Primary Effectiveness Endpoint Research Articles

Outcomes from the ClotTriever Outcomes Registry show symptom duration may underestimate deep vein thrombus chronicity

ObjectiveThe all-comer ClotTriever Outcomes registry assessed indicators of thrombus chronicity in patients with acute, subacute, and chronic lower extremity deep vein thrombosis (DVT). The effectiveness of the ClotTriever System (Inari Medical, Irvine, CA) by chronicity subgroup was also assessed and reported here in this subanalysis. MethodsAll-comer patients with lower extremity DVT were enrolled, with no limitation based on the patients’ symptom duration. Chronicity was assessed three times and compared: before the procedure based on symptom duration, during the procedure based on available pre-thrombectomy imaging, and visual inspection of the extracted thrombus morphology after thrombectomy. Patients were grouped into acute, subacute, and chronic subgroups according to their post-thrombectomy thrombus chronicity based on thrombus morphology. Analyses on baseline and procedural characteristics along with thrombus removal were performed across subgroups. The effectiveness of thrombus removal was determined by Marder scores adjudicated by an independent core laboratory, with a prespecified primary effectiveness end point of complete or near-complete (≥75%) thrombus removal. ResultsOf the 260 treated limbs from 250 patients, using symptom duration alone, 70.7% were considered acute, 20.9% subacute, and 8.4% chronic. Upon visual inspection, the extracted thrombus chronicity was approximately one-third in each subgroup: 32.7% had acute thrombus, 35.4% subacute thrombus, and 31.9% chronic thrombus. Chronicity assessed using symptom duration alone mismatched the post-thrombectomy chronicity in 55.1% of limbs (P < .0001) with 49.0% being more chronic than suggested by the patients’ duration of symptoms. Chronicity assessed using pre-thrombectomy imaging mismatched the post-thrombectomy chronicity in 17.5% of limbs (P < .0001). No patients received thrombolytics and 99.6% were treated in a single session. Complete or near-complete thrombus removal was achieved in a high percentage of limbs regardless of thrombus chronicity: 90.8%, 81.9%, and 83.8% in limbs with acute, subacute, and chronic thrombus, respectively. ConclusionsThis subanalysis from the all-comer ClotTriever Outcomes registry demonstrates that extracted thrombus in DVT may be more chronic than suggested by the patients’ duration of symptoms. The addition of imaging is helpful to determine the ability of thrombus to respond to therapy. Irrespective of thrombus chronicity, the ClotTriever system can be effective at removing acute, subacute, and chronic thrombus in a single-session procedure without the need for thrombolytics.

One-year results of the GORE EXCLUDER Conformable AAA Endoprosthesis system in the United States regulatory trial

ObjectiveTo report the 1-year clinical outcomes from the GORE EXCLUDER Conformable AAA Endoprosthesis system in the US regulatory trial. MethodsThe study is a prospective, multicenter, investigational device exemption clinical trial at 31 US sites with core laboratory assessment of imaging and independent event adjudication. The primary safety (incidence of major adverse events at 30 days) and effectiveness end points (successful aneurysm treatment at 1 year) were assessed in a cohort of patients with abdominal aortic aneurysms (AAAs). ResultsWe enrolled 80 patients between December 19, 2017, and February, 27, 2019. The mean maximum aortic diameter was 57.7 ± 7.95 mm (range, 42.5-82.7 mm) with an average patient age of 73.5 ± 8.14 years (range, 56-96 years). Overall technical success was 100% (80/80). The mean hospital length stay was 1.2 ± 0.6 days (range, 1-4 days). No primary safety end point events were observed, including no death, stroke, myocardial infarction, bowel ischemia, paraplegia, respiratory failure, renal failure, procedural blood loss of more than 1000 mL, or thromboembolic events including limb occlusion or distal emboli. There were no type I or III endoleaks detected on the 1-, 6-, or 12-month follow-up computed tomography scans. There were no stent fractures, device migrations (≥10 mm), AAA ruptures, or conversions to open surgical repair observed. Two patients had AAA sac growth of more than 5 mm at 1 year owing to type II endoleaks. There were no aneurysm-related deaths within the 12-month follow-up, and freedom from aneurysm-related mortality was 100% through 1 year. ConclusionsThe safety and effectiveness of the GORE EXCLUDER Conformable AAA Endoprosthesis system has been demonstrated with 98.5% freedom from primary effectiveness end point events at 1 year and 100% freedom from primary safety end point events assessed through 30 days.

Multicenter, Double-Blinded, Randomized, Active-Sham Controlled Clinical Study Design to Assess the Safety and Effectiveness of a Novel High Frequency Electric Nerve Block System in the Treatment of Post-Amputation Pain (The QUEST Study).

BackgroundChronic pain that follows amputation of a limb is reported as “one of the most severe pains in the human experience,” due to the magnitude of tissue injury and the multiple potential of pain generators at the local peripheral, spinal, and cortical levels. The Altius® System was developed to deliver high-frequency nerve block (HFNB) therapy via a cuff electrode applied to the peripheral nerve(s) and an implantable pulse generator. We report a novel clinical trial design for the first study of an active-implantable medical device in subjects with lower-limb post-amputation pain utilizing a multicenter, double-blinded, randomized, active-sham controlled clinical study protocol called QUEST, which is an ongoing investigational device exemption study to support United States Food and Drug Administration approval.MethodsThe study enrollment of 180 subjects was completed in September 2021. Subjects were randomized 1:1 to the treatment group or the active-sham control group for the 3-month primary effectiveness and safety endpoints. After month 3, the active-sham control program group crossed over to the treatment program group and all subjects continued to the 12-month study endpoint. Study effectiveness success is determined by a superiority test between responder rates in the treatment and control groups at 3 months. A responder is defined as someone who experiences a 50% or greater reduction in pain scores – after a 30-minute treatment session – for more than 50% of all pain episodes in which the treatment was used.DiscussionThe QUEST study design employs an active-sham control group to objectively assess the effectiveness of HFNB therapy. Additionally, the electronic diary repeated measures data collection in QUEST is expected to reduce the intra-subject variation typically observed in pain treatment studies. Finally, the longitudinal measurement of health-related quality of life and use of pain medication may, for example, show effectiveness in reducing opioid use over time.

Polymer-Based Versus Polymer-Free Stents in High Bleeding Risk Patients: Final 2-Year Results From Onyx ONE.

Resolute Onyx polymer-based zotarolimus-eluting stents (ZES) were noninferior in safety and effectiveness to BioFreedom polymer-free biolimus A9-coated stents (DCS) in high-bleeding-risk (HBR) patients treated with 1-month dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) at 1 year. This study reports the final 2-year results of the randomized Onyx ONE trial. The Onyx ONE (A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy (DAPT) for High-Bleeding Risk Patients) trial randomly assigned HBR patients to treatment with ZES or DCS. Following 1-month DAPT, event-free patients received SAPT (either aspirin or a P2Y12 inhibitor at physician discretion). The primary safety endpoint, a composite of cardiac death, myocardial infarction, or stent thrombosis at 1 year, was determined at 1 year. Rates of primary and secondary endpoints were calculated after final follow-up at 2 years. A total of 1,003 patients were randomly allocated to ZES and 993 patients to DCS. Follow-up was complete in 980 (97.7%) ZES patients and 962 (96.9%) DCS patients at 2 years. The primary safety endpoint occurred in 208 (21.2%) patients in the ZES group and 199 (20.7%) patients in the DCS group (risk difference: 0.5%; 95%CI: -3.1% to 4.2%; P=0.78) at 2 years without significant differences in individual components of the composite endpoint. The secondary effectiveness endpoint occurred in 217 (22.1%) patients in the ZES group and 202 (21.0%) patients in the DCS group (risk difference: 1.1%; 95%CI: -2.5% to 4.8%; P=0.54). Among patients at HBR treated with 1-month DAPT followed by SAPT, the Resolute Onyx polymer-based ZES had similar 2-year outcomes for the primary safety and secondary effectiveness endpoint compared with the BioFreedom polymer-free DCS. (A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy [DAPT] for High-Bleeding Risk Patients [Onyx ONE]; NCT03344653).

Safety and feasibility of a novel multilectrode array catheter in mapping atrial and ventricular arrhythmias with high density: results from the multi-center OPTIMUM study

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): This study was funded by Biosense Webster, Inc. Background/Introduction The novel multielectrode array mapping catheter includes 48 electrodes symmetrically distributed across and along 6 splines (Picture), with an additional unipolar reference electrode to reduce far-field signals built in at the tip of the irrigation lumen. Preclinical studies demonstrated its ability to provide high density and high resolution mapping in complex substrates, but its usability and safety in patients with atrial or ventricular arrhythmias have not been investigated. Purpose To assess the safety and mapping performance of the catheter with the electroanatomical navigation system for mapping in the atria and ventricle in patients with a variety of complex arrhythmias. Methods The OPTIMUM study was a prospective, single arm study conducted at 3 European sites. Patients with scar-related atrial tachycardia (AT), PAF and persistent AF (PsAF), ventricular tachycardia (VT), or premature ventricular complexes (PVC) underwent pre-ablation mapping with the study catheter, and subsequent ablation according to institutional standard of care practice; the follow up period was 7 days. The primary safety endpoint was the incidence of device-related serious adverse events (SAE) within 7 days following the procedure. The primary effectiveness endpoint was the completion of protocol-required fast activation and electro anatomical pre-ablation mapping without resort to non-study mapping catheter(s), including fast anatomical mapping, mapping of substrate or any area of interest, and identification of conduction channel(s), gap(s) and critical isthmuses. General procedural characteristics as well as physician feedback (7-point Likert scale: 1 = poor and 7 = excellent) on various aspects of deployment, signal quality, and learning curve were also evaluated. Results Thirty-one patients (mean age: 59.8±14 years, 71.0% male) were enrolled and treated (9 scar-related AT, 12 PAF, and 1 PsAF, 6 VT, and 3 PVC). There was no (0/31) SAE reported, and the primary effectiveness endpoint was achieved in all subjects (31/31). Almost all operators rated highly (≥ 5) on noise reduction in bipolar maps (30/31) and short learning curve (27/31). Bipolar signals and catheter maneuverability were rated highly favorable (≥5) in the left and right atria and met-expectation-and-above (≥4) in the left and right ventricles. Conclusion(s) The first-in-human clinical data demonstrate the safety and effectiveness of the novel microelectrode array mapping catheter to efficiently map various atrial and ventricular complex arrhythmias with good signal quality. Physicians indicated high satisfaction with the learning curve, catheter maneuverability, tissue characterization in all cardiac chambers.

Acute results of a novel flexible tip radiofrequency catheter incorporating contact force sensing

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Abbott Background Catheter ablation is an established therapy for paroxysmal atrial fibrillation (PAF). The TactiFlex Ablation Catheter, Sensor-Enabled (TactiFlex SE) is a next-generation radiofrequency ablation catheter incorporating highly accurate fiber optics-based contact force sensing technology with a flexible, laser-cut tip. This is the first report of results from the TactiFlex IDE clinical study. Purpose To demonstrate that ablation with TactiFlex SE is safe and effective for the treatment of drug refractory, symptomatic PAF. Methods The TactiFlex IDE (NCT04356040) is a prospective, non-randomized, multi-center clinical study which enrolled 305 subjects worldwide in the main study. Enrollment in the main study began on June 26, 2020 and completed on June 8, 2021. Subjects underwent de novo Pulmonary Vein Isolation (PVI) and, if indicated, a Cavotricuspid Isthmus ablation (CTI line) for CTI-dependent atrial flutter. Results Acute procedural success was achieved in 98.6% (274/278) of the main study cohort who underwent an ablation procedure using the TactiFlex SE. First pass success, defined as isolation of all pulmonary veins (PVs) confirmed after a minimum 20 min waiting period was achieved in 89.6% (249/278) of subjects. This was a significant improvement versus the TactiSense IDE trial (TactiCath Ablation Catheter, Sensor-Enabled). Significant decreases were also seen in total procedure time (123 min [101.0, 163.5]), total PV ablation time (55.5 min [35.0, 81.0]), total fluoroscopy time (6.0 min [0.0, 13.0]) and irrigation fluid volume (450.0 mL [346.0, 636.0]) (values given as Median [Q1, Q3]), see FIGURE. All subjects have completed at least 90 days of follow-up. Only 2.6% (7/271) of subjects required a repeat procedure during the 90-day blanking period. The primary safety and effectiveness endpoints will be evaluated at 12-months. At 90 days, 4.3% (12/281) subjects had experienced a primary safety endpoint event. Conclusions The acute data from the TactiFlex IDE clinical study demonstrate safety and effectiveness of the TactiFlex SE catheter in the treatment of PAF. Ablation procedures performed using the next-generation TactiFlex SE catheter were shorter and had improved acute clinical effectiveness outcomes versus the TactiSense IDE. It is anticipated these results will also be reflected in the 12-month safety and effectiveness endpoints.

Treatment of large and giant posterior communicating artery aneurysms with the Surpass streamline flow diverter: results from the SCENT trial

BackgroundThe Surpass flow diverter was developed to treat intracranial aneurysms not amenable to standard treatment. Indications for use allow placement in the internal carotid artery to the terminus, including the...

Effectiveness of three delivery models for promoting access to pre-exposure prophylaxis in HIV-1 serodiscordant couples in Nigeria.

To evaluate the effectiveness of three models for pre-exposure prophylaxis (PrEP) service delivery to HIV-1 serodiscordant couples in Nigeria. 297 heterosexual HIV-1 serodiscordant couples were recruited into three PrEP delivery models and followed up for 18 months. The models were i) Outpatient clinic model providing PreP in routine outpatient care; ii) Antiretroviral therapy (ART) clinic model providing PrEP in ART clinics; and iii) Decentralized care model providing PrEP through primary and secondary care centres linked to a tertiary care centre. The primary effectiveness endpoint was incident HIV-1 infection. The HIV incidence before and after the study was compared and the incidence rate ratio computed for each model. Survival analysis was conducted, Cox regression analysis was used to compare the factors that influenced couple retention in each of the models. Kaplan-Meier survival analysis was used to estimate the median retention time (in months) of the study participants in each of the study models, and log-rank test for equality of survival functions was conducted to test for significant differences among the three models. There was no significant difference (p>0.05) in the couple retention rates among the three models. At months 3, 6 and 9, adherence of the HIV-1-infected partners to ART was highest in the decentralized model, whereas at months 9 and 12, the outpatient model had the highest proportion of HIV-1- uninfected partners adhering to PrEP (p<0.001). The HIV incidence per 100 person-years was zero in the general outpatient clinic and ART clinic models and 1.6 (95% CI: 0.04-9.1) in the decentralized clinic model. The difference in the observed and expected incidence rate was 4.3 (95% CI: 0.44-39.57) for the decentralized clinic model. Although incidence of HIV seroconversion was highest in the decentralized clinic model, this difference may be due to the higher sexual risk behavior among study participants in the decentralized model rather than the type of service delivery. The study findings imply that any of the models can effectively deliver PrEP services.

Evaluation of the effect of targeted Mass Drug Administration and Reactive Case Detection on malaria transmission and elimination in Eastern Hararghe zone, Oromia, Ethiopia: a cluster randomized control trial

BackgroundReactive and proactive case detection measures are widely implemented by national malaria elimination programs globally. Ethiopia decided to include Reactive Case Detection (RCD) and targeted Mass Drug Administration (tMDA) approaches as part of their elimination strategy along with rigorous evaluation. The purpose of this study is to compare the impact of RCD and tMDA on malaria elimination over the 2-year study period, by looking at the annual parasite incidence before and after the intervention.MethodsThe study will be conducted in the East Hararghe zone of Ethiopia. Malaria transmission in the area is low to moderate. This study will deploy a community-based, three-arm, cluster-randomized control trial implemented over 2 years. Forty-eight clusters (16 clusters per arm) will be selected based on the annual number of confirmed malaria cases seen in the cluster. All clusters will receive the current standard of care in terms of malaria elimination interventions provided by the national malaria control program. In addition, following the identification of malaria parasite infection, individuals who reside within a 100-m radius of the index case will receive a diagnosis for malaria and treatment if positive in the RCD arm or presumptive treatment in the tMDA arm. The primary effectiveness endpoint will be measured at baseline and endline for each intervention arm and compared to the control arm using a difference in difference approach.DiscussionThis randomized controlled trial will provide evidence of the impact of the proposed intervention approaches for malaria elimination.Trial registrationClinicalTrials.gov NCT04241705. Registration date: January 27, 2020.

Paclitaxel-coated balloons versus percutaneous transluminal angioplasty for infrapopliteal chronic total occlusions: the IN.PACT BTK randomised trial.

Data are mixed concerning the safety and effectiveness of drug-coated balloons (DCBs) for treating below-the-knee (BTK) lesions. The aim of this study was to assess the safety and effectiveness of the IN.PACT 014 paclitaxel-coated balloon catheter versus conventional percutaneous transluminal angioplasty (PTA) for infrapopliteal chronic total occlusions (CTOs) in patients with chronic limb-threatening ischaemia (CLTI). The IN.PACT BTK randomised study is a prospective, multicentre, randomised pilot study. Fifty CLTI participants (Rutherford clinical category 4-5) with BTK CTOs were randomised 1:1 to DCB (N=23) or PTA (N=27). The primary effectiveness endpoint was late lumen loss (LLL) at 9 months post procedure. Safety outcomes up to 9 months included all-cause mortality, major target limb amputation, and clinically driven target lesion revascularisation (CD-TLR). Mean lesion length was 215.41±83.81 mm in the DCB group and 218.19±80.43 mm for PTA (p=0.806). The 9-month angiographic LLL was 0.892±0.774 mm for the DCB group and 1.312±0.720 mm for the PTA group (p=0.070) in a classic analysis, and 0.592±0.944 mm for DCB and 1.260±0.810 mm for PTA (p=0.017) in a subsegmental analysis. The Kaplan-Meier estimated freedom from CD-TLR up to 9 months was 91.1% for DCB and 91.8% for PTA (log-rank p=0.942). At 9 months, 1 patient died in the DCB group and 2 in the PTA group (p=1.000); there were no major target limb amputations in either arm. The 9-month subsegmental LLL was lower after treatment with the IN.PACT 014 DCB compared with PTA with no differences in safety or revascularisation events in a small complex population of patients with BTK CTOs. gov: NCT02963649.

Twenty-Four Month Results of Tack-Optimized Balloon Angioplasty Using the Tack Endovascular System in Below-the-Knee Arteries

Purpose: To report 24 month safety and efficacy of the Tack Endovascular System for treatment of post-percutaneous transluminal angioplasty (PTA) infrapopliteal dissections in patients with critical limb-threatening ischemia (CLTI). Materials and Methods: The Tack-Optimized Balloon Angioplasty (TOBA) II below-the-knee (BTK) study was a prospective, multicenter, single-arm evaluation of the Tack Endovascular system for post-PTA infrapopliteal dissection repair. Patients with Rutherford Clinical Category (RC) 3 to 5 and a post-PTA dissection(s) of the BTK arteries were enrolled. The 30 day primary safety endpoint was a composite of major adverse limb events (MALE) and all-cause perioperative death (POD). The primary effectiveness endpoint was a composite of MALE at 6 months and 30 day POD. Outcomes were assessed as observational endpoints at 24 months. Results: Tack-Optimized Balloon Angioplasty II BTK enrolled 233 patients; all patients had a post-PTA dissection(s) and received ≥1 Tack implant (range, 1–16). Mean age was 74.4±10.0 years and 67.4% were men. Most patients had CLTI (RC 3: 16.3%; RC 4/5: 83.7%). Mean target lesion length was 80±49 mm. Moderate to severe calcium was present in 89 (35.8%) lesions and total occlusions were present in 118 (47.6%) lesions. Kaplan-Meier freedom from MALE at 24 months + POD at 30 days was 92.2% and 24 month freedom from clinically-driven target lesions revascularization was 73.6%. Kaplan-Meier target limb salvage was 95.7% and amputation-free survival was 75.4%. Improvements in functional status and quality of life were observed through 24 months. Conclusion: The TOBA II BTK study demonstrated sustained safety and efficacy through 24 months in patients treated for post-PTA dissection(s) of BTK lesions. Clinical Trial Registration: ClinicalTrials.gov identifier NCT02942966.

Prospective study on embolization of intracranial aneurysms with the pipeline device (PREMIER study): 3-year results with the application of a flow diverter specific occlusion classification

BackgroundThe pipeline embolization device (PED; Medtronic) has presented as a safe and efficacious treatment for small- and medium-sized intracranial aneurysms. Independently adjudicated long-term results of the device in treating these...

Drug-eluting balloon (DEB) versus plain old balloon angioplasty (POBA) in the treatment of failing dialysis access: A prospective randomized trial.

ObjectiveTo compare the efficacy of angioplasty using drug-eluting balloons (DEB) compared with plain old balloon angioplasty (POBA) to reduce the rate of restenosis.MethodsThis prospective, single-centre, single-blinded, 1:1 randomized, clinical trial enrolled patients that had primary or restenotic lesions in native upper extremity arteriovenous (AV) fistulas or at the graft-venous anastomosis. Patients were randomized to angioplasty with a POBA or a DEB. The primary effectiveness endpoints were freedom from target lesion revascularization (TLR) and functional status of access circuit at 12 months.ResultsA total of 42 (28 male, 14 female; age range, 42–83 years) patients were enrolled. Patients were followed for 12 months. No significant differences were detected between the POBA and DEB groups regarding total number of TLR procedures (31 versus 36, respectively), freedom from TLR (3 versus 4, respectively) and functional status of the access circuit at 12 months (14 of 20 patients [70%] versus 17 of 22 patients [77%], respectively).ConclusionThis clinical trial did not demonstrate any significant differences between DEB angioplasty and standard balloon angioplasty when treating dysfunctional haemodialysis access.

Interim outcomes of mechanical thrombectomy for deep vein thrombosis from the All-Comer CLOUT Registry

ObjectivesThe multicenter, prospective, single arm CLOUT registry assesses the safety and effectiveness of the ClotTriever System (Inari Medical, Irvine, CA) for the treatment of acute and nonacute lower extremity deep vein thrombosis (DVT) in all-comer patients. Reported here are the outcomes of the first 250 patients. MethodsAll-comer patients with lower extremity DVT were enrolled, including those with bilateral DVT, those with previously failed DVT treatment, and regardless of symptom duration. The primary effectiveness end point is complete or near-complete (≥75%) thrombus removal determined by independent core laboratory-adjudicated Marder scores. Safety outcomes include serious adverse events through 30 days and clinical outcomes include post-thrombotic syndrome severity, symptoms, pain, and quality of life through 6 months. ResultsThe median age was 62 years and 40% of patients had contraindications to thrombolytics. A range of thrombus chronicity (33% acute, 35% subacute, 32% chronic) was observed. No patients received thrombolytics and 99.6% were treated in a single session. The median thrombectomy time was 28 minutes. The primary effectiveness end point was achieved in 86% of limbs. Through 30 days, one device-related serious adverse event occurred. At 6 months, 24% of patients had post-thrombotic syndrome. Significant and sustained improvements were observed in all clinical outcomes, including the Revised Venous Clinical Severity Score, the numeric pain rating scale, and the EuroQol Group 5-Dimension Self-Report Questionnaire. ConclusionsThe 6-month outcomes from the all-comer CLOUT registry with a range of thrombus chronicities demonstrate favorable effectiveness, safety, and sustained clinical improvements.

Thrombus Chronicity Subanalysis of Mechanical Thrombectomy For Deep Vein Thrombosis in Real-World Patients: Six-Month Outcomes from the CLOUT Registry

The prospective, multicenter, real-world CLOUT registry assesses the safety and effectiveness of the ClotTriever System (Inari Medical, Irvine, Calif) for the treatment of lower extremity deep venous thrombosis (DVT). The goal of this subanalysis is to evaluate the outcomes of the CLOUT registry based on thrombus chronicity. The CLOUT registry is actively enrolling patients with proximal DVT. Thrombus chronicity was assessed by the treating physician, taking into account patient medical history, intraprocedural imaging, and visual inspection of the extracted thrombus. Patients were classified as having acute (<2 weeks), subacute (2-6 weeks), and/or chronic (>6 weeks) thrombus, using the oldest chronicity extracted per treated limb. The primary effectiveness end point is complete or near-complete (≥75%) thrombus removal as determined by Marder scores adjudicated by an independent core laboratory. Ultrasound and clinical outcomes are reported to 6 months. Of the first 250 patients enrolled in CLOUT, 33% were classified with acute, 35% with subacute, and 32% with chronic thrombus. Median age was 62 years, 52% were male, 23% had prior history of DVT, and 40% were at a high bleeding risk with thrombolytics. All procedures but one were single session (99.6%) with a median of four ClotTriever passes for all chronicity subgroups. No patients required adjunctive thrombolytics. Adjuvant angioplasty was used in 73% (acute: 70%; subacute: 68%; chronic: 84%) and stents in 47% (acute: 46%; subacute: 42%; chronic: 50%) of cases. Median blood loss was 50 mL for all chronicity subgroups. Complete or near-complete thrombus removal was achieved in 85% (acute: 90%; subacute 81%; chronic: 84%) of limbs, including 51% (acute: 54%; subacute: 49%; chronic: 49%) with 100% thrombus removal (Figure ). The post-thrombectomy median hospital stay was 1 day for all chronicity subgroups. At 6 months (Table I), 90% (acute: 88%; subacute: 86%; chronic: 95%) of limbs had flow present and 90% (acute: 86%; subacute: 91%; chronic: 92%) were compressible. Post-thrombotic syndrome was present in 25% (acute: 16%; subacute: 29%; chronic: 29%) of patients and moderate or severe post-thrombotic syndrome in 8% (acute: 2%; subacute: 11%; chronic: 10%) of patients. Outcomes from the real-world CLOUT registry indicate that the ClotTriever System can effectively remove acute, subacute, and chronic thrombus. At six months, significant ultrasound and clinical improvements were observed in all chronicity subgroups. Enrollment to 500 patients and follow-up to 2 years is ongoing (NCT03575364).TableImprovement in ultrasound and clinical outcomes at 6 monthsAcuteSubacuteChronicFlow present888695Compressibility869192PTS rate162929 Moderate or severe PTS rate21110Median decrease in numeric pain rating scale10010090Median decrease in rVCSS715050Median increase in EuroQol group 5-D352235PTS, Post-thrombotic syndrome; rVCSS, Revised Venous Clinical Severity Score.P values are derived from Wilcoxon sign rank or McNemar’s tests. All P values are < .001.Improvements in outcomes at 6 months. Values are percent. Open table in a new tab

Results of the pToWin Study: Using the pCONUS Device for the Treatment of Wide-Neck Intracranial Aneurysms.

Coil embolization has become a well-established option for the treatment of intracranial aneurysms. Yet, wide-neck bifurcation aneurysms (WNBAs) remain a challenge. The pCONUS is the first generation of a stent-like implant for the bridging of WNBAs to enable coiling. The pToWin study was a prospective, single-arm, multicenter study conducted to analyze the safety and efficacy of the pCONUS in the treatment of WNBAs. The primary effectiveness endpoint was the rate of adequate occlusion of the aneurysm at 3–6 and 7–12 months. The primary safety endpoint was the occurrence of major ipsilateral stroke or neurological death during the follow-up. A total of 115 patients were included. Aneurysm locations were the middle cerebral artery in 52 (45.2%), the anterior communicating artery in 35 (30.4%), the basilar artery in 23 (20%), the internal carotid artery terminus in three (2.6%), and the pericallosal artery in two (1.7%) patients. Treatment was successfully performed in all but one patient. The morbi-mortality rate was 1.9% and 2.3% at 3–6 and 7–12 months, respectively. Of the aneurysms, 75.0% and 65.6% showed adequate occlusion at 3–6 and 7–12 months, respectively. pCONUS offers a safe and reasonably effective treatment of WNBAs, demonstrated by acceptable adequate aneurysm occlusion and low rates of adverse neurologic events.

Effectiveness and Safety of P2Y12 Inhibitors Pretreatment in Primary Percutaneous Coronary Intervention with Long Transfer Times

Early initiation of a new P2Y12 inhibitor in ST-elevation myocardial infarction (STEMI) patients prior to primary percutaneous coronary intervention (PCI) is recommended over clopidogrel. However, comparative data remain limited, especially in semi-rural regions with subsequent longer transfer times. We aimed to assess the determinants, effectiveness, and safety of pretreatment with new P2Y12 inhibitors compared with clopidogrel in a primary PCI regional network. Outcomes of 1235 primary PCI patients pretreated with new P2Y12 inhibitors (n=1050) or clopidogrel (n=185) were evaluated using a prospective registry. Primary effectiveness endpoint was the composite of death, recurrent myocardial infarction, stroke, or new revascularization. Serious bleedings were defined as Bleeding Academic Research Consortium ≥ 2. Clopidogrel was more likely to be used in older and female patients with more comorbidities. Mean transfer time was longer in the clopidogrel group (123.3 ± 67.3 vs. 102.3 ± 57.2 min; p < 0.01). The primary endpoint was less frequent with new P2Y12 inhibitors compared with clopidogrel (14.9 vs. 30.3%; odds ratio 0.58, 95% confidence interval [CI] 0.39-0.87; p < 0.01), mostly driven by a reduced rate of death (4.5 vs. 26% respectively; hazard ratio 0.25, 95% CI 0.16-0.38; p < 0.01). Bleeding rates did not differ between groups (1 vs. 0.5%, respectively; p=0.96). Compared with clopidogrel, pretreatment with new P2Y12 inhibitors seems to be associated with lower risks of mortality and ischemic outcomes, and similar risks of bleeding in a real-world registry. Our results are in line with the guidelines recommending the preferential pre-PCI administration of new P2Y12 inhibitors in STEMI patients referred for primary PCI.

Effectiveness of sacubitril-valsartan in patients with cancer therapy-related cardiac dysfunction: a systematic review of clinical and preclinical studies.

Cancer therapy-related cardiac dysfunction (CTRCD) is a critical problem with an impact on both oncological and cardiovascular prognosis, especially when it prevents patients from receiving cancer treatment. However, there are very limited data on the efficacy of sacubitril/valsartan in the prevention and treatment of cardiotoxicity. This systematic review aimed to evaluate the potential benefit of sacubitril/valsartan in patients with CTRCD. The databases included MEDLINE, Embase, LILACS, Scopus and Cochrane Central up to January 20, 2022. All pre-clinical and clinical studies including observational studies (cohorts, case-control, cross-sectional and case reports) that used sacubitril/valsartan for prevention or treatment of CTRCD. The primary effectiveness endpoints was CTRCD, defined as a clinically significant change in left ventricular ejection fraction (LVEF) at the end of the follow-up. And after applying the eligibility criteria, 12 articles (9 in humans and 3 preclinical studies) were included in this systematic review. The 3 preclinical studies demonstrated beneficial effects in preventing, attenuating and/or delaying the onset of myocardial damage at the cellular level, ventricular dysfunction and remodeling. Regardind human studies, most of them were composed of case reports. The largest study consisted of a retrospective multicentric cohort with 64 patients. All clinical studies have demonstrated that used Sac/Val in human showed a significant increase in LVEF, and when reported, a reduction in left ventricular volume and NT-proBNP (or BNP). Randomized clinical trials are needed to confirm this hypothesis.

One-year results with a low-profile endograft in subjects with thoracic aortic aneurysm and ulcer pathologies

ObjectiveThe study objective was to evaluate the safety and effectiveness of the second-generation, low-profile RelayPro (Terumo Aortic) thoracic endograft for the treatment of descending thoracic aortic aneurysm or penetrating atherosclerotic ulcer. MethodA prospective, international, nonblinded, nonrandomized, pivotal trial analyzed a primary safety end point of major adverse events at 30 days (death, myocardial infarction, stroke, renal/respiratory failure, paralysis, bowel ischemia, procedural blood loss) and a primary effectiveness end point of treatment success at 1 year (technical success, patency, absence of aneurysm rupture, type I/III endoleaks, stent fractures, reinterventions, aneurysm expansion, and migration) compared with performance goals from the previous generation Relay pivotal study. The study was conducted in 36 centers in the United States and Japan and enrolled participants between 2017 and 2019. ResultsThe study population of 110 patients had a median (interquartile range) age of 76 (70-81) years, 69 (62.7%) were male, and 43 (39.1%) were Asian. Patients were treated for 76 fusiform aneurysms (69%), 24 saccular aneurysms (22%), and 10 penetrating atherosclerotic ulcers (9%). Most patients (82.7%) were treated with a non-bare stent configuration. Technical success was 100%. The median (interquartile range) procedure time was 91 (64-131) minutes, and the deployment time was 16 (10-25) minutes. A total of 50 patients (73.5%) in the US cohort had percutaneous access, whereas centers in Japan used only surgical cutdown. The 30-day composite major adverse events rate was 6.4% (95% upper confidence interval, 11.6%; P = .0002): 2 strokes, 2 procedural blood losses greater than 1000 mL requiring transfusion, 2 paralysis events, and 1 renal failure. Primary effectiveness was 89.2% (lower 95% confidence interval, 81.8%; P = .0185). Nine subjects experienced 11 events (1 aneurysm expansion, 6 secondary interventions, and 4 type I endoleaks). There was no loss of stent-graft patency, no rupture, no fractures, and no migration. ConclusionsThe low-profile RelayPro thoracic endograft met the study primary end points and demonstrated satisfactory 30-day safety and 1-year effectiveness for the treatment of patients with aneurysms of the descending thoracic aorta or penetrating atherosclerotic ulcers. Follow-up is ongoing to evaluate longer-term outcomes and durability.

Comparative Effectiveness and Safety of Low-Dose Oral Anticoagulants in Patients With Atrial Fibrillation.

Aims: Observational studies of various dose levels of direct oral anticoagulants (DOACs) for patients with atrial fibrillation (AF) found that a high proportion of patients received a dose lower than the target dose tested in randomized controlled trials. There is a need to compare low-dose DOACs with warfarin or other DOACs on effectiveness and safety. Methods: Using administrative data from Quebec province, Canada, we built a cohort of new warfarin or DOAC users discharged from hospital between 2011 and 2017. We determined CHA2DS2-VASc and HAS-BLED scores, and comorbidities for 3-year prior cohort entry. The primary effectiveness endpoint was a composite of ischemic stroke/systemic embolism (SE), and secondary outcomes included a safety composite of major bleeding (MB) events and effectiveness composite (stroke/SE, death) at 1-year follow-up. We contrasted each low-dose DOAC with warfarin or other DOACs as references using inverse probability of treatment weighting to estimate marginal Cox hazard ratios (HRs). Results: The cohort comprised 22,969 patients (mean age: 80–86). We did not find a significant risk reduction for the stroke/SE primary effectiveness endpoint for DOACs vs. warfarin; however, we observed a significantly lower risk for low-dose dabigatran vs. warfarin (HR [95%CI]: 0.59 [0.42–0.81]) for effectiveness composite, mainly due to a lower death rate. The differences in effectiveness and safety composites between low-dose rivaroxaban vs. warfarin were not significant. However, low-dose apixaban had a better safety composite (HR: 0.68 [0.53–0.88]) vs. warfarin. Comparisons of dabigatran vs. apixaban showed a lower risk of stroke/SE (HR: 0.53 [0.30–0.93]) and a 2-fold higher risk of MB. The MB risk was higher for rivaroxaban than for apixaban (HR: 1.58 [1.09–2.29]). Conclusions: The results of this population-based study suggest that low-dose dabigatran has a better effective composite than warfarin. Compared with apixaban, low-dose dabigatran had a better effectiveness composite but a worse safety profile. Low-dose apixaban had a better safety composite than warfarin and other low-dose DOACs. Given that the comparative effectiveness and safety seem to vary from one DOAC to another, pharmacokinetic data for specific populations are now warranted.