Exploratory outcome analyses according to stage and/or residual disease in the ICON7 trial of carboplatin and paclitaxel with or without bevacizumab for newly diagnosed ovarian cancer

Objective: In the randomized phase 3 ICON7 trial (ISRCTN91273375), adding bevacizumab to chemotherapy for newly diagnosed ovarian cancer significantly improved progression-free survival (PFS; primary endpoint) but not overall survival (OS; secondary endpoint) in the intent-to-treat (ITT) population. We explored treatment effect according to stage and extent of residual disease. Methods: Patients with stage IIB–IV or high-risk (grade 3/clear-cell) stage I–IIA ovarian cancer were randomized to receive six cycles of carboplatin and paclitaxel either alone or with bevacizumab 7.5 mg/kg every 3 weeks followed by single-agent bevacizumab for 12 further cycles (total duration 12 months). Post hoc exploratory analyses of subgroups defined by stage and extent of residual disease at diagnosis within the stage IIIB–IV population (European indication) was performed. Results: The PFS benefit from bevacizumab was seen consistently in all subgroups explored. The PFS hazard ratio was 0.77 (95% confidence interval [CI], 0.59–0.99) in 411 patients with stage IIIB–IV ovarian cancer with no visible residuum and 0.81 (95% CI, 0.69–0.95) in 749 patients with stage IIIB–IV disease and visible residuum. As in the ITT population, no OS difference was detected in any subgroup except the previously described ‘high-risk’ subgroup. Safety results in analyzed subgroups were consistent with the overall population. Conclusions: Adding bevacizumab to front-line chemotherapy improves PFS irrespective of stage/residual disease. In patients with stage III with \u3e1 cm residuum, stage IV or inoperable disease, this translates into an OS benefit. No OS benefit or detriment was seen in other subgroups explored

Exploratory outcome analyses according to stage and/or residual disease in the ICON7 trial of carboplatin and paclitaxel with or without bevacizumab for newly diagnosed ovarian cancer

Objective: In the randomized phase 3 ICON7 trial (ISRCTN91273375), adding bevacizumab to chemotherapy for newly diagnosed ovarian cancer significantly improved progression-free survival (PFS; primary endpoint) but not overall survival (OS; secondary endpoint) in the intent-to-treat (ITT) population. We explored treatment effect according to stage and extent of residual disease. Methods: Patients with stage IIB-IV or high-risk (grade 3/clear-cell) stage I-IIA ovarian cancer were randomized to receive six cycles of carboplatin and paclitaxel either alone or with bevacizumab 7.5 mg/kg every 3 weeks followed by single-agent bevacizumab for 12 further cycles (total duration 12 months). Post hoc exploratory analyses of subgroups defined by stage and extent of residual disease at diagnosis within the stage IIIB-IV population (European indication) was performed. Results: The PFS benefit from bevacizumab was seen consistently in all subgroups explored. The PFS hazard ratio was 0.77 (95% confidence interval [CI], 0.59-0.99) in 411 patients with stage IIIB-IV ovarian cancer with no visible residuum and 0.81 (95% CI, 0.69-0.95) in 749 patients with stage IIIB-IV disease and visible residuum. As in the ITT population, no OS difference was detected in any subgroup except the previously described 'high-risk' subgroup. Safety results in analyzed subgroups were consistent with the overall population. Conclusions: Adding bevacizumab to front-line chemotherapy improves PFS irrespective of stage/residual disease. In patients with stage III with >1 cm residuum, stage IV or inoperable disease, this translates into an OS benefit. No OS benefit or detriment was seen in other subgroups explored

Exploratory outcome analyses according to stage and/or residual disease in the ICON7 trial of carboplatin and paclitaxel with or without bevacizumab for newly diagnosed ovarian cancer

Objective: In the randomized phase 3 ICON7 trial (ISRCTN91273375), adding bevacizumab to chemotherapy for newly diagnosed ovarian cancer significantly improved progression-free survival (PFS; primary endpoint) but not overall survival (OS; secondary endpoint) in the intent-to-treat (ITT) population. We explored treatment effect according to stage and extent of residual disease. Methods: Patients with stage IIB–IV or high-risk (grade 3/clear-cell) stage I–IIA ovarian cancer were randomized to receive six cycles of carboplatin and paclitaxel either alone or with bevacizumab 7.5 mg/kg every 3 weeks followed by single-agent bevacizumab for 12 further cycles (total duration 12 months). Post hoc exploratory analyses of subgroups defined by stage and extent of residual disease at diagnosis within the stage IIIB–IV population (European indication) was performed. Results: The PFS benefit from bevacizumab was seen consistently in all subgroups explored. The PFS hazard ratio was 0.77 (95% confidence interval [CI], 0.59–0.99) in 411 patients with stage IIIB–IV ovarian cancer with no visible residuum and 0.81 (95% CI, 0.69–0.95) in 749 patients with stage IIIB–IV disease and visible residuum. As in the ITT population, no OS difference was detected in any subgroup except the previously described ‘high-risk’ subgroup. Safety results in analyzed subgroups were consistent with the overall population. Conclusions: Adding bevacizumab to front-line chemotherapy improves PFS irrespective of stage/residual disease. In patients with stage III with >1 cm residuum, stage IV or inoperable disease, this translates into an OS benefit. No OS benefit or detriment was seen in other subgroups explored

A Genome-Wide Association Study Identifies Susceptibility Variants for Type 2 Diabetes in Han Chinese

To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54×10−10; odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36–1.82), and serine racemase (SRR) (P = 3.06×10−9; OR = 1.28; 95% CI = 1.18–1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65×10−10; OR = 1.29, 95% CI = 1.19–1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations

L'angioplastie facilitée par injection préhospitalière d'abciximab en phase aiguë d'infarctus (expérience nîmoise)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Recanalized Coronary Thrombus Role of OCT in Identifying a Slow-Evolving and Underestimated Coronary Lesion

Pathological studies have revealed spontaneous recanalized coronary thrombi as a frequent evolution of coronary occlusions; however, they are poorly recognized on coronary angiography, and the optimal therapeutic strategy for clinical evolution is unknown. We report the role of optical coherence tomography in identifying a recanalized coronary thrombus causing myocardial ischemia after 11 years of follow-up. (Level of Difficulty: Intermediate.

Syndrome coronaire aigu : y a-t-il une place pour les anticoagulants oraux directs ?

International audienceVenous thromboembolism and atrial fibrillation are two important indications of direct oral anticoagulants. Acute coronary syndrome is another potential indication of prolonged antithrombotic therapy in addition to antiplatelet therapy. Phase 2 and 3 studies were conducted with different molecules at different doses in acute coronary syndrome in addition to dual antiplatelet therapy. Studies have not shown a reduction of ischemic events for dabigatran and apixaban, but an excess of bleeding complications was observed. A reduction of ischemic events and stent thrombosis was observed with low dose of rivaroxaban taken twice a day but with an increased risk of major bleeding complications. This data was used to obtain a European marketing authorization but the positioning of the molecule remains difficult. A new study is currently being conducted to test rivaroxaban in association with a P2Y12 inhibitor without aspirin. Direct oral anticoagulants can also be used after percutaneous coronary intervention in patients requiring long-term oral anticoagulants. Dedicated studies are currently being conducted to confirm the optimal doses and the ideal association of antithrombotic drugs

Post resuscitation electrocardiogram for coronary angiography indication after out-of-hospital cardiac arrest

International audienceBackground: Coronary angiography is the standard of care after Out-of-Hospital Cardiac Arrest (OHCA), but its benefit for patients without persistent ST-segment elevation (STE) remains controversial.Methods: All patients admitted for coronary angiography after a resuscitated OHCA were consecutively included in this prospective study. Three patient groups were defined according to post-resuscitation ECG: STE or new left bundle branch block (LBBB) (group 1); other ST/T repolarization disorders (group 2) and no repolarisation disorders (group 3). The proportion and predictive factors of an acute coronary lesion, defined by acute coronary occlusion or thrombotic lesion or lesion associated with flow impairment, were evaluated according to different groups as well as thirty-day mortality.Results: Among 129 consecutive patients: 62 (48.1%), 30 (23.3%) and 30 (23.3%) patients were included in groups 1, 2 and 3 respectively. An acute coronary lesion was observed in 43% (n = 55) of patients, mainly in group 1 (n = 44, 70.9%). Initial coronary TIMI 0/1 flow was more frequently observed in group 1 than in group 2 (n = 25, 40.3% vs n = 1, 3.3%) and never in group 3. Chest pain and STE or new LBBB were independently associated with an acute coronary lesion (adj. OR = 7.14 [1.85–25.00]; p = 0.004 and adj. OR = 11.10 [3.70–33.33]; p < 0.001 respectively). In absence of any repolarization disorders, acute coronary lesion or occlusion were excluded with negative predictive values of 93.3% and 100% respectively. The one-month survival rate was 38.8% and was better in patients among the group 1 compared to those from the 2 other groups (n = 28, 45.2% vs n = 21, 35%, respectively; p = 0.014).Conclusion: Considering the high negative predictive value of post-resuscitation ECG to exclude acute coronary lesion and occlusion after OHCA, a delayed coronary angiography appears a reliable alternative for patients without repolarization disorders

One-year incidence and clinical impact of bleeding events in patients treated with prasugrel or clopidogrel after ST-segment elevation myocardial infarction

International audienceBACKGROUND:Little information is available on the long-term incidence of bleeding events after ST-segment elevation myocardial infarction (STEMI) with the current antithrombotic strategy.AIMS:To evaluate the effect of bleedings for up to 12months on clinical events and therapeutic compliance in unselected STEMI patients treated with prasugrel or clopidogrel.METHODS:Patients were treated with clopidogrel or prasugrel according to guidelines. The primary endpoint was first occurrence of a bleeding event from hospital discharge to 12months, assessed by the Bleeding Academic Research Consortium (BARC) classification using a dedicated questionnaire. Topography of bleedings, causes of premature cessation and ischaemic events were compared between clopidogrel- and prasugrel-treated patients.RESULTS:A total of 390 patients were enrolled (211 in the prasugrel group, 179 in the clopidogrel group). Elderly, female and low-body weight patients were more likely to receive clopidogrel. At 12months, the incidence of major bleedings (BARC 3) was lower with prasugrel (1% vs 6%; P=0.02), mainly due to fewer transfusions. Elderly age was a risk factor for severe bleeding. Premature treatment cessation was related to ischaemic complications (P=0.03), and occurred more frequently with prasugrel (P=0.001). One-year mortality was very low (1.9 per 100 person-years, 95% confidence interval 0.9-4.0), and was higher in the clopidogrel group (P=0.03).CONCLUSIONS:In this unselected STEMI population, the rate of major bleedings with prasugrel at 12months was low, but nuisance bleedings were frequent and led to more premature cessations than with clopidogrel. Prevention of bleeding complications, even minor, is necessary to prevent disruption of antithrombotic medication