Join Dr. Goodman and Dr. Verma as they review data from late-breaking trials presented at ACC.17 in Washington.
Dr. Sabatine, PI of the FOURIER Trial, will join the panel and the experts will review the most talked about late-breaking sessions and cutting-edge research, and discuss the clinical impact for Canadian cardiologists.
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First of all, absolute contraindications to any anticoagulation treatment include intracranial bleeding, severe active bleeding, recent brain, eye, or spinal cord surgery, pregnancy, and malignant hypertension. Relative contraindications include recent major surgery, recent cerebrovascular accident, and severe thrombocytopenia.
When considering extended therapy for VTE, the goal is to prevent recurrence, extension, and embolism while minimizing the risk of bleeding, which differs among patients depending on the prevalence of risk factors (e.g. age >75 years; previous bleeding; cancer; metastatic cancer; renal failure; liver failure; thrombocytopenia; previous stroke; diabetes; anemia; antiplatelet therapy; poor anticoagulant control; recent surgery; frequent falls; alcohol abuse). The risk of bleeding is the highest during the first three months of anticoagulation and stabilizes after the first year.
Other factors to consider include the burden of anticoagulation (financial, functional, and psychological), quality of life, and patient preference.
Rates of cancer can vary. Generally speaking, studies looking at a connection between VTE and cancer, found that approximately 7-8% of patients with VTE and 17-18% of patients with recurrent VTE also have cancer.
Cancer and its treatments are well-recognized risk factors for venous thromboembolism. The most common malignancies associated with thrombosis are those of the breast, colon, and lung, reflecting the prevalence of these malignancies in the general population. When adjusted for disease prevalence, the cancers most strongly associated with thrombotic complications are those of the pancreas, ovary, and brain.
Idiopathic thrombosis can be the first manifestation of an occult malignancy. However, intensive screening for cancer in patients with VTE often does not improve survival and is not generally warranted.
At this time, no. There are a number of safety trials comparing different combinations of oral anticoagulation (warfarin vs. non-vitamin K antagonists with P2Y12 receptor inhibitors like clopidogrel and/or ASA)—PIONEER AF has been completed and reported and ongoing studies include RE-DUAL, AUGUSTUS, and ENGAGE AF.
Yes, the supplementary appendix to the NEJM published trial provides insights into the effect of evolocumab + statin vs placebo + statin in patient subgroups, including those based on age, sex, and type of atherosclerotic vascular disease. Overall, the results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels. Further analysis of trial results may provide additional insight and identify patients who will most benefit from the addition of evolocumab.
It’s a good question. In the Fourier trial, both approved dosing strategies were used for evolocumab - either 140 mg every 2 weeks or 420 mg monthly. Generally, the results have been pooled and presented together. Both the main article and the supplementary appendix which contains more details are available online at NEJM.org (DOI: 10.1056/NEJMoa1615664.). The supplemental appendix notes that similar reductions in DLL-C with both regimens and consistency of benefit with evolocumab over placebo regardless of which dosing strategy was utilized.
As was observed with statins, the risk reduction with evolocumab was greater after the first year. See NEJM.org for the main publication and the supplementary appendix - DOI: 10.1056/NEJMoa1615664.
There was no routine imaging and it did not come up as an adverse event, however biochemical testing showed no difference in the elevation of aminotransferases.
Prior to the Fourier trial, several studies assessed cost effectiveness of evolocumab and deemed it effective for some high cardiovascular risk patients, but not cost-effective population-wise. However, there were issues with several of the critical modeling assumptions in those analyses and this issue will be reassessed with cost effectiveness analyses based on the Fourier results.