BACKGROUND: The effects of aspirin-free strategy on bleeding and cardiovascular events in patients undergoing percutaneous coronary intervention with oral anticoagulation (OAC) have not been fully elucidated.
RESULTS: We conducted the prespecified subgroup analysis based on the use of OAC, including vitamin K antagonist and direct oral anticoagulants, within 7 days before percutaneous coronary intervention in the STOPDAPT-3 (Short and Optimal Duration of Dual Antiplatelet Therapy-3) trial, which randomly compared prasugrel monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The coprimary end points were major bleeding events (Bleeding Academic Research Consortium types 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. Among 5966 study patients, there were 530 patients (8.9%) with OAC (no aspirin: N=248, and DAPT: N=282) and 5436 patients (91.1%) without OAC (no aspirin: N=2736, and DAPT: N=2700). Regardless of the use of OAC, the effects of no aspirin compared with DAPT were not significant for the bleeding end point (OAC: 4.45% and 4.27%, hazard ratio [HR], 1.04 [95% CI, 0.46-2.35]; no-OAC: 4.47% and 4.75%, HR, 0.94 [95% CI, 0.73-1.20]; P for interaction=0.82), and for the cardiovascular end point (OAC: 4.84% and 3.20%, HR, 1.53 [95% CI, 0.64-3.62]; no-OAC: 4.06% and 3.74%, HR, 1.09 [95% CI 0.83-1.42]; P for interaction =0.46).
CONCLUSIONS: The no-aspirin strategy compared with the DAPT strategy failed to reduce major bleeding events irrespective of the use of OAC. There was a numerical excess risk of the no-aspirin strategy relative to the DAPT strategy for cardiovascular events in patients with OAC.

The optimal antiplatelet regimen after flow diverter treatment of cerebral aneurysms is still a matter of debate. A single antiplatelet therapy might be advantageous in determined clinical scenarios. This study evaluated the efficacy and safety of prasugrel single antiplatelet therapy versus aspirin and clopidogrel dual antiplatelet therapy.
We performed a post hoc analysis of 4 retrospective multicenter studies including ruptured and unruptured aneurysms treated with flow diversion using either prasugrel single antiplatelet therapy or dual antiplatelet therapy. Primary end points were the occurrence of any kind of procedure- or device-related thromboembolic complications and complete aneurysm occlusion at the latest radiologic follow-up (mean, 18 months). Dichotomized comparisons of outcomes were performed between single antiplatelet therapy and dual antiplatelet therapy. Additionally, the influence of various patient- and aneurysm-related variables on the occurrence of thromboembolic complications was investigated using multivariable backward logistic regression.
A total of 222 patients with 251 aneurysms were included, 90 (40.5%) in the single antiplatelet therapy and 132 (59.5%) in the dual antiplatelet therapy group. The primary outcome-procedure- or device-related thromboembolic complications-occurred in 6 patients (6.6%) of the single antiplatelet therapy and in 12 patients (9.0%) of the dual antiplatelet therapy group (P = .62; OR, 0.712; 95% CI, 0.260-1.930). The primary treatment efficacy end point was reached in 82 patients (80.4%) of the single antiplatelet therapy and in 115 patients (78.2%) of the dual antiplatelet therapy group (P = .752; OR, 1.141; 95% CI, 0.599-2.101). Logistic regression showed that non-surface-modified flow diverters (P = .014) and fusiform aneurysm morphology (P = .004) significantly increased the probability of thromboembolic complications.
Prasugrel single antiplatelet therapy after flow diverter treatment may be as safe and effective as dual antiplatelet therapy and could, therefore, be a valid alternative in selected patients. Further prospective comparative studies are required to validate our findings.

Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials.
We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin.
The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 [95% CI, 0.75-1.20]; Psuperiority=0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 [95% CI, 0.87-1.45]; Pnoninferiority=0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 [95%CI, 1.01-3.30]) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 [95% CI, 1.26-9.23]) in the no-aspirin group compared with the DAPT group.
The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.

A drug-drug interaction (DDI) may occur when transitioning from intravenous P2Y12 inhibition with cangrelor to oral P2Y12 inhibition with prasugrel. However, this has never been tested in patients undergoing percutaneous coronary intervention (PCI).
This study sought to rule out a DDI when cangrelor and prasugrel are concomitantly administered in PCI patients.
SWAP-6 (Switching Antiplatelet-6) was a prospective, randomized, 3-arm, open-label pharmacokinetic (PK) and pharmacodynamic (PD) study. Patients (N = 77) were randomized to 1) prasugrel only at the start of PCI, 2) cangrelor plus prasugrel concomitantly at the start of PCI, or 3) cangrelor at the start of PCI plus prasugrel at the end of infusion. Cangrelor infusion was maintained for 2 hours. PK/PD assessments were performed at baseline and 6 time points postrandomization. The primary endpoint was noninferiority in VerifyNow (Werfen) P2Y12 reaction units measured at 4 hours after randomization between cangrelor plus prasugrel concomitantly administered vs prasugrel only. PK assessments included plasma levels of the active metabolite of prasugrel.
Compared with prasugrel, cangrelor further enhances P2Y12 inhibitory effects. At 4 hours postrandomization, P2Y12 reaction unit levels were significantly lower with prasugrel only compared to cangrelor and prasugrel concomitantly administered (least squares means difference = 130; 95% CI: 85-176), failing to meet the prespecified noninferiority margin. Findings were corroborated by multiple PD assays. The active metabolite of prasugrel levels were not affected by concomitant administration of cangrelor and were low at the end of cangrelor infusion.
In patients undergoing PCI, concomitant administration of prasugrel with cangrelor leads to a marked increase in platelet reactivity after stopping cangrelor infusion, supporting the presence of a DDI. (Switching Antiplatelet Therapy-6 [SWAP-6]; NCT04668144).

OBJECTIVE:  The effect of the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor alirocumab on platelet aggregation among patients with acute myocardial infarction (AMI) remains unknown. We aimed to explore the effect of alirocumab added to high-intensity statin therapy on P2Y12 reaction unit (PRU) among AMI patients receiving dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor (ticagrelor or prasugrel). In addition, we assessed circulating platelet-derived noncoding RNAs (microRNAs and YRNAs).
METHODS:  This was a prespecified, powered, pharmacodynamic substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Patients recruited at Bern University Hospital, receiving DAPT with a potent P2Y12 inhibitor, and adherent to the study drug (alirocumab or placebo) were analyzed for the current study. The primary endpoint was PRU at 4 weeks after study drug initiation as assessed by VerifyNow P2Y12 point-of-care assays.
RESULTS:  Among 139 randomized patients, the majority of patients received ticagrelor DAPT at 4 weeks (57 [86.4%] in the alirocumab group vs. 69 [94.5%] in the placebo group, p = 0.14). There were no significant differences in the primary endpoint PRU at 4 weeks between groups (12.5 [interquartile range, IQR: 27.0] vs. 19.0 [IQR: 30.0], p = 0.26). Consistent results were observed in 126 patients treated with ticagrelor (13.0 [IQR: 20.0] vs. 18.0 [IQR: 27.0], p = 0.28). Similarly, platelet-derived noncoding RNAs did not significantly differ between groups.
CONCLUSIONS:  Among AMI patients receiving DAPT with a potent P2Y12 inhibitor, alirocumab had no significant effect on platelet reactivity as assessed by PRU and platelet-derived noncoding RNAs.

After a brief period of dual antiplatelet therapy, P2Y12 inhibitor monotherapy in the absence of aspirin effectively reduces bleeding without increasing recurrent ischemia in patients undergoing percutaneous coronary intervention (PCI). In addition, early anti-inflammatory therapies may have clinical benefits in acute coronary syndrome (ACS) patients.
The aim of this study was to investigate the feasibility of ticagrelor or prasugrel P2Y12 inhibitor monotherapy combined with colchicine immediately after PCI in patients with ACS.
This was a proof-of-concept pilot trial. ACS patients treated with drug-eluting stents were included. On the day after PCI, low-dose colchicine (0.6 mg daily) was administered in addition to ticagrelor or prasugrel maintenance therapy, whereas aspirin therapy was discontinued. The primary outcome was any stent thrombosis at 3 months. The key secondary outcomes were platelet reactivity measured by the VerifyNow assay (Accriva) before discharge and a reduction in high-sensitivity C-reactive protein (hs-CRP) over 1 month.
We enrolled 200 patients, 190 (95.0%) of whom completed the 3-month follow-up. The primary outcome occurred in 2 patients (1.0%): 1 definite and 1 probable stent thrombosis. The level of platelet reactivity overall was 27 ± 42 P2Y12 reaction units, and only 1 patient had high platelet reactivity (>208 P2Y12 reaction units). The hs-CRP levels decreased from 6.1 mg/L (IQR: 2.6-15.9 mg/L) at 24 hours after PCI to 0.6 mg/L (IQR: 0.4-1.2 mg/L) at 1 month (P < 0.001), and the prevalence of high-inflammation criteria (hs-CRP ≥2 mg/L) decreased from 81.8% to 11.8% (P < 0.001).
In ACS patients undergoing PCI, it is feasible to discontinue aspirin therapy and administer low-dose colchicine on the day after PCI in addition to ticagrelor or prasugrel P2Y12 inhibitors. This approach is associated with favorable platelet function and inflammatory profiles. (Mono Antiplatelet and Colchicine Therapy [MACT]; NCT04949516).

From the restriction of access to primary percutaneous coronary intervention, about 46% of patients with ST-elevation acute coronary syndrome (STE-ACS) received fibrinolytic therapy as a reperfusion strategy; streptokinase is frequently used in Thailand. Despite the guidelines recommending potent P2Y12 inhibitors among these patients, the data are limited, especially among patients with STE-ACS post streptokinase therapy. The study was proposed to describe factors for P2Y12 inhibitors selection and evaluate outcomes of pharmacoinvasively treated STE-ACS receiving ticagrelor compared with clopidogrel in Thailand. We performed a retrospective observational study of patients with STE-ACS post streptokinase therapy followed by percutaneous coronary intervention (PCI) with coronary stent placement and receiving ticagrelor or clopidogrel as P2Y12 inhibitor treatment from January 2017 to June 2021. The primary outcomes described factors for P2Y12 inhibitor selection and evaluated safety outcomes with inverse probability weight (IPW) adjustment. The secondary outcome was a composite of all-cause death, myocardial infarction and stroke. The median time from streptokinase therapy to initiating ticagrelor in the switch group was 25.7 (IQR, 1.9-4.4) hours. The factors related to switching from clopidogrel to ticagrelor included young age, history of coronary artery disease (CAD), dose of streptokinase and use of intravascular imaging. Any bleeding events occurred among 83 patients (41.71%) in the switch group and 83 patients (41.09%) in the no switch group (adjusted HR 1.04, 95% CI 0.75-1.44; p = 0.826). The composite of efficacy outcomes occurred in 6 patients in the switch group (3.02%) and 12 patients (5.94%) in the no switch group (adjusted HR 0.57, 95% CI 0.21-1.57; p = 0.279). Conclusion: In real practice, ticagrelor switching among patients with STE-ACS post streptokinase therapy did not differ regarding safety outcomes and composite of efficacy outcomes compared with clopidogrel.

OBJECTIVE: Based on recent clinical data, the 2020 ESC guidelines on non-ST-elevation acute coronary syndrome (NSTE-ACS) suggest to tailor antithrombotic strategy on individual thrombotic risk. Nonetheless, prevalence and prognostic impact of the high thrombotic risk (HTR) criteria proposed are yet to be described. In this analysis from the PROMETHEUS registry, we assessed prevalence and prognostic impact of HTR, defined according to the 2020 ESC NSTE-ACS guidelines, and if the benefits associated with prasugrel vs. clopidogrel vary with thrombotic risk.
RESULTS: PROMETHEUS was a multicentre prospective study comparing prasugrel vs. clopidogrel in ACS patients undergoing percutaneous coronary intervention (PCI). Patients were at HTR if presenting with one clinical plus one procedural risk feature. The primary endpoint was major adverse cardiac events (MACE), composite of death, myocardial infarction, stroke, or unplanned revascularization, at 1 year. Adjusted hazard ratio (adjHR) and 95% confidence intervals (CIs) were calculated with propensity score stratification and multivariable Cox regression. Among 16 065 patients, 4293 (26.7%) were at HTR and 11 772 (73.3%) at low-to-moderate thrombotic risk. The HTR conferred increased incidence of MACE (23.3 vs. 13.6%, HR 1.85, 95% CI 1.71-2.00, P < 0.001) and its single components. Prasugrel was prescribed in patients with less comorbidities and risk factors and was associated with reduced risk of MACE (HTR: adjHR 0.83, 95% CI 0.68-1.02; low-to-moderate risk: adjHR 0.75, 95% CI 0.64-0.88; pinteraction = 0.32).
CONCLUSIONS: High thrombotic risk, as defined by the 2020 ESC NSTE-ACS guidelines, is highly prevalent among ACS patients undergoing PCI. The HTR definition had a strong prognostic impact, as it successfully identified patients at increased 1 year risk of ischaemic events.

To characterize and follow patients with ST-segment elevation myocardial infarction (STEMI) at high bleeding risk (HBR) according to the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score, and to examine the use of P2Y12 inhibitors and the subsequent risk of major adverse cardiovascular events (MACE) and bleeding.
This single-centre cohort study included 6179 consecutive STEMI patients who underwent percutaneous coronary intervention (PCI) at Copenhagen University Hospital, Rigshospitalet, between 2009 and 2016. Individual linkage to nationwide registries was conducted to obtain information on diagnoses, claimed drugs, and vital status. Of the 5532 (89.5%) patients with available PRECISE-DAPT scores, 33.0% were at HBR and more often elderly and female with more comorbidities than non-HBR patients. One-year cumulative incidence rates per 100 person-years were 8.7 and 2.1 for major bleeding and 36.8 and 8.3 for MACE in HBR and non-HBR patients, respectively. Among the 4749 (85.8%) patients who survived and collected a P2Y12 inhibitor ≤7 days from discharge, 68.2% of HBR patients were treated with ticagrelor or prasugrel and 31.8% with clopidogrel, while 18.2% non-HBR patients were treated with clopidogrel. Adherence was high for all (>75% days coverage). The risk of MACE was lower in ticagrelor- and prasugrel-treated patients than in clopidogrel-treated patients without differences in major bleeding.
One-third of PCI-treated all-comer patients with STEMI were at HBR according to the PRECISE-DAPT score and were more often treated with potent P2Y12 inhibitors instead of clopidogrel. Thus, ischaemic risk may be weighted over bleeding risk in STEMI patients at HBR.

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y12 inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y12 inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y12 inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator\'s discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS. (ClinicalTrials.gov: NCT04360720).