Abstract 16688: Effects of Evolocumab in Patients With Prior Percutaneous Coronary Intervention: An Analysis From the Fourier Trial

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Remo H Furtado ◽  
Antonio A Fagundes ◽  
Kazuma Oyama ◽  
Thomas A Zelniker ◽  
Minao Tang ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Absolute Risk ◽  
Coronary Revascularization ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Atherosclerotic Cardiovascular Disease ◽  
History Of ◽  
Coronary Events

Introduction: Among patients with atherosclerotic cardiovascular disease (ASCVD), those with history of PCI represent an important population for potential high risk for cardiovascular (CV) events. We examined the clinical efficacy of the PCSK9 inibitor evolocumab in patients with prior PCI. Methods: FOURIER randomized 27,564 patients with ASCVD on statin therapy to evolocumab or placebo with a median follow-up of 2.2 yrs. The primary end point (PEP) was the composite of CV death, MI, stroke, unstable angina, or coronary revascularization; major coronary events were the composite of coronary death, MI, or coronary revascularization. The risk of events in patients with and without a history of PCI were compared in the placebo arm. The clinical benefit of evolocumab vs. placebo was compared using a Cox proportional hazards model. Results: 17,073 (62%) patients had prior PCI at baseline. Among patients in the placebo arm, those with prior PCI (N=8563) had a 1.6x higher rate of the PEP (16.8 vs 10.7%; adjusted HR 1.61; 95% CI 1.42-1.84 P<0.0001) and nearly double the rate of major coronary events (14.5 vs. 7.8%; P<0.0001; adjusted HR 1.72; 95% CI 1.49-1.99; Figure left). In patients with prior PCI, evolocumab reduced the risk of the PEP by 16% (HR 0.84; 95% CI 0.77-0.91; P<0.0001) and of major coronary events by 18% (HR 0.82; 95% CI 0.75-0.90, P<0.0001; Figure right), including a 30% reduction in fatal or non-fatal MI (P<0.001) and a 24% reduction in coronary revascularization (P<0.001). After the first year, there was a 25% reduction in major coronary events (HR 0.75, 95% CI 0.66-0.86, P<0.0001). The absolute risk reduction at 3 years with evolocumab for major coronary events was 2.8% in patients with prior PCI vs. 0.3% in those without. Conclusions: In a contemporary cohort with ASCVD on statin therapy, patients with prior PCI were at heightened risk for coronary events. Evolocumab was highly effective in this group, reducing major coronary events by 18% with a NNT at 3 years of only 36.

Abstract 17617: History of Bleeding and Outcomes with Apixaban versus Warfarin in Patients with Atrial Fibrillation in the ARISTOTLE Trial

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Raffaele De Caterina ◽  
Ulrika Andersson ◽  
John H Alexander ◽  
M.Cecilia Bahit ◽  
Patrick J Commerford ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Body Weight ◽  
Major Bleeding ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Channel Blockers ◽  
Chads2 Score ◽  
History Of

Background: History of bleeding is important in decisions for anticoagulation. We analyzed outcomes in relation to history of bleeding and randomized treatments in patients with atrial fibrillation (AF) in the ARISTOTLE trial. Methods: The on-treatment safety population included 18,140 patients receiving ≥1 dose of study drug, apixaban 5 mg bd (2.5 mg bd if 2 of the following: age >80 yrs; body weight <60 kg; or creatinine >133 μmol/L) or warfarin aiming for INR 2.0-3.0 (median TTR 66%), for a median of 1.8 yrs. Adjudicated outcomes in relation to randomization and history of bleeding were analyzed using a Cox proportional hazards model. Efficacy endpoints were analyzed in the intention-to-treat population. Results: A history of bleeding was reported in 3033 patients (16.7%), who more often were male (68% vs 64%, p <0.0005); with a history of prior stroke/TIA/systemic embolism (23% vs 19%, p <0.0001); diabetes (27% vs 24%, p=0.0010); higher CHADS2 score (CHADS2 >3: 35% vs 29%), age (mean [SD] 71 [9] vs 69 [10], p <0001) and body weight (86 [21] vs 84 [21], p <0.0001); lower creatinine clearance (77 [33] vs 80 [33], p=0.0007) and mean systolic blood pressure (131 [17] vs 132 [16], p=0.0027). Calcium channel blockers, statins, non-steroidal anti-inflammatory drugs and proton pump inhibitors were used more often in patients with vs without a history of bleeding. Major bleeding was the only outcome event occurring more frequently in patients with vs without a history of bleeding, HR 1.7 (95% CI 1.4-2.3) with apixaban and 1.5 (1.2-1.0) with warfarin. Primary efficacy and safety outcomes in relation to randomization, see Table. Conclusions: In patients with AF, a history of bleeding was associated with several risk factors for stroke and bleeding and, accordingly, a higher bleeding risk during anticoagulation. Benefits with apixaban vs warfarin as to stroke, mortality and major bleeding, are however consistent irrespective of bleeding history.

Predicting self-reported depression after the onset of multiple sclerosis using genetic and non-genetic factors

2020 ◽  
pp. 135245852092107
Author(s):  
Frances M Wang ◽  
Mary F Davis ◽  
Farren BS Briggs
Keyword(s):  
Multiple Sclerosis ◽  
Prediction Model ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Genetic Risk Score ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Depression Risk ◽  
History Of ◽  
History Of Depression

Background: Persons with multiple sclerosis (PwMS) are disproportionately burdened by depression compared to the general population. While several factors associated with depression and depression severity in PwMS have been identified, a prediction model for depression risk has not been developed. In addition, it is unknown if depression-related genetic variants, including Apolipoprotein E ( APOE), would be informative for predicting depression in PwMS. Objective: To develop a depression prediction model for PwMS who did not have a history of depression prior MS onset. Methods: The study population included 917 non-Hispanic white PwMS. An optimized multivariable Cox proportional hazards model for time to depression was generated using non-genetic variables, to which APOE and a depression-related genetic risk score were included. Results: Having a mother who had a history of depression, having obstructive pulmonary disease, obesity and other physical disorders at MS onset, and affect-related symptoms at MS onset predicted depression risk (hazards ratios (HRs): 1.6–2.3). Genetic variables improved the prediction model’s performance. APOE ε4/ε4 and ε2/x conferred increased (HR = 2.5, p = 0.026) and decreased (HR = 0.65, p = 0.046) depression risk, respectively. Conclusion: We present a prediction model aligned with The Precision Medicine Initiative, which integrates genetic and non-genetic predictors to inform depression risk stratification after MS onset.

Analysis of Factors Associated With Outcome in Patients With Malignant Peritoneal Mesothelioma Undergoing Surgical Debulking and Intraperitoneal Chemotherapy

2003 ◽  
Vol 21 (24) ◽  
pp. 4560-4567 ◽  
Author(s):  
Andrew L. Feldman ◽  
Steven K. Libutti ◽  
James F. Pingpank ◽  
David L. Bartlett ◽  
Tatiana H. Beresnev ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Residual Disease ◽  
Tumor Resection ◽  
Regional Chemotherapy ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
History Of

Purpose: Malignant mesothelioma (MM) arising in the peritoneal cavity is a rare neoplasm characterized by peritoneal progression and for which there are limited therapeutic options. We evaluated the peritoneal progression-free and overall survival (PFS and OS, respectively) for patients with peritoneal MM after surgical resection and regional chemotherapy. Patients and Methods: Forty-nine patients (28 males, 21 females; median age, 47 years; range, 16 to 76 years) with MM underwent laparotomy, tumor resection, continuous hyperthermic peritoneal perfusion with cisplatin (median dose 250 mg/m2), and a single postoperative intraperitoneal dwell of fluorouracil and paclitaxel (n = 35) on protocols approved by the Institutional Review Board. Standard techniques for actuarial analyses of potential prognostic variables (Kaplan-Meier method with two-tailed log-rank test and Cox proportional hazards model) were performed. Results: At a median potential follow-up of 28.3 months, median actuarial PFS is 17 months and actuarial OS is 92 months. Factors associated with improved PFS and OS by the Cox proportional hazards model were a history of previous debulking surgery, absence of deep tissue invasion, minimal residual disease after surgical resection (OS only), and age younger than 60 years (OS only). Conclusion: Surgical resection and regional chemotherapy for MM results in durable PFS and OS. Favorable outcome is associated with age, tumor biology (selection of patients with a history of previous debulking), lack of invasive tumor growth, and minimal residual disease after tumor resection.

scholarly journals Additive Hazard Regression Models: An Application to the Natural History of Human Papillomavirus

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Xianhong Xie ◽  
Howard D. Strickler ◽  
Xiaonan Xue
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Model ◽  
Additive Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
History Of ◽  
Oncogenic Hpv ◽  
Hiv Negative

There are several statistical methods for time-to-event analysis, among which is the Cox proportional hazards model that is most commonly used. However, when the absolute change in risk, instead of the risk ratio, is of primary interest or when the proportional hazard assumption for the Cox proportional hazards model is violated, an additive hazard regression model may be more appropriate. In this paper, we give an overview of this approach and then apply a semiparametric as well as a nonparametric additive model to a data set from a study of the natural history of human papillomavirus (HPV) in HIV-positive and HIV-negative women. The results from the semiparametric model indicated on average an additional 14 oncogenic HPV infections per 100 woman-years related to CD4 count < 200 relative to HIV-negative women, and those from the nonparametric additive model showed an additional 40 oncogenic HPV infections per 100 women over 5 years of followup, while the estimated hazard ratio in the Cox model was 3.82. Although the Cox model can provide a better understanding of the exposure disease association, the additive model is often more useful for public health planning and intervention.

scholarly journals Discontinuation rates of different contraceptive methods in Thai women up to 1-year after method initiation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Unnop Jaisamrarn ◽  
Monchai Santipap ◽  
Somsook Santibenchakul
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Intrauterine Device ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Oral Contraceptive Pills ◽  
Thai Women ◽  
Hazards Model ◽  
Contraceptive Implant ◽  
History Of

AbstractWe assessed the discontinuation rate and the reason for discontinuation of common contraceptives used by reproductive-aged Thai women. We recruited 1880 women aged 18–45 years from the Family Planning Clinic of the Chulalongkorn Hospital in Bangkok. The participants were followed at three, six and twelve months. A Cox proportional hazards model was used to determine personal risks of discontinuing contraceptives. The incidence rate for discontinuation of combined oral contraceptive pills (COCs), depot medroxyprogesterone acetate (DMPA), copper intrauterine device (IUD), and contraceptive implant(s) were 21.3, 9.2, 4.4, and 2.3/100 person-years, respectively. Most of the women who discontinued (185/222) discontinued contraceptives due to side effects. Compared to contraceptive implant users, the adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)] of discontinuing COCs, DMPA, and the copper IUD were 9.6 (4.3–21.8), 4.2 (1.8–10.0), and 2.2 (0.8–5.9), respectively. Lower income, higher parity, history of miscarriage, and history of abortion were independent predictors of contraceptive discontinuation in a multivariable model.

scholarly journals External validation of H2ARDD score for the prediction of heart failure events in patients with atrial fibrillation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
N Taniguchi ◽  
Y Miyasaka ◽  
Y Suwa ◽  
S Harada ◽  
E Nakai ◽  
...  
Keyword(s):  
Heart Failure ◽  
Confidence Interval ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Predictive Accuracy ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Kaplan Meier ◽  
History Of

Abstract Background Heart failure is an important consequence in patients with atrial fibrillation (AF) which is associated with worse prognosis. The H2ARDD score, calculated from 5 clinical risk factors, was reported as a predictor of heart failure events in patients with AF. However, this score has not been externally validated. Purpose The purpose of this study was to evaluate and validate the usefulness of the H2ARDD score for the prediction of heart failure events in AF patients. Methods We used prospective data of patients with AF followed up from 2007 to 2017 in our institute. Patients with active cancer were excluded according to the previous report. H2ARDD score was calculated as follows; history of heart disease=2 points, anemia=1 point, renal dysfunction=1 point, diabetes =1 point, diuretic use=1 point (range from 0 to 6 points). Outcome of interest was defined as heart failure events including new-onset heart failure and death with heart failure. Heart failure was ascertained based on the Framingham criteria. Univariable and multivariable Cox-proportional hazards model were used to assess the risk of heart failure events. Heart failure events-free survival was estimated with Kaplan-Meier methods, and the predictive accuracy of the H2ARDD score for the prediction of heart failure events was measured by the area under the receiver operating characteristic (ROC) curve. Results Of 562 AF patients, 522 (age 69±10 year–old, 64.9%men) met study criteria. Patients who had a history of heart disease was 185 (35%), diabetes mellitus was 135 (26%), anemia was 54 (10%), renal dysfunction was 221 (43%), and diuretic use was 193 (37%). The mean H2ARDD score was 1.88±1.57. Of all study patients, 84 (16.2%) developed heart failure events during a mean follow–up of 54±42 months. Patients who developed heart failure events in 1 year was 24 (4.6%). In multivariable Cox–proportional hazards model, H2ARDD score was shown as an significant predictor for heart failure events (hazard ratio: 1.56, 95% confidence interval: 1.36 - 1.79, P&lt;0.0001), independently of age (per 10 years, hazard ratio: 1.35, 95% confidence interval: 1.03 – 1.78, P&lt;0.05). In the Kaplan–Meier analyses stratified by H2ARDD score (0–1, 2–3, 4–6), patients who had a higher H2ARDD sore had significantly worse heart failure event-free survival (log-rank P&lt;0.0001) (Figure 1). The area under the ROC curve for the prediction of heart failure events in 1-year was 0.812 (95% confidence interval: 0.737 – 0.887, P&lt;0.0001), and the best cut-off value was ≥4 points (sensitivity: 67%, specificity: 83%) (Figure 2). Conclusion H2ARDD score was demonstrated as a significant independent predictor for the prediction of heart failure events, with high predictive accuracy. H2ARDD score may be useful for heart failure risk stratification of AF patients. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

Age at Exposure to Parental Suicide and the Subsequent Risk of Suicide in Young People

Crisis ◽  
2018 ◽  
Vol 39 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Kuan-Ying Lee ◽  
Chung-Yi Li ◽  
Kun-Chia Chang ◽  
Tsung-Hsueh Lu ◽  
Ying-Yeh Chen
Keyword(s):  
Young People ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Birth Registry ◽  
Data Set ◽  
Parental Suicide ◽  
The Impact ◽  
Age At Exposure

Abstract. Background: We investigated the age at exposure to parental suicide and the risk of subsequent suicide completion in young people. The impact of parental and offspring sex was also examined. Method: Using a cohort study design, we linked Taiwan's Birth Registry (1978–1997) with Taiwan's Death Registry (1985–2009) and identified 40,249 children who had experienced maternal suicide (n = 14,431), paternal suicide (n = 26,887), or the suicide of both parents (n = 281). Each exposed child was matched to 10 children of the same sex and birth year whose parents were still alive. This yielded a total of 398,081 children for our non-exposed cohort. A Cox proportional hazards model was used to compare the suicide risk of the exposed and non-exposed groups. Results: Compared with the non-exposed group, offspring who were exposed to parental suicide were 3.91 times (95% confidence interval [CI] = 3.10–4.92 more likely to die by suicide after adjusting for baseline characteristics. The risk of suicide seemed to be lower in older male offspring (HR = 3.94, 95% CI = 2.57–6.06), but higher in older female offspring (HR = 5.30, 95% CI = 3.05–9.22). Stratified analyses based on parental sex revealed similar patterns as the combined analysis. Limitations: As only register-­based data were used, we were not able to explore the impact of variables not contained in the data set, such as the role of mental illness. Conclusion: Our findings suggest a prominent elevation in the risk of suicide among offspring who lost their parents to suicide. The risk elevation differed according to the sex of the afflicted offspring as well as to their age at exposure.

Proliferation-dominant high-grade astrocytoma: survival benefit associated with extensive resection of FLAIR abnormality region

2020 ◽  
Vol 132 (4) ◽  
pp. 998-1005 ◽  
Author(s):  
Haihui Jiang ◽  
Yong Cui ◽  
Xiang Liu ◽  
Xiaohui Ren ◽  
Mingxiao Li ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Characteristic Curve ◽  
Extent Of Resection ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
High Grade ◽  
Extensive Resection ◽  
High Grade Astrocytoma

OBJECTIVEThe aim of this study was to investigate the relationship between extent of resection (EOR) and survival in terms of clinical, molecular, and radiological factors in high-grade astrocytoma (HGA).METHODSClinical and radiological data from 585 cases of molecularly defined HGA were reviewed. In each case, the EOR was evaluated twice: once according to contrast-enhanced T1-weighted images (CE-T1WI) and once according to fluid attenuated inversion recovery (FLAIR) images. The ratio of the volume of the region of abnormality in CE-T1WI to that in FLAIR images (VFLAIR/VCE-T1WI) was calculated and a receiver operating characteristic curve was used to determine the optimal cutoff value for that ratio. Univariate and multivariate analyses were performed to identify the prognostic value of each factor.RESULTSBoth the EOR evaluated from CE-T1WI and the EOR evaluated from FLAIR could divide the whole cohort into 4 subgroups with different survival outcomes (p < 0.001). Cases were stratified into 2 subtypes based on VFLAIR/VCE-T1WIwith a cutoff of 10: a proliferation-dominant subtype and a diffusion-dominant subtype. Kaplan-Meier analysis showed a significant survival advantage for the proliferation-dominant subtype (p < 0.0001). The prognostic implication has been further confirmed in the Cox proportional hazards model (HR 1.105, 95% CI 1.078–1.134, p < 0.0001). The survival of patients with proliferation-dominant HGA was significantly prolonged in association with extensive resection of the FLAIR abnormality region beyond contrast-enhancing tumor (p = 0.03), while no survival benefit was observed in association with the extensive resection in the diffusion-dominant subtype (p=0.86).CONCLUSIONSVFLAIR/VCE-T1WIis an important classifier that could divide the HGA into 2 subtypes with distinct invasive features. Patients with proliferation-dominant HGA can benefit from extensive resection of the FLAIR abnormality region, which provides the theoretical basis for a personalized resection strategy.

scholarly journals Adapting the Default Weighted Survival Analysis Modelling Approach to Model IFRS 9 LGD

Risks ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 103
Author(s):  
Morne Joubert ◽  
Tanja Verster ◽  
Helgard Raubenheimer ◽  
Willem D. Schutte
Keyword(s):  
Survival Analysis ◽  
Financial Reporting ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Survival Curve ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Reporting Standard ◽  
International Financial Reporting Standard ◽  
Ifrs 9

Survival analysis is one of the techniques that could be used to predict loss given default (LGD) for regulatory capital (Basel) purposes. When using survival analysis to model LGD, a proposed methodology is the default weighted survival analysis (DWSA) method. This paper is aimed at adapting the DWSA method (used to model Basel LGD) to estimate the LGD for International Financial Reporting Standard (IFRS) 9 impairment requirements. The DWSA methodology allows for over recoveries, default weighting and negative cashflows. For IFRS 9, this methodology should be adapted, as the estimated LGD is a function of in the expected credit losses (ECL). Our proposed IFRS 9 LGD methodology makes use of survival analysis to estimate the LGD. The Cox proportional hazards model allows for a baseline survival curve to be adjusted to produce survival curves for different segments of the portfolio. The forward-looking LGD values are adjusted for different macro-economic scenarios and the ECL is calculated for each scenario. These ECL values are probability weighted to produce a final ECL estimate. We illustrate our proposed IFRS 9 LGD methodology and ECL estimation on a dataset from a retail portfolio of a South African bank.

scholarly journals Risk factors associated with major adverse cardiac and cerebrovascular events following percutaneous coronary intervention: a 10-year follow-up comparing random survival forest and Cox proportional-hazards model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Farhadian ◽  
Sahar Dehdar Karsidani ◽  
Azadeh Mozayanimonfared ◽  
Hossein Mahjub
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Coronary Intervention ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Cerebrovascular Events ◽  
Long Term Follow Up ◽  
Stent Length

Abstract Background Due to the limited number of studies with long term follow-up of patients undergoing Percutaneous Coronary Intervention (PCI), we investigated the occurrence of Major Adverse Cardiac and Cerebrovascular Events (MACCE) during 10 years of follow-up after coronary angioplasty using Random Survival Forest (RSF) and Cox proportional hazards models. Methods The current retrospective cohort study was performed on 220 patients (69 women and 151 men) undergoing coronary angioplasty from March 2009 to March 2012 in Farchshian Medical Center in Hamadan city, Iran. Survival time (month) as the response variable was considered from the date of angioplasty to the main endpoint or the end of the follow-up period (September 2019). To identify the factors influencing the occurrence of MACCE, the performance of Cox and RSF models were investigated in terms of C index, Integrated Brier Score (IBS) and prediction error criteria. Results Ninety-six patients (43.7%) experienced MACCE by the end of the follow-up period, and the median survival time was estimated to be 98 months. Survival decreased from 99% during the first year to 39% at 10 years' follow-up. By applying the Cox model, the predictors were identified as follows: age (HR = 1.03, 95% CI 1.01–1.05), diabetes (HR = 2.17, 95% CI 1.29–3.66), smoking (HR = 2.41, 95% CI 1.46–3.98), and stent length (HR = 1.74, 95% CI 1.11–2.75). The predictive performance was slightly better by the RSF model (IBS of 0.124 vs. 0.135, C index of 0.648 vs. 0.626 and out-of-bag error rate of 0.352 vs. 0.374 for RSF). In addition to age, diabetes, smoking, and stent length, RSF also included coronary artery disease (acute or chronic) and hyperlipidemia as the most important variables. Conclusion Machine-learning prediction models such as RSF showed better performance than the Cox proportional hazards model for the prediction of MACCE during long-term follow-up after PCI.

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