Sex-specific inequalities in the use of drug-coated balloons for small coronary artery disease: a report from the BASKET-SMALL 2 trial.

BACKGROUND AND OBJECTIVES: Recent data have established non-inferiority of drug-coated balloons (DCB) compared to drug-eluting stents (DES) for treatment of small-vessel coronary artery disease. Since coronary vessels in women might have anatomical and pathophysiological particularities, the safety of the DCB strategy among women compared to men needs to be assessed in more detail. METHODS: In BASKET-SMALL 2, patients with de novo lesions in coronary vessels < 3 mm and an indication for percutaneous coronary intervention were randomly allocated (1:1) to DCB vs. DES after successful lesion preparation. The primary objective of the randomized trial was to establish non-inferiority of DCB vs. DES regarding major adverse cardiac events (MACE; i.e., cardiac death, non-fatal myocardial infarction, and target vessel revascularization) after 12 months. The aim of the current sub-analysis is to evaluate whether the DCB strategy is equally safe among women and men after 12 and 36 months. RESULTS: Among 758 randomized patients, 382 were assigned to DCB (23% women) and 376 to DES (30% women). In general, women were older, had more often diabetes mellitus and renal insufficiency, and presented more often with an acute coronary syndrome, whereas men were more often smokers, had multivessel disease and a previous history of acute myocardial infarction, and received a treatment with a statin. After 3 years, the primary clinical end point was not significantly different between groups (13% women vs. 16% men, HR 0.82; 95% CI 0.52-1.30; p = 0.40). There was no interaction between sex and coronary intervention strategy regarding MACE at 36 months (10% women vs. 16% men in DCB, 16% women vs. 15% men in DES; pinteraction = 0.31). CONCLUSION: In small native coronary artery disease, there was no statistically significant effect of sex on the difference between DCB and DES regarding MACE up to 36 months. CLINICAL TRIAL REGISTRATION: URL: http://www. CLINICALTRIALS: gov . Unique identifier: NCT01574534. CAD coronary artery disease, MACE major adverse cardiovascular events, HR Hazard ratio, DCB drug-coated balloon, DES drug-eluting stent.

Incidence, Predictors, and Prognostic Impact of New Permanent Pacemaker Implantation After TAVR With Self-Expanding Valves.

OBJECTIVES: The authors sought to evaluate the incidence, predictors, and outcomes of new permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) with contemporary self-expanding valves (SEV). BACKGROUND: Need for PPI is frequent post-TAVR, but conflicting data exist on new-generation SEV and on the prognostic impact of PPI. METHODS: This study included 3,211 patients enrolled in the multicenter NEOPRO (A Multicenter Comparison of Acurate NEO Versus Evolut PRO Transcatheter Heart Valves) and NEOPRO-2 (A Multicenter Comparison of ACURATE NEO2 Versus Evolut PRO/PRO+ Transcatheter Heart Valves 2) registries (January 2012 to December 2021) who underwent transfemoral TAVR with SEV. Implanted transcatheter heart valves (THV) were Acurate neo (n = 1,090), Acurate neo2 (n = 665), Evolut PRO (n = 1,312), and Evolut PRO+ (n = 144). Incidence and predictors of new PPI and 1-year outcomes were evaluated. RESULTS: New PPI was needed in 362 patients (11.3%) within 30 days after TAVR (8.8%, 7.7%, 15.2%, and 10.4%, respectively, after Acurate neo, Acurate neo2, Evolut PRO, and Evolut PRO+). Independent predictors of new PPI were Society of Thoracic Surgeons Predicted Risk of Mortality score, baseline right bundle branch block and depth of THV implantation, both in patients treated with Acurate neo/neo2 and in those treated with Evolut PRO/PRO+. Predischarge reduction in ejection fraction (EF) was more frequent in patients requiring PPI (P = 0.014). New PPI was associated with higher 1-year mortality (16.9% vs 10.8%; adjusted HR: 1.66; 95% CI: 1.13-2.43; P = 0.010), particularly in patients with baseline EF <40% (P for interaction = 0.049). CONCLUSIONS: New PPI was frequently needed after TAVR with SEV (11.3%) and was associated with higher 1-year mortality, particularly in patients with EF <40%. Baseline right bundle branch block and depth of THV implantation independently predicted the need of PPI.

Incidence, predictors, and prognostic impact of new permanent pacemaker implantation after TAVR with self-expanding valves

OBJECTIVES: The authors sought to evaluate the incidence, predictors, and outcomes of new permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) with contemporary self-expanding valves (SEV). BACKGROUND: Need for PPI is frequent post-TAVR, but conflicting data exist on new-generation SEV and on the prognostic impact of PPI. METHODS: This study included 3,211 patients enrolled in the multicenter NEOPRO (A Multicenter Comparison of Acurate NEO Versus Evolut PRO Transcatheter Heart Valves) and NEOPRO-2 (A Multicenter Comparison of ACURATE NEO2 Versus Evolut PRO/PRO+ Transcatheter Heart Valves 2) registries (January 2012 to December 2021) who underwent transfemoral TAVR with SEV. Implanted transcatheter heart valves (THV) were Acurate neo (n = 1,090), Acurate neo2 (n = 665), Evolut PRO (n = 1,312), and Evolut PRO+ (n = 144). Incidence and predictors of new PPI and 1-year outcomes were evaluated. RESULTS: New PPI was needed in 362 patients (11.3%) within 30 days after TAVR (8.8%, 7.7%, 15.2%, and 10.4%, respectively, after Acurate neo, Acurate neo2, Evolut PRO, and Evolut PRO+). Independent predictors of new PPI were Society of Thoracic Surgeons Predicted Risk of Mortality score, baseline right bundle branch block and depth of THV implantation, both in patients treated with Acurate neo/neo2 and in those treated with Evolut PRO/PRO+. Predischarge reduction in ejection fraction (EF) was more frequent in patients requiring PPI (P = 0.014). New PPI was associated with higher 1-year mortality (16.9% vs 10.8%; adjusted HR: 1.66; 95% CI: 1.13-2.43; P = 0.010), particularly in patients with baseline EF <40% (P for interaction = 0.049). CONCLUSIONS: New PPI was frequently needed after TAVR with SEV (11.3%) and was associated with higher 1-year mortality, particularly in patients with EF <40%. Baseline right bundle branch block and depth of THV implantation independently predicted the need of PPI.

Design and rationale of a prospective, randomized, non-inferiority trial to determine the safety and efficacy of the Biolimus A9™ drug coated balloon for the treatment of in-stent restenosis: First-in-man trial (REFORM).

BACKGROUND: Drug-coated balloon (DCB) angioplasty with paclitaxel-eluting devices is an established treatment for coronary in-stent restenosis (ISR). Biolimus A9™ (BA9), a sirolimus analogue with enhanced lipophilicity, may facilitate enhanced local drug delivery into vascular tissue. A novel DCB coated with Biolimus A9™ represents an alternative to traditional paclitaxel- and sirolimus-coated devices. Hence, we sought to investigate the safety and efficacy of this novel DCB in the treatment of coronary ISR. METHODS AND DESIGN: REFORM (NCT04079192) is a prospective, multicenter, single blind, randomized controlled trial comparing the BA9-DCB (Biosensors Europe SA, Morges, Switzerland) to the paclitaxel-coated SeQuent® Please DCB (Braun Melsungen AG, Germany) in the treatment of coronary ISR. A total of 201 patients with coronary artery disease and an indication for interventional treatment of ISR in a bare-metal stent (BMS) or drug-eluting stent (DES) have been randomized 2:1 to receive treatment with the BA9- or the paclitaxel-DCB comparator. Patients were enrolled across 24 investigational centers in Europe and Asia. The primary endpoint is percent diameter stenosis (%DS) of the target segment as assessed by quantitative coronary angiography (QCA) at 6 months. Key secondary endpoints are in-stent late lumen loss, binary restenosis, target lesion failure, target vessel failure, myocardial infarction and death at 6 months. Subjects will be followed for 24 months from enrolment. IMPLICATIONS: The REFORM trial will seek to prove that the BA9-DCB is non-inferior to the standard paclitaxel-DCB comparator in the treatment of coronary ISR with respect to %DS at 6 months and has similar safety characteristics.

Crystalline sirolimus-coated balloon (cSCB) angioplasty in an all-comers, patient population with stable and unstable coronary artery disease including chronic total occlusions: rationale, methodology and design of the SCORE trial.

BACKGROUND: A decade ago, the iopromide-paclitaxel coated balloon (iPCB) was added to the cardiologist's toolbox to initially treat in-stent restenosis followed by the treatment of de novo coronary lesions. In the meantime, DES technologies have been substantially improved to address in-stent restenosis and thrombosis, and shortened anti-platelet therapy. Recently, sirolimus-coated balloon catheters (SCB) have emerged to provide an alternative drug to combat restenosis. METHODS: The objective of this study is to determine the safety and efficacy of a novel crystalline sirolimus-coated balloon (cSCB) technology in an unselective, international, large-scale patient population. Percutaneous coronary interventions of native stenosis, in-stent stenosis, and chronic total occlusions with the SCB in patients with stable coronary artery disease or acute coronary syndrome were included. The primary outcome variable is the target lesion failure (TLF) rate at 12 months, defined as the composite rate of target vessel myocardial infarction (TV-MI), cardiac death or ischemia-driven target lesion revascularization (TLR). The secondary outcome variables include TLF at 24 months, ischemia driven TLR at 12 and 24 months and all-cause death, cardiac death at 12 and 24 months. DISCUSSION: Since there is a wealth of patient-based all-comers data for iPCB available for this study, a propensity-score matched analysis is planned to compare cSCB and iPCB for the treatment of de novo and different types of ISR. In addition, pre-specified analyses in challenging lesion subsets such as chronic total occlusions will provide evidence whether the two balloon coating technologies differ in their clinical benefit for the patient. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04470934.

Impact of Insulin-Treated Compared to Non-Insulin-Treated Diabetes Mellitus on Outcome of Percutaneous Coronary Intervention with Drug-Coated Balloons versus Drug-Eluting Stents in De Novo Coronary Artery Disease: The Randomized BASKET-SMALL 2 Trial.

BACKGROUND: We evaluated the outcome of PCI of de novo stenosis with drug-coated balloons (DCB) versus drug-eluting stents (DES) in patients with insulin-treated diabetes mellitus (ITDM) versus non-insulin-treated diabetes mellitus (NITDM). METHODS: Patients were randomized in the BASKET-SMALL 2 trial to DCB or DES and followed over 3 years for MACE (cardiac death, non-fatal myocardial infarction [MI], and target vessel revascularization [TVR]). Outcome in the diabetic subgroup (n = 252) was analyzed with respect to ITDM or NITDM. RESULTS: In NITDM patients (n = 157), rates of MACE (16.7% vs. 21.9%, hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.29-1.58, p = 0.37), death, non-fatal MI, and TVR (8.4% vs. 14.5%, HR 0.30, 95% CI 0.09-1.03, p = 0.057) were similar between DCB and DES. In ITDM patients (n = 95), rates of MACE (DCB 23.4% vs. DES 22.7%, HR 1.12, 95% CI 0.46-2.74, p = 0.81), death, non-fatal MI, and TVR (10.1% vs. 15.7%, HR 0.64, 95% CI 0.18-2.27, p = 0.49) were similar between DCB and DES. TVR was significantly lower with DCB versus DES in all diabetic patients (HR 0.41, 95% CI 0.18-0.95, p = 0.038). CONCLUSIONS: DCB compared to DES for treatment of de novo coronary lesions in diabetic patients was associated with similar rates of MACE and numerically lower need for TVR both for ITDM and NITDM patients.

Ticagrelor or prasugrel in patients with acute coronary syndrome with off-hour versus on-hour presentation: a subgroup analysis of the ISAR-REACT 5 trial.

OBJECTIVES: To assess the efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome (ACS) presenting during off- and on-hours. BACKGROUND: The efficacy and safety of ticagrelor versus prasugrel in patients with ACS according to time of hospital presentation remain unknown. METHODS: This post hoc analysis of the ISAR-REACT 5 trial included 1565 patients with ACS presenting off-hours and 2453 patients presenting on-hours, randomized to ticagrelor or prasugrel. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium (BARC) type 3-5 bleeding, both at 12 months. RESULTS: The primary endpoint occurred in 80 patients (10.4%) in the ticagrelor group and 57 patients (7.3%) in the prasugrel group in patients presenting off-hours (hazard ratio [HR] = 1.45; 95% confidence interval [CI] 1.03-2.03; P = 0.033), and 104 patients (8.5%) in the ticagrelor group and 80 patients (6.7%) in the prasugrel group in patients presenting on-hours (HR = 1.29 [0.97-1.73]; P = 0.085), without significant treatment arm-by-presentation time interaction (Pint = 0.62). BARC type 3 to 5 bleeding occurred in 35 patients (5.1%) in the ticagrelor group and 37 patients (5.3%) in the prasugrel group (P = 0.84) in patients presenting off-hours, and 60 patients (5.9%) in the ticagrelor group and 43 patients (4.6%) in the prasugrel group in patients presenting on-hours (P = 0.17). CONCLUSIONS: In patients with ACS planned to undergo an invasive treatment strategy, time of presentation (off-hours vs. on-hours) does not interact significantly with the relative efficacy and safety of ticagrelor vs. prasugrel. CLINICAL TRIAL REGISTRATION: NCT01944800.

Combined Analysis of Two Parallel Randomized Trials of Sirolimus-Coated and Paclitaxel-Coated Balloons in Coronary In-Stent Restenosis Lesions.

BACKGROUND: Paclitaxel-coated balloons (PCBs) are a preferred treatment option for coronary in-stent restenosis. To date, data from randomized trials of alternative drug coatings are lacking. The aim of the randomized Malaysian and German-Swiss randomized trials was to investigate a novel sirolimus-coated balloon (SCB) compared with a PCB in in-stent restenosis. METHODS: One hundred one patients with drug-eluting stent in-stent restenosis were enrolled in 2 identical randomized trials comparing the novel SCB (SeQuent SCB, 4 µg/mm²) with the clinically proven PCB (SeQuent Please, 3 µg/mm²). Primary end point was angiographic late lumen loss at 6 months. Secondary end points included procedural success, major adverse cardiac events, and individual clinical end points such as stent thrombosis, cardiac death, target lesion myocardial infarction, clinically driven target lesion revascularization, and binary restenosis. RESULTS: Quantitative coronary angiography revealed no differences in baseline parameters. After 6 months, in-segment late lumen loss was 0.25±0.57 mm in the PCB group versus 0.26±0.60 mm in the SCB group. Mean difference between SCB and PCB was 0.01 (95% CI, -0.23 to 0.24). Noninferiority at a predefined margin of 0.35 was shown. Clinical events up to 12 months did not differ between the groups. CONCLUSIONS: This first-in man comparison of a novel SCB with a crystalline coating showed similar angiographic and clinical outcomes in the treatment of coronary drug-eluting stent in-stent restenosis compared with PCB. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02996318, NCT03242096.

Efficacy and safety of drug-coated balloons according to coronary vessel size. A report from the BASKET-SMALL 2 trial.

Introduction: In BASKET-SMALL 2, drug-coated balloons (DCB) were non-inferior to drug-eluting stents (DES) in de-novo stenosis of small coronary vessels (≤ 2.75 mm) regarding clinical endpoints up to 36 months. Aim: In the present subgroup analysis, we aimed to analyze the effect of the two treatment strategies in different vessel sizes. Material and methods: Patients were analyzed according to the size of the device used (small > 2.5 mm vs. very small ≤ 2.5 mm). The primary endpoint was major adverse cardiac events (MACE), while secondary endpoints were target vessel revascularization (TVR), non-fatal myocardial infarction, cardiac death, and all-cause mortality, all at 36 months. Interactions for the different groups were assessed with Cox regression analysis. Results: Overall, 758 patients were enrolled in this analysis, of which 437 (58%) had very small vessel disease. There were similar results in both treatment groups for the primary endpoint in both small and very small vessels (DCB vs DES, MACE at 3 years in small vessels HR = 1.31, 95% CI: 0.74-2.32, p = 0.355, and very small vessels HR = 0.82, 95% CI: 0.49-1.39, p = 0.468). Second generation paclitaxel-eluting stents showed significantly higher rates for MACE (p = 0.041), TVR (p = 0.004) and non-fatal myocardial infarction (p = 0.036) compared to DCB in very small coronary arteries at 3 years, while results were similar in small coronary arteries. Conclusions: Efficacy and safety of DCB are similar irrespective of vessel size. However, there is a beneficial effect of DCB over paclitaxel-eluting stents regarding TVR, non-fatal myocardial infarction and MACE that is most pronounced in very small coronary arteries.

Quality of life of patients with coronary heart disease treated with the bioresorbable vascular scaffold (ABSORB™): 2-year results from the GABI-R-registry.

BACKGROUND: Numerous studies have reported clinical endpoints following coronary revascularization using bioresorbable vascular scaffolds (BVS), while information about the impact on health-related quality of life is sparse. In this analysis of the German-Austrian ABSORB RegIstRy, the 2 year results concerning quality of life development in a large cohort of patients treated with BVS were reported. METHODS: Data were collected at baseline as well as 30 days, 6 and 24 months after coronary revascularization using BVS. The EQ-5D score, EQ visual analogue scale (VAS) and Seattle Angina Questionnaire (SAQ) were determined for each time point. Patients were categorized according to the indication for coronary revascularization [acute coronary syndrome (ACS), stable angina pectoris (SAP), silent myocardial ischemia (SMI), or other]. Binary logistic regression analysis was performed to determine factors that predict above-average scores two years after implantation. RESULTS: Data from 1317 patients in 88 centres were included. Reasons for revascularization were: ACS (n = 643), SAP (n = 443), SMI (n = 52), and other (n = 179). Mean EQ-5D was significantly increased after six months, while a value comparable to baseline was found two years after implantation. EQ VAS and four of five dimensions of SAQ were significantly improved over baseline at all follow-up surveys. Particularly strong improvements were seen in SAQ scores angina frequency and quality of life. Binary regressions showed different statistically significant predictors in the respective models. CONCLUSIONS: Following coronary revascularization with BVS strong decrease in self-reported angina frequency and increase of self-reported quality of life were observed with continuous improvements over two years of follow-up. Trial registration ClinicalTrials.gov Identifier: NCT02066623.

Outcomes After Transcatheter Aortic Valve Implantation in Men Versus Women.

Gender-based differences in outcomes after successful transcatheter aortic valve implantation (TAVI) in patients without an indication for oral anticoagulation have not been well studied. We aim to evaluate gender-based differences in clinical outcomes after TAVI. In the present analysis of the GALILEO (Global study comparing a rivaroxaban-based antithrombotic strategy to an antiplatelet-based strategy after transcatheter aortic valve replacement to optimize clinical outcomes) trial, patients with symptomatic severe aortic stenosis and who underwent successful TAVI were stratified by gender. The primary outcome was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause mortality or thromboembolic events (including any stroke, myocardial infarction, symptomatic valve thrombosis, systemic embolism, deep-vein thrombosis, or pulmonary embolism). Major bleeding was defined as a composite of major, life-threatening, or disabling Valve Academic Research Consortium-2 bleeding. Of 1,644 patients, 813 were female, and 831 were male. At baseline, female patients were older and at higher surgical risk (Society of Thoracic Surgeons risk score: 4.7 ± 3.6 versus 3.6 ± 3.0, p <0.0001) than male patients. After adjustment for differences in baseline clinical and procedural parameters, female patients had lower rates of MACCE (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.49 to 0.96), all-cause mortality (HR 0.54, 95% CI 0.34 to 0.87), and noncardiovascular mortality (HR 0.33, 95% CI 0.15 to 0.75) at a median of 17 months of follow-up. By landmark analyses, these differences appeared to emerge with a longer follow-up time. No significant differences in major, life-threatening, or disabling bleeding, cardiovascular mortality, and stroke were noted. In conclusion, compared with male patients, female patients with severe symptomatic aortic stenosis had a lower risk of MACCE and mortality but a similar risk of bleeding events after TAVI.

Two-year clinical outcomes after successful transcatheter aortic valve implantation with balloon-expandable versus self-expanding valves: A subanalysis of the GALILEO trial.

BACKGROUND: Midterm data comparing clinical outcomes after successful implantation of self-expanding and balloon-expandable transcatheter heart valves (THV) are limited. We aimed to compare 2-year outcomes after successful transcatheter aortic valve implantation (TAVI) with the Edwards balloon-expandable or the Medtronic self-expanding THV. METHODS: Two-year outcomes were analyzed according to the implanted THV in the GALILEO trial. Major adverse cardiac and cerebrovascular events (MACCE) was a composite of all-cause death or thromboembolic events including stroke, myocardial infarction, symptomatic valve thrombosis, systemic embolism, deep-vein thrombosis, or pulmonary embolism. RESULTS: Among 1644 patients recruited in 136 centers across 16 countries between 2015 and 2018, 499 received a self-expanding and 757 patients received a balloon-expandable THV. Patients treated with a self-expanding THV were more likely to be female, and had higher surgical risk, lower hemoglobin levels, and more frequent valve-in-valve procedures than those with a balloon-expandable THV. After multivariable adjustment, there were no significant differences in major clinical outcomes between self-expanding versus balloon-expandable THV: MACCE (17.0% vs. 13.4%, adjusted-hazard ratios [HR] 1.18, 95% confidence intervals [CI]: 0.82-1.69); all-cause death (11.4% vs. 9.3%, adjusted-HR 1.26; 95% CI: 0.78-2.05); cardiovascular death (8.5% vs. 4.0%, adjusted-HR 1.53; 95% CI: 0.82-2.86), any stroke (5.1% vs. 3.7%, adjusted-HR 0.86; 95% CI: 0.43-1.73); major or life-threatening bleeding (5.9% vs. 6.8%, adjusted-HR 0.93; 95% CI: 0.53-1.63). CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. NCT02556203. CONCLUSIONS: Two-year follow-up data from the GALILEO trial indicate that successful TAVI either with self-expanding or balloon-expandable THVs according to physician discretion did not show difference in rates of MACCE.

Drug-Coated Balloon for Small Coronary Artery Disease in Patients With and Without High-Bleeding Risk in the BASKET-SMALL 2 Trial.

BACKGROUND: Patients at high-bleeding risk (HBR) undergoing percutaneous coronary intervention represent a challenging patient population. The use of drug-coated balloon (DCB) allows shorter duration of dual antiplatelet therapy compared with drug-eluting stents (DES) and reduces thrombotic risk due to the absence of a permanent implant. The present analysis aimed to investigate if the effect of DCB versus DES differed between patients with and without HBR treated with percutaneous coronary intervention in small coronary arteries. METHODS: This prespecified subgroup analysis of a multicenter, randomized, noninferiority trial included 758 patients with de novo lesions in coronary vessels <3 mm and an indication for percutaneous coronary intervention, randomized to DCB (n=382) or second-generation DES (n=376). Patients were followed over 3 years for major adverse cardiac events. RESULTS: Of the 758 patients randomized, 155 (20%) had HBR; these patients had higher mortality at 3 years (hazard ratio [95% CI], 3.09 [1.78-5.36]; P<0.001). Rates of major bleeding events were overall low but tended to be lower after DCB versus DES (1.6% versus 3.7%; P=0.064), were similar in patients with HBR (4.5% versus 3.4%) but less frequent in DCB-versus DES-treated patients without HBR (0.9% versus 3.8%). There was no difference in major adverse cardiac events between DCB and DES regardless of bleeding risk (HBR, hazard ratio: 1.16 [0.51-2.62]; P=0.719 versus non-HBR, 0.96 [0.62-1.49]; P=0.863). CONCLUSIONS: DCBs were similarly safe and effective as current-generation DES in the treatment of coronary arteries <3 mm, regardless of bleeding risk. In patients treated with DCB, there was a trend towards a reduction of severe bleeding events at 3 years. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01574534.

Efficacy and Safety of ELOM-080 as Add-On Therapy in COVID-19 Patients with Acute Respiratory Insufficiency: Exploratory Data from the Prospective Placebo-Controlled COVARI Trial.

INTRODUCTION: Enhancement of mucociliary clearance (MCC) might be a potential target in treating COVID-19. The phytomedicine ELOM-080 is an MCC enhancer that is used to treat inflammatory respiratory diseases. PATIENTS/METHODS: This randomised, double-blind exploratory study (EudraCT number 2020-003779-17) evaluated 14 days' add-on therapy with ELOM-080 versus placebo in patients with COVID-19 hospitalised with acute respiratory insufficiency. RESULTS: The trial was terminated early after enrolment of 47 patients as a result of poor recruitment. Twelve patients discontinued prematurely, leaving 35 in the per-protocol set (PPS). Treatment with ELOM-080 had no significant effect on overall clinical status versus placebo (p = 0.49). However, compared with the placebo group, patients treated with ELOM-080 had less dyspnoea in the second week of hospitalisation (p = 0.0035), required less supplemental oxygen (p = 0.0229), and were more often without dyspnoea when climbing stairs at home (p < 0.0001). CONCLUSION: These exploratory data suggest the potential for ELOM-080 to improve respiratory status during and after hospitalisation in patients with COVID-19.

Pre-admission antiplatelet therapy and treatment effect of ticagrelor vs. prasugrel in patients with acute coronary syndromes-a subgroup analysis of the ISAR-REACT 5 trial.

AIMS: To assess whether the efficacy and safety of ticagrelor vs. prasugrel in patients with acute coronary syndromes (ACSs) are influenced by pre-admission treatment with aspirin and/or clopidogrel. METHODS AND RESULTS: Patients (n = 4018) were categorized into two groups: pre-admission aspirin and/or clopidogrel group (n = 1455) and no pre-admission aspirin or clopidogrel group (n = 2563). The primary endpoint was the composite of all-cause death, myocardial infarction, or stroke; the secondary safety endpoint was Bleeding Academic Research Consortium (BARC) type 3-5 bleeding, both at 1 year. Patients in the pre-admission aspirin and/or clopidogrel group had a higher risk of ischaemic events, but a similar risk of bleeding to patients in the no pre-admission aspirin or clopidogrel group (cumulative incidences 10.5% vs. 6.7%, and 5.7% vs. 5.7%, respectively). The primary endpoint occurred in 81/717 patients assigned to ticagrelor and 69/738 patients assigned to prasugrel in the pre-admission aspirin and/or clopidogrel group [11.5% vs. 9.5%; hazard ratio (HR) = 1.23; 95% confidence interval (CI) 0.89-1.69], and in 103/1295 patients assigned to ticagrelor and 68/1268 patients assigned to prasugrel in the no pre-admission aspirin or clopidogrel group [8.0% vs. 5.4%; HR = 1.50 (1.10-2.03); Pint = 0.38]. BARC type 3-5 bleeding events did not differ between ticagrelor and prasugrel in patients in the pre-admission aspirin and/or clopidogrel (6.2% vs. 4.5%) or no pre-admission aspirin or clopidogrel (5.3% vs. 5.1%) group (Pint = 0.54). CONCLUSION: In patients with ACS, pre-admission therapy with aspirin and/or clopidogrel has no influence on the relative efficacy and safety of ticagrelor and prasugrel.

Drug-coated balloons for small coronary artery disease in patients with chronic kidney disease: a pre-specified analysis of the BASKET-SMALL 2 trial.

BACKGROUND: Data on the safety and efficacy of drug-coated balloon (DCB) compared to drug-eluting stent (DES) in patients with chronic kidney disease (CKD) are scarce, particularly at long term. This pre-specified analysis aimed to investigate the 3-year efficacy and safety of DCB versus DES for small coronary artery disease (< 3 mm) according to renal function at baseline. METHODS: BASKET-SMALL-2 was a large multi-center, randomized, controlled trial that tested the efficacy and safety of DCBs (n = 382) against DESs (n = 376) in small vessel disease. CKD was defined as eGFR < 60 ml/min/1.73m2. The primary endpoint was the composite of cardiac death, non-fatal myocardial infarction, and target vessel revascularization (MACE) during 3 years. RESULTS: A total of 174/758 (23%) patients had CKD, out of which 91 were randomized to DCB and 83 to DES implantation. The primary efficacy outcome during 3 years was similar in both, DCB and DES patients (HR 0.98; 95%-CI 0.67-1.44; p = 0.937) and patients with and without CKD (HR 1.18; 95%-CI 0.76-1.83; p = 0.462), respectively. Rates of cardiac death and all-cause death were significantly higher among patients with CKD but not affected by treatment with DCB or DES. Major bleeding events were lower in the DCB when compared to the DES group (12 vs. 3, HR 0.26; 95%-CI 0.07-0.92; p = 0.037) and not influenced by presence of CKD. CONCLUSIONS: The long-term efficacy and safety of DCB was similar in patients with and without CKD. The use of DCB was associated with significantly fewer major bleeding events (NCT01574534). Central Illustration. Drug-coated balloon versus drug-eluting stents in small coronary artery disease with and without chronic kidney disease, a prespecified subgroup analysis of the BASKET-SMALL 2 trial.

Safety and Efficacy of Drug-Coated Balloons Versus Drug-Eluting Stents in Acute Coronary Syndromes: A Prespecified Analysis of BASKET-SMALL 2.

BACKGROUND: Drug-coated balloons (DCBs) are an established treatment strategy for coronary artery disease. Randomized data on the application of DCBs in patients with an acute coronary syndrome (ACS) are limited. We evaluated the impact of clinical presentation (ACS versus chronic coronary syndrome) on clinical outcomes in patients undergoing DCB or drug-eluting stent (DES) treatment in a prespecified analysis of the BASKET-SMALL 2 trial (Basel Kosten Effektivitäts Trial-Drug-Coated Balloons Versus Drug-Eluting Stents in Small Vessel Interventions). METHODS: BASKET-SMALL 2 randomized 758 patients with small vessel coronary artery disease to DCB or DES treatment and followed them for 3 years regarding major adverse cardiac events (cardiac death, nonfatal myocardial infarction, and target vessel revascularization). RESULTS: Among 758 patients, 214 patients (28.2%) presented with an ACS (15 patients [7%], ST-segment-elevation myocardial infarction; 109 patients [50.9%], non-ST-segment-elevation myocardial infarction; 90 patients [42.1%], unstable angina pectoris). At 1-year follow-up, there was no significant difference in the incidence of the primary end point by randomized treatment in patients with ACS (hazard ratio, 0.50 [95% CI, 0.19-1.26] for DCB versus DES) or chronic coronary syndrome (hazard ratio, 1.29 [95% CI, 0.67-2.47] for DCB versus DES). There was no significant interaction between clinical presentation and treatment effect (P for interaction, 0.088). For cardiac death (P for interaction, 0.049) and nonfatal myocardial infarction (P for interaction, 0.010), a significant interaction between clinical presentation and treatment was seen at 1 year with lower rates of these secondary end points in patients with ACS treated by DCB. At 3 years, there were similar major adverse cardiac event rates throughout groups without significant interaction between clinical presentation and treatment (P for interaction, 0.301). All-cause mortality was higher in ACS compared with chronic coronary syndrome; however, there was no difference between DCB and DES irrespective of clinical presentation. CONCLUSIONS: In this subgroup analysis of the BASKET-SMALL 2 trial, there was no interaction between indication for percutaneous coronary intervention (acute versus chronic coronary syndrome) and treatment effect of DCB versus DES in patients with small vessel coronary artery disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01574534.

Access Route and Clinical Outcomes After Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome Undergoing Invasive Treatment Strategy.

BACKGROUND: Whether the access site influences the comparative efficacy and safety of ticagrelor and prasugrel in patients with acute coronary syndrome (ACS) undergoing invasive treatment strategy remains unstudied. METHODS: This post-hoc analysis included ACS patients undergoing invasive treatment via radial or femoral access and randomized to either ticagrelor or prasugrel in the ISAR-REACT 5 trial. The primary efficacy endpoint was the composite of death, myocardial infarction (MI) or stroke, safety endpoint was BARC 3 to 5 bleeding. Outcomes were assessed out to 12 months after randomization. RESULTS: Out of 4018 patients, 3984 underwent invasive treatment via radial or femoral access. 1479 had coronary angiography via radial access (ticagrelor, N = 748; prasugrel, N = 731) and 2505 via femoral access (ticagrelor, N = 1245; prasugrel, N = 1260). There was no interaction between access route and assignment to either ticagrelor or prasugrel regarding the primary efficacy or safety endpoints (P for interaction≥0.616). In the radial group, the primary efficacy endpoint (7.6% versus 5.8%, HR: 1.32 [0.88-1.97], P = 0.151) and the safety endpoint (4.3% versus 3.0%, HR: 1.36, [0.73-1.31], P = 0.300) were not statistically different in patients receiving either ticagrelor or prasugrel. In the femoral group, the primary efficacy endpoint occurred more frequently in patients assigned to ticagrelor as compared to prasugrel (10.3% versus 7.3%, HR: 1.44 [1.10-1.88], P = 0.006) without significant difference in terms of safety endpoint (6.4% versus 5.8%, HR: 1.14, [0.81-1.60], P = 0.470). CONCLUSIONS: In patients with ACS undergoing an invasive treatment strategy, the access route does not influence the comparative efficacy and safety of ticagrelor and prasugrel. CLINICAL TRIAL REGISTRATION: NCT01944800.

No Difference in 30-Day Outcome and Quality of Life in Transradial Versus Transfemoral Access - Results From the German Austrian ABSORB Registry (GABI-R).

BACKGROUND: Radial (RA) instead of femoral access (FA) for coronary interventions has become a European Society of Cardiology Class-IA guideline recommendation. But when the decision on the access site is left to the discretion of the operator, differences in adverse event rates mitigate. METHODS: We compared the 30-day outcome for RA and FA in all patients recruited for the observational German Austrian ABSORB Registry (GABI-R) in regard to all-cause mortality, stroke, myocardial infarction (MI), TIMI major bleedings (TMB) and quality of life (QoL). All patients were treated with a bioresorbable vascular scaffold. Access site was left to the discretion of the operator. RESULTS: In total, 3137 patients included by 92 centers received percutaneous coronary interventions (PCI) for acute MI in 51.5% and non-acute settings in 48.5%. RA was performed in 47.8% and had a higher median radiation exposure (3896 vs. 3082 cGycm2, p < 0.001). There was no difference in the amount of contrast used. There was also no difference in all-cause mortality (0.53% vs. 0.49%, p = 0.86), the combination of death, MI and stroke (1.87% vs. 1.83%, p = 0.94), but a trend towards more TMB (0.47% vs. 1.04%, p = 0.07) with FA. These outcomes were consistent across the subgroups of patients with ST-elevation MI, non-ST-elevation-ACS and stable coronary artery disease. Finally, QoL did not differ between RA and FA. CONCLUSIONS: In this contemporary GABI-R cohort, in which access site was left to the discretion of the operator, both access routes were safe and equal concerning QoL (ClinicalTrials.gov; NCT02066623).