Safety and efficacy of high-rate cutoff and long detection interval ICD programming in secondary prevention patients

Screening for a disease must be clearly defined and differentiated from early detection. ‘Screening’ refers to the application of tests to the whole population or to defined segments such as males within certain defined high risk age groups. If applied in such a fashion ‘screening’ for prostate cancer may also be described epidemiologically as ‘secondary prevention’. While high-quality randomized studies show that screening reduces prostate cancer mortality by 21–44%, there is wide agreement that the introduction of population-based screening is at present premature because harms, mainly the high rate of overdiagnosis seen currently outweighs the benefits. This chapter attempts to put current knowledge into perspective with a set of recognized prerequirements for the application of screening, established by Wilson and Jungner in 1968.

Download Full-text

Apixaban for treatment of embolic stroke of undetermined source (ATTICUS) randomized trial – update of patient characteristics and study timeline after interim analysis

European Heart Journal ◽

10.1093/eurheartj/ehab724.2070 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

S Poli ◽

C Meissner ◽

H J Baezner ◽

A Kraft ◽

F Hillenbrand ◽

...

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Embolic Stroke ◽

High Rate ◽

Cardiac Monitoring ◽

Severe Bleeding ◽

Current Standard ◽

Private Company ◽

The Impact

Abstract Background Secondary prevention after embolic stroke of undetermined source (ESUS) has not yet been established. ESUS is associated with high risk of recurrent ischemic stroke and clinically silent ischemic lesions. Secondary prevention with aspirin is the current standard therapy in ESUS patients, despite high prevalence of occult atrial fibrillation (AF). Purpose To determine whether the direct oral factor Xa inhibitor apixaban, started within 28 days after index stroke, is superior to aspirin in preventing new ischemic lesions in subjects with remote cardiac monitoring. Primary endpoint was detection of new ischemic lesions in flair and diffusion-weighted (DWI) MR imaging at 12 months follow-up. Methods The study enrolled ESUS patients with risk profile for cardiac thromboembolism (i.e., left atrium (LA) size >45 mm, spontaneous echo contrast in LA appendage, LA appendage flow velocity ≤0.2 cm/s, atrial high rate episodes, CHA2DS2-Vasc score ≥4, patent foramen ovale). Patients were randomized 1:1 into the aspirin and apixaban arms. Study drug was initiated within 3–28 days after minor/moderate stroke and 14–28 days after major stroke. MRI (Flair/DWI) was conducted within 7 days of AF detection by remote cardiac monitors and at 12 months. ClinicalTrials.gov Identifier: NCT02427126. Funding: The trial is supported by BMS-Pfizer Alliance. Results Enrollment was stopped after interims analysis (including 200 patients) due to futility. Overall, 373 patients were screened with 353 being enrolled (178 and 175 in apixaban and ASA arms, respectively). So far, 130 (73.0%) and 120 (68.6%) subjects from apixaban and ASA arms, respectively, completed the study. 2% death, 1.7% withdrawal, and 1.7% were lost to follow-up. 3.9% did not completed the study for other reasons. Mean age of the ATTICUS population was 68.5 years with 51% males. 80% of the subjects suffered from hypertension. Mean systolic blood pressure at enrollment was 132 mmHg, BMI was 27.7, and CHA2DS-VASc-Score was 4.9. So far, adverse events (AE) occurred in 63% of the subjects, 30% was documented as severe. 6.8% cases of recurrent ischemic stroke and no case of hemorrhagic stroke were reported. Only 1 case of severe bleeding was reported in the aspirin arm. Newly detected AF was reported in 80 patients (23%), 42 occurring in the aspirin arm. As required by protocol, latter were immediately switched from aspirin to apixaban. Due to ongoing data clearing, numbers and % will change until presentation. Conclusions In contrast to the recently published NAVIGATE and RESPECT ESUS trials, patients enrolled in ATTICUS need to exhibit additional AF predicting factors. Furthermore, mandatory cardiac remote monitoring will help to elucidate the impact of AF and the effects of early oral anticoagulation with apixaban compared to antiplatelet therapy with aspirin on the incidence of new ischemic lesions after ESUS. Preliminary data will be presented and discussed in the context of current literature. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): The trial is supported by BMS-Pfizer Alliance.

Download Full-text

Characterization of the exposure-response relationship leading to recommendations for dosing optimization in a new drug application review.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.2510 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 2510-2510

Author(s):

Jun Yang ◽

Nitin Mehrotra ◽

Hong Zhao ◽

Ruthann Marie Giusti ◽

Suzanne Demko ◽

...

Keyword(s):

Controlled Trial ◽

Phase 1 ◽

Drug Application ◽

Dose Intensity ◽

Progression Free Survival ◽

High Rate ◽

Safety And Efficacy ◽

Dose Modification ◽

Exposure Response ◽

Post Marketing

2510 Background: On November 29 2012, the U. S. FDA approved cabozantinib (COMETRIQ) for the treatment of patients with progressive, metastatic medullary thyroid cancer (MTC). Drug-related toxicity was common at a dose of 140 mg once daily across Phase 1 to Phase 3 trials submitted in this NDA. During the review of this application, these safety findings raised the question whether the optimal cabozantinib dose was selected for the treatment of MTC. Exposure-response (E-R) analyses were performed to assess the appropriateness of the cabozantinib dose. Methods: The data were obtained from an international, multi-center, randomized (2:1), placebo-controlled trial enrolling 330 patients with metastatic MTC. To account for variable exposure levels due to dose modification and inter-individual pharmacokinetic variability, average exposure (Starting Dose*Dose intensity/individual CL/F) was used as the exposure metric in the E-R analyses. The relationships between cabozantinib exposure and progression free survival (PFS), and selected safety endpoints including diarrhea, palmar-plantar erythrodysesthesia (PPE) syndrome and time to dose modification (TTDM) were evaluated. Results: Kaplan-Meier analyses of PFS for each quartile of average cabozantinib exposure suggest that patients with lower exposure and those with higher exposure may have equivalent PFS, comparatively. The multivariate Cox proportional analysis identified individual patient’s clearance as a significant covariate for prediction of TTDM with a hazard ratio of 1.95 (95% CI [1.47-2.59]), suggesting that patients with higher exposures required dose modification earlier than patients with lower exposures. The results of the E-R analyses may be difficult to interpret due to the high rate of dose modification. Nevertheless, these results indicate that a lower dose may be as effective with improved tolerability. Conclusions: The E-R analyses along with the observed safety and efficacy data in the clinical trials led to an FDA requirement to conduct a post marketing clinical trial to evaluate the safety and efficacy of a lower cabozantinib dose.

Download Full-text

P1921Impact of cryoballoon freeze duration on long-term durability of pulmonary vein isolation in atrial fibrillation: insights from Re-mapping procedures (the ICE Re-map study)

European Heart Journal ◽

10.1093/eurheartj/ehz748.0668 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

S Chen ◽

B Schmidt ◽

S Bordignon ◽

L Perrotta ◽

F Bologna ◽

...

Keyword(s):

Pulmonary Vein ◽

Pulmonary Vein Isolation ◽

Left Atrial ◽

High Rate ◽

Index Procedure ◽

Safety And Efficacy ◽

Second Procedure ◽

Repeat Procedures ◽

Freeze Duration

Abstract Background Second-generation cryoballoon (CB2) represents a powerful pulmonary vein isolation (PVI) tool. Recently, the randomized time-to-effect guided (ICE-T) CB2 strategy targeting a 240s single freeze demonstrated fast and efficient PVI. To further optimize safety and efficacy, a shortened 3min freeze duration has been suggested but PVI durability remains unclear. Methods Between May 2013 and December 2017 all CB2 ablations followed the ICE-T concept (target-freeze: 240s or 180s). Patients undergoing a second procedure for arrhythmia recurrence were analyzed. Two groups were defined based on the index freeze duration (group 240s vs. group 180s). In all repeat procedures a 3D left-atrial map was obtained. Durability of PVI and localization of conduction gaps were compared. Results A total of 106/788 (13%) patients underwent a second procedure (group 240s: 80/604 vs. group 180s: 26/184) after a mean of 377 days. There was no difference regarding PV occlusion and time-to-isolation in the index procedure between two groups. No major complications occurred. During the second procedure significantly more patients demonstrated durable isolation of all PVs in group 240 (61% vs 35%, p=0.02) along with a significantly increased rate of PVI durability (88% vs. 69%, per vein, p<0.001). Left sided PVs did significantly benefit from 240s freezes (reconnection LSPV: 6% vs 27%, p=0.004, LIPV: 14 vs. 39%, p=0.006). Conclusions The ICE-T strategy is associated with a high rate of durable PVI in patients with arrhythmia recurrence. Target freeze duration of 240s vs. 180s is associated with significantly increased lesion durability, particularly at left sided PVs, without increasing complications.

Download Full-text

SAFETY AND EFFICACY OF COLCHICINE FOR SECONDARY PREVENTION AFTER ACUTE MYOCARDIAL INFARCTION: A SYSTEMATIC REVIEW AND META-ANALYSIS

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(21)02880-1 ◽

2021 ◽

Vol 77 (18) ◽

pp. 1522

Author(s):

Kevin Buda ◽

Michael Megaly ◽

Jessica Padniewski ◽

Philippe Fernand Nyembo ◽

Maen Assali ◽

...

Keyword(s):

Myocardial Infarction ◽

Systematic Review ◽

Acute Myocardial Infarction ◽

Secondary Prevention ◽

Meta Analysis ◽

Safety And Efficacy

Download Full-text

Systemic immune-inflammation index predicts major adverse cardiovascular events in patients with ST-elevation myocardial infarction

European Heart Journal ◽

10.1093/eurheartj/ehab724.1353 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

A Denegri ◽

S Obeid ◽

L Raeber ◽

S Windecker ◽

B Gencer ◽

...

Keyword(s):

Myocardial Infarction ◽

Secondary Prevention ◽

Cox Proportional Hazards ◽

St Elevation Myocardial Infarction ◽

University Hospital ◽

High Rate ◽

Major Adverse Cardiovascular Events ◽

All Cause Mortality ◽

St Elevation ◽

Immune Inflammation

Abstract Background ST-elevation myocardial infarction (STEMI) represents the life-threatening manifestation of atherosclerosis, a chronic inflammatory disease of arterial wall, and is associated with high rate of morbidity and mortality. Thus, inflammatory biomarkers may be useful in identifying high inflammatory burden patients who may benefit from tailored high-intensity secondary prevention therapy. Purpose We therefore assessed the relationship between the systemic immune-inflammation index (SII) and CV outcomesamong 1144 all-comers patients admitted to four Swiss University Hospital for STEMI and enrolled in the prospective multicenter SPUM registry cohort I (NCT 01000701). Methods SII was calculated as platelet counts x neutrophil counts / lymphocyte counts. Patients were subdivided into three groups according to SII tertiles. The composite primary endpoint was major adverse cardiac and cerebrovascular events (MACCE: stroke, myocardial infarction, CV death). Adjusted Cox proportional hazards regression models were implemented to determine the risk associated with SII and outcomes. Results Out of 1144 STEMI patients, 912 patients (79,7%) had available for SII. Patients within the highest tertile were slightly more frequently male (23.0 vs 22.0%, p=0.05), with higher plasma values of neutrophils (11.4±2.4 vs 6.5±3.7 G/l, p<0.001), platelets (275.3±97.5 vs 202.5±51.6 G/l, p<0.001) and lower levels of lymphocytes (1.0±0.6 vs 2.1±1.1 G/l, p<0.001) and LVEF (46.4±11.5% vs 50.4±10.3%, p<0.001) (Fig. 1A). At 1 year, these patients presented the highest rate of all-cause mortality (7.2% vs 2.6%, p=0.02) and MACCE (8.2% vs 3.3, p=0.03). This enhanced risk persisted for all-cause mortality and MACCE, after adjustment for age, sex, ace-inhibitors and statin therapy (Adj. HR 2.85, 95% CI 1.30–6.70, p=0.03 and Adj. HR 2.63, 95% CI 1.25–5.55, p=0.03, respectively, Fig. 1B). Conclusions Among a real-world cohort of STEMI-patients, SII highlights the highest inflammatory risk phenotype, being associated with significant increased rates of MACCE and all-cause of death. These observations might help clinicians to furtherly identify patients who may derive the greatest benefit from tailored more intense secondary prevention therapies including inflammatory modulation. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

Download Full-text

Initial Clinical Experience with the Biodegradable AbsnowTM Device for Percutaneous Closure of Atrial Septal Defect: A 3-Year Follow-Up

Journal of Interventional Cardiology ◽

10.1155/2021/6369493 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Yifan Li ◽

Yumei Xie ◽

Boning Li ◽

Zhaofeng Xie ◽

Junjun Shen ◽

...

Keyword(s):

Atrial Septal Defect ◽

Clinical Experience ◽

Septal Defect ◽

Percutaneous Closure ◽

High Rate ◽

Moderate Degree ◽

Residual Shunt ◽

Safety And Efficacy ◽

Initial Clinical Experience

Objective. We reported the 3-year follow-up results of initial clinical experience with the AbsnowTM device, a novel biodegradable occluder for percutaneous closure of atrial septal defect (ASD). Background. The AbsnowTM device is a total biodegradable septal occluder with double-disc poly-L-lactic acid (PLLA) framework and PLLA membranes intergraded into the device to ensure its biodegradability, clinical safety, and efficacy. Methods. Five pediatric patients were enrolled from May to June 2018 in our institution and were followed up for 3 years. A clinical evaluation and transthoracic echocardiography were performed at 24 hr, 1 month, 3 months, 6 months, 12 months, and yearly after implantation. Primary endpoints were a composite clinical success, comprising of clinical closure success and safety at the 36-month follow-up evaluation. Secondary endpoints included technical success, procedure success, closure success, and safety at each of the follow-up visits. Results. The median subject age was 3.6 years (range 3.1–6.5 years). The mean ASD diameter was (13.7 ± 2.9) mm. The median device size was 20 mm (range 14 to 24 mm). Technical and procedure success was achieved in 100% (5/5) of the patients. At 2-year follow-up, 3 of the 5 patients developed new-onset residual shunts and 2 of them reached a moderate degree. At 3-year follow-up, the residual shunt size increased over time in all the 3 patients, and 1 of them had right ventricular enlargement. All of the 5 patients were free from serious adverse events during the 3-year follow-up, with no device embolization, thromboembolization, or reintervention to the target defect. Conclusion. This 3-year follow-up result of initial experience with the biodegradable AbsnowTM device has demonstrated acceptable safety with no procedural complications. Notably, the high rate of residual shunt significantly affected its efficacy. The long-term safety and efficacy of the device should be further evaluated in a large cohort of patients in future studies.

Download Full-text

Safety and Efficacy of Small Bowel Examination by Capsule Endoscopy for Patients before Liver Transplantation

BioMed Research International ◽

10.1155/2017/8193821 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Kawano Seiji ◽

Takaki Akinobu ◽

Iwamuro Masaya ◽

Yasunaka Tetsuya ◽

Kono Yoshiyasu ◽

...

Keyword(s):

Liver Transplantation ◽

Small Bowel ◽

Transit Time ◽

Capsule Endoscopy ◽

High Rate ◽

Clinical Trial Registry ◽

Safety And Efficacy ◽

Red Color ◽

History Of ◽

The Mean

Background and Aims. Gastrointestinal surveillance is a requirement prior to liver transplantation (LT), but small intestine examination is not generally undertaken. The aim of the present study was to evaluate the safety and efficacy of capsule endoscopy (CE) for patients with end-stage liver disease.Methods. 31 patients who needed LT were enrolled, and 139 patients who underwent CE over the same period of time acted as controls.Results. Frequency of successful achievement of evaluation of the full length of the small bowel, the mean gastric transit time, and the mean small bowel transit time were not significantly different between the two groups. Abnormalities in the small bowel were found in 26 patients. Comparative analysis revealed that history of EV rupture, history of EV treatment, red color sign of EV, and presence of PHG or HCC were significantly associated with patients with >2 two such findings (high score group).Conclusions. Small bowel examination by CE in patients before liver transplantation could be performed safely and is justified by the high rate of abnormal lesions detected particularly in patients with history of EV therapy or bleeding, red color sign, and presence of PHG or HCC. This study was registered in the UMIN Clinical Trial Registry (UMIN000008672).

Download Full-text