Secondary Safety Endpoints Research Articles

Efficacy and safety of direct oral anticoagulants (DOACs) and low molecular weight heparin (LMWH) for primary prevention of venous thromboembolism (VTE) in ambulatory cancer patients.

12088 Background: Active malignancy is a well described risk factor for thrombosis. Randomized clinical trials (RCT) have evaluated anticoagulation (AC) with DOACs or LMWH for prevention of VTE in ambulatory cancer patients. This objective of this meta-analysis is to evaluate the efficacy and safety of DOACs and LMWH thromboprophylaxis in adult patients with active solid organ malignancy or lymphoma. Methods: We conducted a search of MEDLINE, EMBASE, and CENTRAL from 10/31/2009-11/31/2019. Data for meta-analysis was extracted from studies that met inclusion criteria (RCT, ambulatory patients age >18 years with active solid organ malignancy or lymphoma, prophylactic AC with DOAC or LMWH). Risk ratio (RR) were calculated for primary (efficacy) end point of VTE occurrence and secondary (safety) end points of major bleeding (MB) and clinically relevant non-major (CRNMB). Subgroup analyses of efficacy and safety endpoints were conducted based on AC and cancer types. Results: Eleven trials met inclusion criteria with total of 7741 participants. Two trials evaluated DOACs and nine trials evaluated LWMH for thromboprophylaxis. Efficacy results are noted in Table. Safety outcomes for MB and CRNMB for AC were RR 1.83 (95% CI 1.26, 2.65), p=0.001 and RR 1.36 (95% CI 1.05, 1.76), p=0.02. Safety outcomes for MB and CRNMB for DOAC were RR 1.95 (95% CI 0.88, 4.30), p=0.10 and RR 1.35 (95% CI 0.80, 2.27), p=0.26. Safety outcomes for MB and CRNMB for LMWH were RR 2.05 (95% CI 1.19, 3.51), p=0.009 and RR 1.44 (95% CI 1.01, 2.05), p=0.04. Conclusions: Both DOACs and LMWH decrease risk for VTE development in ambulatory adult cancer patients. MB and CRNMB were significantly increased in patients taking LMWH but not in patients taking DOACs. A large clinical trial using DOACs for thromboprophylaxis would help elucidate the thrombosis and bleeding event rate in ambulatory cancer patients. [Table: see text]

Nitrous oxide/oxygen plus acetaminophen versus morphine in ST elevation myocardial infarction: open-label, cluster-randomized, non-inferiority study

BackgroundStudies have shown disparate results on the consequences of morphine use in ST-segment elevation myocardial infarction (STEMI). No study has evaluated alternative treatments that could be at least non-inferior to morphine without its potentially damaging consequences for myocardial function and platelet reactivity. The aim of this study was to evaluate whether nitrous oxide/oxygen plus intravenous acetaminophen (NOO-A) is non-inferior to morphine to control chest pain in STEMI patients.MethodsThis multicenter, open-label, cluster-randomized, controlled, non-inferiority study compared NOO-A with morphine in 684 prehospital patients with ongoing suspected STEMI of < 12 h duration and a pain rating score ≥ 4. The primary endpoint was the proportion of patients achieving pain relief (numeric rating score ≤ 3) after 30 min. Secondary safety endpoints included serious adverse events and death at 30 days.ResultsThe median baseline pain score was 7.0 in both groups. The primary endpoint occurred in 51.7% of the NOO-A group and 73.6% of the morphine group (absolute risk difference − 21.7%; 95% confidence interval − 29.6 to − 13.8). At 30 days, the rate of serious adverse events was 16.0 and 18.8% in the NOO-A and morphine groups respectively (p = NS). The rate of death was 1.8% (NOO-A group) and 3.8% (morphine group) (p = NS).ConclusionAnalgesia provided by NOO-A was inferior to morphine at 30 min in patients with acute STEMI in the prehospital setting. Rates of serious adverse events did not differ between groups.Trial registrationClinicalTrials.gov: NCT02198378.

The impact of pre-procedure heart rate on adverse clinical outcomes in patients undergoing percutaneous coronary intervention: Results from a 2-year follow-up of the GLOBAL LEADERS trial

Background and aimsThe prognostic impact of pre-procedure heart rate (PHR) following percutaneous coronary intervention (PCI) has not yet been fully investigated. This post-hoc analysis sought to assess the impact of PHR on medium-term outcomes among patients having PCI, who were enrolled in the “all-comers” GLOBAL LEADERS trial. Methods and resultsThe primary endpoint (composite of all-cause death or new Q-wave myocardial infarction [MI]) and key secondary safety endpoint (bleeding according to Bleeding Academic Research Consortium [BARC] type 3 or 5) were assessed at 2 years. PHR was available in 15,855 patients, and when evaluated as a continuous variable (5 bpm increase) and following adjustment using multivariate Cox regression, it significantly correlated with the primary endpoint (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03–1.09, p < 0.001). Using dichotomous cut-off criteria, a PHR>67 bpm was associated with increased all-cause mortality (HR 1.38, 95%CI 1.13–1.69, p = 0.002) and more frequent new Q-wave MI (HR 1.41, 95%CI 1.02–1.93, p = 0.037). No significant association was found between PHR and BARC 3 or 5 bleeding (HR 1.04, 95% CI 0.99–1.09, p = 0.099). There was no interaction with the primary (p-inter = 0.236) or secondary endpoint (p-inter = 0.154) when high and low PHR was analyzed according to different antiplatelet strategies. ConclusionsElevated PHR was an independent predictor of all-cause mortality at 2 years following PCI in the “all-comer” GLOBAL LEADERS trial. The prognostic value of increased PHR on outcomes was not affected by the different antiplatelet strategies in this trial.

A drug-eluting Balloon for the trEatment of coronarY bifurcatiON lesions in the side branch: a prospective multicenter ranDomized (BEYOND) clinical trial in China.

Treatment of coronary bifurcation lesions remains challenging; a simple strategy has been preferred as of late, but the disadvantage is ostium stenosis or even occlusion of the side branch (SB). Only a few single-center studies investigating the combination of a drug-eluting stent in the main branch followed by a drug-eluting balloon in the SB have been reported. This prospective, multicenter, randomized study aimed to investigate the safety and efficacy of a paclitaxel-eluting balloon (PEB) compared with regular balloon angioplasty (BA) in the treatment of non-left main coronary artery bifurcation lesions. Between December 2014 and November 2015, a total of 222 consecutive patients with bifurcation lesions were enrolled in this study at ten Chinese centers. Patients were randomly allocated at a 1:1 ratio to a PEB group (n = 113) and a BA group (n = 109). The primary efficacy endpoint was angiographic target lesion stenosis at 9 months. Secondary efficacy and safety endpoints included target lesion revascularization, target vessel revascularization, target lesion failure, major adverse cardiac and cerebral events (MACCEs), all-cause death, cardiac death, non-fatal myocardial infarction, and thrombosis in target lesions. The main analyses performed in this clinical trial included case shedding analysis, base-value equilibrium analysis, effectiveness analysis, and safety analysis. SAS version 9.4 was used for the statistical analyses. At the 9-month angiographic follow-up, the difference in the primary efficacy endpoint of target lesion stenosis between the PEB (28.7% ± 18.7%) and BA groups (40.0% ± 19.0%) was -11.3% (95% confidence interval: -16.3% to -6.3%, Psuperiority <0.0001) in the intention-to-treat analysis, and similar results were recorded in the per-protocol analysis, demonstrating the superiority of PEB to BA. Late lumen loss was significantly lower in the PEB group than in the BA group (-0.06 ± 0.32 vs. 0.18 ± 0.34 mm, P < 0.0001). For intention-to-treat, there were no significant differences between PEB and BA in the 9-month percentages of MACCEs (0.9% vs. 3.7%, P = 0.16) or non-fatal myocardial infarctions (0 vs. 0.9%, P = 0.49). There were no clinical events of target lesion revascularization, target vessel revascularization, target lesion failure, all-cause death, cardiac death or target lesion thrombosis in either group. In de novo non-left main coronary artery bifurcations treated with provisional T stenting, SB dilation with the PEB group demonstrated better angiographic results than treatment with regular BA at the 9-month follow-up in terms of reduced target lesion stenosis. ClinicalTrials.gov, NCT02325817; https://clinicaltrials.gov.

PD23-07 A MULTI-CENTER, PROSPECTIVE, RANDOMIZED, CONTROLLED STUDY TO EVALUATE THE SAFETY OF A VALVE-LESS TROCAR INSUFFLATION SYSTEM (AIRSEAL) VS. CONVENTIONAL INSUFFLATION FOR THE MANAGEMENT OF PNEUMOPERITONEUM DURING ROBOTIC PARTIAL NEPHRECTOMY

You have accessJournal of UrologySurgical Technology & Simulation: Instrumentation & Technology II (PD23)1 Apr 2020PD23-07 A MULTI-CENTER, PROSPECTIVE, RANDOMIZED, CONTROLLED STUDY TO EVALUATE THE SAFETY OF A VALVE-LESS TROCAR INSUFFLATION SYSTEM (AIRSEAL) VS. CONVENTIONAL INSUFFLATION FOR THE MANAGEMENT OF PNEUMOPERITONEUM DURING ROBOTIC PARTIAL NEPHRECTOMY Michael Stifelman*, Sam Bhayani, Robert Figenshau, and James Porter Michael Stifelman*Michael Stifelman* More articles by this author , Sam BhayaniSam Bhayani More articles by this author , Robert FigenshauRobert Figenshau More articles by this author , and James PorterJames Porter More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000873.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The use of valve-less insufflation is gaining significant popularity for robotic partial nephrectomy secondary to its ability to maintain a pneumoperitoneum during constant vigorous suction. This study evaluated a valve-less trocar system (AirSeal) compared with conventional insufflation and the effects of insufflation pressure on peri-operative safety outcomes. METHODS: Subjects from three institutions were randomized equally in a 1:1:1 ratio into three different study arms: AirSeal - 12mmHg pressure (AIS12); AIS - 15mmHg (AIS15); and Conventional Insufflation - 15mmHg (CIS15). The rate of subcutaneous emphysema (SE) constituted the primary safety endpoint and was identified by physical exam intraoperatively, post-operatively and chest x-ray (CXR). Secondary safety endpoints included: pneumothorax, and/or pneumomediastinum identified on post-operative CXR and post-operative shoulder pain measured via a Visual Analogue Scale (VAS) administered during predetermined times after surgery. RESULTS: A total of 198 patients were enrolled (n=66 in each study arm). There were no statistically significant differences in demographics including sex, ethnicity, age or BMI between the three groups. There was a statistically significant reduction in the rate of SE between AIS12 (15.25%) and CIS15 (30.9%) with a p value of 0.008. The incidence of pneumothorax was 0%, 5% and 5% for AIS12, AIS15 and CIS15, respectively (p=0.12). The incidence of pneumomediastinum was 6%, 12% and 11% for AIS12, AIS15 and CIS15, respectively (p=0.36). An 11.5% reduction in postoperative shoulder pain was seen in AIS12 vs. CIS15 ( p=.0.049) and 14% reduction in shoulder pain AIS15 vs. CIS15 ( p=0.01). Two patients randomized to CIS15 required conversion to AIS15 secondary to poor visualization and bleeding. CONCLUSIONS: This study demonstrates that utilizing AIS12 provides a significant reduction in the incidence of SE compared to CIS15 in patients undergoing robotic partial nephrectomy. In addition, the use of the Airseal system at both 12mmHg and 15mmHg reduces postoperative shoulder pain compared with conventional insufflation. This suggests that for patients undergoing robotic partial nephrectomy the use of AIS 12 provides the highest safety profile compared to CIS15. Source of Funding: Conmed © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e466-e466 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Stifelman* More articles by this author Sam Bhayani More articles by this author Robert Figenshau More articles by this author James Porter More articles by this author Expand All Advertisement PDF downloadLoading ...

Safety and immunogenicity of a tetravalent dengue vaccine in children aged 2–17 years: a randomised, placebo-controlled, phase 2 trial

An unmet clinical need remains for an effective tetravalent dengue vaccine suitable for all age groups, regardless of serostatus. We assessed the immunogenicity and safety of three different dose schedules of a tetravalent dengue vaccine (TAK-003) over a 48-month period in children living in dengue-endemic countries. We did a large, phase 2, double-blind, placebo-controlled trial at three sites in the Dominican Republic, Panama, and the Philippines. Healthy participants aged 2-17 years were randomly assigned 1:2:5:1 using an interactive web response system with stratification by age to receive either a two-dose primary series (days 1 and 91), one primary dose (day 1), one primary dose plus booster (days 1 and 365), or placebo. Participants and relevant study personnel were masked to the random assignment until completion of the study at month 48. To maintain masking, TAK-003 recipients were administered placebo doses when appropriate. The primary objective was assessment of neutralising geometric mean titres for each serotype to month 48 assessed in the per-protocol immunogenicity subset. Secondary safety endpoints included proportions of participants with serious adverse events and symptomatic virologically confirmed dengue. This study is registered with ClinicalTrials.gov, NCT02302066. Between Dec 5, 2014, and Feb 13, 2015, 1800 children were randomly assigned to the following groups: two-dose primary series (n=201), one primary dose (n=398), one primary dose plus 1-year booster (n=1002), and placebo (n=199). Of them, 1479 (82%) participants completed the 48-month study. Immunogenicity endpoints were assessed in 562 participants enrolled in the immunogenicity subset, of whom 509 were included in the per-protocol subset. At month 48, antibody titres remained elevated in all TAK-003 groups compared with placebo, irrespective of baseline serostatus. At month 48, geometric mean titres were 378 (95% CI 226-632) in two-dose, 421 (285-622) in one-dose, 719 (538-960) in one-dose plus 1-year booster, and 100 (50-201) in placebo recipients against DENV 1; 1052 (732-1511), 1319 (970-1794), 1200 (927-1553), and 208 (99-437) against DENV 2; 183 (113-298), 201 (135-298), 288 (211-392), and 71 (37-139) against DENV 3; and 152 (97-239), 164 (114-236), 219 (165-290), and 46 (26-82) against DENV 4; and tetravalent seropositivity rate was 89% (79-96), 86% (80-92), 97% (93-99), and 60% (47-72), respectively. Virologically confirmed dengue was recorded in 37 (2%) TAK-003 and 13 (7%) placebo participants, with a relative risk of 0·35 (0·19-0·65). No vaccine-related serious adverse events or severe dengue virus disease were reported. TAK-003 elicited antibody responses against all four serotypes, which persisted to 48 months post-vaccination, regardless of baseline serostatus. No important safety risks were identified. We observed a long-term reduction in risk of symptomatic dengue virus disease in vaccinees. Results from this study provide a long-term safety database and support assessment of the vaccine in the ongoing phase 3 efficacy study. Takeda Vaccines.

Influence of Bleeding Risk on Outcomes of Radial and Femoral Access for Percutaneous Coronary Intervention: An Analysis From the GLOBAL LEADERS Trial

BackgroundRadial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding. MethodsPatients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days. ResultsIn the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; Pinteraction = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; Pinteraction = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant. ConclusionsOur findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because this was not a primary analysis, it should be considered hypothesis generating.

Association of diabetes with outcomes in patients undergoing contemporary percutaneous coronary intervention: Pre-specified subgroup analysis from the randomized GLOBAL LEADERS study

Background and aimsDiabetes has been well recognized as a strong predictor for adverse outcomes after percutaneous coronary intervention (PCI), however, studies in the era of drug-eluting stent and potent P2Y12 inhibitors have shown conflicting results. We aimed to assess ischemic and bleeding outcomes after contemporary PCI according to diabetic status. MethodsWe studied 15,957 patients undergoing PCI for stable or acute coronary syndrome in the GLOBAL LEADERS study with known baseline diabetic status. The primary endpoint was all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was major bleeding defined as bleeding academic research consortium (BARC) type 3 or 5. ResultsA quarter of the study cohort were diabetic (4038/15,957), and these patients had a significantly higher risk of primary endpoint at 2 years compared to non-diabetics (adjusted hazard ratio [HR] 1.38; 95% confidence interval [CI] 1.17–1.63). The difference was driven by a significantly higher risk of all-cause mortality at 2 years in diabetics (adjusted HR 1.47, 95% CI 1.22–1.78). The risk of BARC 3 or 5 bleeding was comparable between the two groups (adjusted HR 1.09, 95% CI 0.86–1.39). The antiplatelet strategy (experimental versus reference strategy) had no significant effect on the rates of primary endpoint and secondary safety endpoint at 2 years in patients with and without diabetes. ConclusionsDiabetic patients had higher risk of ischemic events after PCI than non-diabetic patients, whilst bleeding risk was comparable. The outcomes of diabetic patients following PCI were not affected by the two different antiplatelet strategies.

Real-World Experience With a Tapered Biodegradable Polymer-Coated Sirolimus-Eluting Stent in Patients With Long Coronary Artery Stenoses.

BackgroundTreatment of long coronary stenoses (LCS) with long tapered drug-eluting stents (LT-DES) would offer clinical and economic benefits. However, the feasibility of an interventional strategy based upon the systematic LCS treatment with an LT-DES has not been evaluated so far.MethodsWe performed a multicenter prospective study including consecutive patients with: 1) An LCS > 25 mm at coronary angiography; 2) An attempt to fix the LCS with a single BioMime Morph™ stent, a novel LT-DES available from 30 to 60 mm long. The primary efficacy endpoint was procedural success. The secondary safety endpoints were post-procedural TIMI3 flow, stent detachment during delivery, acute stent thrombosis and in-hospital mortality.ResultsFrom February 2017 to March 2018, we recorded 272 patients with an LCS and an attempt to deploy an LT-DES during percutaneous coronary intervention (PCI) (69.3 ± 11.4 years, 75.7% males, 25.7% diabetic and 43.8% with acute coronary syndromes, mean LCS length 48.8 ± 9.5 mm). LT-DES deployment was successful in 262 patients (96.3%), and failure occurred without stent detachment or other complications. Final TIMI3 flow was present in 270 (99.3%) patients. In-hospital death occurred in five patients (1.8%), with no case of acute stent thrombosis, recurrent myocardial infarction or repeated revascularization.ConclusionIn this real-world study, a strategy of fixing LCS with a single LT-DES was feasible and safe, with a high rate of procedural success and a low rate of in-hospital complications. More extensive randomized studies are warranted to assess the potential clinical and economic benefits of LT-DES.

Early High-Dose Vitamin D3 for Critically Ill, Vitamin D–Deficient Patients

BackgroundVitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study.MethodsWe conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D–deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality.ResultsA total of 1360 patients were found to be vitamin D–deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, −2.1 to 7.9; P=0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality.ConclusionsEarly administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D–deficient patients. (Funded by the National Heart, Lung, and Blood Institute; VIOLET ClinicalTrials.gov number, NCT03096314.)

Primary pulmonary arterial hypertension: Protocol to assess comprehensively in the rat the response to pharmacologic treatments

The identification of new treatments for primary pulmonary arterial hypertension (PAH) is a critical unmet need since there is no a definitive cure for this disease yet. Due to the complexity of PAH, a wide set of methods are necessary to assess the response to a pharmacological intervention. Thus, a rigorous protocol is crucial when experimental studies are designed. In the present experimental protocol, a stepwise approach was followed in a monocrotaline-induced PAH model in the rat, moving from the dose finding study of treatment compounds to the recognition of the onset of disease manifestation, in order to identify when to start a curative treatment. A complete multidimensional evaluation of treatment effects represented the last step. The primary study endpoint was the change in right ventricular systolic pressure after 14 days of treatment; echocardiographic and biohumoral markers together with heart and pulmonary arterial morphometric parameters were considered as secondary efficacy and/or safety endpoints and for the evaluation of the biologic coherence in the different results.

Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial

Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating patients with stroke caused by large vessel occlusion of the anterior circulation. Whether endovascular treatment is beneficial for vertebrobasilar artery occlusion remains unknown. In this study, we aimed to investigate the safety and efficacy of endovascular treatment of acute strokes due to vertebrobasilar artery occlusion. We did a multicentre, randomised, open-label trial, with blinded outcome assessment of thrombectomy in patients presenting within 8 h of vertebrobasilar occlusion at 28 centres in China. Patients were randomly assigned (1:1) to endovascular therapy plus standard medical therapy (intervention group) or standard medical therapy alone (control group). The randomisation sequence was computer-generated and stratified by participating centres. Allocation concealment was implemented by use of sealed envelopes. The primary outcome was a modified Rankin scale (mRS) score of 3 or lower (indicating ability to walk unassisted) at 90 days, assessed on an intention-to-treat basis. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial haemorrhage, device-related complications, and other severe adverse events. The BEST trial is registered with ClinicalTrials.gov, NCT02441556. Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for eligibility. The trial was terminated early after 131 patients had been randomly assigned (66 patients to the intervention group and 65 to the control group) because of high crossover rate and poor recruitment. In the intention-to-treat analysis, there was no evidence of a difference in the proportion of participants with mRS 0-3 at 90 days according to treatment (28 [42%] of 66 patients in the intervention group vs 21 [32%] of 65 in the control group; adjusted odds ratio [OR] 1·74, 95% CI 0·81-3·74). Secondary prespecified analyses of the primary outcome, done to assess the effect of crossovers, showed higher rates of mRS 0-3 at 90 days in patients who actually received the intervention compared with those who received standard medical therapy alone in both per-protocol (28 [44%] of 63 patients with intervention vs 13 [25%] of 51 with standard therapy; adjusted OR 2·90, 95% CI 1·20-7·03) and as-treated (36 [47%] of 77 patients with intervention vs 13 [24%] of 54 with standard therapy; 3·02, 1·31-7·00) populations. The 90-day mortality was similar between groups (22 [33%] of 66 patients in the intervention vs 25 [38%] of 65 in the control group; p=0·54) despite a numerically higher prevalence of symptomatic intracranial haemorrhage in the intervention group. There was no evidence of a difference in favourable outcomes of patients receiving endovascular therapy compared with those receiving standard medical therapy alone. Results might have been confounded by loss of equipoise over the course of the trial, resulting in poor adherence to the assigned study treatment and a reduced sample size due to the early termination of the study. Jiangsu Provincial Special Program of Medical Science.

Ongoing Study of Obinutuzumab Short Duration Infusion in Patients with Previously Untreated Advanced Follicular Lymphoma

Introduction: In the Phase III GALLIUM study (NCT01332968), obinutuzumab (G) in combination with chemotherapy (G-chemo) demonstrated improved progression-free survival (PFS) and a comparable tolerability profile to rituximab (R)-chemo, in patients with previously untreated follicular lymphoma (FL) (Marcus et al. N Engl J Med 2017). In addition to developing more efficacious treatments for FL, there is also a need for more convenient treatments. The administration of G is associated with infusion-related reactions (IRRs). The incidence of IRRs is greatest with the first infusion and decreases significantly with subsequent infusions (Marcus et al. N Engl J Med 2017). To reduce this risk, an IRR risk-reduction strategy is used in clinical practice. However, this means that administration of G can take approximately 4 hours. Shorter infusion times would yield substantial time savings for patients and benefit outpatient infusion facilities by increasing the number of infusion chairs available during clinic hours and improving nursing efficiency. Previous studies with R have led to the development of a 90-minute short duration infusion (SDi), which is now widely used if the first dose of R is well tolerated. Two Phase II studies have previously evaluated the safety and efficacy of a 90-minute SDi of G. The GATHER study (NCT01414855), in patients with previously untreated advanced diffuse large B-cell lymphoma (Sharman et al. Leuk Lymphoma 2018) and the GATS study in Japanese patients with previously untreated non-Hodgkin lymphoma (Ohmachi et al. Jpn J Clin Oncol 2018) both demonstrated that G can be safely administered as a 90-minute SDi, after the initial cycle (C). Here, we report details of the ongoing GAZELLE study (NCT03817853; MO40597), an open-label, multicenter, Phase IV study investigating the safety of G-chemo, with G administered as a SDi (approximately 90 minutes) from C2 onwards in patients with previously untreated advanced FL, who have received G-chemo at the standard infusion rate without experiencing a grade (Gr) 3 or 4 IRR during C1. Methods: Patients with CD20-positive, previously untreated stage III or IV FL, or stage II bulky disease (Groupe d'Etude des Lymphomes Folliculaires [GELF] criteria for initiating treatment, Eastern Cooperative Oncology Group performance status [ECOG PS] 0−2, life expectancy ≥12 months) will receive G (1000mg) intravenously on Day (D) 1, D8, and D15 of C1, and on D1 of subsequent cycles (Figure), in combination with chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP], cyclophosphamide, vincristine, and prednisone [CVP], or bendamustine at the discretion of the investigator site). The standard infusion rate of G will be administered in C1 (obinutuzumab [Gazyva] prescribing information, 2017). The primary endpoint is incidence of Gr ≥3 IRRs during C2 in patients who had previously received G at the standard infusion rate during C1, without experiencing a Gr ≥3 IRR. For the purposes of the study, an IRR was defined as an adverse event (AE) occurring during or ≤24 hours from the end of G infusion and judged by the investigator as related to the infusion. The rate of G administration at subsequent cycles will be adjusted according to the occurrence and severity of IRRs. Only patients who do not experience a Gr ≥3 IRR during C1 will receive the faster SDi infusion from C2 onwards. If any Gr ≥3 IRR occurs during or after C1 then the next dose of G will be administered at the standard infusion rate. The investigator will decide if the patient can restart with the SDi. Secondary safety endpoints include AEs, time to IRRs, type and duration of Gr ≥3 IRRs and duration of G administration by cycle. Secondary efficacy endpoints include investigator-assessed overall response rate at end of induction, PFS and overall survival at the end of the study, and complete response rate at 30 months. Total length of the study, from screening of the first patient to the end of the study, is expected to be approximately 4 years. It is estimated that 112 patients will be enrolled. Disclosures Canales: Novartis: Honoraria; SOBI: Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; iQone: Honoraria; Sandoz: Honoraria; Celgene: Honoraria; Janssen: Honoraria, Speakers Bureau; Gilead: Honoraria; Karyopharm: Honoraria; Takeda: Speakers Bureau. Buchholz:Scripps Health Care System: Employment; Scientific Advisory Committee, Roche/Genetech for the Study of the Abstract: Membership on an entity's Board of Directors or advisory committees. Mason:Abivax: Consultancy. Parreira:F.Hoffmann-La Roche Ltd: Employment, Equity Ownership, Honoraria. Tomiczek:F. Hoffmann-La Roche Ltd: Employment. Hübel:Sanofi: Consultancy, Speakers Bureau; Celgene: Consultancy, Other: Travel, Accommodations, expenses , Speakers Bureau; Hexal: Consultancy; Roche: Consultancy, Other: Travel, Accommodations, expenses , Research Funding, Speakers Bureau; Servier: Consultancy, Research Funding, Speakers Bureau.

Safety and efficacy of the Tablo hemodialysis system for in-center and home hemodialysis.

Introduction: Home hemodialysis remains underutilized despite observational data indicating more favorable outcomes with home compared with in‐center hemodialysis. The Tablo Hemodialysis system is designed to be easy to learn and use and to facilitate adoption of home hemodialysis. The objective of the current investigational device exemption (IDE) study was to evaluate the safety and efficacy of Tablo managed in‐center by health care professionals and in‐home by patients and/or caregivers. Methods: A prospective, multicenter, open‐label, crossover trial comparing in‐center and in‐home hemodialysis using Tablo. There were 4 treatment periods during which hemodialysis was prescribed 4 times per week: 1‐week Run‐In, 8‐week In‐Center, 4‐week Transition, and 8‐week In‐Home. The primary efficacy endpoint was weekly standard Kt/Vurea ≥ 2.1. The secondary efficacy endpoint was delivery of ultrafiltration (UF) within 10% of prescribed UF. We collected safety and usability data. Findings: Thirty participants enrolled and 28 completed all trial periods. Adherence to the protocol requirement of 4 treatments per week was 96% in‐center and 99% in‐home. The average prescribed and delivered session lengths were 3.4 hours for both the In‐Center and the In‐Home periods. The primary efficacy endpoint for the intention‐to‐treat cohort was achieved in 199/200 (99.5%) of measurements during the In‐Center period and 168/171 (98.3%) In‐Home. The average weekly standard Kt/Vurea was 2.8 in both periods. The secondary efficacy UF endpoint was achieved in the ITT cohort in 94% in both in‐center and in‐home. Two prespecified adverse events (AEs) occurred during the In‐Center period and 6 in the In‐Home period. None of the AEs were deemed by investigators as related to Tablo. The median resolution time of alarms was 8 seconds in‐center and 5 seconds in‐home. Conclusion: Primary and secondary efficacy and safety endpoints were achieved during both In‐Center and In‐Home trial periods. This study confirms that Tablo is safe and effective for home hemodialysis use.

Association of Sex With Outcomes in Patients Undergoing Percutaneous Coronary Intervention

Women experience worse ischemic and bleeding outcomes after percutaneous coronary intervention (PCI). To assess the association of sex with patient outcomes at 2 years after contemporary PCI and with the efficacy and safety of 2 antiplatelet strategies. This study is a prespecified subgroup analysis of the investigator-initiated, prospective, randomized GLOBAL LEADERS study evaluating 2 strategies of antiplatelet therapy after PCI in an unselected population including 130 secondary/tertiary care hospitals in different countries. The main study enrolled 15 991 unselected patients undergoing PCI between July 2013 and November 2015. Patients had an outpatient clinic visit at 30 days and 3, 6, 12, 18, and 24 months after the index procedure. Data were analyzed between January 1, 2019, and March 31, 2019. Eligible patients were randomized to either the experimental or reference antiplatelet strategy. Experimental strategy consisted of 1 month of dual antiplatelet therapy (DAPT) followed by 23 months of ticagrelor monotherapy, while the reference strategy comprised of 12 months of DAPT followed by 12 months of aspirin monotherapy. The primary efficacy end point was the composite of all-cause mortality and new Q-wave myocardial infarction at 2 years. The secondary safety end point was Bleeding Academic Research Consortium type 3 or 5 bleeding. Of the 15 968 patients included in this study, 3714 (23.3%) were women. The risk of the primary end point at 2 years was similar between women and men (adjusted hazard ratio [HR], 1.00; 95% CI, 0.83-1.20). Compared with men, women had higher risk of Bleeding Academic Research Consortium type 3 or 5 bleeding (adjusted HR, 1.32; 95% CI, 1.04-1.67) and hemorrhagic stroke at 2 years (adjusted HR, 4.76; 95% CI, 1.92-11.81). At 2 years, there was no between-sex difference in the efficacy and safety of the 2 antiplatelet strategies. At 1 year, compared with DAPT, ticagrelor monotherapy was associated with a lower risk of bleeding in men (HR, 0.72; 95% CI, 0.53-0.98) but not in women (HR, 1.23; 95% CI, 0.80-1.89; P for interaction = .045). Compared with men, women experienced a higher risk of bleeding and hemorrhagic stroke after PCI. The effect of 2 antiplatelet strategies on death and Q-wave myocardial infarction following PCI did not differ between the sexes at 2 years. ClinicalTrials.gov identifier: NCT01813435.

Initial Imaging-Guided Strategy Versus Routine Care in Patients With Non–ST-Segment Elevation Myocardial Infarction

BackgroundPatients with non–ST-segment elevation myocardial infarction and elevated high-sensitivity cardiac troponin levels often routinely undergo invasive coronary angiography (ICA), but many do not have obstructive coronary artery disease. ObjectivesThis study investigated whether cardiovascular magnetic resonance imaging (CMR) or computed tomographic angiography (CTA) may serve as a safe gatekeeper for ICA. MethodsThis randomized controlled trial (NCT01559467) in 207 patients (age 64 years; 62% male patients) with acute chest pain, elevated high-sensitivity cardiac troponin T levels (>14 ng/l), and inconclusive electrocardiogram compared a CMR- or CTA-first strategy with a control strategy of routine clinical care. Follow-up ICA was recommended when initial CMR or CTA suggested myocardial ischemia, infarction, or obstructive coronary artery disease (≥70% stenosis). Primary efficacy and secondary safety endpoints were referral to ICA during hospitalization and 1-year outcomes (major adverse cardiac events and complications), respectively. ResultsThe CMR- and CTA-first strategies reduced ICA compared with routine clinical care (87% [p = 0.001], 66% [p < 0.001], and 100%, respectively), with similar outcome (hazard ratio: CMR vs. routine, 0.78 [95% confidence interval: 0.37 to 1.61]; CTA vs. routine, 0.66 [95% confidence interval: 0.31 to 1.42]; and CMR vs. CTA, 1.19 [95% confidence interval: 0.53 to 2.66]). Obstructive coronary artery disease after ICA was found in 61% of patients in the routine clinical care arm, in 69% in the CMR-first arm (p = 0.308 vs. routine), and in 85% in the CTA-first arm (p = 0.006 vs. routine). In the non-CMR and non-CTA arms, follow-up CMR and CTA were performed in 67% and 13% of patients and led to a new diagnosis in 33% and 3%, respectively (p < 0.001). ConclusionsA novel strategy of implementing CMR or CTA first in the diagnostic process in non–ST-segment elevation myocardial infarction is a safe gatekeeper for ICA.

509P - Second-line treatment after first-line vinorelbine in advanced platinum unfit NSCLC patients: An exploratory analysis of randomized Tempo-Lung trial

BackgroundTempo-Lung trial randomly assessed the role of metronomic oral vinorelbine (OV) vs standard weekly oral vinorelbine in advanced NSCLC patients (pts) unfit to platinum doublets. Little data are available on treatment options after first-line in platinum-unfit pts. MethodsAdvanced NSCLC pts unfit to receive platinum doublets (Creatinine clearance <60 ml/min; heart failure NYHA class II-III; hearing loss >G2; any medical condition impairing platinum treatment according to physician’s opinion) were randomized to arm A (metronomic): OV 50mg x3/week (wk) or arm B (standard): OV 60 mg/m²/wk cycle 1, then 80 mg/m²/wk. Primary endpoint was progression free-survival without grade 4 toxicity (PFSG4) and secondary efficacy and safety end-point, quality of life (QoL). Data on treatment after failure of first-line vinorelbine were collected. ResultsIntention-to-treat population included 165 (arm A 83 - arm B 82) pts. Baseline characteristics were well balanced between both arms. Mean dose intensity by cycle: 73.56 mg/m²/week (arm A), 55.85 mgm²/week (arm B). Median PFSG4 significantly differ in favor of metronomic arm [95%CI]: 4.0 [2.6-4.3] vs 2.2 [1.5-2.9] months (p = 0.0068), HR [95%CI] = 0.63 [0.45-0.88]. Overall treatment related adverse events (61.4% vs 84%): haematological toxicities (27.7% vs 55.6%), G3/4 neutropenia (11% vs 42%), febrile neutropenia (3.6% vs 6.2%) and G3/4 asthenia (4.8% vs 8.6%) were reduced with metronomic OV. It was observed that 40% of patients (subset) had second line treatment: immunotherapy, chemotherapy, protein kinase inhibitor, radiotherapy. No difference was found for changes in EORTC QoL scores. Secondary endpoints will be presented. ConclusionsMetronomic OV could be a suitable option for advanced NSCLC pts unfit to receive platinum doublets. Less toxicity was observed in metronomic arm. QoL scores were similar in both arms. A subset of platinum unfit patients could receive second-line treatment mainly consisting on immunotherapy, chemotherapy. Clinical trial identification2014-003859-61. Legal entity responsible for the studyIRPF, Pierre Fabre Medicament. FundingPierre Fabre Medicament. DisclosureA. Camerini: Speaker Bureau / Expert testimony, expert testimony: Pierre Fabre; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Pierre Fabre. A. Morabito: Speaker Bureau / Expert testimony, speaker bureau: Pfizer; Speaker Bureau / Expert testimony, speaker bureau: BMS; Speaker Bureau / Expert testimony, speaker bureau: MSD; Speaker Bureau / Expert testimony, speaker bureau: Roche; Speaker Bureau / Expert testimony, speaker bureau: AstraZeneca; Speaker Bureau / Expert testimony, speaker bureau: Boehringer Ingelheim. F. Grossi: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Honoraria (self): Eli Lilly; Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Pierre Fabre; Honoraria (self): BMS; Honoraria (self): Novartis; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): BMS; Research grant / Funding (self): MSD. R. Ramlau: Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Boehringer Ingelheim. T-E. Ciuleanu: Advisory / Consultancy: Astellas; Advisory / Consultancy: Janssen; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Amgen; Advisory / Consultancy: Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Lilly; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: MSD; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Servier; Advisory / Consultancy: A et D Pharma; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Boehringer Ingelheim; Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: Servier; Travel / Accommodation / Expenses: Ipsen. G.L. Ceresoli: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Astellas; Advisory / Consultancy: Boehringer Ingelheim. J. Bosch-Barrera: Honoraria (self): Pierre Fabre; Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): BMS; Advisory / Consultancy: Boehringer Ingelheim. P. Landreau: Full / Part-time employment: Pierre Fabre. S. Gautier: Full / Part-time employment: Pierre Fabre. C. Ta Thanh Minh: Full / Part-time employment: Pierre Fabre. All other authors have declared no conflicts of interest.

3331Impact of baseline hemoglobin level and white blood cell count in real-world patients undergoing contemporary percutaneous coronary intervention: insights from the GLOBAL LEADER study

Abstract Introduction The impact of hemoglobin (Hb) level and white blood cell count (WBC) on the outcomes in all-comers PCI patients is unknown. Purpose We sought to assess the association between baseline Hb level, WBC count on 2-year outcomes after PCI in all-comers patients in the GLOBAL LEADERS study. We compared the outcomes between anemic and non-anemic patients according to WHO definition. Methods GLOBAL LEADERS study assessed the efficacy and safety of two antiplatelet strategies in 15,991 patients undergoing PCI. The primary endpoint was all-cause mortality or new Q wave myocardial infarction (MI) at 2 years. Secondary safety endpoint was BARC 3 or 5 bleeding at 2 years. The association between WBC count, Hb level and outcomes at 2 years were assessed in the multivariable Cox model adjusted for age, diabetes, ejection fraction and renal impairment. For Hb level, patients were categorized according to the WHO definition of anemia (Hb &lt;12 g/dL in women, Hb &lt;13 g/dL in men). Results Of 15991 patients randomized in the GLOBAL LEADER study, baseline WBC count and Hb levels were available in 14960 (93.7%) patients and 15215 (95.3%) patients, respectively. Hb level had an inverse association with adverse events after PCI. In the multivariable Cox model, Hb level was an independent predictor for ischemic and bleeding outcomes at 2 years while the WBC count was not (see table). Compared with non-anemic patients, anemic patients had significantly higher risk of primary endpoint (adjusted HR 2.07, 95% CI 1.72–2.49), BARC 3 or 5 bleeding (adjusted HR 1.49 95% CI 1.14–1.96), all-cause mortality (adjusted HR 2.33, 95% CI 1.89–2.86), any MI (adjusted HR 1.41, 95% CI 1.11–1.80), and any revascularization (adjusted HR 1.20, 95% CI 1.03–1.39). Hb level, WBC count and 2-year outcomes Outcomes at 2 years Hemoglobin level (mg/dL) WBC count (109/L) HR (95% CI) P value HR (95% CI) P value All-cause mortality or new Q wave MI 0.87 (0.82–0.91) &lt;0.0001 1.00 (0.999–1.002) 0.33 All-cause mortality 0.82 (0.78–0.87) &lt;0.0001 1.00 (0.999–1.002) 0.37 Any myocardial infarction 0.93 (0.87–0.99) 0.0165 1.00 (0.996–1.001) 0.23 Any revascularization 0.96 (0.93–1.00) 0.0302 1.00 (1.00–1.001) 0.25 BARC 3 or 5 bleeding 0.85 (0.79–0.91) &lt;0.0001 1.00 (0.997–1.002) 0.76 Conclusion In the all-comers patients undergoing PCI, the baseline Hb level was significantly associated with the ischemic and bleeding outcomes at 2 years whereas baseline WBC count was not. Baseline WBC count may not be useful as a prognostic factor after PCI.

920P - First report of efficacy and safety from a phase II trial of tislelizumab, an anti-PD-1 antibody, for the treatment of PD-L1+ locally advanced or metastatic urothelial carcinoma (UC) in Asian patients

BackgroundTislelizumab, an investigational anti-PD-1 antibody, was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Previous reports showed tislelizumab was generally well tolerated and had antitumor activity in patients (pts) with advanced solid tumours, including UC. MethodsThis phase 2 clinical trial (CTR20170071) assessed the safety, tolerability, and efficacy of tislelizumab (200mg Q3W) in Asian pts with PD-L1+ UC previously treated with ≥1 platinum-containing therapy. Prior treatment with a PD-(L)1 inhibitor was not allowed. During screening, archival tissue or fresh biopsy from all pts was sent to a central laboratory for PD-L1 testing via the VENTANA SP263 IHC assay. Patients were considered PD-L1+ if≥25% of tumor or immune cells had PD-L1 expression. The primary efficacy endpoint was ORR (RECIST v1.1), assessed by an independent review committee (IRC). Secondary efficacy endpoints included DoR, PFS, and OS; AE incidence and severity were secondary safety endpoints. ResultsBetween 04 Jul 2017 and 28 Feb 2019, 113 pts received tislelizumab for a median of 15 weeks and were followed up for a median of 8mo. Urinary bladder (n=51) and renal pelvis (n=31) were common primary tumor sites. Of 104 evaluable pts, a confirmed objective response was observed in 24 pts (ORR=23%, 95% CI: 15.4, 32.4), including 8 CR and 16 PR per IRC assessment. Median DoR per IRC was not reached at the time of protocol-defined analysis; 19/24 (79%) responders had ongoing responses at data cutoff. Median PFS and OS were 2.1 and 9.8mo, respectively. Anemia (27%), decreased appetite (19%), and pyrexia (17%) were the only TRAEs occurring in>15% of pts; anemia (7%) was the only grade 3-4 TRAE occurring in≥5% pts. Four pts experienced a grade 5 AE considered related to disease progression but also possibly related to treatment (hepatic failure, n=2; respiratory arrest, n=1; renal impairment, n=1). ConclusionsTislelizumab was generally well tolerated and demonstrated clinical activity in pts with PD-L1+ UC. Clinical trial identificationCTR20170071. Editorial acknowledgementStephan Lindsey, PhD, at OPEN Health Medical Communications (Chicago, IL). Legal entity responsible for the studyBeiGene, Ltd. FundingBeiGene, Ltd. DisclosureX. Qiu: Full / Part-time employment: BeiGene. L. Zhang: Full / Part-time employment: BeiGene. W. Shen: Full / Part-time employment: BeiGene. All other authors have declared no conflicts of interest.

Efficacy and Safety of Ticagrelor Monotherapy in Patients Undergoing Multivessel PCI

BackgroundData on optimal antiplatelet treatment regimens in patients who undergo multivessel percutaneous coronary intervention (PCI) are sparse. ObjectivesThis post hoc study investigated the impact of an experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus a reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) according to multivessel PCI. MethodsThe GLOBAL LEADERS trial is a prospective, multicenter, open-label, randomized controlled trial, allocating all-comer patients in a 1:1 ratio to either the experimental strategy or the reference regimen. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was Bleeding Academic Research Consortium type 3 or 5 bleeding. ResultsAmong the overall study population (n=15,845), 3,576 patients (22.4%) having multivessel PCI experienced a significantly higher risk of ischemic and bleeding events at 2 years, compared to those having single-vessel PCI. There was an interaction between the experimental strategy and multivessel PCI on the primary endpoint (hazard ratio: 0.62; 95% confidence interval: 0.44 to 0.88; pinteraction = 0.031). This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of Bleeding Academic Research Consortium type 3 or 5 bleeding was statistically similar between the 2 regimens (hazard ratio: 0.92; 95% confidence interval: 0.61 to 1.39; pinteraction = 0.754). ConclusionsLong-term ticagrelor monotherapy following 1-month DAPT can favorably balance ischemic and bleeding risks in patients with multivessel PCI. These findings should be interpreted as hypothesis-generating and need to be replicated in future dedicated randomized trials. (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation; NCT01813435).