Arterial thromboembolic events

The serious adverse effects associated with bevacizumab include GI perforation, hemorrhage, hypertension, complications in wound healing, nephritic syndrome, congestive heart failure and arterial thromboembolic events. Patients receiving bevacizumab commonly experience pain, asthenia, headache, abdominal pain, nausea, vomiting, anorexia, upper respiratory infection and exfoliative dermatitis. 

Scappaticci FA et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. Journal of the National Cancer Institute 2007 99 1232-1239. 

Observational studies In a prospective study of bevacizumab combined with chemotherapy for first-line treatment of metastatic colorectal cancer, bevacizumab-related adverse events were gastrointestinal perforation (1.9%), arterial thromboembolic events (2%), grade 3—4 bleeding (2.2%), and de novo hypertension requiring medication (22%) [81 =]. 

In a meta-analysis of randomized controlled trials, the incidences of all-grade and high-grade arterial thromboembolic events in patients who received bevacizumab were 3.3% and 2.0% respectively. Patients who received bevacizumab had a significantly increased risk of arterial thromboembolic events compared with controls (RR = 1.4 95% CI = 1.1, 1.9). The risk was similarly increased by bevacizumab at 2.5 and 5 mg/kg/week in addition, there were... 

Ranpura V, Hapani S, Chuang J, Wu S. Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis inhibitor bevacizumab in cancer patients a metaanalysis of randomized controlled trials. Acta Oncol 2010 49(3) 287-97. 

Bevadzumab (vascular endothelial growth factor-specific angiogenesis inhibitor) Arterial thromboembolic events, e.g., myocardial infarction, cerebral infarction, hypertension... 

Clinically, hypertension is a common (up to 34 %) cardiovascular event associated with bevacizumab treatment (Avastin PI 2013). Other cardiovascular events that may be associated with bevacizumab treatment include congestive cardiac failure, supraventricular tachycardia, and arterial thromboembolic events including cerebral infarction, transient ischemic attacks, myocardial infarction, angina, and hemorrhage (Nazer et al. 2011). The congestive heart failure may, in some cases, be associated with prior or concomitant use of anthacyclines. 

In randomized clinical trials, the incidence of arterial thromboembolic events, including strokes, transient ischemic attacks, and myocardial infarctions, was higher in patients receiving bevacizumab in combination with chemotherapy compared with those who received chemotherapy alone [194 ]. 

Cardiovascular Heart The incidence of Antiplatelet Trialists Collaboration and arterial thromboembolic events (ATEs) were 2.7% in the sham group (one acute myocardial infarction and one carotid artery stenosis) and 0.9% in the treatment group (one myocardial infarction) [5]. 

J Heparin-induced thrombocytopenia (HIT) is a serious immune-mediated problem that requires immediate intervention. For patients receiving therapeutic UFH doses, a baseline platelet count should be obtained before therapy is initiated and then every-other-day for 14 days or until therapy is stopped, whichever occurs first. HIT should be suspected if a patient develops a thromboembolic event (e.g., DVT, PE, stroke, myocardial infarction, limb artery occlusion) during or soon after receiving UFH. The platelet... 

Many causes of acute spinal cord infarction (of arterial and venous origin) have been reported (Table 17.2). They include diseases of the aorta and aortic surgery, thromboembolic events and cartilaginous disc embolism, vasculitis, coagulopathy, radiation-induced vasculopathy, toxic effects of contrast medium, epidural anesthesia, periradicu-lar nerve root therapy with crystalline corticoids, decompression illness, shock or cardiac arrest, lumbar artery compression and other etiologies... 

Previous ischaemic stroke/ transient ischaemic attack or thromboembolic event Age > 75 years with hypertension, diabetes, or vascular disease (coronary artery disease or peripheral artery disease) Age > 65 years with no high risk factors Age < 75 years with hypertension, diabetes, or vascular disease (coronary artery disease or peripheral artery disease) Age less than 65 years with no moderate or high risk factors... 

Higher aspirin doses of 900 to 1,500 mg per day have not been shown to have increased efficacy in arterial thromboembolism prevention when compared with 300 mg per day or lower doses. In one metaanalysis of 19 antiplatelet trials in several thrombotic disorders, the issue of aspirin dosage was indirectly analyzed (44). It was found that trials employing 900 to 1,500 mg of daily aspirin versus placebo had similar outcomes to trials employing doses of 300 to 325 mg per day versus placebo. Patients treated with 900 to 1,500 mg experienced a 23% reduction in new vascular events, whereas those taking 320 mg showed a decrease of 24%. Thus a dose-response plateau appears to exist in aspirin s antithrombotic effect. Clinical and laboratory observations are complimentary in this reqrect since aspirin inhibition of in vitro platelet PG synthesis shows a similar dose-re nse plateau with maximal blockade at micromolar concentrations (2,25,28). 

Venous thromboembolism, including thrombosis of the deep veins of the legs and embolism to the pulmonary arteries, is uncommon in the general population. The absolute risk of venous thromboembolism in non-hormone therapy users is approximately 1 in 10,000 women. Women taking hormone therapy have a twofold increase in risk for thromboembolic events, with the highest risk occurring in the first... 

Nausea and vomiting (may be dose-limiting) diarrhea cardiovascular lowers arterial circulation ischemic heart disease patients with CHE may develop increased symptoms of heart failure thromboembolic events gynecomastia, nipple tenderness increased liver function tests... 

The largest cause of morbidity and mortality comes from involvement of the vascular system, particularly from thromboembolic events which can occur in both arteries and veins and in all sizes of vessels [6], Thrombophlebitis and pulmonary embolism are the most frequent vascular accidents, whereas thromboses of large and medium arteries, especially carotid and renal arteries, are frequent causes of death [7]. Ischemic heart disease is less common. Nenroimaging may demonstrate evidence of infarction or thrombosis. Association with other genotypes linked to increased risk of vascular disease, such as factor V Leiden and thermola-bile methylenetetrahydrofolate reductase, may increase the risk of thrombosis in individuals with homocystinuria [17, 18]. 

In 1995, the Guglielmi detachable coil technique was approved by the FDA for endovascular treatment of aneurysms. This method involves the use of deploying metallic coils into the aneurysm to induce a clotting response and seal off the aneurysm from the artery. Since its inception, over 200,000 patients worldwide have been treated with this technique [52]. However, difficulties in multicoil placement, thromboembolic events during placement, coil-induced rupture, and incomplete filling of fhe aneurysm are some of the challenges associated with the procedure [52]. 

Bevacizumab plus first-line chemotherapy has been evaluated in the Bevacizumab Expanded Access Trial (BEAT) in patients with unresectable metastatic colorectal cancer [82 ]. The serious/grade 3-5 adverse events with bevacizumab included hypertension (5.3%), bleeding (3%), gastrointestinal perforation (2%), arterial thromboembolism (1%), proteinuria (1%), and wound-healing complications (1%). 

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