Preventing Venous Thromboembolism in Ambulatory Cancer Patients: The ONKOTEV Study.

BACKGROUND: The efficacy of risk model scores to predict venous thromboembolism (VTE) in ambulatory cancer patients is under investigation, aiming to stratify on an individual risk basis the subset of the cancer population that could mostly benefit from primary thromboprophylaxis. MATERIALS AND METHODS: We prospectively assessed 843 patients with active cancers, collecting clinical and laboratory data. We screened all the patients with a duplex ultrasound (B-mode imaging and Doppler waveform analysis) of the upper and lower limbs to evaluate the right incidence of VTE (both asymptomatic and symptomatic). The efficacy of the existing Khorana risk model in preventing VTE was also explored in our population. Several risk factors associated with VTE were analyzed, leading to the construction of a risk model. The Fine and Gray model was used to account for death as a competing risk in the derivation of the new model. RESULTS: The risk factors significantly associated with VTE at univariate analysis and further confirmed in the multivariate analysis, after bootstrap validation, were the presence of metastatic disease, the compression of vascular/lymphatic structures by tumor, a history of previous VTE, and a Khorana score >2. Time-dependent receiving operating characteristic (ROC) curve analysis showed a significant improvement in the area under the curve of the new score over the Khorana model at 3 months (71.9% vs. 57.9%, p = .001), 6 months (75.4% vs. 58.6%, p < .001), and 12 months (69.8% vs. 58.3%, p = .014). CONCLUSION: ONKOTEV score steps into history of cancer-related-VTE as a promising tool to drive the decision about primary prophylaxis in cancer outpatients. The validation represents the goal of the prospective ONKOTEV-2 study, endorsed and approved by the European Organization for Research and Treatment of Cancer Young Investigators Program. The Oncologist 2017;22:601-608 IMPLICATIONS FOR PRACTICE: Preventing venous thromboembolism in cancer outpatients with a risk model score will drive physicians' decision of starting thromboprophylaxis in high-risk patients.

Causative mutations and premature cardiovascular disease in patients with heterozygous familial hypercholesterolaemia.

Background Familial hypercholesterolemia is a common autosomal dominant disease, caused by mutations leading to elevated low-density lipoprotein (LDL) cholesterol and, if untreated, to premature cardiovascular disease. Methods Patients (young adults with a family history of hypercholesterolaemia or premature cardiovascular disease) with LDL cholesterol concentration ≥4.9 mmol/l, after excluding Familial Combined Hyperlipidaemia, were evaluated for causative mutations, Dutch Lipid Clinic Network score calculation and non-invasive ultrasound examination of carotid arteries. Results Of the 263 patients, 210 were heterozygotes for LDL receptor ( LDLR) mutations, four had APOB gene mutations, one PCSK9 gene mutation, while 48 had no evidence of mutations. Among 194 unrelated index cases 149 had mutations (77%). Among patients with LDLR mutations ( n = 145), there were five compound heterozygotes, 75 patients with null mutations and 65 with missense mutations. As many as 178 patients underwent a follow-up and treatment (statin ± ezetimibe), achieving a mean reduction of 49% in LDL cholesterol, with 21% of patients reaching the LDL goal of 2.6 mmol/l. In a multivariate analysis, carotid plaques, at ultrasound examination, were associated with the presence of genetic mutation ( p = 0.001), LDL cholesterol ( p < 0.001), Dutch Lipid Clinic Network score ( p < 0.001), independently of age, gender, smoking habits and systolic blood pressure. The presence of carotid plaque ( p = 0.017), LDL cholesterol ( p < 0.003), Dutch Lipid Clinic Network score ( p < 0.001) were independently associated with premature cardiovascular disease. Conclusions We identified patients with causative mutations in 82% of the cases under study. In addition to LDL cholesterol and Dutch Lipid Clinic Network score, carotid plaques in ultrasound evaluation provide direct evidence of premature vascular disease and are associated with high risk for cardiovascular events.