Characterization of thromboembolic and bleeding risks in cancer patients with acute myocardial infarction under the use of guideline-recommended dual-antiplatelet therapy

Background Atherosclerotic cardiovascular disease including acute myocardial infarction (AMI) has become one of major co-existing diseases in cancer patients due to their improved survival rate. Current guideline recommends dual-antiplatelet therapy (DAPT) in patients with AMI. Given that the presence of cancer elevates not only coagulability but bleeding risks, these substrate may further worsen cardiovascular outcomes and bleeding risks in cancer subjects with AMI receiving DAPT. Methods We retrospectively analyzed 712 AMI patients treated by primary PCI with drug-eluting stent and DAPT between 2007 and 2017. The diagnosis of cancer was determined through medical record review. Clinical characteristics, thromboembolic (=all-cause death+non-fatal MI+stroke) and bleeding events were compared in AMI subjects with vs. without cancer. Results Cancer was identified in 11.1% (=79/712) of study subjects. Of these, around 40% of them had gastrointestinal cancer (=35/79), followed by lung cancer (=5/79) and breast cancer (=8/79). Cancer patients were more likely to be older (77±7 v. 69±13 years, p<0.001) with a history of Af (25 v. 10%, p<0.001), CKD (eGFR<60: 60 v. 42%, p=0.002), anemia (hemoglobin: 12.8±1.8 v. 13.9±1.8 g/dl, p<0.001). Under anti-thrombotic (DAPT=86%, triple-antiplatelet therapy=14%) and optimal medical therapies (ACE-I=90%, beta-blocker=76%, statin=96%), more frequent occurrence of thromboembolic events was observed in patients with cancer (34.2 v. 12.6%, p=0.004, Picture). Furthermore, the presence of cancer was associated with more than four times greater risk of bleeding events compared to non-cancer subjects (18.9 v. 4.3%, p<0.001, Picture). In particular, the frequency of both major (10.1 vs. 3.3%, p=0.003) and minor (8.9 vs. 0.9%, p<0.001) bleeding events was significantly higher in patients with cancer. In multivariate analysis, cancer independently predicted bleeding events (Table). Conclusions Under the use of guideline recommended DAPT, the concomitance of cancer in AMI subjects was a predictor for thromboembolic as well as bleeding events. In particular, the relationship between cancer and bleeding was significant. These observations underscore the appropriate selection and duration of anti-thrombotic agents in AMI subjects with cancer. Cardiac/Bleeding Events in AMI Subjects Funding Acknowledgement Type of funding source: None

Essential Thrombocythemia Complicated by Occlusive Thrombosis of the Abdominal Aorta

Introduction. Essential thrombocythemia (ET) is a myeloproliferative neoplasm of excessive platelet production complicated by thrombohemorrhagic events. Thrombosis typically occurs in small to medium vessels; thrombosis of large vessels is rare. Case Presentation. A 75-year-old woman with ET complicated by bilateral retinal vein occlusion was evaluated for fatigue, early satiety, and unintentional weight loss. Her hypertension was well controlled, and her chronic lower extremity claudication from peripheral artery disease was stable. She reported adherence to aspirin 81 mg and hydroxyurea 1000 mg daily, and her platelets (375 × 109/L) were at goal. Bone marrow biopsy was consistent with ET without progression to myelofibrosis or leukemia. CT abdomen demonstrated complete occlusion of the infrarenal aorta, extending into the common iliac arteries, with reconstitution of flow distally via collaterals. The addition of clopidogrel, for platelet inhibition, and cilostazol, for claudication, caused symptom improvement without further thrombosis or bleeding. Discussion. There are few published reports of ET complicated by aortic thrombosis. To our knowledge, this is the first report of aortic thrombosis occurring in an ET patient with normal platelet count on antiplatelet and cytoreductive therapies. There is limited evidence to guide treatment, but medical management with triple antiplatelet therapy may be effective in selected patients.

The safety of triple antiplatelet therapy under thromboelastography guidance in patients undergoing stenting for ischemic cerebrovascular disease

ObjectiveTo investigate the safety of triple antiplatelet therapy (TAT) with cilostazol in patients undergoing stenting for extracranial and/or intracranial artery stenosis.MethodsA prospectively collected database was reviewed to identify patients who underwent stenting for extracranial and/or intracranial artery stenosis and showed resistance to aspirin and/or clopidogrel as assessed by pre-stenting thromboelastography (TEG) testing. Patients were assigned to a TAT group and a dual antiplatelet therapy (DAT) group. Major complications were defined as thromboembolic events (transient ischemic attack (TIA), ischemic stroke, and stent thrombosis) or major bleeding events within 30 days, and minor complications were defined as extracranial bleeding that did not require vascular surgery or transfusion within 30 days.ResultsA total of 183 patients were identified. The incidence of major complications was significantly lower in the TAT group than in the DAT group (TAT group vs. DAT group, 1/110 vs. 6/73; P=0.017). TIAs occurred in four patients, with one in the TAT group and three in the DAT group (1/110 vs. 3/73; P=0.303). Ischemic strokes occurred in three patients in the DAT group (TAT group vs. DAT group, P=0.062). No major bleeding events or stent thrombosis was recorded in either group. Two patients (one in each group) experienced minor complications that resolved without additional treatment (1/110 vs. 1/73; P>0.999).ConclusionsTAT under TEG guidance appears to be a safe antiplatelet strategy in patients undergoing stenting for extracranial and/or intracranial artery stenosis. By employing TAT under TEG guidance, favorable outcomes can be achieved in these patients.

Anticoagulant therapy for recurrent in-stent thrombosis following carotid artery stenting: A case report

We report a case in which strict anticoagulant therapy management was useful for a recurrent in-stent thrombosis after carotid artery stenting (CAS). An 84-year-old man presented with cognitive decline that progressed rapidly over two months. Head magnetic resonance imaging showed an acute-stage infarct occurring frequently in the right cerebral hemisphere, and he underwent hospitalization and treatment. On neck magnetic resonance angiography (MRA), severe stenosis was found at the origin of the right internal carotid artery. Since he took aspirin, clopidogrel, and a statin after placement of an indwelling coronary stent, we treated him by adding argatroban and edaravone drip therapy to his existing medication. CAS was performed on day 15 of the hospitalization. A small in-stent thrombosis with plaque protrusion was observed on a carotid sonogram performed at the second day after CAS, and re-examination at the seventh day confirmed enlargement of the lesion and an increase in peak systolic velocity; thus, a second CAS procedure was performed on the same day. After the second CAS, oral cilostazol was added for triple antiplatelet therapy (TAPT), but as the in-stent thrombosis increased further, we started a continuous infusion of heparin with the goal of an activated partial thromboplastin time (APTT) of 50 to 65 seconds. After starting heparin, the lesion did not progress; after 14 days of continuous heparin infusion, the patient was switched to TAPT, and regression of the plaque was confirmed. This case demonstrated to us that controlled anticoagulation therapy can be an effective treatment for cases in which a thrombus recurs within a stent after CAS.

Abstract WP76: Baseline Characteristics of the 3,096 Patients Recruited Into the ‘Triple Antiplatelets for Reducing Dependency After Ischaemic Stroke’ (TARDIS) Trial

Background: The risk of recurrence following ischaemic stroke (IS) or transient ischaemic attack (TIA) is highest immediately after the event. Antiplatelet agents are effective in reducing the risk of recurrence and two agents are superior to one in the early phase after ictus. Design: The Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial was an international multicentre prospective randomised open-label blinded-endpoint trial that assessed the safety and efficacy of short-term intensive antiplatelet therapy with three agents (combined aspirin, clopidogrel and dipyridamole) as compared with guideline treatment in acute IS or TIA. The primary outcome was stroke recurrence and its severity, measured using the modified Rankin Scale at 90 days. Secondary outcomes included recurrent vascular events, functional measures (cognition, disability, mood, quality of life) and safety (bleeding, death, serious adverse events). Data are number (%) or mean (standard deviation, SD). Results: Recruitment ran from April 2009 to March 2016. 3,096 patients were recruited from 106 sites in 4 countries (Denmark 1.6%, Georgia 2.7%, New Zealand 0.2%, UK 95.4%). Randomisation characteristics included: age 69.0 (10.1) years; male 1945 (62.8%); time onset to randomisation 29.4 (11.9) hours; stroke severity (National Institutes for Health Stroke Scale) 2.8 (3.6); blood pressure 143.5 (18.2)/79.5 (11.4) mmHg; IS 2143 (69.2%), TIA 953 (30.8%). Conclusion: TARDIS was a large international trial of intensive/triple antiplatelet therapy in acute IS and TIA, and included participants representative of patients in many western stroke services. Funders: National Institute of Health Research Health Technology Assessment Programme and British Heart Foundation. Trial registration: ISRCTN47823388