Ischemic Stroke and Cancer: Stroke Severely Impacts Cancer Patients, While Cancer Increases the Number of Strokes

Background

Cancer and ischemic stroke are two of the most common causes of death among the elderly, and associations between them have been reported. However, the main pathomechanisms of stroke in cancer patients are not well known, and can only be established based on accurate knowledge of the characteristics of cancer-related strokes. We review herein recent studies concerning the clinical, laboratory, and radiological features of patients with cancer-related stroke.

Main Contents

This review covers the epidemiology, underlying mechanisms, and acute and preventive treatments for cancer-related stroke. First, the characteristics of stroke (clinical and radiological features) and systemic cancer (type and extent) in patients with cancer-specific stroke are discussed. Second, the role of laboratory tests in the early identification of patients with cancer-specific stroke is discussed. Specifically, serum D-dimer levels (as a marker of a hypercoagulable state) and embolic signals on transcranial Doppler (suggestive of embolic origin) may provide clues regarding changes in the levels of coagulopathy related to cancer and anticoagulation. Finally, strategies for stroke treatment in cancer patients are discussed, emphasizing the importance of preventive strategies (i.e., the use of anticoagulants) over acute revascularization therapy in cancer-related stroke.

Conclusion

Recent studies have revealed that the characteristics of cancer-related stroke are distinct from those of conventional stroke. Our understanding of the characteristics of cancer-related stroke is essential to the correct management of these patients. The studies presented in this review highlight the importance of a personalized approach in treating stroke patients with cancer.     

Stroke prevention in atrial fibrillation patients

Importance of the field: Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice and is associated with an increased risk of stroke, mortality and significant morbidity. Given the rapidly increasing incidence and prevalence of AF, and the resulting public health burden of the consequences associated with this arrhythmia, stroke prevention is an extremely important topic.

Areas covered in this review: This review covers the epidemiology of AF, the pathophysiology of ischemic stroke in AF and current antithrombotic therapy choices for stroke prevention in this condition. In addition, this article discusses important topics such as the assessment of stroke risk stratification and bleeding risk assessment, which are key issues in deciding upon thromboprophylaxis for AF patients. Finally, the review highlights the advent of new anticoagulant therapies and discusses the future challenges for researchers in this area.

What the reader will gain: This review summarizes all of the major antithrombotic trials conducted in AF patients over the last twenty years and highlights the importance of anticoagulation therapy for the prevention of stroke, after appropriate individual stroke and bleeding risk assessment.

Take home message: Assessment of individual stroke risk and bleeding risk is key in determining appropriate thromboprophylaxis for AF patients, given the associated thromboembolic and hemorrhagic complications. The availability of newer, safer and more convenient drugs will mean that oral anticoagulation is available for a larger proportion of AF patients who may benefit from it.     

凝血酶抑制剂的研究进展

动脉和静脉血栓是发病率和死亡率均高的疾病。虽然目前可用的抗凝血剂可有效防治血栓性疾病,但各有缺点。低分子量肝素和磺达肝素能产生可预见的抗凝水平,且不需要凝血功能监测,但需注射给药,不便长期用药。华法林是一种口服有效的维生素K拮抗剂,但由于遗传多态性、膳食维生素K的摄入以及多重药物相互作用等因素,使其产生可变的抗凝反应,需要进行凝血功能监测和频繁调整剂量以确保达到抗凝治疗水平。鉴于此,以凝血因子Ⅹ和凝血酶为靶点的新型口服有效的抗血栓药成为开发热点。     

Warfarin therapy in Chinese patients with atrial fibrillation treated with percutaneous coronary intervention: a 5 year follow-up retrospective cohort study

Objective: To evaluate warfarin use in Chinese patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) by investigating the stroke and major adverse cardiac and cerebral events (MACCEs) and bleeding events.

Methods: Retrospective cohort study of the 5?year follow-up of 1134 patients with AF who underwent PCI. The patients were grouped according to whether they received warfarin or not. Baseline characteristics and the occurrence of MACCEs and bleeding events were compared between the two groups using the CHA2DS2-VASc and HAS-BLED scoring. Cox regression analysis was used to identify factors related to the occurrence of MACCEs and bleeding.

Results: Overall MACCE (p?=?.008) and mortality (p?=?.004) rates were significantly lower in the warfarin group compared with the non-warfarin group. Major bleeding, minor bleeding and overall bleeding were comparable in the two groups. Recurrent myocardial infarction (HR?=?10.129, 95% CI?=?4.737–21.655; p?<?.001) and a baseline CHA2DS2-VASc score >4 (HR?=?2.035, 95% CI?=?1.121–3.692; p?=?.019) were independent predictors of MACCEs in the warfarin group. A baseline HAS-BLED score ≥3 (HR?=?5.498, 95% CI?=?3.773–8.013; p?<?.001) and previous bleeding (HR?=?3.058, 95% CI?=?1.319–7.088; p?=?.009) were independent predictors of bleeding.

Conclusions: Warfarin reduces the incidence of MACCEs but does not increase bleeding events in Chinese patients with AF who underwent PCI. For patients taking warfarin, recurrent myocardial infarction and a baseline CHA2DS2-VASc score >4 were related to MACCE occurrence.     

Antithrombotics in atrial fibrillation and coronary disease

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and approximately 18–45% of AF patients have concomitant coronary artery disease (CAD). Several studies have demonstrated that oral anticoagulation is the mainstay of therapy for stroke prevention in AF. Similarly, antiplatelet therapy including aspirin and P2Y12 inhibitor is recommended in the management of acute coronary syndrome and stable CAD. Despite the high prevalence of CAD with AF, practice guidelines are scarce on the appropriate antithrombotic regimen due to lack of large-scale randomized clinical trials. The use of direct thrombin and factor Xa inhibitors for stroke prevention in AF has also complicated the possible combinations of antithrombotic therapies. This review aims to discuss the available evidence regarding aspirin as an antithrombotic strategy, the role of novel anticoagulants and the specific clinical situations where aspirin may be beneficial in patients with AF and CAD.     

Anticoagulation for prevention and treatment of cancer‐related venous thromboembolism

The close relationship between malignancy and venous thromboembolism (VTE) is well established, with malignancy increasing VTE risk and accounting for a substantial proportion of presentations with VTE. Moreover, VTE impacts significantly on morbidity and mortality in cancer patients. Anticoagulation for prevention and treatment of VTE requires a patient‐centred approach due to the heterogeneous patient population and inherent increased thrombotic and bleeding risks. In recent years, low molecular weight heparin (LMWH) injections have come to be the mainstay for treatment and prevention of cancer‐related VTE. For treatment, this is usually administered for at least 6 months and continued in patients with active cancer or those receiving treatment for cancer. The use of LMWH for thromboprophylaxis in hospitalised cancer patients is also well accepted, but out‐of‐hospital prophylaxis remains contentious. The development of risk assessment models may help identify the patients at highest risk. The role of the new oral factor Xa and thrombin inhibitors in this setting remains to be determined.     

褐家鼠对杀鼠灵和溴敌隆抗药性的测定

目的试验观察虹口区城区褐家鼠对第一代抗凝血剂杀鼠灵和第二代抗凝血剂溴敌隆的抗药性发生率,为家栖鼠防治提供依据。方法采用0.005%杀鼠灵毒饵和0.005%溴敌隆毒饵进行无选择性摄食试验。结果 0.005%杀鼠灵毒饵,25只褐家鼠未监测到抗药性个体;0.005%溴敌隆毒饵,27只褐家鼠抗药性发生率为3.7%(1/27)。结论在虹口区城区,褐家鼠对第一代抗凝血剂杀鼠灵敏感,但存在对第二代抗凝血剂溴敌隆的抗药性,应加强对灭鼠药物的敏感性监测,科学、合理用药。     

Mixed Treatment Comparison Meta-Analysis of Aspirin,Warfarin, and New Anticoagulants for Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation

Background

Warfarin and aspirin are used to prevent stroke in patients with atrial fibrillation (AF). There are inherent challenges with both treatments, including variable and inconsistent benefit and increased bleeding risks. The availability of new anticoagulants offers some alternatives.

Objective

A mixed treatment comparison meta-analysis to evaluate direct and indirect treatment data including aspirin, warfarin apixaban, dabigatran, edoxaban, and rivaroxaban for the prevention of primary or secondary stroke in patients with AF.

Methods

A comprehensive, systematic literature search was conducted to identify randomized trials comparing aspirin, warfarin, apixaban, dabigatran, edoxaban, and rivaroxaban in patients with AF requiring treatment for stroke prevention. Open-label and blinded designs were included if they evaluated any stroke or any bleeding event. Data on stroke and bleeding events were abstracted, verified, evaluated, scored, and entered into Aggregate Data Drug Information System version 1.16 to generate a mixed treatment comparison meta-analysis. Direct and indirect comparisons were evaluated, and we looked for inconsistency in closed loop structures. Data are reported as rate ratios with 95% credible intervals. In addition, we reviewed variance statistics and explored variance with node-splitting models.

Results

Our literature search yielded 30 articles, 21 of which were included. All treatments except aspirin reduced the risk of any stroke compared with placebo. Warfarin (0.43 [0.33–0.57]), apixaban (0.37 [0.27–0.54]), dabigatran (0.34 [0.21–0.57]), rivaroxaban (0.36 [0.22–0.60]), and aspirin with clopidogrel (0.73 [0.53–0.99]) were more protective than aspirin alone. Warfarin and the new anticoagulants were similar in the reduction of stroke, vascular death, and mortality. There was no difference in major bleeding between any treatment group. There were more nonmajor bleeding events when comparing warfarin and apixaban (1.83 [1.05–4.03]); no other differences between warfarin and the other new anticoagulants were found.

Conclusions

This mixed treatment comparison meta-analysis found similarity between warfarin and the new anticoagulants with the exception of one comparison, in which warfarin was associated with more non-major bleeding than apixaban. Thus, the new anticoagulants are therapeutically comparable when warfarin is inappropriate.     

Anticoagulant-related gastrointestinal bleeding—could this facilitate early detection of benign or malignant gastrointestinal lesions?

Abstract

Introduction. The higher incidence of gastrointestinal (GI) bleeding with the non-vitamin K oral anticoagulants (NOACs) may be related to pre-existing malignancies; diagnostic measures triggered by these bleedings could lead to early detection of these malignancies.

Methods. We retrieved the preferred terms on GI bleeding and GI cancer reported as adverse events (AEs) from phase III studies in patients with atrial fibrillation for each NOAC on ClinicalTrials.gov. We also analyzed the RE-LY trial database.

Results. From ClinicalTrials.gov, AE-GI bleeding incidence was: dabigatran 110 mg b.i.d. (D110: 1.42% versus 1.37%), dabigatran 150 mg b.i.d. (D150: 1.93% versus 1.37%), rivaroxaban (3.52% versus 2.68%), and apixaban (1.93% versus 1.59%), compared with warfarin, respectively. The incidence of AE-GI cancer was similar between the NOACs (D110 [0.79%], D150 [0.61%], rivaroxaban [0.83%], and apixaban [0.69%]), but numerically higher compared with warfarin (0.37%; 0.73%; 0.57%, respectively). In the RE-LY database, the same pattern was seen for dabigatran, with an association between GI bleeding and GI cancer diagnosis.

Conclusion. Anticoagulant-related GI bleeding may represent the unmasking of pre-existing malignancies leading to increased detection of GI cancer. This may be especially in the first month of treatment and could explain the numerically higher numbers of GI malignancies observed with NOACs.