Single Antiplatelet Treatment Research Articles

Early dual antiplatelet therapy in patients with minor ischemic stroke after intravenous thrombolysis

ObjectivesMinor stroke is defined by a score of 5 or less on the National Institutes of Health Stroke Scale (NIHSS). Prior trials have shown efficacy of short term dual antiplatelet therapy (DAPT) in secondary prevention of stroke among patients with transient ischemic attack (TIA) or minor ischemic stroke, but no randomized clinical trials have studied this benefit after intravenous thrombolysis (IVT). Our aim was to investigate the safety of DAPT within 90 days after IVT in patients with acute minor ischemic stroke. Patients and methodsWe reviewed medical records of patients older than 18 years that received IVT between January 2015 and December 2022. Patients had a diagnosis of acute minor stroke or averted stroke (complete recovery and negative image on follow-up). Single or dual antiplatelet treatment was started 24 hours after thrombolysis according to the physician's judgment. Patients were divided in two groups: single and dual antiplatelet therapy. We assessed clinical outcome using the modified Rankin scale (mRS), symptomatic intracranial hemorrhage (SICH) and mortality at 90 days. ResultsFifty-three patients met the inclusion criteria, 68% men aged 64±16,5 years. Seventy five percent had an ischemic stroke and 25% had an averted stroke. Median door-to-needle time was 50 minutes. Fifty one percent were in the single antiplatelet group and 49% in the dual antiplatelet therapy group. There were no differences in demographic and clinical characteristics between groups. The 90-day mRS did not show significant difference between groups. No patients had SICH nor died during follow-up. One patient in the single antiplatelet group had stroke recurrence. ConclusionsDual antiplatelet therapy after IVT with rtPA for acute minor ischemic stroke appears not to increase the risk of bleeding and mortality compared to single antiplatelet therapy in the first three months after the event. This is the first study to assess this subject in a Latin American population.

Phenox HPC and Phenox flow modulation devices for the endovascular treatment of intracranial aneurysms: a systematic review and meta-analysis

BackgroundSurface-modified flow diverters are increasingly used in clinical settings. However, their safety profiles and additional benefits over non-coated devices still need to be explored. In this meta-analysis, we aimed to...

Using an agonist panel and aggregation to assess antiplatelet therapy in mice

Abstract Platelets play a crucial role in hemostasis. For cardiovascular and stroke prophylaxis, patients are commonly placed on either single or dual antiplatelet drugs, such as aspirin and/or clopidogrel. Here we outline a mouse model examining antiplatelet therapy and the resulting changes in platelet activation and aggregation. Using commercially available transgenic mice with platelets expressing green fluorescent protein (GFP) or red fluorescent protein (RFP), endogenous platelets were inhibited with a single, dual, or control antiplatelet treatment. We used 100µg aspirin/g mouse or 50µg clopidogrel/g mouse for a single dose; dual antiplatelet therapy was a combined dose of 100µg aspirin/g mouse and 50µg clopidogrel/g; control treatment was DMSO alone. One hour after treatment, whole blood (WB) was collected by aseptic cardiac puncture and mixed in the following groups: aspirin treated RFP and GFP WB, clopidogrel treated RFP and GFP WB, aspirin and clopidogrel treated RFP and GFP WB, control treated RFP and GFP WB. Each combined sample was then treated with a panel of agonists: no agonist, 0.5U/mL thrombin, 20µM ADP, and 500µg/mL arachidonic acid. Thrombin samples were activated for 2 minutes at room temperature while ADP and arachidonic acid samples were activated for 10 minutes at 37°C. Platelets were labeled with anti-CD41a to label all platelets and anti-CD62P to label activated platelets. Aggregation is measured as double-colored GFP and RFP platelet events. Compared to control mice, mice treated with antiplatelet agents demonstrated statistically significant decreases in activation following thrombin administration (ranging from 90% to 83% activated); there was no significant difference in platelet aggregation following thrombin among the samples from different antiplatelet therapies. Following ADP activation, clopidogrel treatment decreased platelet activation (1% activation) compared to control (3% activation) and aspirin-treated (5% activation) mice with no additional decrease in dual treatment (1% activation); unexpectedly, aspirin treatment alone or dual therapy decreased platelet aggregation with ADP (15% and 17% aggregated, respectively) compared to control and clopidogrel (23% and 27% aggregated, respectively). Finally, after arachidonic acid activation, aspirin treatment significantly decreased activation (7% activated) compared to control (20% activated), while clopidogrel decreased activation more than that of aspirin (3% activated), with no additional decrease from dual therapy (3% activated). Though not significant, aspirin treatment (1.4% aggregation) and dual therapy (1.2%) demonstrated a trend with decreased platelet aggregation following arachidonic acid activation compared to control (1.8% aggregation) and clopidogrel-treated platelets (3.2%). These data presented here show a novel application of platelet activation and aggregation of GFP and RFP platelet populations in a mouse model following aspirin and/or clopidogrel treatment. This model can be applied generally to other drugs and disease models for platelet dysfunction using additional markers for platelet activation. Additionally, these experiments can be used to further investigate the function of transfused murine platelets.

Single antiplatelet therapy after left atrial appendage closure in patients with AF: safety and effectiveness

Introduction and objectivesThe optimal antithrombotic strategy following left atrial appendage closure (LAAC) is poorly defined in patients with nonvalvular atrial fibrillation. We assessed the safety and effectiveness of a single antiplatelet treatment (SAPT) strategy after LAAC in a population at high risk of ischemic and bleeding events. MethodsThis single-center, observational, prospective study included a consecutive cohort of patients who underwent LAAC using the LAmbre device (Lifetech Scientific, China) and who were discharged with SAPT. The primary outcome was a composite of stroke, systemic embolism, and device-related thrombosis during follow-up. Secondary endpoints were cardiovascular mortality and major bleeding events (BARC ≥3a). Clinical follow-up was performed at 1, 6, and 12 months and subsequently on an annual basis. Transesophageal echocardiography was performed at 1 and 12 months of follow-up. ResultsThe study comprised 74 patients. The median age was 77 [72-83] years and 43% were women. The cohort exhibited a high prevalence of comorbidities and cardiovascular risk factors. The median CHA2DS2-VASc and HAS-BLED scores were 4 [3-6] and 4 [4-5], respectively. The median length of follow-up was 2.5 years (188 patients-year). During follow-up, device-related thrombosis occurred in 3 patients (4%). Ischemic stroke occurred in 1 patient (1.3%, rate 0.5%/y), representing a 90.9% relative risk reduction compared with the risk predicted by CHA2DS2-VASc. Major bleeding events occurred in 12 patients (16%, 6.4%/y), with a relative risk reduction of 26.4% of that predicted by HAS-BLED. Cardiovascular-related mortality was observed in 2 patients (2.7%). ConclusionsSAPT appears to be a safe and effective treatment following LAAC in patients at high ischemic and hemorrhagic risk. Further studies are needed to confirm our findings.

Efectividad y seguridad de una estrategia de antiagregación plaquetaria simple tras cierre percutáneo de orejuela izquierda en pacientes con FA

Introduction and objectivesThe optimal antithrombotic strategy following left atrial appendage closure (LAAC) is poorly defined in patients with nonvalvular atrial fibrillation. We assessed the safety and effectiveness of a single antiplatelet treatment (SAPT) strategy after LAAC in a population at high risk of ischemic and bleeding events. MethodsThis single-center, observational, prospective study included a consecutive cohort of patients who underwent LAAC using the LAmbre device (Lifetech Scientific, China) and who were discharged with SAPT. The primary outcome was a composite of stroke, systemic embolism, and device-related thrombosis during follow-up. Secondary endpoints were cardiovascular mortality and major bleeding events (BARC ≥ 3a). Clinical follow-up was performed at 1, 6, and 12 months and subsequently on an annual basis. Transesophageal echocardiography was performed at 1 and 12 months of follow-up. ResultsThe study comprised 74 patients. The median age was 77 [72-83] years and 43% were women. The cohort exhibited a high prevalence of comorbidities and cardiovascular risk factors. The median CHA2DS2-VASc and HAS-BLED scores were 4 [3-6] and 4 [4-5], respectively. The median length of follow-up was 2.5 years (188 patients-year). During follow-up, device-related thrombosis occurred in 3 patients (4%). Ischemic stroke occurred in 1 patient (1.3%, rate 0.5%/y), representing a 90.9% relative risk reduction compared with the risk predicted by CHA2DS2-VASc. Major bleeding events occurred in 12 patients (16%, 6.4%/y), with a relative risk reduction of 26.4% of that predicted by HAS-BLED. Cardiovascular-related mortality was observed in 2 patients (2.7%). ConclusionsSAPT appears to be a safe and effective treatment following LAAC in patients at high ischemic and hemorrhagic risk. Further studies are needed to confirm our findings.

Carotid artery stenting or carotid endarterectomy for residual significant stenosis after thrombectomy in acute tandem occlusion stroke?

AbstractA 82‐year‐old male presented with right‐sided hemiplegia and aphasia. CT‐scan showed hyperdensity of the left middle cerebral artery (MCA). CT‐angiography revealed occlusion of the left MCA and intra‐cranial internal carotid artery (ICA) in combination with occlusion of the left extra‐cranial ICA. Complete recanalization of intra‐cranial vessels was obtained after thrombectomy within 6 h from symptom onset, but residual significant extra‐cranial stenosis remained. Non‐contrast CT‐scan after thrombectomy revealed large hyperdensities secondary to contrast extravasation in the left MCA territory. Residual extra‐cranial ICA stenosis was not treated with emergent stenting. At 24 h, NIHSS score was 0, but follow‐up CT‐scan showed an ischemic lesion with spontaneous hemorrhagic transformation. A single antiplatelet treatment was reintroduced after 24 h and carotid endarterectomy was done without complications after 2 weeks.

Percutaneous coronary intervention with drug-coated balloon-only strategy combined with single antiplatelet treatment in patients at high bleeding risk:Single center experience of a novel concept.

At least 1 month of dual antiplatelet therapy is required after coronary stenting. The aim of this all-comers retrospective registry study was to assess the efficacy and safety of percutaneous coronary intervention (PCI) using drug-coated balloon (DCB) with single antiplatelet treatment (SAPT). Between 2011 and 2020, 232 PCIs were performed in 172 patients using the DCB-only strategy and discharged with SAPT. The mean age of the patients was 75 ± 11 years and 59% were male. The clinical presentation was stable coronary artery disease (CAD) in 42% of the patients and acute coronary syndrome (ACS) in 58%. The lesions were mainly de novo (96%). The majority (58%) of treated lesions were in large coronary arteries (≥3.0 mm). Most (87%) of the patients were at high bleeding risk (HBR) with at least one major or two minor Academic Research Consortium (ARC) risk factors for bleeding. Periprocedural DAPT was used in 49% of the patients. The 12-month major adverse cardiac events (MACE, the composition of cardiovascular death, nonfatal myocardial infarction, and target-lesion revascularization) rate was 1.4% in stable CAD and 7.1% in ACS. The 12-month all-cause mortality after DBC only + SAPT strategy was 4.1% in stable CAD and 12.1% in ACS. The rate of ischemia-driven target lesion revascularisation (TLR) was 0% in stable CAD and 3.0% in ACS at 12 months. The 12-month rate of significant bleeding (BARC type 2-5) was 10.5%. There were no acute or subacute vessel closures. Despite the aged patient population with comorbidities, the TLR, MACE, and bleeding rates were low with DCB-only PCI combined with SAPT. This novel approach could reduce the post-PCI bleeding risk in patients with CAD and HBR compared to stenting.

Tailoring oral antiplatelet therapy in acute coronary syndromes: from guidelines to clinical practice.

The assessment of bleeding and ischemic risk is a crucial step in establishing appropriate composition and duration of dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) treated with percutaneous coronary angioplasty. Evidence from recent randomized clinical trials led to some paradigm shifts in current guidelines recommendations. Options alternative to the standard 12-month DAPT duration include shorter periods of DAPT followed by single antiplatelet treatment with either aspirin or P2Y12 monotherapy, guided or unguided de-escalation DAPT, prolonged DAPT beyond the 12-month treatment period. Although DAPT composition and duration should be selected for each ACS patient on an individual basis weighing clinical and procedural variables, data from latest trials and meta-analyses may permit suggesting the most appropriate DAPT strategy according to the ischemic and bleeding risk assessed using validated tools and scores.

Coating (Coating to Optimize Aneurysm Treatment in the New Flow Diverter Generation) study. The first randomized controlled trial evaluating a coated flow diverter (p64 MW HPC): study design

BackgroundDue to its high efficacy, flow diversion is increasingly used in the management of unruptured and recanalized aneurysms. Because of the need for perioperative dual antiplatelet treatment (DAPT), flow diversion...

Treatment of Secondary Hydrocephalus after Subarachnoid Hemorrhage

Hydrocephalus is one of the major complications secondly occurring with or after subarachnoid hemorrhage(SAH). Hydrocephalus can be classified into acute(≦ 48 h), subacute(3-14 days), or chronic phases(≧ 2 weeks)in which a cerebrospinal fluid(CSF)shunt is required as the curative treatment at the rate of approximately 30%. On the mechanism of hydrocephalus development, it is generally accepted that an inflammatory reaction and the ensuing fibrosis process impede continuous CSF flow outward to the sinus, terminally from arachnoid granulation, leptomeninges, or ventricle walls, in addition to the mechanical blockage due to SAH clots. Several factors associated with the severity of SAH, such as a high Hunt and Hess grade, intraventricular hemorrhage, and a ruptured aneurysm in the posterior circulation also predict the development of shunt-dependent hydrocephalus. The predictive scoring system is available. Effective treatment of hydrocephalus still involves the use of CSF shunts. No superiority between ventriculoperitoneal and lumboperitoneal shunts has been established. Even during oral, single antiplatelet treatment after coil embolization for ruptured aneurysms, curative shunt operation is possible with low frequency of hemorrhagic complications. Hydrocephalus should be diagnosed early and treated appropriately to improve the functional outcome of the patients after SAH.

PREVENTION OF HAEMORRHAGIC COMPLICATIONS AFTER DENTAL EXTRACTION IN PATIENTS ON UNINTERRUPTED SINGLE OR DUAL ANTIPLATELET THERAPY

The purpose of the research was to compare and assess the efficacy of autologous Platelet-rich fibrin (PRF) as well as gelatin sponges in patients receiving continuous single or dual antiplatelet treatment in preventing hemorrhagic complications after tooth extraction.
 Methods: In order to achieve haemostasis, one excision site was implanted with Abgel (control site) while the other was randomly chosen to have PRF (study area) . In addition to having antihemorrhagic properties, PRF accelerates tissue repair and wound closure, enabling a speedy recovery without excruciatingly painful experiences.
 Results: Soft tissue healing is sped up and improved because to the PRF membrane's delayed release of growth factors and the clot's sturdy fibrin structure. Immediate bleeding, delayed bleeding, and soft tissue healing were the criteria examined. Fisher's Exact Test was used to statistically assess the data.
 Conclusion: In patients receiving dual antiplatelet medication, PRF demonstrated to be a better option than abgel. Aspirin, however, continues to be the gold standard for both patients at high and low risk of these events in terms of preventing vascular death, ischemic stroke and myocardial infarctions.

Clopidogrel Resistance in Patients With Stroke Recurrence Under Single or Dual Antiplatelet Treatment.

Background: The factors associated with clopidogrel resistance in patients with stroke recurrence receiving single or dual antiplatelet treatment (SAPT or DAPT) may differ. This study compared the high on-treatment platelet reactivities (HPRs) and the factors associated with clopidogrel resistance in recurrent ischemic stroke patients receiving clopidogrel or aspirin and clopidogrel.Methods: We enrolled and allocated 275 recurrent ischemic stroke patients to the clopidogrel and DAPT groups and compared their demographics, conventional risk factors, and P2Y12 reaction units (PRUs). Clopidogrel resistance was categorized as PRU higher than 275. We performed a multivariate logistic regression analysis to determine the factors underlying clopidogrel resistance during SAPT and DAPT.Results: In total, 145 (52.7%) and 130 (47.3%) patients received clopidogrel and DAPT, respectively at recurrence. The risk factors of the two groups were not significantly different, except that coronary artery disease was more frequent in the DAPT group. The PRU was higher (255 ± 91 vs. 221 ± 84; p = 0.002) and clopidogrel resistance was more frequent (45.5 vs. 31.5%; p = 0.018) in the SAPT than in the DAPT group. Hyperlipidemia was associated with clopidogrel resistance during SAPT, and smoking (Odds ratio = 0.426, 95% confidence interval 0.210–0.861; p = 0.018) had a protective effect against clopidogrel resistance. For those receiving DAPT, old age, female, low hemoglobin A1c level, and high ARU were associated with clopidogrel resistance.Conclusions: HPR and clopidogrel resistance were more frequent in recurrent ischemic stroke patients receiving clopidogrel than in those receiving DAPT. Smoking was independently associated with less clopidogrel resistance among those receiving clopidogrel SAPT but not in those receiving DAPT.

Early clinical experience with the p48MW HPC and p64MW HPC flow diverters in the anterior circulation aneurysm using single anti-platelet treatment.

BackgroundThe p64MW HPC and p48MW HPC flow diverters have reduced thrombogenicity due to hydrophilic coating. The purpose of this study was to evaluate its safety and efficacy in Mongolian patients under single antiplatelet therapy (SAPT) with prasugrel.Materials and methodsWe performed a retrospective review of patients enrolled into our prospectively maintained database to identify all patients treated with either the p48MW HPC or p64MW HPC under SAPT. We recorded baseline demographics, aneurysm size and location, procedural complications, angiographic and clinical results.Results24 patients, (female = 21, 87.5%), age 48.2 ± 11.6 years (range 25–63) underwent treatment of 30 aneurysms with either p64MW HPC or p48MW HPC. All aneurysms were saccular with dome width 8.2 ± 6.5 (range 1.6–26.0 mm) and dome height 7.6 ± 6.7 (range 1.6–30.0 mm). None of the aneurysms were previously treated. The average PRU was 54.6 ± 31.2 (range 1–127) on pre-operative VerifyNow testing. Angiographic follow-up was available for 13 patients (17 aneurysms), 183 ± 36 days post-procedure, at which point 64.7% of aneurysms (n = 11/17) were completely occluded and 11.8% (n = 2/17) had only neck remnants resulting in 76.5% of aneurysms being adequately occluded A single intra-operative complication (4.2%) occurred however all patients were mRS ≤1 at last follow-up. There were two post-operative complications neither of which resulted in permanent neurological morbidity. There were no instances of post-operative aneurysmal rupture or delayed parenchymal haemorrhage. The overall mortality was 0%.ConclusionThe efficacy and safety of p64MW HPC coated devices under SAPT is similar to uncoated flow diverters that require DAPT.

Acute gastrointestinal bleeding among patients on antiplatelet and anticoagulant therapy after percutaneous coronary intervention

Background Patients undergoing percutaneous coronary intervention (PCI) require dual antiplatelet therapy and some require additional anticoagulation. We aimed to investigate the incidence of acute gastrointestinal bleeding (AGIB) among PCI patients receiving antiplatelet and anticoagulant therapy. Methods A population-based study that included all patients undergoing PCI during 2008–2016 in Iceland. Data from the Icelandic Medicines Registry were obtained on all outpatient prescriptions 1 year after first PCI. Patients receiving single or dual-antiplatelet therapy with or without anticoagulation cotherapy were analyzed. Rehospitalization for AGIB and endoscopic data were obtained within the 12-month follow-up period. Results A total of 5166 patients (male 75%) underwent PCI during the study period. The incidence of AGIB was 1% (54/5166) per year. The mean age among non-bleeders 65 (±11) years was lower than among bleeders 69 (±9) years (p = .002). The proportion of acute upper GIB (AUGIB) was 56%, whereas lower GIB occurred in 44%. Overall, 41% with AUGIB had PPIs compared to 39% of non-bleeders (NS). The incidence of AGIB among patients on single antiplatelet therapy combined with an anticoagulant was 2.5% compared to 0.9% among those on single antiplatelet treatment alone (p = .028). The number needed to harm (NNH) for treatment with single antiplatelet therapy and anticoagulant therapy compared to single antiplatelet therapy was 62 but no deaths related to AGIB. Conclusions The 1-year incidence of AGIB was low with no mortality. Bleeding risk was found to be higher among patients on single antiplatelet therapy combined with anticoagulant therapy compared to patients on single antiplatelet therapy alone.

Do we have a unified consensus on antithrombotic management of PAD?

Peripheral artery disease (PAD) is one of the most frequent manifestations of atherosclerosis with high rates of morbidity and mortality. Platelets and coagulation are involved in the progression of atherosclerosis and thromboembolic complications. PAD patients have increased prothrombotic potential, which includes platelet hyperaggregability and increased pro-coagulant state. Therefore, antithrombotic treatment is of utmost importance for the prevention of cardiovascular events in this group of patients. Aspirin is the basic antiplatelet drug, but with limited efficacy in PAD. In contrast to coronary artery disease, its effect on the prevention of cardiovascular events in PAD has been limited proven. Particularly in asymptomatic PAD, there is no evidence for risk reduction with aspirin. Clopidogrel and ticagrelor are more effective than aspirin. Clopidogrel is thus an effective alternative to aspirin for prevention of cardiovascular events in symptomatic PAD. In patients who are non-responders to clopidogrel, ticagrelor is indicated. Dual antiplatelet treatment (DAPT) with aspirin and ticagrelor in patients with coronary artery disease and concomitant PAD significantly decreased the rate of major adverse cardiovascular events, including adverse limb events. However, in the CHARISMA Trial, aspirin and clopidogrel were not more effective than aspirin alone and increased bleeding complications. Therefore, DAPT seems effective only in PAD accompanied by coronary artery disease. Anticoagulant treatment for symptomatic PAD with vitamin K antagonists alone or in combination with aspirin is not more effective than single antiplatelet treatment but increases the rate of major bleeding. Low dose rivaroxaban combined with aspirin in PAD patients significantly reduces cardiovascular events, including limb-threatening ischemia and limb amputations. Anticoagulation and antiplatelet treatment after percutaneous or surgical revascularization of PAD improve the patency of treated vessels. Aspirin with or without dipyridamole improved patency of infra-inguinal by-pass grafts at one year. The combination of clopidogrel with aspirin was more effective than aspirin alone in the prevention of prosthetic graft occlusions in patients undergoing below-knee by-pass-grafting. Oral vitamin K antagonists were not more effective than aspirin in the prevention of infra-inguinal by-pass occlusion. The combination of low dose rivaroxaban and aspirin was effective in preventing major adverse cardiovascular events and adverse limb events after infrainguinal endovascular or surgical revascularization in patients with intermittent claudication. However, the data on antithrombotic treatment after revascularization for limb-threatening ischemia is scanty and inconclusive. In conclusion: Antithrombotic treatment of PAD is a cornerstone for the management of these patients. Antiplatelet drugs prevent the initiation and progression of atherosclerosis and are effective also in the prevention of thromboembolic events. Simultaneous use of antiplatelet and anticoagulation drugs is accompanied by an increased risk of bleeding. However, combined treatment with aspirin and low-dose rivaroxaban is more effective than single antithrombotic treatment and safer than full-dose combined treatment.

Atrial fibrillation and ischaemic heart disease: should we use acetylsalicylic acid beside anticoagulants?

Coexistence of atrial fibrillation and ischaemic heart disease is very common and patients affected by these conditions are exposed to both a high ischaemic and haemorrhagic risk. The choice of an appropriate combination of anticoagulant therapy with single or dual antiplatelet treatment is indeed one of the most relevant and contemporary challenges in clinical practice. Several studies and meta-analyses pointed out that 1 year after an acute coronary syndrome or percutaneous revascularization, the use of the sole anticoagulant therapy is not associated with increased risk of major cardiovascular events, whereas there is a substantial reduction of clinical significant bleeding events, as compared to patients treated also with antiplatelet medications. However, there are no clear-cut data regarding the possibility to implement this strategy in each patient, regardless the cardiovascular risk class. Furthermore, for patients requiring a combined anticoagulant and antiplatelet treatment, the available data seem to favour an association of direct anticoagulant and inhibitors of P2Y12, rather than regimens including aspirin. These data are derived mainly from observational studies, with all their limitations. The use of aspirin could be beneficial in patients with significant comorbidities, such as diabetes mellitus, or with severe peripheral atherosclerotic disease, involving the carotids and other large arteries.

Mortality benefit with different antithrombotic therapies in patients with stable vascular disease: from pathophysiology to the clinical impact in the real world. The COMPASS study

The evaluation and application of antithrombotic strategies able to reduce total and cardiovascular mortality in patients with documented vascular disease have an important clinical and epidemiological role and may also impact on health costs. In the COMPASS trial, the association of rivaroxaban at the dose of 2.5 mg twice daily with aspirin in a population with stable vascular disease has significantly reduced the incidence of cardiovascular events compared to the standard regimen of aspirin alone; this reduction translated into greater cardiovascular and total survival. Such mortality benefit was not observed in previous randomized trials that in this setting of patients had previously evaluated antiplatelet strategies alternative to aspirin (with clopidogrel) or had compared a dual antiplatelet therapy with aspirin plus clopidogrel, vorapaxar, or ticagrelor vs a single antiplatelet treatment with aspirin. The results of the COMPASS trial strengthen the role of antithrombotic strategies that, beside the platelet phase, also involve the coagulative phase with the aim at preventing the recurrence of cardiovascular, atherothrombotic events at the site of polyvascular beds, with a degree of benefit proportional to the baseline risk of the patient.

Antithrombotic Therapy for Peripheral Revascularisation.

Lower extremity artery disease (LEAD) represents a major public health burden, affecting hundreds of millions of people worldwide. Although risk-factor modification, exercise training and medical treatment are the mainstays of the management of LEAD, endovascular or surgical revascularisation is recommended when there is the risk of limb amputation and when drug-resistant claudication severely affects patient lifestyle. Over recent years, the number of peripheral vascular interventions (PVI) has soared worldwide, driven by the improvements in endovascular techniques and devices. This growth was accompanied by a large number of clinical trials aimed at assessing the safety and efficacy of the various revascularisation modalities, while very little evidence was collected regarding the best antithrombotic treatment in patients undergoing peripheral revascularisation. In particular, considering the extensive length of diseased vessels usually treated in PVI, an optimised approach to both platelet function and coagulation cascade is of paramount importance. However, the role of antiplatelet and anticoagulant drugs following lower extremity revascularisation is largely extrapolated from the coronary field. Current guidelines recommend long-term single antiplatelet treatment for the majority of both endovascular and surgical revascularisation procedures, preceded by an initial short-term dual antiplatelet treatment in case of PVI. We present an overview of the indications and techniques of both endovascular and surgical peripheral revascularisation, followed by an in-depth analysis of the available evidence regarding type and duration of antiplatelet and anticoagulant treatment following revascularisation.

Risk of bleeding in patients with continued dual antiplatelet therapy during orthopedic surgery.

Background:To prevent risk of life-threatening stent thrombosis, all patients need to undergo dual antiplatelet therapy (DAPT) for at least 6 weeks to 12 months after stent implantation. If DAPT is continued during noncardiac surgery, there is a risk of severe bleeding at the surgical site. Our study was to assess the risk of bleeding in patients with continued DAPT during orthopedic surgery.Methods:The clinical data of 78 patients with coronary heart disease who underwent orthopedic surgery from February 2006 to July 2018 were retrospectively analyzed. Prior to orthopedic surgery, DAPT was continued in 16 patients (group I), 24 patients were treated with single antiplatelet therapy (group II), and 26 patients received low-molecular-weight heparin therapy for more than 5 days after the discontinuation of all antiplatelet therapies (group III). Twelve patients were excluded, as they had undergone minimally invasive surgery such as transforaminal endoscopy and vertebroplasty. The perioperative blood loss of each patient was calculated using Nadler's formula and Gross’ formula. The intraoperative bleeding volume, total volume of intraoperative bleeding in addition to postoperative drainage, and total blood loss were compared between groups. The level of significance was set at P < 0.05.Results:There were no significant differences between the three groups in age, intraoperative bleeding volume, total volume of intraoperative bleeding in addition to postoperative drainage, and total perioperative blood loss calculated by Nadler's formula and Gross’ formula (all P > 0.05). Six patients experienced postoperative cardiovascular complications due to the delayed restart of antiplatelet therapy; one of these patients in group III died from myocardial infarction.Conclusions:Continued DAPT or single antiplatelet treatment during orthopedic surgery does not increase the total intraoperative and perioperative bleeding compared with switching from antiplatelet therapy to low-molecular-weight heparin. However, the discontinuation of antiplatelet therapy increases the risk of serious cardiac complications.

Platelet inhibition during ticagrelor monotherapy versus ticagrelor plus aspirin in patients with coronary artery disease (TEMPLATE study): study protocol for a randomised controlled trial

BackgroundDual antiplatelet therapy (DAPT) with aspirin (ASP) and a P2Y12 blocker is currently standard care after percutaneous coronary intervention (PCI) with stent insertion, and aims to inhibit platelet function in order to prevent stent thrombosis. The P2Y12 blocker ticagrelor (TIC) has greater antiplatelet effect than the previously used members of this class, such as clopidogrel. In healthy volunteers, TIC is sufficient to cause strong platelet inhibition, with little additional effect from ASP. Omission of ASP may improve the safety of antiplatelet regimes by reducing bleeding. However, the effect of single antiplatelet treatment with TIC, compared to DAPT with TIC + ASP, has not been studied in detail in patients with coronary artery disease.MethodsTo compare TIC with TIC + ASP, we have initiated a single centre, open-label randomised controlled trial (TEMPLATE study) in adults receiving DAPT following PCI with a sample size of 110 patients. Patients are invited to join the study when, as part of standard care, they are due to switch from DAPT (ASP + any P2Y12 blocker) to single antiplatelet treatment with ASP alone after 6–12 months. Patients are randomised to receive either TIC or TIC + ASP for 4 weeks. All patients then revert to standard care with ASP alone. Blood samples and clinical data are collected at three study visits: at baseline during treatment with ASP + any P2Y12 blocker (visit 1); approximately 4 weeks after visit 1 during treatment with either TIC or TIC + ASP (visit 2); and approximately 8 weeks after visit 1 when treatment has reverted to ASP alone (visit 3). The primary outcome is the extent of platelet inhibition, measured by light transmission aggregation, flow cytometry, flow chamber and plasma biomarker tests. The primary analysis will compare the extent of platelet inhibition between the TIC and TIC + ASP groups at visit 2, adjusted for baseline platelet reactivity. Secondary analyses will compare the extent of platelet inhibition at visit 2 with that at visit 3.DiscussionThis is the first study to compare in detail the extent of platelet inhibition in patients who are receiving TIC compared with TIC + ASP. The study findings will complement larger-scale trials of the clinical efficacy and safety of TIC compared to TIC + ASP.Trial registrationISRCTN registry, identifier ISRCTN84335288. Registered on 23 June 2014.