Abstract 17220: Treatment Persistence and Discontinuation With Rivaroxaban, Dabigatran and Warfarin for Stroke Prevention in Patients With Non-valvular Atrial Fibrillation

Introduction: Continuous use of oral anticoagulant (OAC) therapy is essential for reducing the risk of stroke in patients with non-valvular atrial fibrillation. To date, no single study has compared persistence and discontinuation rates between rivaroxaban, dabigatran and warfarin users. Hypothesis: To compare persistence and discontinuation rates between rivaroxaban, dabigatran and warfarin users with non-valvular atrial fibrillation. Methods: A retrospective cohort analysis of the United States MarketScan claims databases was performed. This included adult patients newly initiated on rivaroxaban, dabigatran or warfarin between 1 November 2011 and 31 December 2013 with a baseline CHA2DS2-VASc score ≥2, ≥2 atrial fibrillation diagnosis codes (427.31) and ≥6 months of continuous medical and pharmacy benefits prior to OAC initiation (index date). Propensity score matching was performed in a two-step process to match patients on rivaroxaban with dabigatran 1:1 and with warfarin 1:1. Patients were followed until the earliest of in-hospital death, end of continuous enrolment or end of study period. Persistence was defined as absence of refill gap of >60 days. Discontinuation was defined as no additional refill for >90 days and through end of follow-up. Cox proportional hazards models were estimated to examine hazard ratios (HRs) of OAC non-persistence and discontinuation. Results: A total of 32,634 patients were included (N=10,878/OAC group). At 3 months’ follow-up, treatment persistence was 79.2%, 69.6% and 70.9% for rivaroxaban, dabigatran and warfarin users, respectively, dropping to 70.2%, 57.8% and 58.8% after 6 months, 60.1%, 44.7% and 42.0% after 1 year and 50.4%, 30.6% and 26.5% after 2 years. On regression, rivaroxaban use was associated with a decreased hazard of non-persistence compared with dabigatran (HR=0.64; 95% confidence interval [CI] 0.62-0.67) and warfarin (HR=0.62; 95% CI 0.59-0.64), and a decreased rate of discontinuation versus dabigatran (HR=0.61; 95% CI 0.58-0.64) and warfarin (HR=0.65; 95% CI 0.62-0.68). Conclusions: This matched patient analysis indicated significantly higher persistence and lower discontinuation rates with rivaroxaban compared with dabigatran and warfarin.

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P993Incidence of atrial fibrillation early after cavotricuspid isthmus ablation

EP Europace ◽

10.1093/europace/euaa162.184 ◽

2020 ◽

Vol 22 (Supplement_1) ◽

Author(s):

P Krisai ◽

O Streicher ◽

P Meyre ◽

P Haemmerle ◽

F Steiner ◽

...

Keyword(s):

Atrial Fibrillation ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Right Atrial ◽

Left Ventricular Ejection ◽

Proportional Hazards Models ◽

Holter Ecg ◽

Cavotricuspid Isthmus ◽

Cox Proportional Hazards Models

Abstract Background Atrial fibrillation (AF) is a common finding in patients undergoing cavotricuspid isthmus ablation for isthmus dependent right atrial flutter (RAF). Little is known about the time of its occurrence. Purpose We aimed to investigate the incidence of AF early after RAF ablation in a well-defined, prospective cohort. Methods A total of 255 participants with RAF ablation from 5 centers and at least one completed follow-up were included. Structured clinical follow-up was performed at 3, 6 and 12 months including a 24 hour Holter-ECG. The endpoint was incidence of AF detected clinically or by Holter-ECG. Risk factors associated with the occurrence of AF were assessed using separate, univariate Cox proportional-hazards models. Results Mean age was 67 years, 80% were male and previous episodes of AF were known in 40%. Over a mean follow-up of 7.4 (±4.4) months AF was detected in 35 (13.7%) participants after RAF ablation (Figure A). After 3, 6 and 12 months AF was detected in 18 (7.1%), 30 (11.7%) and 34 (13.3%) patients. No difference in the incidence of AF after RAF ablation was found comparing patients with and without a history of AF (log-rank p value = 0.44) (Figure B). Comparing patients with and without AF during follow-up, there was no difference in age (68 vs 66 years, p = 0.36), sex (69 vs 81% male, p = 0.08), prior heart failure (29 vs 19%, p = 0.20), hypertension (43 vs 38%, p = 0.56) or left atrial volume (46.6 vs 39.6 ml, p = 0.10), but patients with previous AF had a lower left ventricular ejection fraction (LVEF) (45.7 vs 52.3%, p = 0.02). In separate, univariate Cox proportional-hazards models only increasing LVEF (Hazard ratio 0.97, 95% confidence interval (0.95; 0.99, p = 0.02)) was associated with a lower risk of incident AF after RAF ablation, but no other risk factor. Conclusions AF occurred in 13.7% of patients early after cavotricuspid isthmus ablation for RAF. There was no difference in the occurrence of AF between patients with and without previously known episodes of AF. Only impaired LVEF was associated with AF occurrence. Abstract Figure

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Impact of cardiology follow-up care on treatment and outcomes of patients with new atrial fibrillation discharged from the emergency department

EP Europace ◽

10.1093/europace/euz302 ◽

2019 ◽

Vol 22 (5) ◽

pp. 695-703 ◽

Cited By ~ 4

Author(s):

Nathaniel M Hawkins ◽

Frank X Scheuermeyer ◽

Erik Youngson ◽

Roopinder K Sandhu ◽

Justin A Ezekowitz ◽

...

Keyword(s):

Atrial Fibrillation ◽

Emergency Department ◽

Proportional Hazards ◽

Beta Blockers ◽

Primary Diagnosis ◽

Cox Proportional Hazards ◽

Specialist Care ◽

Cox Proportional Hazards Models ◽

Time Varying Covariates

Abstract Aims The first presentation of atrial fibrillation (AF) is often to an emergency department (ED). We evaluated the association of subsequent specialist care with morbidity and mortality. Methods and results Retrospective cohort study of all adults in Alberta, Canada, with a new primary diagnosis of AF treated and released during an index ED visit between 2009 and 2015. Types of physician follow-up within 3 months of ED visit was analysed using Cox proportional hazards models with time-varying covariates. Outcomes were evaluated at 1 year. Of 7986 patients, 476 (6.0%) had no physician follow-up within 3 months, whereas 2730 (34.2%) attended a non-specialist only, 1277 (16.0%) an internal medicine specialist, and 3503 (43.9%) cardiology. An increasing gradient of cardiac investigations occurred across these groups. Cardiology compared with non-cardiologist care was associated with approximately two-fold greater electrophysiology interventions and revascularization, and increased use of beta-blockers (48.9% vs. 43.0%, P < 0.0001), statins (31.4% vs. 26.7%, P < 0.0001), and oral anticoagulation in patients with CHADS2 scores ≥1 (53.7% vs. 43.6%, P < 0.0001). In the subsequent year, cardiology care was associated with fewer deaths [adjusted hazard ratio (aHR) 0.72, 95% confidence interval (CI) 0.55–0.93], strokes (aHR 0.60, 95% CI 0.37–0.96), or major bleeds (aHR 0.69, 95% CI 0.53–0.89). No differences in the risk of hospitalization or ED visits were associated with cardiology care. Conclusion Cardiology care after an ED visit for symptomatic new-onset AF is associated with better prognosis. The benefit may be mediated through more intensive investigation, identification, and treatment of cardiovascular risk factors and disease.

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Stroke, Timing of Atrial Fibrillation Diagnosis, and Risk of Death

Neurology ◽

10.1212/wnl.0000000000011633 ◽

2021 ◽

Vol 96 (12) ◽

pp. e1655-e1662

Author(s):

Anjali Bhatla ◽

Yuliya Borovskiy ◽

Ronit Katz ◽

Matthew C. Hyman ◽

Parin J. Patel ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Inception Cohort ◽

Stroke Event ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

Multivariable Adjustment

ObjectiveTo evaluate the prognosis of patients with ischemic stroke according to the timing of an atrial fibrillation (AF) diagnosis, we created an inception cohort of incident stroke events and compared the risk of death between patients with stroke with (1) sinus rhythm, (2) known AF (KAF), and (3) AF diagnosed after stroke (AFDAS).MethodsWe used the Penn AF Free study to create an inception cohort of patients with incident stroke. Mortality events were identified after linkage with the National Death Index through June 30, 2017. We also evaluated initiation of anticoagulants and antiplatelets across the study duration. Cox proportional hazards models evaluated associations between stroke subtypes and death.ResultsWe identified 1,489 individuals who developed an incident ischemic stroke event: 985 did not develop AF at any point during the study period, 215 had KAF before stroke, 160 had AF detected ≤6 months after stroke, and 129 had AF detected >6 months after stroke. After a median follow-up of 4.9 years (interquartile range 1.9–6.8), 686 deaths occurred. The annualized mortality rate was 8.8% in the stroke, no AF group; 12.2% in the KAF group; 15.8% in the AFDAS ≤6 months group; and 12.7% in the AFDAS >6 months group. Patients in the AFDAS ≤6 months group had the highest independent risk of all-cause mortality even after multivariable adjustment for demographics, clinical risk factors, and the use of antithrombotic therapies (hazard ratio 1.62 [1.22–2.14]). Compared to the stroke, no AF group, those with KAF had a higher mortality risk that was rendered nonsignificant after adjustment.ConclusionsThe AFDAS group had the highest risk of death, which was not explained by comorbidities or use of antithrombotic therapies.

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Abstract 14354: Persistence to Oral Anticoagulation Treatment in Non-valvular Atrial Fibrillation Patients in the United States

Circulation ◽

10.1161/circ.142.suppl_3.14354 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Amol Dhamane ◽

Manuela Di Fusco ◽

Cynthia Gutierrez ◽

Mauricio Ferri ◽

Cristina Russ ◽

...

Keyword(s):

Atrial Fibrillation ◽

Lower Risk ◽

Proportional Hazards ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

The United States ◽

Cox Proportional Hazards ◽

Nonvalvular Atrial Fibrillation ◽

Cox Proportional Hazards Models ◽

Time Varying Covariates

Background: Studies have shown that nonvalvular atrial fibrillation (NVAF) patients who discontinue direct oral anticoagulants (DOAC) are at higher risk of complications, such as stroke. This analysis compared the risk of non-persistence of OACs among NVAF patients. Methods: Adult NVAF patients who initiated apixaban, dabigatran, rivaroxaban, or warfarin were identified using 01JAN2013-31MAR2019 data from the IQVIA commercial claims database. Non-persistence was defined as discontinuation (no evidence of index OAC use for 60 days from the last days’ of supply) or switch to another OAC. Kaplan-Meier (KM) curves were generated to illustrate time-to-non-persistence along with cumulative incidences of non-persistence. Adjusted cox proportional hazards models, including time-varying covariates (e.g., major bleeding, stroke), were used to evaluate non-persistence risk. Results: A total of 32,103 apixaban, 5,906 dabigatran, 29,385 rivaroxaban, and 21,420 warfarin patients were included; mean age: 63. Apixaban was associated with a lower risk of non-persistence compared to dabigatran (hazard ratio [HR]: 0.54; 95% confidence interval [CI]: 0.52-0.56), rivaroxaban (HR: 0.79; 95% CI: 0.78-0.81), and warfarin (HR: 0.66; 95% CI: 0.65-0.68). Dabigatran was associated with a higher risk of non-persistence compared to warfarin (HR: 1.23; 95% CI: 1.19-1.28) and rivaroxaban (HR: 1.47; 95% CI: 1.42-1.52), and rivaroxaban was associated with a lower risk compared to warfarin (HR: 0.84; 95% CI: 0.82-0.86). KM curves and cumulative incidences are presented below (Figure). Conclusions: In this group of NVAF patients, apixaban was associated with a significantly lower risk of non-persistence compared to dabigatran, rivaroxaban, and warfarin. Rivaroxaban was associated with a lower risk of non-persistence compared to warfarin and dabigatran. Such differences are critical as persistence with OACs is essential to prevent thromboembolic complications.

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Abstract TP413: Baseline Characteristics and Clinical Outcomes of a Non-valvular Atrial Fibrillation Patient Population Treated with Dabigatran or Warfarin - A Retrospective Database Analysis

Stroke ◽

10.1161/str.48.suppl_1.tp413 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Shannon L Reynolds ◽

Srinivas Annavarapu ◽

Chad Moretz ◽

Stephen Stemkowski ◽

Richard Sheer ◽

...

Keyword(s):

Atrial Fibrillation ◽

Risk Score ◽

Proportional Hazards ◽

Atrial Fibrillation Patient ◽

Bleeding Risk ◽

Cox Proportional Hazards ◽

Administrative Claims ◽

Principal Diagnosis ◽

Diagnosis Codes ◽

Cox Proportional Hazards Models

Objective: This study evaluated safety and effectiveness outcomes among non-valvular atrial fibrillation (NVAF) patients treated with dabigatran or warfarin using an administrative claims database. Methods: NVAF patients with no oral anticoagulant (OAC) use prior to their first prescription claim for FDA-approved dosages of either dabigatran or warfarin between 01-Oct-2010 and 30-Apr-2014 were identified. Patients aged 18-89 years with medical and pharmacy benefits were selected. Patients with valvular heart disease, transient causes of AF, or hyperthyroidism at baseline were excluded. Patients were followed until discontinuation of index medication, OAC switch, disenrollment, death, or end of observation period. Dabigatran and warfarin patients were propensity score matched (PSM, 1:2) using baseline demographics and clinical characteristics. Outcomes were measured either using diagnosis codes from all service lines in medical claims (Method A) or using an algorithm to derive principal diagnosis (Method B). Outcome measurements using Method B are comparable to prior database studies that used principal diagnosis. Safety and effectiveness outcomes of the matched cohorts were assessed using Cox-proportional hazards models. Results: A total of 7,245 dabigatran (1,016 receiving 75 mg and 6,229 receiving 150 mg) and 14,490 warfarin patients were analyzed (Table 1). The patients were 56% male, with a mean age of 74 years, mean CHADS 2 stroke risk score of 2.2, and mean HAS-BLED bleeding risk score of 3.4. Based on the hazard ratios, lower risks for primary (major bleeding) and secondary (hemorrhagic stroke, major intracranial bleeding, major extracranial bleeding [major urogenital and other bleeding], and death) outcomes were observed in the PSM dabigatran cohort compared to warfarin cohort (Method B). Conclusions: These results are largely consistent with findings from previous studies that support the benefits of dabigatran therapy in NVAF patients.

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Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

Journal of Clinical Medicine ◽

10.3390/jcm10071514 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1514

Author(s):

Hilde Espnes ◽

Jocasta Ball ◽

Maja-Lisa Løchen ◽

Tom Wilsgaard ◽

Inger Njølstad ◽

...

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Pressure Management ◽

Reference Models ◽

Proportional Hazards Regression ◽

Hazard Ratios ◽

Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

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Association of poor sleep burden in middle age and older adults with risk for delirium during hospitalization

The Journals of Gerontology Series A ◽

10.1093/gerona/glab272 ◽

2021 ◽

Author(s):

Ma Cherrysse Ulsa ◽

Xi Zheng ◽

Peng Li ◽

Arlen Gaba ◽

Patricia M Wong ◽

...

Keyword(s):

Sleep Disturbances ◽

Proportional Hazards ◽

Time Lag ◽

Cox Proportional Hazards ◽

Poor Sleep ◽

Cardiovascular Risks ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

The Uk

Abstract Background Delirium is a distressing neurocognitive disorder recently linked to sleep disturbances. However, the longitudinal relationship between sleep and delirium remains unclear. This study assessed the associations of poor sleep burden, and its trajectory, with delirium risk during hospitalization. Methods 321,818 participants from the UK Biobank (mean age 58±8y[SD]; range 37-74y) reported (2006-2010) sleep traits (sleep duration, excessive daytime sleepiness, insomnia-type complaints, napping, and chronotype–a closely-related circadian measure for sleep timing), aggregated into a sleep burden score (0-9). New-onset delirium (n=4,775) was obtained from hospitalization records during 12y median follow-up. 42,291 (mean age 64±8; range 44-83y) had repeat sleep assessment on average 8y after their first. Results In the baseline cohort, Cox proportional hazards models showed that moderate (aggregate scores=4-5) and severe (scores=6-9) poor sleep burden groups were 18% (hazard ratio 1.18 [95% confidence interval 1.08-1.28], p<0.001) and 57% (1.57 [1.38-1.80], p<0.001), more likely to develop delirium respectively. The latter risk magnitude is equivalent to two additional cardiovascular risks. These findings appeared robust when restricted to postoperative delirium and after exclusion of underlying dementia. Higher sleep burden was also associated with delirium in the follow-up cohort. Worsening sleep burden (score increase ≥2 vs. no change) further increased the risk for delirium (1.79 [1.23-2.62], p=0.002) independent of their baseline sleep score and time-lag. The risk was highest in those under 65y at baseline (p for interaction <0.001). Conclusion Poor sleep burden and worsening trajectory were associated with increased risk for delirium; promotion of sleep health may be important for those at higher risk.

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Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in “real-world” clinical practice

Thrombosis and Haemostasis ◽

10.1160/th17-01-0068 ◽

2017 ◽

Vol 117 (06) ◽

pp. 1072-1082 ◽

Cited By ~ 69

Author(s):

Xiaoyan Li ◽

Steve Deitelzweig ◽

Allison Keshishian ◽

Melissa Hamilton ◽

Ruslan Horblyuk ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Real World ◽

Proportional Hazards ◽

Significant Risk ◽

Haemorrhagic Stroke ◽

Cox Proportional Hazards ◽

Kaplan Meier ◽

Cox Proportional Hazards Models ◽

Warfarin Treatment

SummaryThe ARISTOTLE trial showed a risk reduction of stroke/systemic embolism (SE) and major bleeding in non-valvular atrial fibrillation (NVAF) patients treated with apixaban compared to warfarin. This retrospective study used four large US claims databases (MarketScan, PharMetrics, Optum, and Humana) of NVAF patients newly initiating apixaban or warfarin from January 1, 2013 to September 30, 2015. After 1:1 warfarin-apixaban propensity score matching (PSM) within each database, the resulting patient records were pooled. Kaplan-Meier curves and Cox proportional hazards models were used to estimate the cumulative incidence and hazard ratios (HRs) of stroke/SE and major bleeding (identified using the first listed diagnosis of inpatient claims) within one year of therapy initiation. The study included a total of 76,940 (38,470 warfarin and 38,470 apixaban) patients. Among the 38,470 matched pairs, 14,563 were from MarketScan, 7,683 were from PharMetrics, 7,894 were from Optum, and 8,330 were from Humana. Baseline characteristics were balanced between the two cohorts with a mean (standard deviation [SD]) age of 71 (12) years and a mean (SD) CHA2DS2-VASc score of 3.2 (1.7). Apixaban initiators had a significantly lower risk of stroke/SE (HR: 0.67, 95 % CI: 0.59–0.76) and major bleeding (HR: 0.60, 95 % CI: 0.54–0.65) than warfarin initiators. Different types of stroke/SE and major bleeding – including ischaemic stroke, haemorrhagic stroke, SE, intracranial haemorrhage, gastrointestinal bleeding, and other major bleeding – were all significantly lower for apixaban compared to warfarin treatment. Subgroup analyses (apixaban dosage, age strata, CHA2DS2-VASc or HAS-BLED score strata, or dataset source) all show consistently lower risks of stroke/SE and major bleeding associated with apixaban as compared to warfarin treatment. This is the largest “real-world” study on apixaban effectiveness and safety to date, showing that apixaban initiation was associated with significant risk reductions in stroke/SE and major bleeding compared to warfarin initiation after PSM. These benefits were consistent across various high-risk subgroups and both the standard-and low-dose apixaban dose regimens.Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.Supplementary Material to this article is available online at www.thrombosis-online.com.

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Efficacy outcomes of nivolumab + cabozantinib versus pembrolizumab + axitinib in patients with advanced renal cell carcinoma (aRCC): Matching-adjusted indirect comparison (MAIC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4578 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4578-4578

Author(s):

Bradley Alexander McGregor ◽

Daniel M. Geynisman ◽

Mauricio Burotto ◽

Camillo Porta ◽

Cristina Suarez Rodriguez ◽

...

Keyword(s):

Proportional Hazards ◽

Objective Response ◽

Indirect Comparison ◽

Progression Free Survival ◽

Wald Test ◽

Patient Characteristics ◽

Cox Proportional Hazards ◽

Published Data ◽

Cox Proportional Hazards Models

4578 Background: Nivolumab in combination with cabozantinib (N+C) has demonstrated significantly improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS), compared with sunitinib as a first-line (1L) treatment for aRCC in the phase 3 CheckMate (CM) 9ER trial. As there are no head-to-head trials comparing N+C with pembrolizumab in combination with axitinib (P+A), this study compared the efficacy of N+C with P+A as 1L treatment in aRCC. Methods: An MAIC was conducted using individual patient data on N+C (N = 323) from the CM 9ER trial (median follow-up: 23.5 months) and published data on P+A (N = 432) from the KEYNOTE (KN)-426 trialof P+A (median follow-up: 30.6 months). Individual patients within the CM 9ER trial population were reweighted to match the key patient characteristics published in KN-426 trial, including age, gender, previous nephrectomy, International Metastatic RCC Database Consortium risk score, and sites of metastasis. After weighting, hazards ratios (HR) of PFS, duration of response (DoR), and OS comparing N+C vs. P+A were estimated using weighted Cox proportional hazards models, and ORR was compared using a weighted Wald test. All comparisons were conducted using the corresponding sunitinib arms as an anchor. Results: After weighting, patient characteristics in the CM 9ER trial were comparable to those in the KN-426 trial. In the weighted population, N+C had a median PFS of 19.3 months (95% CI: 15.2, 22.4) compared to a median PFS of 15.7 months (95% CI: 13.7, 20.6) for P+A. Using sunitinib as an anchor arm, N+C was associated with a 30% reduction in risk of progression or death compared to P+A, (HR: 0.70, 95% CI: 0.53, 0.93; P = 0.015; table). In addition, N+C was associated with numerically, although not statistically, higher improvement in ORR vs sunitinib (difference: 8.4%, 95% CI: -1.7%, 18.4%; P = 0.105) and improved DoR (HR: 0.79; 95% CI: 0.47, 1.31; P = 0.359). Similar OS outcomes were observed for N+C and P+A (HR: 0.99; 95% CI: 0.67, 1.44; P = 0.940). Conclusions: After adjusting for cross-trial differences, N+C had a more favorable efficacy profile compared to P+A, including statistically significant PFS benefits, numerically improved ORR and DoR, and similar OS.[Table: see text]

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Abstract 2646: Aortic Arch Plaques and Risk of Vascular Events in Subjects Without Prior Stroke

Circulation ◽

10.1161/circ.118.suppl_18.s_760 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Cesare Russo ◽

Zhezhen Jin ◽

Ralph L Sacco ◽

Shunichi Homma ◽

Tatjana Rundek ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Aortic Arch ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Study Cohort ◽

Vascular Events ◽

Increased Risk ◽

Prior Stroke

BACKGROUND: Aortic arch plaques (AAP) are a risk factor for cardiovascular embolic events. However, the risk of vascular events associated with AAP in the general population is unclear. AIM: To assess whether AAP detected by transesophageal echocardiography (TEE) are associated with an increased risk of vascular events in a stroke-free cohort. METHODS: The study cohort consisted of stroke-free subjects over age 50 from the Aortic Plaques and Risk of Ischemic Stroke (APRIS) study. AAP were assessed by multiplane TEE, and considered large if ≥ 4 mm in thickness. Vascular events including myocardial infarction, ischemic stroke and vascular death were recorded during the follow-up. The association between AAP and outcomes was assessed by univariate and multivariate Cox proportional hazards models. RESULTS: A group of 209 subjects was studied (mean age 67±9 years; 45% women; 14% whites, 30% blacks, 56% Hispanics). AAP of any size were present in 130 subjects (62%); large AAP in 50 (24%). Subjects with AAP were older (69±8 vs. 63±7 years), had higher systolic BP (146±21 vs.139±20 mmHg), were more often white (19% vs. 8%), smokers (20% vs. 9%) and more frequently had a history of coronary artery disease (26% vs. 14%) than those without AAP (all p<0.05). Lipid parameters, prevalence of atrial fibrillation and diabetes mellitus were not significantly different between the two groups. During the follow up (94±29 months) 30 events occurred (13 myocardial infarctions, 11 ischemic strokes, 6 vascular deaths). After adjustment for other risk factors, AAP of any size were not associated with an increased risk of combined vascular events (HR 1.07, 95% CI 0.44 to 2.56). The same result was observed for large AAP (HR 0.94, CI 0.34 to 2.64). Age (HR 1.05, CI 1.01 to 1.10), body mass index (HR 1.08, CI 1.01 to 1.15) and atrial fibrillation (HR 3.52, CI 1.07 to 11.61) showed independent association with vascular events. In a sub-analysis with ischemic stroke as outcome, neither AAP of any size nor large AAP were associated with an increased risk. CONCLUSIONS: In this cohort without prior stroke, the incidental detection of AAP was not associated with an increased risk of future vascular events. Associated co-factors may affect the AAP-related risk of vascular events reported in previous studies.

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