A growing body of evidence supports short-term DAPT as safe and efficacious following PCI with DES. However, methodological criticism of RCTs has led to caution when translating results into clinical practice. This study aimed to critically appraise the methodological rigour of included studies and consolidate the evidence on the safety and efficacy of short-term DAPT.

Medline, Cochrane Library and Embase were searched from inception until August 2022. The primary outcome was the methodological quality of published primary studies. Risk of bias was assessed using RoB 2.0 and the CASP tool. Evidence was rated for quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) score approach. Other endpoints were all-cause mortality and major bleeding.

Eighteen RCTs were included. Based on GRADE score, there was a moderate level of certainty that the reported results for both outcomes are probably close to the true effect. A total of 78% (14/18) of RCTs had a low risk of bias when assessing all-cause mortality and 61% (11/18) when assessing major bleeding. The CASP tool confirmed methodological rigour; however, only 33% (6/18) of studies were applicable beyond the studied populations. Compared with 12 months of DAPT, short-term DAPT was associated with a reduced risk of major bleeding [relative risk (RR): 0.69, 95% CI: 0.54-0.88, P = 0.003, I2 = 45%] and trended towards a reduced risk in all-cause mortality (RR: 0.90, 95% CI: 0.79-1.01, P = 0.08, I2 = 0%).

With moderate certainty evidence, short-term DAPT appears safe and efficacious post-PCI with DES in the studied populations.

We conducted a retrospective observational study to examine whether anti-inflammatory medications prescribed peri-operatively of resective brain surgery can reduce long-term seizure recurrence for individuals with drug-resistant focal epilepsy. We used insurance-claims data from across the United States to screen medications prescribed to 1,993 individuals undergoing epilepsy. We then validated the results in a well-characterized cohort of 671 epilepsy patients from a major surgical center. Twelve medications met the screening criteria and were evaluated, identifying dexamethasone and zonisamide as potentially beneficial. Dexamethasone reduced seizure recurrence by 42% over 9 years of follow-up (hazard-ratio = 0.742; 95% CI = 0.662, 0.831), and zonisamide reduced recurrence by 33% (HR = 0.782; 95% CI = 0.667, 0.917). While dexamethasone could not be validated, analysis of zonisamide in the clinical cohort corroborated the beneficial effect (HR = 0.828; 95% CI = 0.706, 0.971). If prospectively validated, this study suggests surgeons could improve long-term outcomes of epilepsy surgery by medically reducing neuro-inflammation in the surgical bed.

Flow diverter stents (FDS) are used to treat aneurysms by modifying the intraaneurysmal hemodynamics and promoting a prothrombotic milieu. Thrombotic in-stent stenosis (ISS) is a common complication of endovascular treatment for intracranial aneurysms with flow diverter stents. The dominant approach to address ISS has been to either increase the dose of antiplatelet therapy agents or extend dual antiplatelet therapy (DAPT) causing ISS to resolve, while potentially exacerbating the side effects associated with DAPT. To decrease the risk of thrombotic ISS, surface coatings have been applied to flow diverter stents with promising results.

The thrombotic signature of a bare metal and a heparin coated FDS was assessed in vitro. The flow diverter stents were exposed to pulsatile blood flow in a one-pass system to assess platelet and fibrin deposition, while flow cytometry was used to assess different markers of platelet activation in blood incubated with flow diverter stents for 30, 60, and 90 minutes.

Immunofluorescence and scanning electron microcopy results demonstrated greater fibrin and platelet deposition on bare metal flow diverter stents, while the heparin coated flow diverter stents had less fibrin and platelet deposition. A greater percentage of platelets were not only activated, but also presented higher levels of activation markers, in blood exposed to the bare metal flow diverter stents at the 90 minute time point in comparison to the heparin coated FDS.

The findings demonstrate that heparin coated flow diverter stents are characterized by a lower thrombotic signature than bare metal flow diverter stents and raise the possibility of an additional therapeutic option to treat intracranial aneurysms.

The hemostatic function of platelets is complementary to blood coagulation. However, traditional platelet function tests have primarily focused on measuring platelet aggregation, reducing their clinical effectiveness for antiplatelet drug monitoring. To address this limitation, we propose a new test principle that evaluates platelet function and the effects of antiplatelet drugs through blood coagulation reactions. This principle was validated in model experimental systems using blood samples from healthy volunteers (n = 11), where antiplatelet drugs such as aspirin, prostaglandin E1, or ticagrelor were added to the blood samples. Ticagrelor was tested at four concentration levels, covering the expected therapeutic range. We found that the complementary function of platelets can be assessed by monitoring the 1 MHz dielectric permittivity during the blood coagulation process, particularly the peak value. When reagents such as agonists (arachidonic acid, collagen, or adenosine diphosphate ADP) and calcium were mixed into the citrated blood with turbulence by pipetting, platelets became activated and aggregated before thrombin generation, resulting in a "consumed" state of platelets. Consequently, the contribution to the permittivity peak was minimal. By contrast, when blood spiked with antiplatelet drugs was tested, agonist-induced platelet aggregation was inhibited during the initial stage of the measurement. However, after thrombin generation, platelets were activated through the thrombin receptor. These activated platelets interacted with fibrin, thereby affecting the permittivity peak. The results of this validation process with Student's t-tests confirm the fundamental operating principle of the proposed platelet function assay, thereby contributing to antiplatelet therapy monitoring.

Postprocedural anticoagulation (PPAC) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) can mitigate thrombotic events. However, current clinical guidelines do not recommend PPAC after PCI considering the scarce evidence supporting its use. A comprehensive literature search of electronic databases was conducted to identify studies comparing PPAC to no anticoagulation (AC) after PCI for AMI. Using the inverse-variance random-effects model, we pooled risk ratios (RRs) with 95% confidence intervals (CIs), with P < 0.05 considered statistically significant. Seven studies with a total of 47,981 patients (32,010: PPAC and 15,971: no AC) were included in the final analysis. PPAC administration demonstrated no significant difference in 30-day all-cause mortality [RR, 0.73 (95% CI, 0.47-1.16); P = 0.19], 30-day cardiovascular mortality [RR, 0.76 (95% CI, 0.45-1.30); P = 0.32], 30-day myocardial infarction [RR, 0.68 (95% CI, 0.41-1.12); P = 0.13], 30-day stroke [RR, 0.89 (95% CI, 0.47-1.67); P = 0.71], 30-day target vessel revascularization [RR, 0.74 (95% CI, 0.37-1.47); P = 0.39], 30-day stent thrombosis [RR, 1.08 (95% CI, 0.75-1.57); P = 0.67], and 30-day bleeding [RR, 1.25 (95% CI, 0.83-1.88); P = 0.29] compared with no AC. This meta-analysis concludes that there are no benefits of routine PPAC after PCI in AMI. The decision to prolong anticoagulant use post-PCI depends on risk versus benefits, which vary from case to case. Future large-scale multicentric randomized trials are warranted to corroborate the results of this meta-analysis.

Current practice guidelines recommend dual antiplatelet therapy for at least 30 days postoperatively after transcarotid artery revascularization (TCAR) to promote stent patency. However, many patients are already taking other antithrombotic medications. The optimal pharmacologic regimen in this patient population remains unclear, especially as it pertains to postoperative bleeding complications.

All TCAR procedures performed at a large academic medical center from January 1, 2017, to April 30, 2023, were identified via current procedural terminology codes and retrospectively reviewed via electronic medical records. Data were collected on patient demographics, procedural details, postoperative complications, and antithrombotic regimen. Bleeding complications were categorized as surgical and nonsurgical, which included any bleeding diatheses that were not related to the neck incision, such as epistaxis, hematuria, melena, or noncervical hematoma.

A total of 116 TCAR procedures were performed. The 30-day incidence of bleeding complications was 12.1% (n = 14), which included 8 (6.9%) symptomatic neck hematomas and 6 (5.2%) nonsurgical site bleeding complications. Aside from patient age (median 72 years [66-79] vs. 79 years [70.5-88], P = 0.03), demographics, medical comorbidities, surgical indication, risk-related indication for TCAR, and inpatient/outpatient status were similar between patients who experienced bleeding versus no bleeding complications. Patients who developed bleeding complications experienced higher 30-day hospital readmission (42.9% vs. 9.8%, P < 0.001) and reintervention rates (21.4% vs. 2.0%, P < 0.001) and trended toward longer postoperative length of stay (1.5 days [1-3] vs. 1 [1-2] days, P = 0.07). Reasons for readmission (n = 16) included: epistaxis (1), hematuria (1), headache and melena (1), melena and myocardial infarction (1), fall (1), headache (1), dyspnea (5), delirium (1), diarrhea (1), atrial fibrillation (1), and neck hematoma (1); 1 patient did not have a readmission reason documented. Reinterventions (n = 6) included neck hematoma evacuation (2), epistaxis cauterization (1), emergent cricothyroidotomy (1), and repeat carotid stenting (1). The management of antithrombotic medications during bleeding events were highly variable among providers (11 patients with nothing held, 1 apixaban held, 1 aspirin held, 1 clopidogrel held); however, no patients suffered carotid stent thrombosis.

Bleeding complications are common within 30 days of TCAR and frequently result in unplanned hospital readmission and reintervention. There is significant provider-level variability in management of antithrombotic medications during these events. These data highlight need for evidence-based guidelines for the optimal pharmacologic strategy for patients post-TCAR who develop bleeding complications.

There was no previous trial comparing aspirin monotherapy with a P2Y12 inhibitor monotherapy following short dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stents.

In the STOPDAPT-3, patients with acute coronary syndrome or high bleeding risk (HBR) were randomly assigned to either 1-month dual antiplatelet therapy with aspirin and prasugrel followed by aspirin monotherapy (aspirin group) or 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group). This secondary analysis compared aspirin monotherapy with clopidogrel monotherapy by the 30-day landmark analysis. The co-primary endpoints were the cardiovascular endpoint defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischaemic stroke and the bleeding endpoint defined as Bleeding Academic Research Consortium 3 or 5.

Of the 6002 assigned patients, 5833 patients (aspirin group: N = 2920 and clopidogrel group: N = 2913) were included in the 30-day landmark analysis. Median age was 73 (interquartile range 64-80) years, women 23.4%, acute coronary syndrome 74.6%, and high bleeding risk 54.1%. The assigned monotherapy was continued at 1 year in 87.5% and 87.2% in the aspirin and clopidogrel groups, respectively. The incidence rates beyond 30 days and up to 1 year were similar between the aspirin and clopidogrel groups for both cardiovascular endpoint [4.5 and 4.5 per 100 person-year, hazard ratio 1.00 (95% confidence interval .77-1.30), P = .97], and bleeding endpoint [2.0 and 1.9, hazard ratio 1.02 (95% confidence interval .69-1.52), P = .92].

Aspirin monotherapy compared with clopidogrel monotherapy was associated with similar cardiovascular and bleeding outcomes beyond 1 month and up to 1 year after percutaneous coronary intervention with drug-eluting stents (STOPDAPT-3 ClinicalTrials.gov number, NCT04609111).

As the number of neuroendovascular therapies in Japan increases, the current trends in periprocedural antithrombotic therapy must be understood.We retrospectively analyzed data on periprocedural antithrombotic therapy in the Japanese Registry of Neuroendovascular Therapy (JR-NET) 4, a nationwide survey carried out in Japan between January 2015 and December 2019. Details on antithrombotic therapy in neuroendovascular therapy for ruptured cerebral aneurysms, unruptured cerebral aneurysms, and percutaneous transluminal angioplasty or stenting were collected from the JR-NET 4 database. These data were analyzed and compared with those from the JR-NET 2 (January 2008 to December 2009) and JR-NET 3 (January 2010 to December 2014). A total of 36,560 cases were analyzed in the JR-NET 4. The frequency of preprocedural dual antiplatelet therapy (DAPT) significantly increased from the JR-NET 2 to 4 (48.1%, 53.4%, and 62.3%, respectively; P < 0.001), whereas the frequency of monotherapy significantly decreased (15.7%, 13.9%, and 8%, respectively; P < 0.001). Postprocedural antiplatelet therapy exhibited similar trends, and postprocedural anticoagulant therapy was discontinued. Particularly, heparin use significantly decreased from the JR-NET 2 to 4 (23.4% vs. 12.7% vs. 7.9%, respectively; P < 0.001). In terms of periprocedural complications, the incidence of ischemic complications increased from the JR-NET 3 to 4 (5.8% vs. 6.2%; P = 0.05). In the JR-NET 4, severe adverse events and hemorrhagic and all complications were significantly more frequent in the preprocedural triple or more therapy group.The rate of postprocedural anticoagulant therapy decreased, whereas that of antiplatelet therapy increased. Overall, in Japan, periprocedural DAPT has become increasingly common.

Patients with symptomatic lower extremity arterial disease (LEAD) are recommended to receive antiplatelet therapy, while direct oral anticoagulants (DOACs) are standard for stroke prevention in patients with atrial fibrillation (AF). For patients with concomitant LEAD and AF, data comparing dual antithrombotic therapy (an antiplatelet agent used in conjunction with a DOAC) vs. DOAC monotherapy are scarce. This retrospective cohort study, based on data from the Taiwan National Health Insurance Research Database, aimed to compare the efficacy and safety of these antithrombotic strategies.

Patients with AF who underwent revascularisation for LEAD between 2012 - 2020 and received any DOAC within 30 days of discharge were included. Patients were grouped by antiplatelet agent exposure into the dual antithrombotic therapy and DOAC monotherapy groups. Inverse probability of treatment weighting was used to mitigate selection bias. Major adverse limb events (MALEs), ischaemic stroke or systemic embolism, and bleeding outcomes were compared. Patients were followed until the occurrence of any study outcome, death, or up to two years.

A total of 1 470 patients were identified, with 736 in the dual antithrombotic therapy group and 734 in the DOAC monotherapy group. Among them, 1 346 patients received endovascular therapy as the index revascularisation procedure and 124 underwent bypass surgery. At two years, dual antithrombotic therapy was associated with a higher risk of MALEs than DOAC monotherapy (subdistribution hazard ratio [SHR] 1.34, 95% confidence interval [CI] 1.15 - 1.56), primarily driven by increased repeat revascularisation. Dual antithrombotic therapy was also associated with a higher risk of major bleeding (SHR 1.43, 95% CI 1.05 - 1.94) and gastrointestinal bleeding (SHR 2.17, 95% CI 1.42 - 3.33) than DOAC monotherapy.

In patients with concomitant LEAD and AF who underwent peripheral revascularisation, DOAC monotherapy was associated with a lower risk of MALEs and bleeding events than dual antithrombotic therapy.

Patients who undergo percutaneous coronary intervention (PCI) with stenting usually require a period of dual antiplatelet therapy (DAPT) but, when an indication for long-term oral anticoagulation (OAC) such as atrial fibrillation (AF) coexists, triple antithrombotic therapy (TAT) with DAPT and OAC causes concern for excessive bleeding. Achieving the right balance between bleeding and adequate protection from ischemic events remains an issue of debate and subject to ongoing investigation of various antithrombotic regimens and durations.

This review describes the landmark clinical trials comparing TAT to a period of dual antithrombotic therapy (DAT) and subsequent meta-analyses. It also describes the international recommendations that have been derived from this evidence and identifies outstanding issues that could be addressed in upcoming or future trials.

The current recommended default strategy of a short period of TAT with clopidogrel followed by the withdrawal of aspirin faces a challenge from the prospect of more consistent P2Y12 inhibition provided by ticagrelor and prasugrel. Ticagrelor monotherapy has already been trialed in patients after PCI without an indication for OAC. DAT with ticagrelor or prasugrel immediately post-procedure could emerge as a comparably safe and more efficacious regimen than one involving clopidogrel in the right setting.

The current guidelines for acute coronary syndrome (ACS) discourage the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation is not well supported by evidence. In this post hoc analysis of the ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3 (STOPDAPT-3) trial, 30-day outcomes were compared between the 2 groups with and without post-PCI heparin administration among patients with ACS who did not receive mechanical support devices. The co-primary end points were the bleeding end point, defined as the Bleeding Academic Research Consortium type 3 or 5 bleeding, and the cardiovascular end point, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4,088 patients with ACS, 2,339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher among those with ST-elevation myocardial infarction compared with others (72.3% and 38.8%, p <0.001), and among patients with intraprocedural adverse angiographic findings compared with those without (67.6% and 47.5%, p <0.001). Post-PCI heparin compared with no post-PCI heparin was associated with a significantly increased risk of the bleeding end point (4.75% and 2.52%, adjusted hazard ratio 1.69, 95% confidence interval 1.15 to 2.46, p = 0.007) and a numerically increased risk of the cardiovascular end point (3.16% and 1.72%, adjusted hazard ratio 1.56, 95% confidence interval 0.98 to 2.46, p = 0.06). Higher hourly dose or total doses of heparin were also associated with higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in patients with ACS. Post-PCI heparin use was associated with harm in terms of increased bleeding without the benefit of reducing cardiovascular events. Trial identifier: STOPDAPT-3 ClinicalTrials.gov number, NCT04609111.

Triple antithrombotic therapy (TAT) with aspirin, a P2Y12 inhibitor, and oral anticoagulation in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) raises concerns about increased bleeding. Regimens incorporating more potent P2Y12 inhibitors over clopidogrel have not been investigated adequately.

A retrospective observational study was performed on 387 patients with AF receiving TAT for 1 month (n = 236) or ≤1 week (n = 151) after PCI. Major and clinically relevant non-major bleeding and major adverse cardiac and cerebrovascular events (MACCE) were assessed up to 30 days post-procedure.

Bleeding was less frequent with ≤1 week versus 1 month of TAT (3.3 vs 9.3%; p = 0.025) while MACCE were similar (4.6 vs 4.7%; p = 0.998). No differences in bleeding or MACCE were observed between ticagrelor/prasugrel and clopidogrel regimens. For patients receiving ≤1 week of TAT, no excess of MACCE was seen in the subgroup given no further aspirin post-PCI compared with those given aspirin for up to 1 week (3.6 vs 5.2%).

TAT post-PCI for ≤1 week was associated with less bleeding despite greater use of ticagrelor/prasugrel but similar MACCE versus 1-month TAT. These findings support further studies on safety and efficacy of dual therapy with ticagrelor/prasugrel immediately after PCI.

Transcatheter aortic valve implantation (TAVI) now represents the mainstay of treatment for severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as the cornerstone. Leveraging data from multiple randomized controlled trials, the current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without or with atrial fibrillation, respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment.

Concomitant presence of atrial fibrillation and coronary artery disease requiring percutaneous coronary intervention is a frequent occurrence. The choice of optimal antithrombotic therapy, in this context, is still challenging. To offer the best protection both in terms of stroke and stent thrombosis, triple therapy with oral anticoagulation and dual antiplatelet therapy would be required. Several drug combinations have been tested in recent years, including direct oral anticoagulants, with the aim of balancing ischemic and bleeding risk. Both pharmacokinetic aspects of the molecules and patient's characteristics should be analyzed in choosing oral anticoagulation. Then, as suggested by guidelines, triple therapy should start with a seven-day duration and the aim to prolong to thirty days in high thrombotic risk patients. Dual therapy should follow to reach twelve months after coronary intervention. Even not fully discussed by the guidelines, in order to balance ischemic and bleeding risk it should also be considered: 1) integrated assessment of coronary artery disease and procedural complexity of coronary intervention; 2) appropriateness to maintain the anticoagulant drug dosage indicated in technical data sheet; the lack of data on the suspension of antiplatelet drugs one year after percutaneous intervention; 3) the possibility of combination therapy with ticagrelor; and 4) the need to treat the occurrence of paroxysmal atrial fibrillation during acute coronary syndrome. With data provided clinician should pursue a therapy as personalized as possible, both in terms of drug choice and treatment duration, in order to balance ischemic and bleeding risk.

Optimal platelet inhibition is critical in patients with carotid and intracranial artery stenosis undergoing carotid artery stenting (CAS) and intracranial artery stenting (ICS). Many reports have highlighted the importance of dual antiplatelet therapy (DAPT) in reducing adverse neurological outcomes without a significant increase in bleeding complications during CAS. DAPT has commonly used CAS and ICS, typically with aspirin and clopidogrel, but clopidogrel resistance occurs in approximately 20% of Japanese and other Asian populations. One solution to clopidogrel resistance is using adjunctive cilostazol to suppress the frequency of stroke events and in-stent restenosis after CAS. Other antiplatelet agents such as prasugrel, ticagrelor, cangrelor, and glycoprotein (GP) IIb/IIIa inhibitors are under investigation. The duration of DAPT after CAS remains controversial, as a longer duration of DAPT after CAS is associated with lower rates of readmission for stroke, but increased risk of hemorrhagic complications. Regarding antithrombotic therapy in CAS with concomitant atrial fibrillation, the use of direct oral anticoagulants plus a P2Y12 inhibitor may be suggested for the optimal safety and efficacy of antithrombotic management. For emergent CAS in acute ischemic stroke (AIS), intraprocedural DAPT loading and GP IIb/IIIa inhibitors, as necessary, may improve stent patency without increasing the risk of intracranial hemorrhage. In ICS, aggressive antiplatelet therapy based on an assessment of platelet aggregation is also important to improve clinical outcomes. In addition, rescue stenting for AIS caused by intracranial atherosclerotic stenosis-related large vessel occlusion is gaining attention. GP IIb/IIIa inhibitors have shown promise, but are not approved in Japan. In conclusion, DAPT is essential for the perioperative management of CAS and ICS. Specific perioperative antithrombotic management remains unclear, but the potential benefits of antithrombotic agents must be weighed against the corresponding increased risk of bleeding complications.

One percent of primary care visits are due to chest pain. It is critical for the primary care physician to have a high index of suspicion for acute coronary syndrome and understand the management of this important condition. This article reviews the outpatient evaluation and management of chest pain and summarizes the key points of inpatient evaluation and treatment of acute coronary syndrome.

In-stent restenosis (ISR) and stent thrombosis (ST) are the most serious complications of coronary angioplasty and stenting. Although the evolution of drug-eluting stents (DES) has significantly restricted the incidence of ISR, they are associated with an enhanced risk of ST. In the present study, we explore the photothermal ablation of a thrombus using a nano-enhanced thermogenic stent (NETS) as a modality for revascularization following ST. The photothermal activity of NETS, fabricated by coating bare metal stents with gold nanorods generating a thin plasmonic film of gold, was found to be effective in rarefying clots formed within the stent lumen in various in vitro assays including those under conditions mimicking blood flow. NETS implanted in the rat common carotid artery generated heat following exposure to a NIR-laser that led to effective restoration of blood flow within the occluded vessel in a model of ferric chloride-induced thrombosis. Our results present a proof-of-concept for a novel photothermal ablation approach by employing coated stents in the non-invasive management of ST.

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.

The efficacy and safety of ticagrelor or prasugrel vs. clopidogrel in patients with atrial fibrillation (AF) on oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI) have not been established.

This was a nationwide cohort study of patients on OAC for AF who underwent PCI for MI from 2011 through 2019 and were prescribed a P2Y12 inhibitor at discharge. The primary efficacy outcome was major adverse cardiovascular events (MACE), defined as a composite of death from any cause, stroke, recurrent MI, or repeat revascularization. The primary safety outcome was cerebral, gastrointestinal, or urogenital bleeding requiring hospitalization. Absolute and relative risks for outcomes at 1 year were calculated through multivariable logistic regression with average treatment effect modelling. Outcomes were standardized for the individual components of the CHA2DS2-VASc and HAS-BLED scores as well as type of OAC, aspirin, and proton pump inhibitor use. We included 2259 patients of whom 1918 (84.9%) were prescribed clopidogrel and 341 (15.1%) ticagrelor or prasugrel. The standardized risk of MACE was significantly lower in the ticagrelor or prasugrel group compared with the clopidogrel group (standardized absolute risk, 16.3% vs. 19.4%; relative risk, 0.84, 95% confidence interval, 0.70-0.98; P = 0.02), while the risk of bleeding did not differ (standardized absolute risk, 5.5% vs. 5.1%; relative risk, 1.07, 95% confidence interval, 0.73-1.41; P = 0.69).

In patients with AF on OAC who underwent PCI for MI, treatment with ticagrelor or prasugrel vs. clopidogrel was associated with reduced ischaemic risk, without a concomitantly increased bleeding risk.

Percutaneous coronary intervention with stent implantation is an integral aspect of minimally interventional cardiac procedures. The technology and techniques behind stent design and implantation have evolved rapidly over several decades. However, continued discourse remains around optimal peri- and post-interventional management with dual antiplatelet therapy to minimise both major cardiovascular or cerebrovascular events and iatrogenic bleeding risk. Standard guidelines around dual antiplatelet therapy historically recommended long-term dual antiplatelet therapy for 12 months (with consideration for >12 months in certain patients); however, emerging data and generational improvements in the safety of drug-eluting stents have ushered in a new era of short-term therapy to reduce the incidence of major bleeding events. This case review will provide an overview of the current state of guidelines around duration of dual antiplatelet therapy and examine recent updates and continued gaps in existing research.

Cardiovascular disease, including ischemic heart disease, is the leading cause of death worldwide, and percutaneous coronary interventions (PCIs) have been demonstrated to improve the prognosis of these patients on top of optimal medical therapy. PCIs have evolved from plain old balloon angioplasty to coronary stent implantation at the end of the last century. There has been a constant technical and scientific improvement in stent technology from bare metal stents to the era of drug-eluting stents (DESs) to overcome clinical challenges such as target lesion failure related to in-stent restenosis or stent thrombosis. A better understanding of the underlying mechanisms of these adverse events has led DESs to evolve from first-generation DESs to thinner and ultrathin third-generation DESs with improved polymer biocompatibility that seems to have reached a peak in efficiency. This review aims to provide a brief historical overview of the evolution of coronary DES platforms and an update on clinical studies and major characteristics of the most currently used DESs.

P2Y12 inhibitor monotherapy is a promising novel strategy to reduce bleeding complications compared to dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI). In order to personalise treatment with DAPT based on patients' bleeding risk, we compared outcomes after PCI between P2Y12 inhibitor monotherapy and DAPT according to bleeding risk.

A search for randomized clinical trials (RCTs) comparing P2Y12 inhibitor monotherapy after a short period of DAPT to standard DAPT after PCI was performed. Outcome differences between treatment groups regarding major bleedings, major adverse cardiac and cerebral events (MACCE) and net adverse clinical events (NACE) were assessed with hazard ratios (HRs) and corresponding credible intervals (CrI) according a Bayesian random effects model in patients with and without high bleeding risk (HBR).

Five RCTs including 30,084 patients were selected. P2Y12 inhibitor monotherapy compared to DAPT reduced major bleedings in the total population (HR: 0.65, 95 % CrI: 0.44 to 0.92). The HRs of the HBR and non-HBR subgroups showed a similar reduction of bleedings for monotherapy (HBR: HR 0.66, 95 % CrI: 0.25 to 1.74; non-HBR: HR 0.63, 95 % CrI: 0.36 to 1.09). No notable differences between treatments on MACCE and NACE were observed in either sub-group or in the total population.

Regardless of bleeding risk, P2Y12 inhibitor monotherapy is the favourable choice after PCI regarding major bleedings and does not increase ischemic events compared to DAPT. This suggests that bleeding risk is not decisive when considering P2Y12 inhibitor monotherapy.

For acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI), the choice of the duration and kind of dual antiplatelet therapy (DAPT) offering the most accurate balance between ischemic and bleeding risk remains unknown.

A network meta-analysis was performed including all Randomized Controlled Trials (RCTs) comparing different DAPT regimens and duration in ACS patients undergoing PCI. Trial-defined MACE and major bleedings were the primary endpoints. Stroke, stent thrombosis (ST), all-cause and cardiovascular death, myocardial infarction (MI) represented secondary endpoints.

13 RCTs encompassing 46145 patients were included. Mean age was 62 (61-64) years old, 42% being admitted with STEMI, 33% with NSTEMI and 25% with UA. The competitive arms were: clopidogrel and aspirin for 12 months (6 arms/18183 patients), clopidogrel and aspirin for 6 months (4/3329), clopidogrel and aspirin >12 months (3/2238), ticagrelor and aspirin for 12 months (6/12942) and prasugrel and aspirin for 12 months (3/9453). Trial-defined MACE and major bleedings, stroke and death were similar among the different arms. DAPT with prasugrel and aspirin for 12 months reduced MI compared to aspirin and clopidogrel for 12 months (OR 0.71, 95% CI: 0.54.0.94) and reduced the risk of ST compared to ticagrelor (OR 0.66, 95% CI: 0.49-0.90). Both prasugrel and ticagrelor reduced ST as compared to clopidogrel and aspirin for 12 months.

Different DAPT strategies yield similar risk of MACE, major bleeding, death and stroke in ACS patients. Prasugrel and aspirin for 12 months proved to be the most effective strategy regarding ST and MI.

Platelets have a crucial role in haemostasis and atherothrombosis. Pharmacological control of platelet hyper-reactivity has become a cornerstone in the prevention of thrombo-ischaemic complications in atherosclerotic diseases. Current antiplatelet therapies substantially improve clinical outcomes in patients with coronary artery disease, but at the cost of increased risk of bleeding. Beyond their role in thrombosis, platelets are known to regulate inflammatory (thrombo-inflammatory) and microcirculatory pathways. Therefore, controlling platelet hyper-reactivity might have implications for both tissue inflammation (myocardial ischaemia) and vascular inflammation (vulnerable plaque formation) to prevent atherosclerosis. In this Review, we summarize the pathophysiological role of platelets in acute myocardial ischaemia, vascular inflammation and atherosclerotic progression. Furthermore, we highlight current clinical concepts of antiplatelet therapy that have contributed to improving patient care and have facilitated more individualized therapy. Finally, we discuss novel therapeutic targets and compounds for antiplatelet therapy that are currently in preclinical development, some of which have a more favourable safety profile than currently approved drugs with regard to bleeding risk. These novel antiplatelet targets might offer new strategies to treat cardiovascular disease.

The aim of this study was to assess the association between high on-aspirin treatment platelet reactivity (HAPR) and the subsequent risk of restenosis after percutaneous coronary intervention (PCI) with predominantly drug-eluting stents.

The association between HAPR and subsequent risk of restenosis after PCI is unclear.

This study included 4839 patients undergoing PCI (02/2007-12/2011) in the setting of the Intracoronary Stenting and Antithrombotic Regimen-ASpirin and Platelet Inhibition (ISAR-ASPI) registry. Platelet function was assessed with impedance aggregometry using the multi-plate analyzer immediately before PCI and after intravenous administration of aspirin (500 mg). The primary outcome was clinical restenosis, defined as target lesion revascularization at 1 year. Secondary outcomes included binary angiographic restenosis and late lumen loss at 6- to 8-month angiography.

The upper quintile cut-off of platelet reactivity measurements (191 AU × min) was used to categorize patients into a group with HAPR (platelet reactivity > 191 AU × min; n = 952) and a group without HAPR (platelet reactivity ≤ 191 AU × min; n = 3887). The primary outcome occurred in 94 patients in the HAPR group and 405 patients without HAPR (cumulative incidence, 9.9% and 10.4%; HR = 0.96, 95% CI 0.77-1.19; P = 0.70). Follow-up angiography was performed in 73.2% of patients. There was no difference in binary restenosis (15.2% vs. 14.9%; P = 0.79) or late lumen loss (0.32 ± 0.57 vs. 0.32 ± 0.59 mm; P = 0.93) between patients with HAPR versus those without HAPR.

This study did not find an association between HAPR, measured at the time of PCI, and clinical restenosis at 1 year after PCI.

Dual antiplatelet therapy (DAPT)-aspirin in conjunction with a P2Y12 inhibitor-is the cornerstone of managing patients with acute coronary syndromes post-revascularization, but the clinical response is highly variable, with potentially devastating consequences. Herein, we review the mechanisms underpinning said variability and explore emerging approaches to normalizing therapeutic benefit.

The potent P2Y12 inhibitors, prasugrel and ticagrelor, exhibit minimal inter-individual variability, replacing clopidogrel in DAPT and achieving greater rates of therapeutic response. However, these benefits decline in later phases when bleeding risk begins to supersede that of ischemia. Guided de-escalation of P2Y12 inhibition as well as shortening DAPT duration have emerged as strategies that retain antithrombotic efficacy while reducing bleeding risk. Aspirin is the other component of DAPT but is also used in isolation for secondary prevention of thrombotic disease. In contrast to the P2Y12 inhibitors, genetic influences on aspirin non-response appear to be outweighed by a triad of clinical factors: non-adherence, enteric aspirin use, and inappropriate dosing according to bodyweight and BMI. Multiple de-escalation strategies for DAPT have been shown to mitigate bleeding risk, but it remains unclear which approach is ideal, necessitating head-to-head investigations to determine which exhibits the most favorable cost-to-benefit ratio. However, there is likely a role for more than one approach in clinical practice, depending on patient risk profile. Our approach to aspirin use is also in need of reassessment: strategies to improve adherence, avoidance of enteric aspirin in cardiac patients, and dose adjustment according to bodyweight and/or BMI are all likely to improve rates of therapeutic response. Moreover, platelet function testing may have a role in identifying patients expected to benefit from primary prophylactic aspirin.

Dual antiplatelet therapy (DAPT) has been paramount in preventing thrombosis following percutaneous coronary intervention for nearly 3 decades. However, over the years, DAPT has seen significant changes in the agents utilized and duration of therapy as trials have raced to keep up with advancements made in stent technology and our understanding of bleeding and ischemic risk. Recently, there have been a number of trials demonstrating significant reductions in bleeding events with shorter DAPT durations, which are not yet reflected in practice guidelines. Further, there has been a shift toward more individualized antiplatelet regimens to meet patient-specific risk profiles. This review provides a comprehensive summary of the major trials that have informed current DAPT strategies, puts into context recent trials driving a shift toward more tailored antiplatelet regimens, and highlights gaps in knowledge that remain and the ongoing trials designed to address them.

Coronary artery revascularisation can be performed surgically or percutaneously. Surgery is associated with higher procedural risk and longer recovery than percutaneous interventions, but with long-term reduction of recurrent cardiac events. For many patients with obstructive coronary artery disease in need of revascularisation, surgical or percutaneous intervention is indicated on the basis of clinical and anatomical reasons or personal preferences. Medical therapy is a crucial accompaniment to coronary revascularisation, and data suggest that, in some subsets of patients, medical therapy alone might achieve similar results to coronary revascularisation. Most revascularisation data are based on prevalently White, non-elderly, male populations in high-income countries; robust data in women, older adults, and racial and other minorities, and from low-income and middle-income countries, are urgently needed.

Dual antiplatelet therapy (DAPT), consisting of the combination of aspirin and an inhibitor of the platelet P2Y₁₂ receptor for ADP, remains among the most investigated treatments in cardiovascular medicine. While a substantial amount of research initially stemmed from the observations of late and very late stent thrombosis events in the first-generation drug-eluting stent (DES) era, DAPT has been recently transitioning from a purely stent-related to a more systemic secondary prevention strategy. Oral and parenteral platelet P2Y₁₂ inhibitors are currently available for clinical use. The latter have been shown to be extremely suitable in drug-naïve patients with acute coronary syndrome (ACS), mainly because oral P2Y₁₂ inhibitors are associated with delayed efficacy in patients with STEMI and because pre-treatment with P2Y₁₂ inhibitors is discouraged in NSTE-ACS, and in patients with recent DES implantation and in need of urgent cardiac and non-cardiac surgery. More definitive evidence is needed, however, about optimal switching strategies between parenteral and oral P2Y₁₂ inhibitors and about newer potent subcutaneous agents that are being developed for the pre-hospital setting.

Cardiovascular disease, particularly coronary artery disease (CAD), remains the leading cause of mortality and morbidity in industrialized countries. Platelet activation and aggregation at the site of endothelial injury play a key role in the processes ultimately resulting in thrombus formation with vessel occlusion and subsequent end-organ damage. Consequently, antiplatelet therapy has become a mainstay in the pharmacological treatment of CAD. Several drug classes have been developed over the last decades and a broad armamentarium of antiplatelet agents is currently available. This review portrays the evolution of antiplatelet therapy, and provides an overview on previous and current antiplatelet drugs and strategies.

The continuation of antiplatelet agents in the periprocedural period around carotid stenting (CAS) procedures is felt to be mandatory to minimize the risk of periprocedural stroke. However, the optimal antiplatelet regimen is unclear, with some advocating dual antiplatelet therapy, and others supporting the use of P2Y₁₂ inhibitors alone. The objective of this study was to evaluate the periprocedural effect of P2Y₁₂ inhibitors for CAS.

The Vascular Quality Initiative was used from years 2007 to 2020. All transcarotid artery revascularization (TCAR) and transfemoral carotid artery stenting (TF-CAS) procedures were included. Patients were stratified based on perioperative use of P2Y₁₂ inhibitors as well as symptomatic status. Primary end points were perioperative neurological events (strokes and transient ischemic attacks). Secondary end points were mortality and myocardial infarction.

A total of 31,036 CAS procedures were included for analysis, with 49.8% TCAR and 50.2% TF-CAS cases; 63.8% of patients were male and 82.3% of patients were on a P2Y₁₂ inhibitor. P2Y₁₂ inhibitor use was more common in males, asymptomatic patients, those older than 70 years, and concurrent statin use. P2Y₁₂ inhibitors were more likely to be used in TCAR cases than in TF-CAS cases (87.3% vs 76.8%; P < .001). The rate of periprocedural neurological events in the whole cohort was 2.6%. Patients on P2Y₁₂ inhibitors were significantly less likely to experience a periprocedural neurological event (2.3% vs 3.9%; P < .001) and mortality (0.6% vs 2.1%; P < .001) than those who were not on a P2Y₁₂ inhibitor. There was no effect on the rates of myocardial infarction. On multivariate analysis, both symptomatic and asymptomatic patients on P2Y₁₂ inhibitors were significantly less likely to develop perioperative neurological events. Additionally, the use of P2Y₁₂ inhibitors demonstrated an independent significant effect in reducing of the rate of perioperative stroke (odds ratio, 0.29; 95% confidence interval, 0.25-0.33). Finally, additional analysis of the types of P2Y₁₂ inhibitors used revealed that all seemed to be equally effective in decreasing the periprocedural neurological event rate.

The use of perioperative P2Y₁₂ inhibitors seems to markedly decrease the perioperative neurological event rate with TCAR and TF-CAS in both symptomatic and asymptomatic patients and should be strongly considered. Patients with contraindications to P2Y₁₂ inhibitors may not be appropriate candidates for any CAS procedure. Additionally, alternative types of P2Y₁₂ inhibitors seem to be equally effective as clopidogrel. Finally, an analysis of the Vascular Quality Initiative demonstrates that, even for TCAR cases, only 87.3% of patients seem to be on P2Y₁₂ inhibitors in the periprocedural period, leaving room for significant improvement.

Little is known about current patterns of antithrombotic therapy in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) in clinical practice in Germany.

The RIVA-PCI is a prospective, non-interventional, multicenter study with follow-up until hospital discharge including consecutive patients with AF undergoing PCI.

Between January 2018 and March 2020, 1636 patients (elective in 52.6%, non-ST elevation acute coronary syndrome [NSTE-ACS] in 39.3%, ST-elevation myocardial infarction in 8.2%) from 51 German hospitals were enrolled in the study. After PCI a dual antithrombotic therapy (DAT) consisting of OAC and a P2Y12 inhibitor was given to 66.0%, triple antithrombotic therapy (TAT) to 26.0%, dual antiplatelet therapy to 5.5%, and a mono-therapy to 2.5% of the patients. Non-vitamin K antagonist oral anticoagulants (NOACs) were given to 82.4% and vitamin K antagonists to 11.5% of the patients. In-hospital events included death in 12 cases (0.7%), myocardial infarction, stent thrombosis, and ischemic stroke in four (0.2%) patients each, while 2.8% of patients had bleeding complications. The recommended durations for DAT or TAT at discharge were 1 month (1.5%), 3 months (2.1%), 6 months (43.1%), and 12 months (45.6%), with a 6-month course of DAT (47.7%) most often recommended after elective PCI and a 12-month course of DAT (40.1%) after ACS.

The preferred therapy after PCI in patients with AF is DAT with a NOAC and clopidogrel. In-hospital ischemic and bleeding events were rare. The recommended durations for combination therapy vary considerably.

To compare the long-term clinical outcomes of dual antiplatelet therapy (DAPT) with clopidogrel and DAPT with ticagrelor or prasugrel in patients with acute myocardial infarction (AMI) who underwent coronary intervention.

Between November 2011 and December 2015, a total of 13,104 patients with AMI were enrolled in the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) registry. Among them, 4,696 patients who received DAPT for more than 24 months were categorized into two groups: the clopidogrel group (n = 4,053) and ticagrelor or prasugrel group (n = 643). Propensity score matching (PSM) was used to reduce the bias due to confounding variables. Following PSM, the impacts of P2Y12 inhibitors on the clinical outcomes in both groups were compared during a 36-month clinical follow-up period.

There were no significant differences in clinical outcomes in terms of cardiac death (7.1% vs. 9.7%, p = 0.101), stroke (1.4% vs. 1.0%, p = 0.436), major bleeding (0.5% vs. 0.8%, p = 0.478), major adverse cardiac events (MACE) (21.6% vs. 20.5%, p = 0.626), and net adverse cardiac event (NACE) (22.1% vs. 21.3%, p = 0.731) between the groups. The ticagrelor or prasugrel group had a lower incidence of recurrent percutaneous coronary intervention (PCI) (12.2% vs. 7.6%, p = 0.006) than the clopidogrel group. However, no differences were observed in the cumulative incidences of 3-year NACE between the ticagrelor or prasugrel and clopidogrel groups.

Cumulative incidences of long-term NACE did not differ between the two groups. Therefore, the type and duration of DAPT should be customized for each patient with AMI.

AF is a highly prevalent disease, often requiring long-term oral anticoagulation to prevent stroke or systemic embolism. Coronary artery disease, which is common among AF patients, is often referred for myocardial revascularisation by percutaneous coronary intervention (PCI), which requires dual antiplatelet therapy to minimise the risk of stent-related complications. The overlap of AF and PCI is a clinical conundrum, especially in the early post-procedural period, when both long-term oral anticoagulation and dual antiplatelet therapy are theoretically indicated as a triple antithrombotic therapy. However, stacking drugs is not a desirable option because of the increased bleeding risk. Several strategies have been investigated to mitigate this concern, including shortening triple antithrombotic therapy duration and switching to a dual antithrombotic regimen. This review analyses the mechanisms underlying thrombotic complications in AF-PCI, summarises evidence surrounding antithrombotic therapy regimens and reports and comments on the latest European guidelines.