 2 ), and high eGFR (≥90 mL/min/1.73 m 2 ). The primary endpoint was a composite of all-cause death, myocardial infarction, and stroke; the secondary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding, both at 1 year., Results: Patients with low eGFRs had a higher risk for the primary endpoint compared with patients with intermediate eGFRs (adjusted HR: 1.89; 95% CI: 1.46-2.46]) and those with high eGFRs (adjusted HR: 2.33; 95% CI: 1.57-3.46). A risk excess for low eGFR was also observed for bleeding (adjusted HR: 1.55 [95% CI: 1.12-2.13] vs intermediate eGFR; adjusted HR: 1.59 [95% CI: 1.01-2.50] vs high eGFR). However, eGFR did not affect the relative efficacy and safety of ticagrelor versus prasugrel. In patients with low eGFR, the primary endpoint occurred in 20.5% with ticagrelor and in 14.7% with prasugrel (HR: 1.47; 95% CI: 1.04-2.08; P = 0.029); there was no significant difference in bleeding., Conclusions: These results show that among patients with ACS, reduction of eGFR is associated with increased risk for ischemic and bleeding events but has no significant impact on the relative efficacy and safety of ticagrelor versus prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800)., Competing Interests: Funding Support and Author Disclosures This research was supported by a grant (FKZ 81X1600501) from the German Center for Cardiovascular Research and Deutsches Herzzentrum München. Dr Angiolillo has received grants and personal fees from Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Janssen, Merck, Sanofi, and CeloNova; has received personal fees from Haemonetics, PhaseBio, PLx Pharma, Pfizer, The Medicines Company, and St. Jude Medical; and has received grants from CSL Behring, Eisai, Gilead, Idorsia Pharmaceuticals, Matsutani Chemical Industry, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. Dr Hochholzer has received personal fees from Bayer Vital, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Novartis, AstraZeneca, and The Medicines Company. Dr Kufner has received personal fees from Bristol Myers Squibb, AstraZeneca, and Translumina. Dr Sager has received grants from the European Research Council, Else-Kröner-Fresenius-Stiftung, Deutsche Herzstiftung, and Deutsche Forschungsgemeinschaft. Dr Neumann has received personal fees from Amgen, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, and Ferrer; has received grants and personal fees from Pfizer, Biotronik, Edwards Lifesciences, Bayer Healthcare, and Boston Scientific; and has received grants from Medtronic and GlaxoSmithKline outside the submitted work. Dr Schüpke has received the Else Kröner memorial grant from Else Kröner-Fresenius Stiftung; has received financial support from the German Center for Cardiovascular Research; has received consulting fees from Bayer Vital; and has received lecture fees from Daiichi-Sankyo and Biopas Laboratories. Dr Sibbing has received personal fees from Daichi-Sankyo, Sanofi, AstraZeneca, Bayer, Pfizer, and Servier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Drug-coated balloons (DCB) and drug-eluting stents (DES) represent the currently recommended treatments for in-stent restenosis (ISR). Optical coherence tomography (OCT) allows detailed neointimal characterisation which can guide treatment strategies., Aims: The aims of this study were first, to assess the relation between neointimal pattern and clinical outcomes following in-stent restenosis (ISR) treatment, and second, to explore a potential interaction between neointimal pattern and treatment modality relative to clinical outcomes., Methods: Patients undergoing OCT-guided treatment (DCB or DES) of ISR in three European centres were included. Based on the median of distribution of non-homogeneous neointima quadrants, patients were categorised into low and high inhomogeneity groups., Results: A total of 197 patients (low inhomogeneity=100 and high inhomogeneity=97) were included. There were no significant differences in terms of major adverse cardiac events (MACE) (p=0.939) or target lesion revascularisation (TLR) (p=0.732) between the two groups. The exploratory analysis showed a significant interaction between neointimal pattern and treatment modality regarding MACE (pint=0.006) and TLR (pint=0.022). DES showed a significant advantage over DCB in the high (MACE: HR 0.26 [0.10-0.65], p=0.004; TLR: HR 0.28 [0.11-0.69], p=0.006), but not in the low inhomogeneity group (MACE: p=0.917; TLR: p=0.797)., Conclusions: In patients with ISR treated with DCB or DES, there were no significant differences in terms of MACE or TLR between the low and high inhomogeneity groups. A significant interaction was observed between treatment modality and neointimal pattern with an advantage of DES over DCB in the high and no difference in the low inhomogeneity group. This warrants confirmation from prospective dedicated studies.

Importance: The assessment of new antithrombotic agents with a favorable safety profile is clinically relevant., Objective: To test the efficacy and safety of revacept, a novel, lesion-directed antithrombotic drug, acting as a competitive antagonist to platelet glycoprotein VI., Design, Setting, and Participants: A phase 2 randomized clinical trial; patients were enrolled from 9 centers in Germany from November 20, 2017, to February 27, 2020; follow-up ended on March 27, 2020. The study included patients with stable ischemic heart disease (SIHD) undergoing elective percutaneous coronary intervention (PCI)., Interventions: Single intravenous infusion of revacept, 160 mg, revacept, 80 mg, or placebo prior to the start of PCI on top of standard antithrombotic therapy., Main Outcomes and Measures: The primary end point was the composite of death or myocardial injury, defined as an increase in high-sensitivity cardiac troponin to at least 5 times the upper limit of normal within 48 hours from randomization. The safety end point was bleeding type 2 to 5 according to the Bleeding Academic Research Consortium criteria at 30 days., Results: Of 334 participants (median age, 67.4 years; interquartile range, 60-75.1 years; 253 men [75.7%]; and 330 White participants [98.8%]), 120 were allocated to receive the 160-mg dose of revacept, 121 were allocated to receive the 80-mg dose, and 93 received placebo. The primary end point showed no significant differences between the revacept and placebo groups: 24.4%, 25.0%, and 23.3% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .98). The high dose of revacept was associated with a small but significant reduction of high-concentration collagen-induced platelet aggregation, with a median 26.5 AU × min (interquartile range, 0.5-62.2 AU × min) in the revacept, 160 mg, group; 43.5 AU × min (interquartile range, 22.8-99.5 AU × min) in the revacept, 80 mg, group; and 41.0 AU × min (interquartile range, 31.2-101.0 AU × min) in the placebo group (P = .02), while adenosine 5'-diphosphate-induced aggregation was not affected. Revacept did not increase Bleeding Academic Research Consortium type 2 or higher bleeding at 30 days compared with placebo: 5.0%, 5.9%, and 8.6% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .36)., Conclusions and Relevance: Revacept did not reduce myocardial injury in patients with stable ischemic heart disease undergoing percutaneous coronary intervention. There were few bleeding events and no significant differences between treatment arms., Trial Registration: ClinicalTrials.gov Identifier: NCT03312855.

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.

Purpose: To evaluate myocardial viability assessment with hybrid 2-deoxy-2-[ 18 F]fluoro-D-glucose positron emission tomography/magnetic resonance imaging ([ 18 F]FDG-PET/MR) in predicting left ventricular (LV) wall motion recovery after percutaneous revascularisation of coronary chronic total occlusion (CTO)., Methods and Results: Forty-nine patients with CTO and corresponding wall motion abnormality (WMA) underwent [ 18 F]FDG-PET/MR imaging for viability assessment prior to percutaneous revascularisation. After 3-6 months, 23 patients underwent follow-up MR to evaluate wall motion recovery. In total, 124 segments were assigned to the CTO territories, while 80 segments displayed impaired wall motion. Of these, 68% (54) were concordantly viable in PET and MR; conversely, only 2 segments (2%) were assessed non-viable by both modalities. However, 30% showed a discordant viability pattern, either PET non-viable/MR viable (3 segments, 4%) or PET viable/MR non-viable (21 segments, 26%), and the latter revealed a significant wall motion improvement at follow-up (p = 0.033). Combined imaging by [ 18 F]FDG-PET/MR showed a fair accuracy in predicting myocardial recovery after CTO revascularisation (PET/MR area under ROC curve (AUC) = 0.72, p = 0.002), which was superior to LGE-MR (AUC = 0.66) and [ 18 F]FDG-PET (AUC = 0.58) alone., Conclusion: Hybrid PET/MR imaging prior to CTO revascularisation predicts more accurately the recovery of dysfunctional myocardium than PET or MR alone. Its complementary information may identify regions of viable myocardium with increased potential for functional recovery.

Objectives: The aim of this study was to assess the efficacy and safety of ticagrelor versus prasugrel in patients with diabetes mellitus (DM) presenting with acute coronary syndromes (ACS) in whom invasive therapy was planned., Background: The efficacy and safety of ticagrelor versus prasugrel in patients with ACS with DM undergoing invasive treatment remain unknown., Methods: This pre-specified analysis of the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial included 892 patients with ACS with DM and 3,124 patients with ACS without DM randomized to prasugrel or ticagrelor. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding (both assessed 12 months after randomization)., Results: The primary endpoint occurred in 51 patients (11.2%) in the ticagrelor group and 55 patients (13.0%) in the prasugrel group in the DM cohort (hazard ratio: 0.84; 95% confidence interval: 0.58 to 1.24; p = 0.383) and in 132 patients (8.6%) in the ticagrelor group and 81 patients (5.2%) in the prasugrel group in the non-DM cohort (hazard ratio: 1.70; 95% confidence interval: 1.29 to 2.24; p < 0.001). There was a significant treatment arm-by-diabetic status interaction (p int  = 0.0035). Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 27 patients (6.9%) in the ticagrelor group and 19 patients (5.5%) in the prasugrel group (p = 0.425) in the DM cohort and in 68 patients (5.2%) in the ticagrelor group and 60 patients (4.6%) in the prasugrel group in the non-DM cohort (p = 0.500)., Conclusions: DM seems to affect the efficacy of ticagrelor and prasugrel in patients with ACS. In patients with DM, the efficacy of ticagrelor was comparable with that of prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800)., (Copyright © 2020. Published by Elsevier Inc.)

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: Current guidelines recommend intensified platelet inhibition by prasugrel or ticagrelor in patients with unstable angina (UA) or non-ST-segment elevation (NSTE) myocardial infarction (MI).Objectives: This study sought to investigate the benefits and risks of ticagrelor as compared with prasugrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and planned invasive management.Methods: This post hoc analysis combines the pre-specified subgroups of UA and NSTEMI of the randomized ISAR-REACT 5 trial. It included 1,179 patients assigned to ticagrelor and 1,186 assigned to prasugrel. Ticagrelor was started immediately after randomization and prasugrel after coronary angiography. The primary endpoint was a composite of death, MI, or stroke during 1-year follow-up, and the safety endpoint was Bleeding Academic Research Consortium class 3-5.Results: The primary endpoint was reached in 101 (8.7%) patients in the ticagrelor and in 73 (6.3%) patients in the prasugrel group (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.04 to 1.90). The HR for all-cause death was 1.43 (95% CI: 0.93 to 2.21) and that for MI 1.43 (95% CI: 0.94 to 2.19). The safety endpoint occurred in 49 (5.2%) patients in the ticagrelor and in 41 (4.7%) patients in the prasugrel group (HR: 1.09; 95% CI: 0.72 to 1.65). Landmark analysis revealed persistence of the efficacy advantage with prasugrel after the first month.Conclusions: In patients with NSTE-ACS, we found that prasugrel was superior to ticagrelor in reducing the combined 1-year risk of death, MI, and stroke without increasing the risk of bleeding. Due to the post hoc nature of the analysis, these findings need confirmation by further studies. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome; NCT01944800). [ABSTRACT FROM AUTHOR]