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Using data from the SENSCIS trial, these analyses were undertaken to assess the effects of nintedanib versus placebo in subgroups of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), based on characteristics previously identified as being associated with the progression of SSc-ILD.Patients with SSc-ILD were randomized to receive either nintedanib or placebo, stratified by anti-topoisomerase I antibody (ATA) status. We assessed the rate of decline in forced vital capacity (FVC) (expressed in ml/year) over 52 weeks in subgroups based on baseline ATA status, modified Rodnan skin thickness score (MRSS) (18 versus ≥18), and SSc subtype (limited cutaneous SSc [lcSSc] versus diffuse cutaneous SSc [dcSSc]).At baseline, 60.8% of 576 patients who received treatment with either nintedanib or placebo were positive for ATA, 51.9% had dcSSc, and 77.5% of 574 patients with MRSS data available had an MRSS of18. The effect of nintedanib versus placebo on reducing the rate of decline in FVC (ml/year) was numerically more pronounced in ATA-negative patients compared to ATA-positive patients (adjusted difference in the rate of FVC decline, 57.2 ml/year [95% confidence interval (95% CI) -3.5, 118.0] versus 29.9 ml/year [95% CI -19.1, 78.8]), in patients with a baseline MRSS ≥18 compared to those with a baseline MRSS of18 (adjusted difference in the rate of FVC decline, 88.7 ml/year [95% CI 7.7, 169.8] versus 26.4 ml/year [95% CI -16.8, 69.6]), and in patients with dcSSc compared to those with lcSSc (adjusted difference in the rate of FVC decline, 56.6 ml/year [95% CI 3.2, 110.0] versus 25.3 ml/year [95% CI -28.9, 79.6]). However, all exploratory interaction P values were nonsignificant (all P 0.05), indicating that there was no heterogeneity in the effect of nintedanib versus placebo between these subgroups of patients.In patients with SSc-ILD, reduction in the annual rate of decline in FVC among patients receiving nintedanib compared to those receiving placebo was not found to be heterogenous across subgroups based on ATA status, MRSS, or SSc subtype.

Objective The aim of these analyses was to investigate the rate of decline in forced vital capacity (FVC) in patients with SSc-associated interstitial lung disease (SSc-ILD) with and without cough or dyspnoea in the SENSCIS trial. Methods Patients in the SENSCIS trial were randomized to receive nintedanib or placebo. Subgroups with and without cough or dyspnoea at baseline were defined by responses to the St George’s Respiratory Questionnaire. Results At baseline, 114/575 patients (19.8%) did not have cough and 172/574 patients (30.0%) did not have dyspnoea. In the placebo group, the rate of FVC decline over 52 weeks was similar in patients with and without cough (−95.6 and −83.4 mL/year, respectively) or dyspnoea (−95.8 and −87.7 mL/year, respectively). The effect of nintedanib vs placebo on reducing the rate of FVC decline was numerically more pronounced in patients without than with cough [difference: 74.4 (95% CI −11.1, 159.8) vs 31.5 (−11.1, 74.1)] and without than with dyspnoea [79.8 (9.8, 149.7) vs 25.7 (−19.9, 71.3)], but interaction P-values did not indicate heterogeneity in the treatment effect between these subgroups (P = 0.38 and P = 0.20, respectively). Conclusion In the placebo group of the SENSCIS trial, the rate of FVC decline was similar irrespective of the presence of cough or dyspnoea at baseline. The effect of nintedanib on reducing the rate of FVC decline was numerically more pronounced in patients without than with cough or dyspnoea at baseline, but no statistically significant heterogeneity was observed between the subgroups. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT02597933.

Background: Little is known about the optimal antithrombotic therapy in patients with atrial fibrillation undergoing PCI for ST-elevation myocardial infarction (STEMI). Aims: The aim of this study was to investigate the safety and efficacy of dabigatran dual therapy (110 or 150 mg twice daily, plus clopidogrel or ticagrelor) versus warfarin triple therapy in patients with atrial fibrillation and STEMI. Methods: In the RE-DUAL PCI trial, 305 patients with STEMI were randomised to dabigatran 110 mg (n=113 versus 106 warfarin) or 150 mg (n=86 versus 84 warfarin). The primary endpoint was the time to first major/clinically relevant non-major bleeding event (MBE/CRNMBE). The thrombotic endpoint was a composite of death, thromboembolic events, or unplanned revascularisation. Results: In STEMI patients, dabigatran 110 mg (HR 0.39, 95% CI: 0.20-0.74) and 150 mg (0.43, 0.21-0.89) dual therapy reduced the risk of MBE/CRNMBE versus warfarin triple therapy (p for interaction vs all other patients=0.31 and 0.16). The risk of thrombotic events for dabigatran 110 mg (HR 1.61, 95% CI: 0.85-3.08) and 150 mg (0.56, 0.20-1.51) had p interactions of 0.20 and 0.33, respectively. For net clinical benefit, the HRs were 0.74 (95% CI: 0.46-1.17) and 0.49 (0.27-0.91) for dabigatran 110 and 150 mg (p for interaction=0.80 and 0.12), respectively. Conclusions: After PCI for STEMI, patients on dabigatran dual therapy had lower risks of bleeding events versus warfarin triple therapy with similar risks of thromboembolic events, supporting dabigatran dual therapy even in patients with high thrombotic risk.

Aims Patients with atrial fibrillation undergoing coronary intervention are at higher bleeding risk due to the concomitant need for oral anticoagulation and antiplatelet therapy. The RE-DUAL PCI trial demonstrated better safety with dual antithrombotic therapy (DAT: dabigatran 110 or 150 mg b.i.d., clopidogrel or ticagrelor) compared to triple antithrombotic therapy (TAT: warfarin, clopidogrel or ticagrelor, and aspirin). We explored the impact of baseline bleeding risk based on the PRECISE-DAPT score for decision-making regarding DAT vs. TAT. Methods and results A score ≥25 points qualified high bleeding risk (HBR). Comparisons were made for the primary safety endpoint International Society of Thrombosis and Haemostasis major or clinically relevant non-major bleeding, and the composite efficacy endpoint of death, thrombo-embolic events, or unplanned revascularization, analysed by time-to-event analysis. PRECISE-DAPT was available in 2336/2725 patients, and 37.9% were HBR. Compared to TAT, DAT with dabigatran 110 mg reduced bleeding risk both in non-HBR [hazard ratio (HR) 0.42, 95% confidence interval (CI) 0.31–0.57] and HBR (HR 0.70, 95% CI 0.52–0.94), with a greater magnitude of benefit among non-HBR (Pint = 0.02). Dual antithrombotic therapy with dabigatran 150 mg vs. TAT reduced bleeding in non-HBR (HR 0.60, 95% CI 0.45–0.80), with a trend toward less benefit in HBR patients (HR 0.92, 95% CI 0.63–1.34; Pint = 0.08). The risk of ischaemic events was similar on DAT with dabigatran (both 110 and 150 mg) vs. TAT in non-HBR and HBR patients (Pint = 0.45 and Pint = 0.56, respectively). Conclusions PRECISE-DAPT score appeared useful to identify AF patients undergoing PCI at further increased risk of bleeding complications and may help clinicians identifying the antithrombotic regimen intensity with the best benefit–risk ratio in an individual patient.

Background The RE-DUAL PCI trial demonstrated that in patients with nonvalvular atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), dual therapy with dabigatran and a P2Y12 inhibitor, either clopidogrel or ticagrelor, reduced the risk of bleeding without an increased risk of thromboembolic events as compared to triple therapy with warfarin in addition to a P2Y12 inhibitor and aspirin. What remains unclear is whether this effect is consistent between males and females undergoing PCI. Hypothesis The reduction in risk of bleeding without increased risk of thromboembolic events with dual therapy with dabigatran and a P2Y12 inhibitor in comparison to triple therapy with warfarin, a P2Y12 inhibitor and aspirin is consistent in females and males. Methods The primary safety endpoint was the first International Society on Thrombosis and Hemostasis (ISTH) major bleeding event (MBE) or clinically relevant non-major bleeding event (CRNMBE). The efficacy endpoint was the composite of death, thromboembolic event (stroke, myocardial infarction, and systemic embolism) or unplanned revascularization. Cox proportional hazard regression analyses were applied to calculate corresponding hazard ratios and interaction p values for each endpoint. Results A total of 655 women and 2070 men were enrolled. The risk of major or CRNM bleeding was lower with both dabigatran 110 mg dual therapy and dabigatran 150 mg dual therapy compared with warfarin triple therapy in female and male patients (for 110 mg: females: HR 0.69, 95% CI 0.47-1.01, males: HR 0.46, 95% CI 0.37-0.59, interaction p value: 0.084 and for 150 mg: females HR 0.74, 95% CI 0.48-1.16, males HR 0.71, 95% CI 0.56-0.90, interaction p value: 0.83). There was also no detectable difference in the composite efficacy endpoint of death, thromboembolic events or unplanned revascularization between dabigatran dual therapy and warfarin triple therapy, with no statistically significant interaction between sex and treatment (interaction p values: 0.73 and 0.72, respectively). Conclusions Consistent with the overall study results, the risk of bleeding was lower with dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy, and risk of thromboembolic events was comparable with warfarin triple therapy independent of the patient's sex.

Previous standard of care for patients with atrial fibrillation and percutaneous coronary intervention (PCI) was triple therapy including warfarin and dual antiplatelet therapy, but new strategies have been developed to reduce bleeding risk while maintaining antithrombotic efficacy using direct oral

Time in therapeutic range (TTR) predicts risk of thromboembolic and bleeding events in patients on vitamin K antagonists (VKAs). Guidelines recommend maintaining the international normalized ratio (INR) between 2.0 to 3.0 for an average TTR ≥70% to prevent stroke and minimize bleeds in patients

BACKGROUND: In the RE-DUAL PCI trial of patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI), dabigatran dual therapy (110 or 150 mg bid, plus clopidogrel or ticagrelor) reduced International Society on Thrombosis and Haemostasis bleeding events compared with warfarin triple therapy, with noninferiority in overall thromboembolic events. This analysis assessed outcomes in relation to patient bleeding and stroke risk profiles, based on the modified HAS-BLED and CHA2DS2-VASc scores.METHODS: The primary endpoint, major bleeding event (MBE) or clinically relevant nonmajor bleeding event (CRNMBE), was compared across study arms in patients categorized by modified HAS-BLED score 0-2 or ≥3. The composite endpoint of death, thromboembolic event, and unplanned revascularization rates was compared in patients categorized by CHA2DS2-VASc score 0-1, 2, or ≥3.RESULTS: Risk of MBE or CRNMBE was lower with dabigatran dual therapy (both doses) versus warfarin triple therapy, irrespective of modified HAS-BLED category (treatment-by-subgroup interaction P-value 0.584 and 0.273 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin). Risk of the composite thromboembolic endpoint was similar across CHA2DS2-VASc categories and consistent with overall study results (interaction P-value 0.739 and 0.075 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin). Higher HAS-BLED scores were associated with higher risks of bleeding in AF patients after PCI in a treatment-independent analysis.CONCLUSION: Dabigatran dual therapy reduced bleeding events irrespective of bleeding risk category and demonstrated similar efficacy regardless of stroke risk category when compared with warfarin triple therapy.

OBJECTIVES The aim of this study was to explore the early versus late benefits and risks of dabigatran dual therapy versus warfarin triple therapy in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabi-gatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.BACKGROUND Patients with atrial fibrillation who undergo percutaneous coronary intervention are at increased risk for both bleeding and thrombotic events.METHODS A total of 2,725 patients with atrial fibrillation underwent percutaneous coronary intervention and were randomized to receive dabigatran 110 mg, or dabigatran 150 mg plus a P2Y(12) inhibitor (and no aspirin), or warfarin plus a P2Y(12) inhibitor plus aspirin. Landmark analysis was performed at 30 and 90 days.RESULTS There was a consistent and large reduction in major or clinically relevant nonmajor bleeding in patients randomized to dual therapy during the first 30 days (110 mg: hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.31 to 0.66; p < 0.0001; 150 mg: HR: 0.46; 95% CI: 0.30 to 0.72; p = 0.0006) compared with warfarin triple therapy. There was early net clinical benefit in both dabigatran groups versus warfarin (110 mg: HR: 0.65; 95% CI: 0.47 to 0.88; p = 0.0062; 150 mg: HR: 0.54; 95% CI: 0.37 to 0.79; p = 0.0015), due to larger reductions in bleeding than increased thrombotic events for dabigatran 110 mg and bleeding reduction without increased thrombotic risk for dabigatran 150 mg dual therapy versus warfarin triple therapy. After the removal of aspirin in the warfarin group, bleeding remained lower with dabigatran 110 mg and was similar with dabigatran 150 mg versus warfarin.CONCLUSIONS In RE-DUAL PCI, in which patients in the dual-therapy arms were treated with aspirin for an average of only 1.6 days, there was early net clinical benefit with both doses of dabigatran dual therapy, without an increase in thrombotic events with dabigatran 150 mg. This could be helpful in the subset of patients with elevated risk for both bleeding and thrombotic events. (c) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Copyright © 2021 by World Stroke Organization., Background: The effect of different anticoagulants on recanalization after cerebral venous thrombosis has not been studied in a randomized controlled trial. Methods: RE-SPECT CVT (ClinicalTrials.gov number: NCT02913326) was a Phase III, prospective, randomized, parallel-group, open-label, multicenter, exploratory trial with blinded endpoint adjudication. Acute cerebral venous thrombosis patients were allocated to dabigatran 150 mg twice daily, or dose-adjusted warfarin, for 24 weeks, after 5-15 days' treatment with unfractionated or low-molecular-weight heparin. A standardized magnetic resonance protocol including arterial spin labeling, three-dimensional time-of-flight venography, and three-dimensional contrast-enhanced magnetic resonance angiography was obtained at the end of the treatment period. Cerebral venous recanalization at six months was assessed by two blinded adjudicators, using the difference in a score of occluded sinuses and veins (predefined secondary efficacy endpoint) and in the modified Qureshi scale (additional endpoint), between baseline and the end of the treatment. Results: Of 120 cerebral venous thrombosis patients randomized, venous recanalization could be evaluated in 108 (55 allocated to dabigatran and 53 to warfarin, 1 patient had a missing occlusion score at baseline). No patient worsened in the score of occluded cerebral veins and sinuses, while 33 (60%) on dabigatran and 35 (67%) on warfarin improved. The mean score change from baseline in the occlusion score was similar in the two treatment groups (dabigatran -0.8, SD 0.78; warfarin -1.0, SD 0.92). In the modified Qureshi score, full recanalization was adjudicated in 24 (44%) and 19 (36%), and partial recanalization in 23 (42%) and 26 (49%) patients in the dabigatran and warfarin arms, respectively. No statistically significant treatment difference in the modified Qureshi score could be detected (p = 0.44). Conclusion: The majority of patients with cerebral venous thrombosis, anticoagulated with either dabigatran or warfarin for six months, showed partial or complete recanalization of occluded sinuses and veins at the end of the treatment.

Background: Body mass index (BMI) affects drug levels of nonvitamin K antagonist oral anticoagulants. We sought to assess whether BMI affected outcomes in the RE-DUAL PCI trial. Methods: RE-DUAL PCI (NCT02164864) evaluated the safety and efficacy of a dual-antithrombotic-therapy regimen using dabigatran (110 mg or 150 mg twice daily and a P2Y12 platelet antagonist) in comparison with triple therapy of warfarin, aspirin, and a P2Y12 platelet inhibitor in 2725 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI). We compared the risk of first International Society on Thrombosis and Haemostasis (ISTH)-defined major or clinically relevant nonmajor bleeding events (primary endpoint) and the composite of death, myocardial infarction, stroke, systemic embolism, or unplanned revascularization (main efficacy endpoint) in relation to baseline BMI. Results: Median (range) BMI was 28.1 (14-66) kg/m2. Dabigatran dual therapy versus warfarin triple therapy had relevantly and similarly lower rates of bleeding at both 110 mg and 150 mg twice-daily doses, irrespective of BMI. Thromboembolic event rates appeared consistent across categories of BMI, including those, This work was supported by Boehringer Ingelheim International GmbH.

Introduction: Previous studies suggested there may be an association between gastroesophageal reflux disease (GERD) or use of anti-acid therapy (AAT) and progression of SSc-ILD. In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in FVC vs placebo. Aim: Investigate FVC decline and adverse events (AEs) by use of AAT at baseline in the SENSCIS trial. Methods: In post-hoc analyses, we investigated the rate of decline in FVC over 52 weeks in subgroups by AAT use at baseline. AEs were assessed descriptively. Results: Of 576 patients randomized to nintedanib (n=288) or placebo (n=288), 79.3% took AAT at baseline. The annual rate of FVC decline was numerically greater in patients taking vs not taking AAT at baseline in the placebo group (99.6 vs 70.2 mL/year) and the nintedanib group (55.8 vs 39.6 mL/year). The effect of nintedanib vs placebo on reducing the annual rate of FVC decline was similar between patients taking (difference: 43.7 mL/year [95% CI 0.9, 86.6]; relative difference: 43.9%) and not taking (difference: 30.6 mL/year [-52.1, 113.3]; relative difference: 43.6%) AAT at baseline (p=0.78 for interaction). In the nintedanib and placebo groups, respectively, the proportions of patients with serious AEs were 27.5% and 21.1% in those taking AAT and 10.2% and 23.3% in those not taking AAT. Conclusion: Post-hoc analyses of data from the SENSCIS trial suggest that the effect of nintedanib on reducing FVC decline in patients with SSc-ILD was similar between patients taking and not taking AAT at baseline. Confounding factors limit interpretation of the differences observed between subgroups based on use of AAT. The effects of GERD and AAT in patients with SSc-ILD warrant further study.

Background and Objective In patients with atrial fibrillation following percutaneous coronary intervention, if a proton pump inhibitor is used, could that allow the use of warfarin triple therapy, or is there additional reduction in bleeding while using it with dual therapy? Methods The RE-DUAL PCI trial randomized 2725 patients with atrial fibrillation post-percutaneous coronary intervention to dabigatran dual therapy (110 or 150 mg twice daily, with clopidogrel or ticagrelor) or warfarin triple therapy (with clopidogrel or ticagrelor, and aspirin for 1–3 months). This prespecified subgroup analysis evaluated risks of a first major bleeding event or clinically relevant non-major bleeding event, all gastrointestinal bleeding, and a composite efficacy endpoint of all-cause mortality/thromboembolic event or unplanned revascularization according to baseline use of a proton pump inhibitor. Results Of 2678 analyzed patients, 1641 (61.3%) were receiving a proton pump inhibitor at baseline. Dabigatran 110 and 150 mg dual therapy reduced the risk of major bleeding events or clinically relevant non-major bleeding events vs warfarin triple therapy regardless of proton pump inhibitor use, with comparable risk of the composite efficacy endpoint (all interaction p values > 0.05). For gastrointestinal bleeding, no interaction was observed between study treatment and proton pump inhibitor use (interaction p values 0.84 and 0.62 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin triple therapy). Conclusions Dabigatran 110 and 150 mg dual therapy reduced the risk of major bleeding events or clinically relevant non-major bleeding events vs warfarin triple therapy, regardless of proton pump inhibitor use at baseline, in patients with atrial fibrillation who underwent percutaneous coronary intervention. Risk of the composite efficacy endpoint appeared to be similar for dabigatran dual therapy vs warfarin triple therapy in patients receiving/not receiving a proton pump inhibitor. ClinicalTrials.gov unique identifier NCT02164864. Video abstract Electronic supplementary material The online version of this article (10.1007/s40265-020-01323-x) contains supplementary material, which is available to authorized users.

The RE-DUAL PCI trial reported that dabigatran dual therapy (110/150 mg twice daily, plus clopidogrel or ticagrelor) reduced bleeding events versus warfarin triple therapy (warfarin plus aspirin and clopidogrel or ticagrelor) in patients with atrial fibrillation who underwent percutaneous coronary intervention, with noninferiority in composite thromboembolic events. In this prespecified analysis, risks of first major or clinically relevant nonmajor bleeding event and composite end point of death, thromboembolic events, or unplanned revascularization were compared between dabigatran dual therapy and warfarin triple therapy in older (≥ 75 years) and younger (< 75 years) patients, using Cox proportional hazard regression. Of 2,725 patients randomized to treatment, 1,026 (37.7%) were categorized into older and 1,699 (62.3%) into younger age groups. Dabigatran 110 mg dual therapy lowered bleeding risk versus warfarin triple therapy in older (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.51 to 0.89) and younger patients (HR 0.40; 95% CI 0.30 to 0.54); interaction p value: 0.0125. Dabigatran 150 mg dual therapy lowered bleeding risk versus warfarin triple therapy in younger patients (HR 0.57; 95% CI 0.44 to 0.74), whereas no benefit could be observed in older patients (HR 1.21; 95% CI 0.83 to 1.77); interaction p value: 0.0013. For the thromboembolic end point, there was a trend for a higher risk with dabigatran 110 mg dual therapy in older patients, compared with warfarin triple therapy, whereas the risk was similar in younger patients. For dabigatran 150 mg dual therapy, the thromboembolic risk versus warfarin triple therapy was similar in older and younger patients. In conclusion, the benefits of dabigatran dual therapy differed in the 2 age groups, which may help dose selection when using dabigatran dual therapy.

Body mass index (BMI) affects drug levels of nonvitamin K antagonist oral anticoagulants. We sought to assess whether BMI affected outcomes in the RE-DUAL PCI trial.RE-DUAL PCI (NCT02164864) evaluated the safety and efficacy of a dual-antithrombotic-therapy regimen using dabigatran (110 mg or 150 mg twice daily and a P2YMedian (range) BMI was 28.1 (14-66) kg/mThe reduction in bleeding with dabigatran dual therapy compared with warfarin triple therapy in patients here evaluated appears consistent across BMI categories.

Funding Acknowledgements Boehringer Ingelheim International GmbH On Behalf The Re-DUAL PCI Investigators Background The RE-DUAL PCI study (NCT02164864) compared dabigatran dual antithrombotic therapy (D-DAT) with warfarin triple antithrombotic therapy (W-TAT) in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). As previously reported D-DAT reduced bleeding compared with W-TAT and was non-inferior with regard to thromboembolic events. Aim The aim of this subgroup analysis of RE-DUAL was to assess the relationship between sex and treatment effects of D-DAT and W-TAT on bleeding and thromboembolic outcomes. Methods Patients were randomized to receive W-TAT (warfarin, clopidogrel or ticagrelor, and aspirin) or D-DAT (dabigatran 110 or 150 mg twice daily with clopidogrel or ticagrelor; D110- or D150-DAT). Younger patients (aged < 80 yrs. [< 70 yrs. in Japan]) and US patients irrespective of age received D110-DAT, D150-DAT or W-TAT; older patients (aged ≥ 80 yrs. in non-US countries [≥ 70 yrs. in Japan]) received only D110-DAT or W-TAT. Bleeding and thromboembolic outcomes were assessed according to treatment group and by sex (female vs. male). Results A total of 2725 patients were randomized; 2070 patients were male (76.0%) and 655 (24.0%) were female. Overall females were older at time of PCI than males (73.2 ± 7.9 vs. 70.0 ± 8.8 years). The mean CHA2DS2-VASc and modified HAS-BLED scores were higher in women at 4.5 and 2.8, respectively, than in men at 3.3 and 2.7, respectively. For the primary endpoint of major bleeding events or clinically relevant non-major bleeding events, treatment effects of D110-DAT vs. W-TAT were consistent for female and male patients (females: HR 0.69, 95% CI 0.47-1.01, males HR 0.46, 95%CI 0.37-0.59, interaction p-value 0.084). Similarly, consistent treatment effects were seen for the primary endpoint with D150-DAT vs W-TAT in female and male patients (females HR 0.74, 95% CI 0.48-1.16, males HR 0.71, 95% CI 0.56-0.90, interaction p value 0.83). No interaction between sex and treatment was observed for D110- or D150-DAT vs W-TAT with regard to the composite efficacy endpoint of death, thromboembolic events or unplanned revascularization (interaction p values 0.73 and 0.72, respectively) (figure). Conclusion The treatment effect of dabigatran 110 mg and 150 mg dual therapy vs warfarin triple therapy was consistent across sex groups. This suggests that female and male patients with AF undergoing PCI should be treated equally in terms of the dosage of dabigatran selected for dual therapy strategies. Abstract P34 Figure. Re-DUAL sex subgroup analysis

Background and Purpose: This analysis examined the frequency of dural arteriovenous fistulae (dAVF) after cerebral venous thrombosis (CVT) in patients included in a randomized controlled trial comparing dabigatran etexilate with dose-adjusted warfarin (RE-SPECT CVT [A Clinical Trial Comparing Efficacy and Safety of Dabigatran Etexilate With Warfarin in Patients With Cerebral Venous and Dural Sinus Thrombosis]), who had systematic follow-up magnetic resonance (MR) imaging. Methods: RE-SPECT CVT was a Phase 3, prospective, randomized, parallel-group, open-label, multicenter, exploratory trial with blinded end point adjudication. We allocated patients with acute CVT to dabigatran 150 mg twice daily or dose-adjusted warfarin, for 24 weeks and obtained a standardized MR protocol including time-of-flight MR angiography, 3-dimensional phase-contrast venography, and 3-dimensional contrast-enhanced MR venography at the end of the treatment period. A blinded adjudication committee assessed the presence of dAVF in a predefined substudy of the trial. Results: We analyzed development of dAVF in 112 of 120 randomized patients; 57 allocated to dabigatran and 55 to warfarin. For 3 (2.7%) of these 112 patients, quality of follow-up imaging was insufficient to evaluate dAVF. A dAVF (Borden I) was found in 1 patient (0.9%) allocated to warfarin; however, this dAVF was already present at baseline. The patient did not present with hemorrhage at baseline or during the trial and was asymptomatic at follow-up. Conclusions: Despite systematic imaging, we found no new dAVF 6 months after CVT. Routine follow-up cerebral MR angiography aiming to detect new dAVF 6 months after CVT has a very low yield. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02913326.

Background: The REDUAL PCI trial (Evaluation of Dual Therapy With Dabigatran vs Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting) demonstrated that, in patients with atrial fibrillation following percutaneous coronary intervention, bleeding risk was lower with dabigatran plus clopidogrel or ticagrelor (dual therapy) than warfarin plus clopidogrel or ticagrelor and aspirin (triple therapy). Dual therapy was noninferior for risk of thromboembolic events. Whether these results apply equally to patients at higher risk of ischemic events due to lesion complexity or clinical risk factors is unclear. Methods: The primary end point was time to first major or clinically relevant nonmajor bleeding event. The composite efficacy end point was death, thromboembolic event, or unplanned revascularization. Our prespecified subgroup analysis categorized patients by presence of procedural complexity and/or clinical complexity factors at baseline. A modified dual antiplatelet therapy score categorized patients according to degree of clinical risk. Results: Of 2725 patients, 43.1% had clinical complexity factors alone, 9.9% procedural factors alone, 10.0% both, and 37.0% neither. Risk of the primary bleeding end point was lower in both dabigatran dual therapy groups than warfarin triple therapy groups, regardless of procedural and/or clinical lesion complexity (interaction P values: 0.90 and 0.37, respectively). Importantly, a similar risk of the efficacy end point was observed between dabigatran dual and warfarin triple therapy, regardless of the presence of clinical or procedural complexity factors (interaction P values: 0.67 and 0.54, dabigatran 110 and 150 mg dual therapy, respectively). Similar benefit was seen for each dose of dabigatran dual therapy for bleeding events regardless of dual antiplatelet therapy score (interaction P values: 0.53 and 0.54, respectively), with similar risk of thromboembolic events (interaction P values: 0.20 and 0.08, respectively). Conclusions: In patients with atrial fibrillation undergoing percutaneous coronary intervention, dabigatran 110 and 150 mg dual therapy reduced bleeding risk compared with warfarin triple therapy, with a similar risk of thromboembolic outcomes, irrespective of procedural and/or clinical complexity and modified dual antiplatelet therapy score. Registration: URL: https://clinicaltrials.gov/ ; Unique identifier: NCT02164864.

OBJECTIVES: The aim of this study was to evaluate dabigatran dual therapy versus warfarin triple therapy in patients with or without diabetes mellitus in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.BACKGROUND: It is unclear whether dual therapy is as safe and efficacious as triple therapy in patients with atrial fibrillation with diabetes following percutaneous coronary intervention.METHODS: In RE-DUAL PCI, 2,725 patients with atrial fibrillation (993 with diabetes) who had undergone PCI were assigned to warfarin triple therapy (warfarin, clopidogrel or ticagrelor, and aspirin) or dabigatran dual therapy (dabigatran 110 mg or 150 mg twice daily and clopidogrel or ticagrelor). Median follow-up was 13 months. The primary outcome was the composite of major bleeding or clinically relevant nonmajor bleeding, and the main efficacy outcome was the composite of death, thromboembolic events, or unplanned revascularization.RESULTS: Among patients with diabetes, the incidence of major bleeding or clinically relevant nonmajor bleeding was 15.2% in the dabigatran 110 mg dual therapy group versus 27.5% in the warfarin triple therapy group (hazard ratio [HR]: 0.48; 95% confidence interval [CI] 0.35 to 0.67) and 23.8% in the dabigatran 150 mg dual therapy group versus 25.1% in the warfarin triple therapy group (HR: 0.87; 95% CI: 0.62 to 1.22). Risk for major bleeding or clinically relevant nonmajor bleeding was also reduced with both dabigatran doses among patients without diabetes (dabigatran 110 mg dual therapy: HR: 0.54; 95% CI: 0.42 to 0.70; dabigatran 150 mg dual therapy: HR: 0.63; 95% CI: 0.48 to 0.83). Risk for the efficacy endpoint was comparable between treatment groups for both patients with and those without diabetes. No interaction between treatment and diabetes subgroup could be observed, either for bleeding or for composite efficacy endpoints.CONCLUSIONS: In this subgroup analysis, dabigatran dual therapy had a lower risk for bleeding and a comparable rate of the efficacy endpoint compared with warfarin triple therapy in patients with atrial fibrillation with or without diabetes following percutaneous coronary intervention.

Background:SSc is a heterogeneous autoimmune disease characterised by fibrosis of the skin and internal organs. In most patients with SSc-ILD, organs other than the lungs are also affected. In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in forced vital capacity (FVC) (mL/year) over 52 weeks by 44% versus placebo.Objectives:We investigated the extent of organ involvement related to SSc at baseline in patients in the SENSCIS trial and the effect of nintedanib versus placebo on the rate of FVC decline in subgroups by internal organ involvement.Methods:The SENSCIS trial enrolled patients with SSc-ILD with first non-Raynaud symptom ≤7 years before screening, extent of fibrotic ILD ≥10% on high-resolution computed tomography (HRCT) and FVC ≥40% predicted. Patients with clinically significant pulmonary hypertension were excluded. Patients were randomised to receive nintedanib or placebo until the last patient reached week 52 but for ≤100 weeks. In post-hoc analyses, we analysed the rate of decline in FVC (mL/year) over 52 weeks in subgroups with and without different types of SSc-related internal organ involvement (upper gastrointestinal; lower gastrointestinal; cardiovascular [CV]; peripheral vascular; muscular; joint). These subgroups were defined based on patients’ SSc-related medical history as reported in the case report form. A random slope and intercept model was used to assess the rate of decline in FVC (mL/year) and an interaction test applied to assess potential heterogeneity in the treatment effect of nintedanib between the subgroups.Results:Of 576 patients, 96.9% had peripheral vascular involvement, 75.5% had upper gastrointestinal and 39.8% lower gastrointestinal involvement, 45.7% had CV involvement, 40.6% had joint involvement, and 27.1% had muscular involvement at baseline. In the placebo group, the rate of decline in FVC (mL/year) was numerically greater in patients with than without upper gastrointestinal involvement and in patients without than with joint involvement or muscular involvement (Figure). The exploratory interaction p-values did not indicate heterogeneity in the treatment effect of nintedanib versus placebo on reducing the rate of decline in FVC (mL/year) between the subgroups based on organ involvement (p>0.05 for all treatment-by-time-by-subgroup interactions) (Figure).Conclusion:Patients in the SENSCIS trial had diverse complications related to SSc. There was no evidence of a differential treatment effect of nintedanib on reducing the rate of decline in FVC based on gastrointestinal, CV, joint, or muscular involvement at baseline.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by FleishmanHillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Yannick Allanore Consultant of: Boehringer Ingelheim, Medsenic, Menarini and Sanofi, Grant/research support from: Alpine Pharmaceuticals, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Lilly, MSD and Roche, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, MSD and Roche, Grant/research support from: Boehringer Ingelheim, Maureen Mayes Consultant of: Paid consultant or member of Advisory Board/Steering Committee for Boehringer Ingelheim, Eicos, Galapagos and Mitsubishi Tanabe Pharma, Grant/research support from: Clinical trial research support from Boehringer Ingelheim, Corbus, Eicos and Galapagos, Madelon Vonk Speakers bureau: Boehringer Ingelheim, GlaxoSmithKline, Janssen and Roche, Consultant of: Boehringer Ingelheim and Janssen, Grant/research support from: Boehringer Ingelheim, Ferrer, Galapagos and Janssen, Corinna Miede Employee of: Currently an employee of mainanalytics GmbH, contracted by Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Gabriela Riemekasten Speakers bureau: Actelion, Boehringer Ingelheim, Cellgene, GlaxoSmithKline, Janssen, Novartis and Roche, Consultant of: Actelion, Boehringer Ingelheim and Janssen, Grant/research support from: Janssen

Background:Some patients with SSc-ILD develop dyspnoea secondary to parenchymal lung disease, while others do not report dyspnoea even when their lung function is impaired. It is unclear whether the presence of dyspnoea is associated with a worse course of SSc-ILD or with response to therapy.Objectives:To investigate the rate of decline in FVC in patients with SSc-ILD in the SENSCIS trial in subgroups by patient-reported dyspnoea at baseline.Methods:The SENSCIS trial enrolled patients with SSc-ILD with first non-Raynaud symptom within ≤7 years before screening, extent of fibrotic ILD ≥10% on HRCT and FVC ≥40% predicted. Patients were randomised to receive nintedanib or placebo until the last patient reached week 52. In post-hoc analyses, we analysed the rate of decline in FVC (mL/year) over 52 weeks in patients with and without dyspnoea at baseline based on the question about dyspnoea in the St. George’s Respiratory Questionnaire (SGRQ). Patients who reported having shortness of breath “most days a week”, “several days a week” or “a few days a month” (rather than “only with chest infection” or “not at all”) over the last month were considered to have dyspnoea at baseline. A random slope and intercept model was used to assess the rate of decline in FVC (mL/year) and an interaction test was applied to assess potential heterogeneity in the treatment effect of nintedanib between the subgroups.Results:Of 576 patients, 69.8% had dyspnoea at baseline. At baseline, in patients with and without dyspnoea, respectively, mean (SD) extent of fibrotic ILD on HRCT was 37.7 (21.7)% and 31.6 (19.4)%; mean (SD) FVC was 71.0 (16.3) and 76.5 (16.8) % predicted; 50.7% and 44.8% were taking mycophenolate; 53.5% and 41.9% were taking corticosteroids. In the placebo group, the rate of decline in FVC (mL/year) was similar in patients with and without dyspnoea at baseline (Figure). The effect of nintedanib versus placebo on reducing the rate of decline in FVC (mL/year) was numerically more pronounced in patients without dyspnoea (difference: 79.8 [95% CI: 9.8, 149.7]) than with dyspnoea (difference: 25.7 [-19.9, 71.3]), but the exploratory interaction p-value did not indicate heterogeneity in the treatment effect between subgroups (p=0.20).Conclusion:In the SENSCIS trial, patients with SSc-ILD who had dyspnoea at baseline had a numerically greater extent of fibrotic ILD on HRCT and numerically lower FVC % predicted at baseline. The rate of decline in FVC in the placebo group was similar in patients with and without dyspnoea. Nintedanib had a numerically greater treatment effect in patients without dyspnoea. These data suggest that the presence of dyspnoea should not be used as a criterion for starting nintedanib in patients with SSc-ILD.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by Fleishman Hillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus and Forbius, Michael Kreuter Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim and Roche, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Lilly, Merck Sharp & Dohme and Roche, Consultant of: Actelion, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche, Grant/research support from: Boehringer Ingelheim, Marlies Wijsenbeek Speakers bureau: Boehringer Ingelheim (fees paid to institution) and Hoffmann-La Roche (fees paid to institution), Consultant of: Boehringer Ingelheim (fees paid to institution), Bristol-Myers Squibb (fees paid to institution), Galapagos NV (fees paid to institution), Hoffmann-La Roche (fees paid to institution), NeRRe Therapeutics (fees paid to institution), OncoArendi Therapeutics (fees paid to institution), Respivant Sciences (fees paid to institution) and Savara (fees paid to institution), Grant/research support from: Boehringer Ingelheim (fees paid to institution) and Hoffmann-La Roche (fees paid to institution), Vanessa Smith Speakers bureau: Boehringer Ingelheim and Janssen-Cilag NV, Consultant of: Boehringer Ingelheim, Grant/research support from: Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim, Janssen-Cilag NV and Research Foundation - Flanders (FWO), Dinesh Khanna Shareholder of: Eicos Sciences, Inc. (less than 5%), Consultant of: Acceleron Pharma, Actelion, AbbVie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead Sciences, Galapagos NV, Genentech/Roche, GlaxoSmithKline, Horizon Therapeutics, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Sanofi-Aventis and United Therapeutics, Grant/research support from: Bayer, Bristol-Myers Squibb, Horizon Therapeutics, Immune Tolerance Network, National Institutes of Health and Pfizer, Employee of: Chief Medical Officer- CiviBioPharma/Eicos Sciences, Inc., Christopher Denton Speakers bureau: Boehringer Ingelheim, Corbus, Janssen, and Mallinckrodt Pharmaceuticals, Consultant of: Acceleron Pharma, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos NV, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mallinckrodt Pharmaceuticals, Roche, Sanofi and UCB, Grant/research support from: Arxx Therapeutics, GlaxoSmithKline and Servier, Wim Wuyts: None declared, Corinna Miede Employee of: Currently an employee of mainanalytics GmbH, contracted by Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Steven Sambevski Employee of: Currently an employee of Boehringer Ingelheim, Yannick Allanore Consultant of: Boehringer Ingelheim, Medsenic, Menarini and Sanofi, Grant/research support from: Alpine Pharmaceuticals

Background:Gastrointestinal (GI) involvement is common in patients with SSc and may lead to weight loss and malnutrition. In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in forced vital capacity (FVC) (mL/year) over 52 weeks, with mainly GI adverse events. The Malnutrition Universal Screening Tool (MUST) was developed to identify adults who are at risk of malnutrition and has been used in studies of patients with SSc.Objectives:To evaluate nutritional status over 52 weeks in the SENSCIS trial based on a modified MUST score.Methods:The SENSCIS trial enrolled patients with SSc-ILD with first non-Raynaud symptom ≤7 years before screening, extent of fibrotic ILD ≥10% on HRCT and FVC ≥40% predicted. Patients who had taken a stable dose of mycophenolate for ≥6 months were eligible to participate. Patients were randomised to receive nintedanib 150 mg bid or placebo. Dose reductions to 100 mg bid and treatment interruptions were allowed to manage adverse events and specific recommendations were provided for the management of diarrhoea. We calculated a modified MUST score at baseline and weeks 12, 24, 36 and 52 based on (A) BMI, (B) weight loss (week 12 vs baseline; week 24 vs week 12; week 36 vs week 24; week 52 vs week 36), and (C) a surrogate for acute disease effect (if the patient had any serious adverse event that led to hospitalisation between weight assessments and received ≥1 medication from the WHO classification code for “solutions for parenteral nutrition” for ≥5 days). MUST score at baseline was based solely on BMI. With scores ranging from 0 to 6, the risk of malnutrition is defined as low (score = 0), medium (score = 1) or high (score ≥2).Results:Among 576 patients who received nintedanib (n=288) or placebo (n=288), mean (SD) age at baseline was 54.0 (12.2) years, weight was 69.7 (15.9) kg and BMI was 25.9 (5.0) kg/m2; median time since onset of first non-Raynaud symptom was 3.4 years; and 75.2% of patients were female. In the nintedanib and placebo groups, respectively, MUST scores suggested that 74.0% and 78.1% of patients were at low risk of malnutrition at baseline and remained at low risk at their last measurement (Table 1). At weeks 12 and 52, respectively, mean (SD) MUST scores were 0.3 (0.6) and 0.4 (0.7) in the nintedanib group and 0.2 (0.5) and 0.2 (0.6) in the placebo group. At weeks 12, 24, 36 and 52, respectively, the proportions of patients at low risk of malnutrition were 81.8%, 80.9%, 72.9% and 76.5% in the nintedanib group and 86.6%, 86.4%, 88.3% and 80.8% in the placebo group; the proportions at medium risk were 12.1%, 13.1%, 18.0% and 13.5% in the nintedanib group and 8.5%, 8.6%, 5.8% and 13.1% in the placebo group; and the proportions of patients at high risk were 6.1%, 5.6%, 8.3% and 9.6% in the nintedanib group and 4.9%, 4.3%, 4.7% and 5.4% in the placebo group.Table 1.Risk of malnutrition at baseline and at last assessment over 52 weeks in the SENSCIS trial.Last assessment of riskNintedanib (n=288)Placebo (n=288)Baseline riskBaseline riskLowMediumHighTotalLowMediumHighTotalLow213 (74.0)1 (0.3)0214 (74.3)225 (78.1)7 (2.4)0232 (80.6)Medium31 (10.8)8 (2.8)039 (13.5)20 (6.9)14 (4.9)4 (1.4)38 (13.2)High13 (4.5)8 (2.8)7 (2.4)28 (9.7)3 (1.0)2 (0.7)10 (3.5)15 (5.2)Missing7 (2.4)007 (2.4)3 (1.0)003 (1.0)Total264 (91.7)17 (5.9)7 (2.4)288 (100)251 (87.2)23 (8.0)14 (4.9)288 (100)MUST score ranges from 0 to 6. Score of 0 = low risk: score of 1 = medium risk; score of ≥2 = high risk. Baseline MUST score was based solely on BMI.Conclusion:In the SENSCIS trial, scores based on a modified MUST indicated that most patients treated with nintedanib were at low risk of malnutrition at baseline and remained at low risk over 52 weeks. The proportions of patients at high risk of malnutrition were low but were numerically greater in patients who received nintedanib than placebo. Management of disease manifestations and gastrointestinal adverse events that may be associated with weight loss is important to reduce the risk of malnutrition in patients with SSc-ILD treated with nintedanib.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by FleishmanHillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus and Forbius, Zsuzsanna McMahan: None declared, Sindhu Johnson Consultant of: Boehringer Ingelheim, CSL Behring and Ikaria, Grant/research support from: Bayer, Boehringer Ingelheim, Corbus, GlaxoSmithKline, Merck and Roche, Vanessa Smith Speakers bureau: Boehringer Ingelheim and Janssen, Consultant of: Boehringer Ingelheim, Grant/research support from: Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim, Research Foundation - Flanders (FWO) and Janssen, Stéphane Jouneau Speakers bureau: Actelion, AIRB, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chiesi, Genzyme, GlaxoSmithKline, LVL Mediphar, Mundipharma, Novartis, Pfizer, Roche and Sanofi, Consultant of: AIRB, Boehringer Ingelheim, Novartis and Roche, Grant/research support from: AIRB, Boehringer Ingelheim, LVL Mediphar, Novartis and Roche, Corinna Miede Employee of: Currently an employee of mainanalytics GmbH, contracted by Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Ariane Herrick Speakers bureau: Janssen, Consultant of: Boehringer Ingelheim, Camurus, CSL Behring and Gesynta Pharma, Grant/research support from: Actelion and Gesynta Pharma

Background:In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in forced vital capacity (FVC) over 52 weeks. Elevated CRP is a marker of an inflammatory phenotype and has been associated with a greater rate of decline in FVC and higher mortality in patients with SSc.Objectives:To assess the effects of nintedanib in subgroups by CRP at baseline in the SENSCIS trial.Methods:Patients with SSc-ILD with onset of first non-Raynaud symptom 4.99 mg/L) at baseline.Results:Of patients with available data, 78/270 (28.9%) and 74/261 (28.4%) in the nintedanib and placebo groups, respectively, had CRP >4.99 mg/L at baseline. Compared with patients with lower CRP, those with CRP >4.99 mg/L included a similar proportion of patients who were ATA-positive (61.8% vs 60.2%, respectively), a greater proportion with diffuse cutaneous SSc (63.2% vs 49.3%) and had a higher mean mRSS (13.7 vs 10.2) and lower mean FVC % predicted (68.6% vs 73.9%). The adjusted annual rate of decline in FVC in the placebo group was numerically greater in patients with CRP >4.99 than ≤4.99 mg/L at baseline (-106.6 [SE 27.6] vs -83.0 [17.1] mL/year). The effect of nintedanib vs placebo on reducing the rate of decline in FVC was numerically more pronounced in patients with CRP >4.99 than ≤4.99 mg/L at baseline but the treatment-by-time-by-subgroup interaction p-value did not indicate heterogeneity in the effect of nintedanib between subgroups (p=0.70) (Figure). In the nintedanib and placebo groups, respectively, the proportions of patients with an absolute increase in FVC ≥3% predicted at week 52 were 20.4% and 15.0% in those with CRP ≤4.99 mg/L and 24.4% and 14.9% in those with CRP >4.99 mg/L at baseline (treatment-by-subgroup interaction p=0.59); adjusted mean changes in mRSS at week 52 were -2.2 (SE 0.3) and -2.1 (0.3) in those with CRP ≤4.99 mg/L (difference -0.1 [95% CI -1.0, 0.8]) and -2.3 (0.5) and -1.0 (0.5) in those with CRP >4.99 mg/L at baseline (difference -1.2 [-2.7, 0.2]; treatment-by-visit-by-subgroup interaction p=0.20).Conclusion:In the SENSCIS trial, the rate of decline in FVC over 52 weeks in the placebo group was numerically greater in patients with elevated CRP at baseline. Nintedanib reduced the rate of decline in FVC both in patients with normal and elevated CRP at baseline, with a numerically greater effect in patients with elevated CRP.Disclosure of Interests:Gabriela Riemekasten Consultant of: Cell Trend GmbH, Janssen, Actelion, Boehringer Ingelheim, Speakers bureau: Actelion, Novartis, Janssen, Roche, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Patricia Carreira Grant/research support from: Actelion, Roche, MSD, Consultant of: GlaxoSmithKline, VivaCell Biotechnology, Emerald Health Pharmaceuticals, Boehringer Ingelheim, Roche, Speakers bureau: Actelion, GlaxoSmithKline, Roche, Lesley Ann Saketkoo Grant/research support from: Corbus Pharmaceuticals, United Therapeutics, Consultant of: Boehringer Ingelheim, Eicos Sciences, Speakers bureau: Boehringer Ingelheim, Martin Aringer Consultant of: Boehringer Ingelheim, Roche, Speakers bureau: Boehringer Ingelheim, Roche, Lorinda Chung Grant/research support from: United Therapeutics, Boehringer Ingelheim, Consultant of: Bristol-Myers Squibb, Boehringer Ingelheim, Mitsubishi Tanabe, Eicos Sciences, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB, Corinna Miede Employee of: Employee of Boehringer Ingelheim, Susanne Stowasser Employee of: Employee of Boehringer Ingelheim, Martina Gahlemann Employee of: Employee of Boehringer Ingelheim, Margarida Alves Employee of: Employee of Boehringer Ingelheim, Dinesh Khanna Shareholder of: Eicos Sciences, Inc./Civi Biopharma, Inc., Grant/research support from: Dr Khanna was supported by NIH/NIAMS K24AR063120, Consultant of: Acceleron, Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Corbus Pharmaceuticals, Horizon Therapeutic, Galapagos, Roche/Genentech, GlaxoSmithKline, Mitsubishi Tanabe, Sanofi-Aventis/Genzyme, UCB

We thank Dr. Yang and colleagues for their interest in our diabetes subgroup analysis of the RE-DUAL PCI (Evaluation of Dual Therapy With Dabigatran vs. Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting) study ([1][1],[2][2]). We agree that diabetes is associated with