Acute stroke therapy: A review

This review summarizes the modern early diagnosis and acute phase treatment of acute stroke. The guidelines for treatment of acute ischemic stroke underwent major changes in 2015 and endovascular therapy (catheter-based mechanical thrombectomy with a stent retriever) became the class IA indication for patients presenting within less than 6 h from symptom onset who have proven occlusion of large intracerebral artery in anterior circulation. Acute stroke care organization should enable to perform effective revascularization therapy as soon as possible after the initial brain imaging whenever this examination provides indication for the procedure.     

Acute myocardial infarction and acute stroke: What are the differences? Focus on reperfusion therapy

This review compares acute myocardial infarction and acute stroke— their similarities and differences. The focus is given on reperfusion therapy: pharmacologic, mechanical or combined. The key trials and metaanalyses are described.The published data on iv. thrombolysis show, that even among a subgroup of patients treated within 90 min from stroke onset the trend to lower mortality is not significant and in all other subgroups (i.e. treated after >90 min) there is a trend towards increased mortality with thrombolytic treatment.The data on combined therapy demonstrate, that there is no benefit from facilitated intervention (iv. thrombolysis followed by ia. thrombolysis ± catheter intervention) over iv. thrombolysis alone in acute stroke. This is very similar to the situation in acute myocardial infarction 25 years ago (intracoronary thrombolysis was not superior to intravenous thrombolysis) or more recently (facilitated PCI was not shown to be superior in several trials).The latest generation of stent retrievers is able to recanalize >70% of occluded intracranial arteries—approximately twice more compared to thrombolysis. However, it is not yet known whether this translates to better clinical outcomes. The sufficient data on clinical outcomes after primary catheter-based thrombectomy (without thrombolysis) are still missing and trials comparing iv. thrombolysis versus primary catheter-based thrombectomy are urgently needed.The future trials in acute stroke may follow the way paved by acute myocardial infarction trials. If such trials would demonstrate superiority of catheter-based thrombectomy, we can face in future similar revolution in acute stroke treatment as we have been facing in acute MI treatment in the past years.     

Clinical outcome in patients with venous thromboembolism receiving concomitant anticoagulant and antiplatelet therapy

IntroductionPatients with arterial disease receiving antiplatelet agents may develop venous thromboembolism (VTE) and need anticoagulant therapy, although concomitant use of these drugs may increase bleeding risk. We analyzed RIETE data and compared clinical outcomes depending on decision to discontinue or maintain antiplatelet therapy at VTE diagnosis.MethodsConsecutive patients with acute VTE were enrolled in RIETE. Only patients receiving antiplatelet therapy at baseline were included in this analysis. Primary outcomes were: rate of subsequent ischemic events, major bleeding or death during anticoagulation course.Results1178 patients who received antiplatelet drugs at VTE diagnosis were included. Antiplatelet therapy was discontinued in 62% of patients. During anticoagulation course, patients also receiving antiplatelet therapy had higher rates of lower limb amputations (2.28 vs. 0.21 events per 100 patients-years; p < 0.01), any ischemic events (5.7 vs. 2.28 events per 100 patients-years; p < 0.05) or death (23.6 vs. 13.9 deaths per 100 patients-years; p < 0.01). No differences in the rate of major bleeding or recurrent VTE were revealed. In matched analysis, patients on antiplatelet therapy were found to have a significantly higher rate of limb amputations (odds ratio: 15.3; 95% CI: 1.02–229) and an increased number of composite outcomes including all-cause deaths, arterial and VTE events (odds ratio: 1.46; CI: 1.03–2.06), with no differences in major bleeding rate.ConclusionConcomitant anticoagulant and antiplatelet therapy in patients with VTE and arterial disease is not associated with increased risk for bleeding, recurrent VTE or death. The worse outcome observed in patients who continued antiplatelet therapy requires further investigations.     

Transjugular local thrombolysis with/without TIPS in patients with acute non-cirrhotic,non-malignant portal vein thrombosis

Background & aimsTherapeutic anticoagulation is the standard treatment in patients with acute non-cirrhotic portal vein thrombosis (PVT). In critically ill patients, anticoagulation only may not suffice to achive rapid and stable recanalization. This study evaluates efficacy and safety of transjugular interventional therapy in acute non-cirrhotic PVT.MethodsThis retrospective study includes 17 consecutive patients with acute noncirrhotic, non-malignant PVT. Main indication for interventional therapy was imminent intestinal infarction (n = 10). Treatment consisted of a combination of transjugular thrombectomy, local fibrinolysis and – depending on thrombus resolution – transjugular intrahepatic portosystemic shunt.ResultsRecanalization was successful in 94.1%. One- and two-year secondary PV patency rates were 88.2%. Major complications (n = 3) resolved spontaneously in all but one patient (heparin induced thrombocytopenia type 2 with intestinal infarction). Symptoms improved in all patients. However, segmental bowel resection had to be performed in two (11.8%). During a median follow-up of 28.6 months, no patient experienced portal hypertensive complications. Presence of JAK2 V617F mutation predicted both short-term and long-term technical success.ConclusionsTransjugular recanalization is safe and effective in patients with acute non-cirrhotic, non-malignant PVT. It should be considered especially in patients with imminent bowel infarction and low likelihood of recanalization following therapeutic anticoagulation. Patients with JAK2 mutation ought to be followed meticulously.     

Contrast-induced thrombocytopenia following percutaneous coronary intervention

Contrast-induced thrombocytopenia is a rare complication distinguished by acute and severe platelet consumption, with spontaneous recovery within days. We describe a case of acute thrombocytopenia 6 hours after coronary angioplasty in a patient with a negative antiplatelet factor 4 test. The count reached 1 × 10³/µL, but improved spontaneously to 210 × 10³/µL after 8 days. In conclusion, physicians should be aware of this complication, particularly when dual antiplatelet therapy is being considered.     

Prasugrel loading dose in diabetic patients with acute STEMI – Always sufficiently effective? Observation in two cases and review of current knowledge

The activation and subsequent platelet aggregation play a key role in the formation of arterial thrombosis and therefore is the key therapeutic target in the treatment of acute coronary syndromes. Dual antiplatelet therapy containing aspirin and P2Y12 ADP receptor antagonist forms currently the basis in acute ST – elevation myocardial infarction (STEMI) pharmacological treatment. Nevertheless, there is a wide variability in pharmacodynamic response to administration of clopidogrel, the most frequently used P2Y12 ADP receptor antagonist. High platelet reactivity after clopidogrel administration is associated with increased risk of stent thrombosis and points to the suitability of laboratory monitoring of antiplatelet therapy efficacy in clinical practice. Laboratory monitoring of antiplatelet therapy by ex vivo platelet function tests may help to identify individuals with poor antiplatlet response. Recently, there is a growing number of data reporting a failure in antiplatelet response following clopidogrel administration, which is specifically associated with insulin resistance and diabetes mellitus. Prasugrel, a new, potent P2Y12 ADP receptor antagonist, provides faster and more consistent inhibition of platelet function compared with clopidogrel. Prasugrel therapy was repeatedly described as an effective method to overcome clopidogrel resistance and prasugrel resistance has not yet been reliably described. We report two cases of patients with diabetes mellitus type 2 at the stage of organ complications, in whom a prasugrel loading dose of 60 mg did not reach adequate antiplatelet response in 60 min after prasugrel administration. The antiplatelet response was measured by light transmission aggregometry and by VASP protein phosphorylation assessment.     

Riesgo de eventos tromboembólicos en función del manejo de la terapia anticoagulante y antiagregante en pacientes sometidos a colangiopancreatografía retrógrada endoscópica

Background and objectivesThe main clinical practice guidelines recommend adequate periprocedural withdrawal and reintroduction of antithrombotic drugs in case of invasive techniques. The main objective of this study was to assess whether, in patients receiving anticoagulant or antiplatelet therapy, the suppression or reduction of the pharmacological dose for the performance of endoscopic retrograde cholangiopancreatography (ERCP) implies a greater risk of thromboembolic events.Patients and methodsA prospective observational study was carried out, which included 644 ERCP performed with therapeutic intention during 2019 at the Reina Sofía University Hospital with follow-up during the 30 days after the endoscopic intervention.ResultsSix patients presented a thromboembolic event, finding no differences between the incorrect withdrawal/reintroduction of antithrombotic treatment and a higher proportion of thromboembolic or hemorrhagic events after the procedure (P > .05). The incidence of thrombotic events was significantly higher in patients treated with heparin or apixaban (P = .001), as well as with a history of atrial fibrillation (P = .05), rheumatic valve disease (P = .037) and recurrent pulmonary embolism (P = .035), this being also an independent risk factor. Likewise, the incidence of hemorrhage in the 30 days post-sphincterotomy was significantly lower in those with implantation of a biliary prosthesis (P = .04).ConclusionsInadequate periprocedural management of antithrombotic therapy is not associated with a significant increase in the incidence of thromboembolic events in the 30 days after ERCP. However, close follow-up and surveillance during the days after this is essential in those patients with a condition that significantly increases the risk of thrombosis.     

Pre-admission antithrombotic use is associated with 3-month mRS score after thrombectomy for acute ischemic stroke

Journal of Thrombosis and Thrombolysis - In patients who undergo thrombectomy for acute ischemic stroke, the relationship between pre-admission antithrombotic (anticoagulation or antiplatelet) use...     

Simplified swift and safe vascular closure device deployment without a local arteriogram: Single center experience in 2074 consecutive patients

ObjectiveVascular closure devices (VCDs), such as the Angio-Seal, a three-component hemostatic plug, have greatly facilitated the routine clinical practice in the catheterization laboratory. The manufacturer recommends a local angiogram before Angio-Seal deployment. However, from the outset, we employed a simplified routine of deploying this VCD, i.e. without use of local angiography.MethodsThe Angio-Seal was employed without a preceding femoral arteriogram over 8 years in 2074 consecutive patients, 72% presenting with acute coronary syndromes and subjected to coronary angiography (n = 1032) or PCI n = 1042) via a transfemoral approach with use of heparin and dual antiplatelet therapy.ResultsDeployment of the VCD was successful in 99.4%. Complete hemostasis was obtained in 98% of cases. In 14 patients, Angio-Seal deployment failed. Mean time for placement of Angio-Seal was <1 min, to-hemostasis 1 min, and to-mobilization 3 h. Only 3 (0.15%) patients had a major complication with vessel occlusion that required emergent vascular surgery with a successful outcome. Two patients developed a local pseudoaneurysm treated with ultrasonography-guided compression. Six small and 4 large inguinal hematomas (one requiring blood transfusion) and 5 cases of retroperitoneal bleeding (one requiring blood transfusion) were recorded.ConclusionDeployment of Angio-Seal without use of local angiography was efficacious and safe, characterized by a high success rate of deployment and hemostasis with few correctable complications in a large patient cohort undergoing transfemoral catheterization for PCI and non-PCI procedures under anticoagulation and antiplatelet drug therapy. VCD reduced the time-to-hemostasis and time-to-mobilization and minimized the incidence of complications.     

Atrial fibrillation and acute myocardial infarction: antithrombotic therapy and outcomes

BackgroundAtrial fibrillation guidelines recommend long-term use of warfarin according to a patient's predicted risk of stroke. After acute myocardial infarction, however, combining warfarin and antiplatelet medications poses challenges.MethodsBy using data from more than 69,255 patients with acute myocardial infarction who were enrolled in the National Cardiovascular Data Registry's Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines at 309 hospitals from July 1, 2008, to September 30, 2009, we describe the characteristics and outcomes of the population with myocardial infarction with atrial fibrillation diagnosed within 2 weeks before index myocardial infarction admission (7.1%, N = 4947). Use of discharge antithrombotic therapy is described overall and across levels of predicted stroke and bleeding risks.ResultsCompared with patients without atrial fibrillation, those with atrial fibrillation before their index myocardial infarction were older and had more comorbidities and worse in-hospital outcomes. Only 32.5% of patients with atrial fibrillation were taking warfarin before their myocardial infarction admission. In these patients, use of warfarin at discharge increased with higher Congestive heart failure, Hypertension, Age, Diabetes, Stroke [Doubled] (CHADS₂) risk strata (28.5%, 34.6%, and 43.5% for CHADS₂ scores 0, 1, and ≥2; P < .001) and increased in patients at low, intermediate, and high risk of bleeding (25.4%, 42.3%, and 42.1%; P = .004). Triple therapy at discharge (aspirin plus clopidogrel plus warfarin) was used in a minority of this population (14.6%).ConclusionsUse of warfarin at discharge in patients with atrial fibrillation is greater among those with higher stroke and bleeding risks, but despite higher-risk profiles, less than half received warfarin at discharge. These findings highlight that clarification is needed to guide choice of antithrombotic therapy for patients with both atrial fibrillation and acute myocardial infarction.     

Comparison of high reloading ROsuvastatin and Atorvastatin pretreatment in patients undergoing elective PCI to reduce the incidence of MyocArdial periprocedural necrosis. The ROMA II trial

ObjectivesThe objective of this study is to compare a reloading dose of Rosuvastatin and Atorvastatin administered within 24 h before coronary angioplasty (PCI) in reducing the rate of periprocedural myonecrosis and major cardiac and cerebrovascular events (MACCE) in patients on chronic statin treatment undergoing elective PCI.BackgroundElective PCI may be complicated with elevation of cardiac biomarkers. Several studies suggested that pretreatment with statins may be associated with a reduction in periprocedural myocardial necrosis.MethodsThree hundred and fifty patients with stable angina who underwent elective PCI were randomly assigned to receive a pre-procedural reloading dose of Rosuvastatin (40 mg) (Rosuvastatin Group—RG n = 175) or Atorvastatin (80 mg) (Atorvastatin Group—AG n = 175) and a control group on chronic statin therapy without reloading (Control-Group—CG). The primary end-point was periprocedural myocardial necrosis and the occurrence of MACCE at 30-day,6–12 month follow-up. Also we evaluate the rise of periprocedural Troponin T serum levels > 3 × the upper limit of normal.ResultsTwelve and 24-hour post-PCI Creatine Kinase Muscle and Brain (CK-MB) elevation > 3 × occurred more frequently in the CG than in the RG and in the AG (at 24-h: 25.0 vs 7.1; p = 0.003 and 25.0 vs 6.1; p = 0.001). At 30-day, 6-and 12-month follow-up the incidence of cumulative MACCE was higher in CG than in the RG or AG (at 12-month: 41.0% vs 11.4% vs 12.0%; p = 0.001). There was no difference between the RG and AG in terms of myocardial post-procedural necrosis and MACCE occurrence at follow-up.ConclusionsHigh-dose statin reloading improves procedural and long term clinical outcomes in stable patients on chronic statin therapy. Both Rosuvastatin and Atorvastatin showed similar beneficial effects on procedural and long-term outcomes.     

Efficacy and safety of high dose versus low dose streptokinase for treatment of submassive pulmonary embolism

Pulmonary embolism (PE) remains a major cause of morbidity and mortality in the general population, the established treatment for PE is anticoagulation. It has previously been demonstrated that thrombolytic therapy can be lifesaving in patients with massive PE (haemodynamic instability and right heart failure). However, the use of thrombolytic therapy in patients with submassive PE (haemodynamically stable) remains a controversial topic. Recent clinical studies, however, support evidence that thrombolysis may favorably affect the outcomes in a wider spectrum of high risk PE patients presenting with right ventricular dysfunction (RVD) as evidenced by decreased right ventricular end diastolic diameter (RVEDD), disappearance of paradoxical septal motion (PSM), and tricuspid regurge (TR) as well as decrease in the pulmonary artery pressure. The aim of this study was to evaluate the efficacy and safety of high dose streptokinase (SK) in 1 h versus low dose SK in 24 h in patients with submassive PE and RVD (high risk PE). The study included 60 patients (28 males and 32 females, mean age 45.5 ± 13.6 years) with submassive PE (positive spiral CT chest) and RVD (proved by echocardiography). Those without contraindications to SK were randomly assigned to receive either high dose (group I) or low dose (group II) of SK. Those with contraindication(s) to SK received anticoagulation (group III). Echocardiography was done before and 72 h after treatment. Right ventricular dysfunction (RVEDD, PSM, and TR) and mean pulmonary artery pressure (PAP) improved significantly 72 h after treatment in groups I and II, while a slight improvement in PAP was observed after treatment in group III. No significant difference was noticed between groups I and II regarding the effect of treatment on RVD or PAP. Statistically nonsignificant difference was found between groups I and II regarding the complications of SK, however a slightly higher risk of bleeding was observed in group I (high dose SK). No significant difference was found between the three groups regarding the mortality. These data suggest that SK can rapidly and safely reverse the pulmonary hypertension and RVD in contrast to anticoagulation. Both protocols of SK are equieffective in rapid reversal of RVD and pulmonary hypertension. Both protocols were safe as proved by absence of difference in mortality over anticoagulant group.     

The fate of post-myocardial infarction thrombi

We are reporting a patient who sustained a large myocardial infarction with large kissing thrombi in echocardiogram that disappeared within 1 month without the administration of thrombolytic, anticoagulation or antiplatelet therapy. The patient did not manifest any embolic events. This unusual course calls for specific studies on the natural history of thrombi post myocardial infarction and the best modality to treat such thrombi.     

Cierre de la orejuela izquierda por ictus pese a la anticoagulación oral (ictus resistente): resultados del registro Amplatzer Cardiac Plug

Introduction and objectivesDespite the efficacy of oral anticoagulant (OAC) therapy, some patients continue to have a high residual risk and develop a stroke on OAC therapy (resistant stroke [RS]), and there is a lack of evidence on the management of these patients. The aim of this study was to analyze the safety and efficacy of left atrial appendage occlusion (LAAO) as secondary prevention in patients with nonvalvular atrial fibrillation who have experienced a stroke/transient ischemic attack despite OAC treatment.MethodsWe analyzed data from the Amplatzer Cardiac Plug multicenter registry on 1047 consecutive patients with nonvalvular atrial fibrillation undergoing LAAO. Patientes with previous stroke on OAC therapy as indication for LAAO were identified and compared with patients with other indications.ResultsA total of 115 patients (11%) with RS were identified. The CHA₂DS₂-VASc and the HAS-BLED score were significantly higher in the RS group (respectively 5.5 ± 1.5 vs 4.3 ± 1.6; P < .001; 3.9 ± 1.3 vs 3.1 ± 1.2; P < .001). No significant differences were observed in periprocedural major safety events (7.8 vs 4.5%; P = .1). With a mean clinical follow-up of 16.2 ± 12.2 months, the observed annual stroke/transient ischemic attack rate for the RS group was 2.6% (65% risk reduction) and the observed annual major bleeding rate was 0% (100% risk reduction).ConclusionsPatients with RS undergoing LAAO showed similar safety outcomes to patients without RS, with a significant reduction in stroke/transient ischemic attack and major bleeding events during follow-up. Adequately powered controlled trials are needed to further investigate the use of LAAO in RS patients.     

Acute stroke in a young healthy woman with hormonal contraception: Direct percutaneous thrombectomy with stent-retriever followed by full neurologic recovery

Healthy 46 years old woman with hormonal contraception suffered from severe acute hemispheral stroke caused by occlusion of medial cerebral artery. Percutaneous intervention using Solitaire^® stent-retriever was started within 30 min of arrival. Complete thrombectomy was followed by full recovery of neurological deficit within several hours. Neither thrombolysis nor general anesthesia was used.     

Infarto de miocardio con elevación del segmento ST revascularizado. Tendencias temporales de los tratamientos contemporáneos y su impacto en los resultados

Introduction and objectivesTo assess, in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous intervention, the pace of introduction in clinical practice (2010-2017) of drug-eluting stents (DES), ticagrelor, prasugrel, and prolonged dual antiplatelet therapy (DAPT) duration, and their potential impact on the risk of 2-year outcomes.MethodsProspective and exhaustive community-wide cohort of 14 841 STEMI patients undergoing primary percutaneous intervention between 2010 and 2017. Index episodes were obtained from the Catalan Codi IAM Registry, events during follow-up from the Minimum Data Set and DAPT were defined by pharmacy dispensation. Follow-up was 24 months. The temporal trend for exposures and outcomes was assessed using regression models.ResultsAge > 65 years, diabetes, renal failure, previous heart failure, and need for anticoagulation at discharge were more frequent in later periods (P < .001). From 2010 to 2017, the use of DES increased from 31.1% to 69.8%, ticagrelor from 0.1% to 28.6%, prasugrel from 1.5% to 23.8%, and the median consecutive months on DAPT from 2 to 10 (P < .001 for all). Adjusted analysis showed a temporal trend to a lower risk of the main outcome over time: the composite of death, acute myocardial infarction, stroke and repeat revascularization (absolute odds reduction 0.005% each quarter; OR, 0.995; 95%CI, 0.99-0.999; P = .028). The odds of all individual components except stroke were reduced, although significance was only reached for revascularization.ConclusionsDespite a strong increase between 2010 and 2017 in the use and duration of DAPT and the use of ticagrelor, prasugrel and DES, there was no substantial reduction in major cardiovascular outcomes.Full English text available from:www.revespcardiol.org/en     

The effects of Ramadan fasting on patients with prosthetic heart valve taking warfarin for anticoagulation

Introduction

Oral anticoagulation with warfarin is indicated for patients with prosthetic heart valves. The effects of religious fasting during Ramadan month (in the Islamic calendar) on anticoagulation aren’t clear.

Fermeture d’auricule gauche percutanée chez le sujet âgé

Left atrial appendage occlusion (LAAO) is an alternative option to oral anticoagulation therapy in patients with non-valvular atrial fibrillation. According to French regulations, this procedure is currently reserved for patients with formal contraindications to VKA and direct thrombin inhibitors. LAAO procedures reduce ischemic and stroke risks compared to no treatment and also reduce bleeding events compared to VKA therapy in eligible patients. The peri-procedural complications risk has been reported to be limited in the different series published so far. Although elderly patients (> 75 years) have either higher ischemic and bleeding risk than younger subjects, they hardly benefit from optimal anticoagulation. Thus, these subjects might greatly benefit from LAAO. Published studies reported excellent feasibility and efficiency of LAAO procedure in elderly patients. Yet there is a trend towards a higher incidence of peri-procedural complications (including tamponade), long-term safety is excellent and comparable to what is observed in patients < 75 years. Therefore, interventional percutaneous LAAO is an attractive strategy in elderly patients with atrial fibrillation that should be incorporated in a multidisciplinary management.     

Off-pump coronary artery bypass grafting using continuous heparin infusion

ObjectivesLevels of anticoagulation during off-pump coronary artery bypass grafting (OPCAB) remain controversial. Prolonged activated clotting time (ACT) during OPCAB increases blood loss during surgery and can also cause paradoxical increase in postoperative myocardial infarction. Shorter ACT can increase thrombotic complication. Maintaining a steady ACT level is challenging. We have used continuous heparin infusion after initial bolus during OPCAB to maintain a steady low target ACT. The objective of the present study was to assess the effectiveness and safety of heparin infusion in maintaining a steady target ACT level.MethodsThis was a prospective study of consecutive OPCAB patients. ACT was measured after initial bolus dose of heparin. Once ACT of more than 200 seconds was achieved, heparin infusion was started to maintain the required level of anticoagulation. CPK-MB was measured in operation room, 6 and 24 hours postoperatively to rule out ischemic complication.ResultsACT could be maintained in target range with heparin infusion in 80.1% patients (161/201). Of the 40 patients with one or more ACT reading less than 200 seconds, 38 patients were managed by increasing the dose of heparin infusion and only 2 patients required additional bolus dose of heparin.ConclusionsHeparin infusion maintains a steady target ACT level and avoids peaks and troughs associated with bolus doses. Lower level of anticoagulation using continuous heparin infusion does not increase ischemic complications. This is the first ever study of use of heparin infusion during OPCAB. We may conclude that heparin infusion is a safe anticoagulation strategy for OPCAB.