Prespecified Analysis Of Patients Research Articles

Treat-to-target versus high-intensity statin treatment in patients with or without diabetes mellitus: a pre-specified analysis from the LODESTAR trial

The impact of titrated versus fixed intensity statin therapy in patients with coronary artery disease (CAD) and diabetes mellitus (DM) remains to be elucidated. This was a pre-specified analysis of patients with and without DM from the LODESTAR trial. Patients with CAD were randomly assigned to receive either a treat-to-target strategy with a target LDL-C level of 50-70mg/dL or a high-intensity statin treatment. Primary outcome was the 3-year composite of all-cause death, myocardial infarction, stroke, or coronary revascularization. Secondary outcomes were safety endpoints. This trial is registered with ClinicalTrials.gov, NCT02579499. Between September 9, 2016 and November 27, 2019, 4400 patients with CAD were enrolled in the LODESTAR trial. The median age was 65 years (interquartile range, 59-73 years), 3172 (72%) were male, and 1468 (33%) had DM at baseline. There was no significant difference in the occurrence of the primary outcome between the treat-to-target group and high-intensity statin group among patients with DM (10.5% versus 11.1%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.69-1.29, p=0.70) and those without DM (6.9% versus 7.5%, HR 0.93, 95% CI 0.71-1.21, p=0.58). Among patients without DM, there was a trend towards a lower risk of new-onset DM in the treat-to-target group (8.4% versus 10.4% in the high-intensity statin group, HR 0.79, 95% CI 0.62-1.01; p=0.06). In patients with CAD, a treat-to-target LDL-C strategy of 50-70mg/dL as the goal was comparable to high-intensity statin therapy in terms of 3-year clinical efficacy and safety outcomes regardless of the presence of DM. Sam Jin Pharmaceutical, Seoul, Korea and Chong Kun Dang Pharmaceutical, Seoul, Korea.

Efficacy of secukinumab and adalimumab in patients with psoriatic arthritis and concomitant moderate-to-severe plaque psoriasis: results from EXCEED, a randomized, double-blind head-to-head monotherapy study.

SummaryBackgroundSecukinumab [an interleukin (IL)‐17A inhibitor] has demonstrated significantly higher efficacy vs. etanercept (a tumour necrosis factor inhibitor) and ustekinumab (an IL‐12/23 inhibitor) in patients with moderate‐to‐severe plaque psoriasis.ObjectivesTo report 52‐week results from a prespecified analysis of patients with active psoriatic arthritis (PsA) having concomitant moderate‐to‐severe plaque psoriasis from the head‐to‐head EXCEED monotherapy study comparing secukinumab with adalimumab.MethodsPatients were randomized to receive secukinumab 300 mg via subcutaneous injection at baseline, week 1–4, and then every 4 weeks until week 48 or adalimumab 40 mg via subcutaneous injection every 2 weeks from baseline until week 50. Assessments in patients with concomitant moderate‐to‐severe psoriasis, defined as having affected body surface area > 10% or Psoriasis Area and Severity Index (PASI) ≥ 10 at baseline, included musculoskeletal, skin and quality‐of‐life outcomes. Missing data were handled using multiple imputation.ResultsOf the 853 patients [secukinumab (N = 426), adalimumab (N = 427)], 211 (24·7%) had concomitant moderate‐to‐severe psoriasis [secukinumab (N = 110, 25·8%), adalimumab (N = 101, 23·7%)]. Up to week 50, 5·5% of patients discontinued secukinumab vs.17·8% in the adalimumab group. The proportion of patients who achieved American College of Rheumatology (ACR) 20 response was 76·4% with secukinumab vs. 68·3% with adalimumab (P = 0·175), PASI 100 response was 39·1% vs. 23·8% (P = 0·013), and simultaneous improvement in ACR 50 and PASI 100 response at week 52 was 28·2% vs. 17·7%, respectively (P = 0·06). Secukinumab demonstrated consistently higher responses vs. adalimumab across skin endpoints.ConclusionsThis prespecified analysis in PsA patients with concomitant moderate‐to‐severe plaque psoriasis in the EXCEED study provides further evidence that IL‐17 inhibitors offer a comprehensive biological treatment to manage the concomitant features of psoriasis and PsA.

Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: A randomized controlled trial (PAM study).

12015 Background: Chemotherapy is associated with cognitive problems. Physical exercise is a promising intervention. We investigated whether exercise improves cognition in chemotherapy-exposed breast cancer (BC) patients 2-4 years after diagnosis. Methods: In the PAM study, we randomized chemotherapy-exposed BC patients with self-reported and test-confirmed cognitive problems to an exercise or control group. The 6-month exercise intervention consisted of 2 hours of supervised aerobic and resistance training and two hours of Nordic/power walking. Memory function measured with the Hopkins Verbal Learning Test-Revised (HVLT-R) was our primary outcome. Further measurements included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognitive complaints (MDASI-MM, EORTC QLQ C-30 cognitive functioning), physical fitness (VO2peak), fatigue (MFI, EORTC fatigue), quality of life (QoL; EORTC), anxiety (HADS) and depression (HADS, PHQ9). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement of ≥5 words. Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. An hypothesis driven but not pre-specified analysis in patients with high baseline EORTC fatigue levels (≥39) was performed. Results: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise program and physical fitness significantly improved compared to the control patients ( VO2peak1.4 ml/min/kg, 95% CI 0.6; 2.2). No difference in favor of the intervention group was seen on the primary cognitive outcome or other cognitive tests. However, significant beneficial intervention effects were found for self-reported cognition (MDASI-MM Severity (-0.7, -1.2;-0.1)), fatigue (general fatigue (-2.2, -3.3; -1.1), physical fatigue (-3.3, -4.4; -2.2), mental fatigue (-1.0, -2.0; 0.0), reduced motivation (-1.1, -2.0; -0.2) and reduced activity (-2.1, -3.2; -1.1)), QoL (summary score (4.0, 1.2; 6.7), global health status (5.8, 1.1; 10.6), role functioning (7.2, 1.3; 13.1) and social functioning (5.9, 0.2; 11.6)) and depression (PHQ9 (-1.16, -2.19; -0.13)). In high-fatigued patients, exercise did show significant positive effects on objective cognitive function (ACS Reaction Time (-26.8, -52.9; -0.6) and ACS Wordlist Learning (4.4, 0.5; 8.3)). Conclusions: A 6-month exercise intervention did not improve objectively measured cognitive function in chemotherapy-exposed BC patients with cognitive problems. However, self-reported cognitive function, physical fitness, fatigue, QoL and depression did improve. Unplanned analysis indicated a small positive effect of exercise on cognitive functioning in high-fatigued patients. Clinical trial information: NTR6104.

Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin.

Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events. In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-30) or placebo added to aspirin (300-325 mg on day 1 followed by 75-100 mg daily for days 2-30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days. Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56-0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19-171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74-1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04-16.9], P=0.001). In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19-171). Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429.

Randomized study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Pre-specified analysis of the Chinese population from the BERSON clinical trial.

AimThe aim of this study was to evaluate the efficacy and safety of evolocumab with background atorvastatin in Chinese patients with type 2 diabetes mellitus (T2DM) and hyperlipidaemia or mixed dyslipidaemia.Materials and methodsThis is a pre‐specified analysis of patients in the BERSON study (ClinicalTrials.gov, NCT02662569) in China. Patients initiated background atorvastatin 20 mg/d, after which they were randomized 2:2:1:1 to evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) or to placebo Q2W or QM. Co‐primary endpoints were percentage change in LDL cholesterol (LDL‐C) from baseline to week 12 and from baseline to the mean of weeks 10 and 12. Additional endpoints included atherogenic lipids, glycaemic measures and adverse events (AEs).ResultsAmong 453 patients randomized in China, 451 received at least one dose of study drug (evolocumab or placebo). Evolocumab significantly reduced LDL‐C compared with placebo at week 12 (Q2W, −85.0%; QM, −74.8%) and at the mean of weeks 10 and 12 (Q2W, −80.4%; QM, −81.0%) (adjusted P < 0.0001 for all) when administered with background atorvastatin. Non‐HDL‐C, ApoB100, total cholesterol, Lp(a), triglycerides, HDL‐C and VLDL‐C significantly improved with evolocumab vs placebo. No new safety findings were observed with evolocumab. The incidence of diabetes AEs was higher with evolocumab compared with placebo. There were no differences over time between evolocumab and placebo in measures of glycaemic control.ConclusionsIn patients in China with T2DM and hyperlipidaemia or mixed dyslipidaemia receiving background atorvastatin, evolocumab significantly reduced LDL‐C and other atherogenic lipids, was well tolerated, and had no notable impact on glycaemic measures.

Nebulized Versus Dry Powder Long-Acting Muscarinic Antagonist Bronchodilators in Patients With COPD and Suboptimal Peak Inspiratory Flow Rate.

Patients with chronic obstructive pulmonary disease (COPD) and suboptimal peak inspiratory flow rate (sPIFR) may not benefit optimally from dry powder inhalers (DPI) because of inadequate inspiratory flow. Nebulized bronchodilators may provide a better alternative. We compared bronchodilation with the long-acting muscarinic antagonist (LAMA) revefenacin for nebulization versus the DPI LAMA tiotropium, in patients with COPD and sPIFR (< 60 L/min against the resistance of Diskus®). This was a randomized, double-blind, double-dummy, 28-day Phase 3b study in patients with COPD enrolled based on sPIFR. The primary endpoint was trough forced expiratory volume in 1 second (FEV1) on Day 29 for revefenacin for nebulization versus tiotropium HandiHaler® DPI. We enrolled 206 patients with mean (standard deviation) age, 65 (8) years; percent predicted FEV1, 37 (16)%; PIFR, 45 (12) L/min. In the intent-to-treat (ITT) population, revefenacin improved trough FEV1 from baseline; however, the difference versus tiotropium was not significant (least squares [LS] mean difference [standard error], 17.0 [22.4] mL, P=0.4461). In a prespecified analysis of patients with FEV1 < 50% predicted, revefenacin produced an LS mean difference (95% confidence interval [CI]), 49.1 (6.3-91.9) mL in trough FEV1 and 103.5 (7.7-199.3) mL in forced vital capacity versus tiotropium. Revefenacin produced >100 mL increase in FEV1 in 41.6% versus 34.4% of patients with tiotropium in ITT and 41.4% versus 25.7% of patients in FEV1 < 50% predicted populations. Revefenacin did not produce significant improvements in FEV1 versus tiotropium in the ITT population, but increased trough FEV1 in patients with FEV1 < 50% predicted and sPIFR. Clinical Trial Registration (www.Clinicaltrials.gov): Study 0149 (NCT03095456).

Assessment of denosumab treatment effects and imaging response in patients with giant cell tumor of bone

BackgroundDenosumab has been shown to reduce tumor size and progression, reform mineralized bone, and increase intralesional bone density in patients with giant cell tumor of bone (GCTB); however, radiologic assessment of tumors in bone is challenging. The study objective was to assess tumor response to denosumab using three different imaging parameters in a prespecified analysis in patients with GCTB from two phase 2 studies.MethodsThe studies enrolled adults and adolescents (skeletally mature and at least 12 years of age) with radiographically measurable GCTB that were given denosumab 120 mg every 4 weeks, with additional doses on days 8 and 15 of cycle 1. The proportion of patients with an objective tumor response was assessed using either Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST), European Organisation for Research and Treatment of Cancer response criteria (positron emission tomography [PET] scan criteria), or inverse Choi density/size (ICDS) criteria. Target lesions were measured by computed tomography or magnetic resonance imaging (both studies), PET (study 2 only), or plain film radiograph (study 2 only).ResultsMost patients (71.6%) had an objective tumor response by at least one response criteria. Per RECIST, 25.1% of patients had a response; per PET scan criteria, 96.2% had a response; per ICDS, 76.1% had a response. 68.5% had an objective tumor response ≥ 24 weeks. Using any criteria, crude incidence of response ranged from 56% (vertebrae/skull) to 91% (lung/soft tissue), and 98.2% had tumor control ≥ 24 weeks. Reduced PET avidity appeared to be an early sign of response to denosumab treatment.ConclusionModified PET scan criteria and ICDS criteria indicate that most patients show responses and higher benefit rates than modified RECIST, and therefore may be useful for early assessment of response to denosumab.Trial registrationClinicalTrials.gov Clinical Trials Registry NCT00396279 (retrospectively registered November 6, 2006) and NCT00680992 (retrospectively registered May 20, 2008).

Goal-directed perfusion to reduce acute kidney injury: A randomized trial

ObjectiveTo determine whether a goal-directed perfusion (GDP) strategy aimed at maintaining oxygen delivery (DO2) at ≥280 mL·min−1·m−2 reduces the incidence of acute kidney injury (AKI). MethodsThis multicenter randomized trial enrolled a total of 350 patients undergoing cardiac surgery in 9 institutions. Patients were randomized to receive either GDP or conventional perfusion. A total of 326 patients completed the study and were analyzed. Patients in the treatment arm were treated with a GDP strategy during cardiopulmonary bypass (CPB) aimed to maintain DO2 at ≥280 mL·min−1·m−2. The perfusion strategy for patients in the control arm was factored on body surface area and temperature. The primary endpoint was the rate of AKI. Secondary endpoints were intensive care unit length of stay, major morbidity, red blood cell transfusions, and operative mortality. ResultsAcute Kidney Injury Network (AKIN) stage 1 was reduced in patients treated with GDP (relative risk [RR], 0.45; 95% confidence interval [CI], 0.25-0.83; P = .01). AKIN stage 2-3 did not differ between the 2 study arms (RR, 1.66; 95% CI, 0.46-6.0; P = .528). There were no significant differences in secondary outcomes. In a prespecified analysis of patients with a CPB time between 1 and 3 hours, the differences in favor of the treatment arm were more pronounced, with an RR for AKI of 0.49 (95% CI, 0.27-0.89; P = .017). ConclusionsA GDP strategy is effective in reducing AKIN stage 1 AKI. Further studies are needed to define perfusion interventions that may reduce more severe levels of renal injury (AKIN stage 2 or 3).

MTE17.02 Maintenance Therapy versus Early Second-Line Therapy in Advanced NSCLC

MTE17.02 Maintenance Therapy versus Early Second-Line Therapy in Advanced NSCLC

Durable Overall Survival Benefit in Patients ≥ 60 Years with Relapsed or Refractory AML Treated with Vosaroxin/Cytarabine Vs Placebo/Cytarabine: Updated Results from the Valor Trial

Durable Overall Survival Benefit in Patients ≥ 60 Years with Relapsed or Refractory AML Treated with Vosaroxin/Cytarabine Vs Placebo/Cytarabine: Updated Results from the Valor Trial

Anti-angiogenic-specific adverse events in patients with non-small cell lung cancer treated with nintedanib and docetaxel.

LUME-Lung 1 was a randomized, placebo-controlled, Phase III trial investigating nintedanib+docetaxel versus placebo+docetaxel in patients with advanced NSCLC progressing after first-line chemotherapy. Progression-free survival was significantly improved with nintedanib+docetaxel in the overall population and overall survival was significantly improved in the pre-specified analysis of patients with adenocarcinoma. We evaluated the frequency of characteristic adverse events (AEs) commonly seen with existing anti-angiogenic agents. The incidence and intensity of AEs were evaluated in all patients who received at least one dose of study medication (N=1307) and for the two main histologies: adenocarcinoma (n=653) and squamous cell carcinoma (SCC; n=553). AEs of special interest were analyzed by category, preferred term, and worst CTCAE grade and included perforation, hypertension, bleeding, thromboembolic events, and skin disorders. The incidence of patients with all-grade gastrointestinal (GI) perforations was low and balanced between arms (0.5% in both) and across histologies; the incidence of non-GI perforations was 1.2% with nintedanib+docetaxel versus 0.2% with placebo+docetaxel. The incidence of some events was higher with nintedanib+docetaxel versus placebo+docetaxel; hypertension (3.5% vs 0.9%), rash (11.0% vs 8.1%), and cutaneous adverse reactions (13.0% vs 10.7%). Rash and cutaneous adverse reactions were predominantly Grade 1-2 with both treatments. The incidence of all-grade bleeding was also slightly higher in nintedanib+docetaxel-treated patients (14.1% vs 11.6%) driven by between-treatment differences in the SCC subpopulation; most events were Grade 1-2. The proportion of patients with a thromboembolic event was low and comparable between arms for all grades (5.1% vs 4.6%) and Grade ≥3 (2.1% vs 3.1%). Safety evaluation of the LUME-Lung 1 study showed that the frequency of AEs commonly associated with other anti-angiogenic agents was lower with nintedanib+docetaxel. Survival benefits from addition of nintedanib to docetaxel in patients with adenocarcinoma after first-line therapy can be achieved alongside a manageable safety profile.

PP.35.03

Objective: Inhibitors of the renin-angiotensin-aldosterone system (RAAS) increase the risk of hyperkalaemia (serum K+ >5.0 mmol/L). This often leads to suboptimal dosing or RAASi treatment discontinuation, despite proven benefit in hypertensive and chronic kidney disease (CKD) patients. Sodium zirconium cyclosilicate (ZS-9) is a non-absorbed cation exchanger specifically designed to trap excess K+ in the gastrointestinal (GI) tract. ZS-9 rapidly controlled normal serum K+ in 2 Phase 3 trials (Packham, NEJM 2014; Kosiborod, JAMA 2014). Here we present results from a pre-specified analysis of patients from the Phase 3 HARMONIZE study who were receiving RAASi. Design and method: HARMONIZE was a multicenter, randomised, double-blind, placebo-controlled trial designed to evaluate efficacy and safety of ZS-9 in patients with hyperkalaemia. All patients received 10 g of ZS-9 thrice daily (TID) for 48 hours (open-label phase). Patients achieving normal K+ (3.5–5.0 mEq/L) were randomised to one of 3 ZS-9 doses (5 g, 10 g, or 15 g QID) or placebo for 28 days (randomised phase). Per protocol, RAASi dose was unchanged for the duration of the study. Results: Among 258 enrolled patients, the median age was 65 years, 36% had heart failure, 69% had eGFR<60 mL/min/1.73m2, 66% had diabetes and 70% were receiving RAASi at baseline. During the open-label phase in the overall population, mean K+ declined from 5.6 to 4.5 mmol/L following ZS-9 10 g TID, with 83% and 98% of patients showing normalized K+ by 24 h and 48 h, respectively. During the randomised phase in the RAASi subgroup, patients in the 5 g, 10 g, and 15 g ZS-9 groups maintained serum K+ at 4.8, 4.6, and 4.4 mmol/L, respectively, compared with 5.1 mmol/L in the placebo group (P < 0.05 across all ZS-9 groups; Figure). Overall, ZS-9 was well tolerated, with a GI adverse event profile similar to that of placebo.Conclusions: In patients on RAASi, ZS-9 led to rapid and sustained reduction of serum K+ and was well tolerated. The results of this prospective analysis of the 3rd randomised, placebo-controlled study of ZS-9 provide further evidence that ZS-9 may enable continued optimal use of cardiorenal protective and life-saving RAASi therapies in patients with hyperkalaemia.

Ziv-aflibercept (Z) in combination with FOLFIRI for second-line treatment of patients with metastatic colorectal cancer (mCRC): Interim safety data from the global Aflibercept Safety and Quality-of-Life Program (ASQoP and AFEQT) in patients age 65 or older.

588 Background: The prespecified analysis of patients (pts) ≥65 y in the VELOUR study demonstrated a safety profile similar to that of ziv-aflibercept (Z) (known as aflibercept outside the United States) plus FOLFIRI in the overall VELOUR population. The global ASQoP/AFEQT Program comprises 2 clinical studies (ASQoP [NCT01571284]; AFEQT [NCT01670721]) designed to capture QoL and safety data from a population similar to VELOUR but treated in a real-life setting. We report safety data from the fourth interim analysis of pts ≥65 y. Methods: ASQoP/AFEQT are single-arm, open-label trials evaluating Z in metastatic colorectal cancer pts previously treated with an oxaliplatin-containing regimen. Eligible pts received Z (4 mg/kg) q2w on day 1 of each cycle followed by FOLFIRI until disease progression, unacceptable toxicity, death, or investigator/pt decision. Initial starting doses of FOLFIRI and dose modifications are at treating physician’s discretion. The % of pts ≥65 y with grade (G) 3 or 4 AEs in the combined safety population of ASQoP/AFEQT are compared with the prespecified analysis in pts ≥65 y from the Z + FOLFIRI arm of VELOUR. Results: At data cutoff, the overall safety population comprised 688 pts with ≥1 completed treatment cycle; 303 (44.1%) were ≥65 y. In the overall safety population ≥1 G3/4 AE was reported in 72.2% of pts vs. 83.5% in overall VELOUR. Most G3/4 AEs were G3. There were no reports of G4 hypertension, diarrhea, or fatigue. Median number of cycles was 6 in ASQoP/AFEQT and 9 in the Z + FOLFIRI arm of VELOUR. Table shows summary of AEs in pts ≥65 y. Conclusions: This interim analysis from ASQoP/AFEQT in pts ≥65 y has identified no new safety signals and provides additional safety data suggesting an acceptable toxicity profile in this real-life setting. Clinical trial information: NCT01571284. [Table: see text]

Statin Helps Endothelial Function in COPD Subgroup

Statin Helps Endothelial Function in COPD Subgroup

Ziv-aflibercept in combination with FOLFIRI for second-line treatment of patients with metastatic colorectal cancer (mCRC): Interim safety data from the global aflibercept safety and quality-of-life program (ASQoP and AFEQT studies) in patients ≥65.

545 Background: The prespecified analysis of patients ≥65 years of age in the VELOUR study demonstrated a safety profile similar to that of ziv-aflibercept (Z) (known as aflibercept outside the United States) plus FOLFIRI in the overall VELOUR study. Results from VELOUR supported the initiation of the global Aflibercept Safety and Quality-of-Life (QoL) Program composed of two clinical studies (ASQoP [NCT01571284]; AFEQT [NCT01670721]) to capture QoL and safety data from a target population similar to that of VELOUR in a real-life setting. We report early safety data from this interim analysis for patients ≥65 y. Methods: ASQoP and AFEQT are single-arm, open-label trials evaluating safety and QoL of Z in mCRC patients previously treated with an oxaliplatin-containing regimen. Eligible patients received Z (4 mg/kg) q2wks on day 1 of each cycle followed by FOLFIRI until disease progression, unacceptable toxicity, death, or investigator/patient decision. Initial starting doses and subsequent dose modifications are at the treating physician’s discretion. The percentage of patients ≥65 y with grade (G) 3/4 adverse events (AEs) in the combined safety population of ASQoP and AFEQT are compared with that of the prespecified analysis in patients ≥65 y from VELOUR. Results: At data cut-off, the safety population comprised 116 patients with at least 1 completed cycle of treatment; 53 (45.7%) were ≥65 y. At least 1 G3/4 AE was experienced by 64.2% of patients vs 89.3% in VELOUR. Most reported G3/4 AEs were G3. There were no reports of G4 hypertension, diarrhea, stomatitis, or proteinuria. Conclusions: Thisinterim safety analysis from ASQoP and AFEQT in patients ≥65 y has identified no new safety signals. The early interim analysis provides additional safety data and suggests an acceptable toxicity profile in this real-life setting. Clinical trial information: NCT01571284. [Table: see text]

Managing atrial fibrillation in the CRT patient: Controversy or consensus?

The cumulative incidence of new onset atrial fibrillation (AF) in patients undergoing cardiac resynchronization therapy (CRT) is substantial, exceeding 25% in multiple recent studies. Although AF patients undergoing CRT show improved echocardiographic parameters, functional status, and quality of life in, they benefit to a lesser degree than do patients in normal sinus rhythm. They also exhibit a trend toward increased mortality. Understanding the barriers to response from CRT among AF patients is critical to addressing the needs of growing populations of patients with AF and HF. Foremost among these are suboptimal biventricular pacing, often characterized by fusion or pseudo-fusion complexes, leading to inefficient CRT delivery. Furthermore, AF increases the risk of inappropriate shocks, which lead to substantial psychiatric morbidity, increased risk of heart failure hospitalization, and may also increase mortality. Assiduous rate control is reasonable for all AF patients receiving CRT, but there is a paucity of data regarding specific antiarrhythmic drug therapy recommendations. For patients with permanent AF and severe symptoms, atrioventricular junction ablation appears effective in improving response by ensuring biventricular capture and reducing implantable cardioverter-defibrillator shock burden in selected patients. Catheter-based techniques such as pulmonary vein isolation appear more attractive and in the future may offer further advantages and lower risks, particularly for patients with paroxysmal AF.

Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients

Objective To determine whether inclusion of glutamine, selenium, or both in a standard isonitrogenous, isocaloric preparation of parenteral nutrition influenced new infections and mortality among critically ill patients.Design Randomised, double...