Evaluation Of Endpoints Research Articles

Prognostic factors affecting long-term outcomes in patients with concurrent IgA nephropathy and membranous nephropathy

BackgroundThe incidence of concurrent immunoglobulin A nephropathy and membranous nephropathy (cIgAN/MN) is low and rarely reported, and the prognosis of patients with cIgAN/MN remains unclear. This study was designed to compare the clinical and prognostic characteristics of cIgAN/MN with IgAN and MN and to identify crucial factors influencing the outcomes of patients with cIgAN/MN. MethodsWe included biopsy-proven cIgAN/MN patients between December 2012 and December 2020 at Xijing Hospital. In the same period, propensity score matching was employed to select an equal number of IgAN and MN patients according to the following criteria: age, sex, and follow-up time. The primary endpoint was defined as a composite of eGFR decline ≥30 %, end-stage renal disease, or death. The patient survival rate was examined using Kaplan–Meier survival curves. Univariate and multivariate Cox regression analysis models were utilized to identify the risk factors affecting renal prognosis. ResultsA total of 135 patients were finally included in this study and 35 (25.9 %) reached the primary endpoint. The median follow-up time of cIgAN/MN was 45.9 (24.0, 72.0) months. Compared to the IgAN group, the cIgAN/MN group exhibited a lower cumulative incidence rate of composite renal endpoints (P = 0.044), while no significant difference was found between MN and cIgAN/MN patients (P = 0.211). Univariate Cox analysis revealed that mean arterial pressure, serum potassium, blood urea nitrogen, serum IgA, segmental glomerulosclerosis (S1), and MN staging were associated with an increased risk of renal composite endpoints. The multivariate Cox regression analysis of clinical variables plus histological lesion scoring demonstrated that potassium (HR = 14.350, 95 % CI 2.637–78.090, P = 0.002), serum IgA (HR = 1.870, 95 % CI 1.109–3.153, P = 0.019), and S1 (HR = 11.965, 95 % CI 2.166–66.105, P = 0.004) were independent risk factors influencing renal outcomes in cIgAN/MN patients. ConclusionThe prognosis of cIgAN/MN patients may exhibit an intermediate pattern between IgAN and MN, leaning towards being more similar to MN in certain aspects. Within the cIgAN/MN cohort, potassium, and serum IgA may be more predictive of rapid progression of renal endpoints, and S1 may indicate a more aggressive disease course.

Impact of Empagliflozin on Insulin Use in Patients with Heart Failure with Preserved Ejection Fraction (HFpEF) and Type 2 Diabetes: Sub-Analysis from EMPEROR-Preserved Trial

AimWe assessed the impact of empagliflozin on insulin requirement, and outcomes according to insulin use in patients with heart failure with preserved ejection fraction (HFpEF). MethodsOf 5988 patients randomised to empagliflozin or placebo, 2938 (49%) had type 2 diabetes mellitus (T2DM) and 1980 (33%) preDM at baseline. We analysed the effects of empagliflozin vs. placebo on time-to-first sustained insulin initiation in patients with T2DM or preDM not using insulin at baseline. ResultsAt baseline, 861 patients were using insulin. Patients on insulin were younger, had longer DM duration, lower eGFR, and more co-morbidities such as coronary artery disease and macroalbuminuria. During a median observation time of 26 months, among patients with T2DM or preDM not using insulin at baseline, empagliflozin reduced the risk of sustained initiation of insulin by 31% (HR 0.69 [95% CI 0.49, 0.98], p=0.038). Among patients with T2DM, those using insulin at baseline had higher incidence rates of the primary endpoint (first hospitalisation for HF [HHF] or cardiovascular [CV] death), total HHFs and first HHF that were reduced by empagliflozin but still remained higher than in the placebo arm of those not using insulin. Beneficial effects of empagliflozin on CV outcomes did not differ by baseline insulin use. ConclusionsEmpagliflozin reduced the rate of insulin initiation by 31% in patients with HFpEF and T2DM or preDM. Insulin-users at baseline were at higher risk of adverse CV outcomes; still, the effects of empagliflozin on CV outcomes were consistent in patients with T2DM irrespective of insulin treatment.Figure: The effect of empagliflozin vs placebo on clinical outcomes and mortality in patients with HFpEF and baseline T2DM with or without insulin.

Optimal treatment of asymptomatic patients with severe aortic stenosis: protocol of a prospective, multicentre, registry study

IntroductionDecisions regarding the optimal timing of intervention for asymptomatic aortic stenosis (AS) are controversial. The study aims to identify potential risk factors for asymptomatic patients with severe AS that are...

Outcomes of atherectomy in patients undergoing lower extremity revascularisation.

There is a paucity of real-world data on the in-hospital (IH) and post-discharge outcomes in patients undergoing lower extremity peripheral vascular intervention (PVI) with adjunctive atherectomy. In this retrospective, registry-based study, we evaluated IH and post-discharge outcomes among patients undergoing PVI, treated with or without atherectomy, in the National Cardiovascular Data Registry PVI Registry. The IH composite endpoint included procedural complications, bleeding or thrombosis. The primary out-of-hospital endpoint was major amputation at 1 year. Secondary endpoints included repeat endovascular or surgical revascularisation and death. Multivariable regression was used to identify predictors of atherectomy use and its association with clinical endpoints. A total of 30,847 patients underwent PVI from 2014 to 2019, including 10,971 (35.6%) treated with atherectomy. The unadjusted rate of the IH endpoint occurred in 524 (4.8%) of the procedures involving atherectomy and 1,041 (5.3%) of non-atherectomy procedures (p=0.07). After adjustment, the use of atherectomy was not associated with an increased risk of the combined IH endpoint (p=0.68). In the 6,889 (22.4%) patients with out-of-hospital data, atherectomy was associated with a reduced risk of amputation (adjusted hazard ratio [aHR] 0.67, 95% confidence interval [CI]: 0.51-0.85; p<0.01) and surgical revascularisation (aHR 0.63, 95% CI: 0.44-0.89; p=0.017), no difference in death rates (p=0.10), but an increased risk of endovascular revascularisation (aHR 1.21, 95% CI: 1.06-1.39; p<0.01) at 1 year. The use of atherectomy during PVI is common and is not associated with an increase in IH adverse events. Longitudinally, patients treated with atherectomy undergo repeat endovascular reintervention more frequently but experience a reduced risk of amputation and surgical revascularisation.

Optional therapeutic management of intermediate-risk pulmonary embolism patients

Background: Few studies have evaluated the thrombolytic treatment in patients with intermediate-high risk pulmonary embolism, making this study more valuable. Material and methods: It was a prospective, non-randomized, open-label, single-center study. Eligible patients at the age of 18 or older with an acute pulmonary embolism (PE) confirmed by CT pulmonary angiography with onset until 14 day and signs of right ventricular (RV) overload on echocardiography took part in the study. Pulmonary Arterial CT Obstruction Index Rate (PACTOIR) was used to define the localization and the expansion zone of thromboembolism. This study included 18 patients with intermediate risk and acute submassive pulmonary thromboembolism. In thrombolysis (TT) group (n=9) were used 50 mg of tissue-plasminogen activator (t-PA) administered in infusion as 0.4 mg/h for 2 hours. In the standard anticoagulation group, unfractioned heparin (UFH) was administered as a bolus of 70 units/kg or a maximum of 5000 units, followed by continuous infusion at an initial rate of 16 units/kg or a maximum of 1000 units/h. Results: The mean age for TT group was 69 vs 63 for the UFH group. PACTOIR was 100% in 3 patients in the half-dose rt-PA group and in 2 patients in the UFH group. RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p &lt; 0.0001). Mean pulmonary artery systolic pressure was 55 mm Hg in both groups (p &lt; 0.05), with 53 [43–60] in TT group vs. 41.5 [37–45] mmHg in UFH group, P&lt;0.05. Also, RV/ LV ratio and systolic PAP decreased significantly in both groups. Severe bleeding with a need in red blood cell transfusion was seen in 0.11% (1 patient) in the TT group vs 0 in UFH group. The hospitalization length of stay was significantly shorter in the TT group (3.8±1.8, p &lt; 0.05). The rate of secondary endpoints was significantly higher in the UFH group with a high rate of pulmonary hypertension (0 vs. 19%, p=0.003). Conclusions: Half-dose thrombolytic therapy in patients diagnosed with submassive pulmonary embolism significantly reduced death and hemodynamic decompensation in the first 7 days compared to anticoagulant therapy only. With all that being said, it can be concluded that patients with high-intermediate risk PE could benefit from reduced-dose TT.

De-escalation from ticagrelor to clopidogrel in patients with acute myocardial infarction: the TALOS-AMI HBR substudy.

The benefits of de-escalation of P2Y12 inhibition after percutaneous coronary intervention (PCI) may differ by high bleeding risk (HBR) status. We investigated the efficacy and safety of de-escalation from ticagrelor to clopidogrel after PCI by HBR status. This is a non-prespecified post hoc analysis of the TicAgrelor Versus CLOpidogrel in Stabilized Patients with Acute Myocardial Infarction (TALOS-AMI) trial. Net adverse clinical events (a composite of cardiovascular death, myocardial infarction, stroke, or Bleeding Academic Research Consortium [BARC] bleeding type 2, 3, or 5) at 1 year post-PCI were compared between the de-escalation (clopidogrel plus aspirin) and the active control (ticagrelor plus aspirin) groups by HBR status, as defined by the modification of the Academic Research Consortium (ARC) criteria. A total of 2,625 patients in the TALOS-AMI trial were analysed. Of these, 589 (22.4%) met the modified ARC-HBR criteria. The de-escalation group had lower primary endpoint rates than the control group in both HBR (hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.26-0.84) and non-HBR (HR 0.59, 95% CI: 0.41-0.84) patients. There were no differences in treatment effect for the primary endpoint regardless of HBR status (p for interaction=0.904). BARC bleeding type 3 or 5 was less common in the de-escalation than the control group among HBR patients only (HR 0.24, 95% CI: 0.07-0.84). In stabilised acute myocardial infarction patients, unguided de-escalation from ticagrelor to clopidogrel was associated with a lower rate of net adverse clinical outcomes irrespective of HBR status. The effect of de-escalation of P2Y12 inhibition on reducing haemorrhagic events was greater in patients with HBR.

A new home‐based cognitive test using phone calls in mild cognitive impairment

AbstractBackgroundMild cognitive impairment (MCI) is a risk group of dementia. Despite of plethora of hospital‐based neuropsychological tests, assessment tools that can be performed at home to detect cognitive progression are lacking. We thought that a home‐based cognitive test (HCT) is useful for regular cognitive monitoring without visiting the hospital. Our study aimed to validate the HCT by assessing relationships with existing hospital‐based neuropsychological tests scores.MethodThis pilot study was conducted in a university‐affiliated dementia clinic from July 2019 to December 2021. We had developed a new HCT that can be examined using phone calls without visiting the hospital. The newly developed HCT is composed of 20 questions (score ranges 0‐30), a higher score indicates better general cognition. Participants with MCI were enrolled and underwent regular HCT during 6 months. Brain MRI, plasma amyloid, baseline and endpoint neuropsychological tests, and assessment for clinical progression were performed. Associations between HCT scores and in‐person neuropsychological tests were investigated. We additionally assessed whether the HCT scores are correlated with Alzheimer’s disease (AD)‐related biomarkers including plasma amyloid values and regional brain volumes. To assess relevance, partial correlation coefficient adjusted by age, sex, and education was performed.ResultHCT had good intraclass correlation coefficient values (test‐retest Cronbach’s alpha 0.839 &amp; inter‐rater reliability Cronbach’s alpha 0.627). Totally 38 participants were enrolled and 32 completed the endpoint evaluations at 6 months. Seven participants progressed to mild dementia. Baseline HCT score showed good correlations with Mini‐Mental State Examination (MMSE) score, verbal memory delayed recall scores, and stroop test scores after adjustment for age, sex, and education. However, HCT scores did not show significant associations with AD‐biomarkers. MCI with higher risk of progression (APOE4 carrier or positivity in plasma amyloid values) showed numerical trends of faster HCT declines compared with MCI with lower risk of progression, although it did not reach statistical significance (p&gt;0.05).ConclusionWe demonstrated good reliability and correlations of the newly developed HCT with existing in‐person neuropsychological tests. It also showed good applicability on the elderly with MCI. Hence, HCT could be a promising and alternative option to monitor cognitive declines without visiting the hospital.

PTau181 plasma biomarker performance as an inclusion criterion for Alzheimer’s Disease clinical trials

AbstractBackgroundAdvances in ultrasensitive detection techniques for blood biomarkers allow the quantification of AD‐specific phosphorylated Tau proteins, including Tau phosphorylated at threonine 181 (pTau181) in patient plasma. pTau blood‐based biomarker have shown great promise as inclusion criteria and secondary endpoint evaluation in clinical trials.MethodThe University of British Columbia (UBC) CARD biobank plasma samples from clinically diagnosed AD and non‐AD patients were used to establish clinical and analytical validity of the pTau181 plasma assay per FDA fit‐for‐purpose guildelines (Neurcode USA, Inc.). We assessed the analytical measurement interval, clinical reportable range, linearity, intra‐laboratory precision, specimen stability, interference, and clinical performance.ResultThe pTau181 plasma assay provides a robust and accurate biomarker approach for independent determination of AD, with an AUC of 0.9 in our validation study cohort. The cut‐point (≥ 30 ng/L) had 100% sensitivity and 88% specificity for AD diagnosis in autopsy‐confirmed samples. The plasma pTau181 assay appears to be performing well as additional screening metric for inclusion of mild‐to‐moderate AD subjects in Phase 3 clinical trials (i.e. RETHINK‐ALZ and REFOCUS‐ALZ). 89% of the clinical sites participating in the REFOCUS‐ALZ study and 80% of sites participating in the RETHINK‐ALZ had at least 70% of screened subjects meeting this criterion.ConclusionAD plasma biomarker (pTau181) quantified using an RUO assay has great potential both as a diagnostic tool and to streamline clinical trials in AD.

SA13 Can Models for Surrogate Endpoint Evaluation Be Used to Predict Generic Measures From Disease Specific Measures of Health Related Quality of Life Based on Summary Data?

SA13 Can Models for Surrogate Endpoint Evaluation Be Used to Predict Generic Measures From Disease Specific Measures of Health Related Quality of Life Based on Summary Data?

Long-term outcomes of periprocedural coronary dissection and perforation for patients undergoing percutaneous coronary intervention in a Japanese multicenter registry

Long-term outcomes of iatrogenic coronary dissection and perforation in patients undergoing percutaneous coronary intervention (PCI) remains under-investigated. We analyzed 8,721 consecutive patients discharged after PCI between 2008 and 2019 from Keio Cardiovascular (KiCS) PCI multicenter prospective registry in the Tokyo metropolitan area. Significant coronary dissection was defined as persistent contrast medium extravasation or spiral or persistent filling defects with complete distal and impaired flow. The primary outcome was a composite of all-cause death, acute coronary syndrome, heart failure, bleeding, stroke requiring admission, and coronary artery bypass grafting two years after discharge. We used a multivariable Cox hazard regression model to assess the effects of these complications. Among the patients, 68 (0.78%) had significant coronary dissections, and 61 (0.70%) had coronary perforations at the index PCI. Patients with significant coronary dissection had higher rates of the primary endpoint and heart failure than those without (25.0% versus 14.3%, P = 0.02; 10.3% versus 4.2%, P = 0.03); there were no significant differences in the primary outcomes between the patients with and without coronary perforation (i.e., primary outcome: 8.2% versus 14.5%, P = 0.23) at the two-year follow-up. After adjustments, patients with coronary dissection had a significantly higher rate of the primary endpoint than those without (HR 1.70, 95% CI 1.02–2.84; P = 0.04), but there was no significant difference in the primary endpoint between the patients with and without coronary perforation (HR 0.51, 95% CI 0.21–1.23; P = 0.13). For patients undergoing PCI, significant coronary dissection was associated with poor long-term outcomes, including heart failure readmission.

Randomized clinical trial to compare the efficacy of self-expanding bare metal nitinol stent and balloon angioplasty alone for below-the-knee lesions following successful balloon angioplasty: 1-year clinical outcomes.

This prospective, multicenter, randomized study aimed to compare the 1-year clinical outcomes after primary stenting with self-expanding bare metal nitinol stent (SENS) and plain old balloon angioplasty (POBA) in patients with critical limb ischemia (CLI) and below-the-knee (BTK) lesions. Overall, 119 patients with CLI and BTK lesions were randomized to POBA alone (POBA group, 61 patients) or primary stenting with SENS (stenting group, 58 patients) after achieving acceptable POBA results in target BTK lesions. Clinical outcomes including amputation and revascularization rates were prospectively compared for 1 year. After 1 year, similar incidence rates of individual clinical endpoints, including cardiac death (6.5% vs. 5.1%, p > 0.999), myocardial infarction (1.6% vs. 0.0%, p > 0.999), repeat revascularization (19.6% vs. 18.9%, p = 0.922), target lesion revascularization (13.1% vs. 17.2%, p = 0.530), and amputation (4.9% vs. 0.0%, p = 0.244), were observed. POBA appeared to have acceptable treatment outcomes compared with primary stenting with SENS after 1 year in CLI patients with BTK lesions undergoing percutaneous transluminal angioplasty (PTA).

Poor Nutritional Status during Recovery from Acute Myocardial Infarction in Patients without an Early Nutritional Intervention Predicts a Poor Prognosis: A Single-Center Retrospective Study.

Whether malnutrition during the early phase of recovery from acute myocardial infarction (AMI) could be a predictor of mortality or morbidity has not been ascertained. We examined 289 AMI patients. All-cause mortality and composite endpoints (all-cause mortality, nonfatal stroke, nonfatal acute coronary syndrome, and hospitalization for acute decompensated heart failure) during the follow-up duration (median 39 months) were evaluated. There were 108 (37.8%) malnourished patients with GNRIs of less than 98 on arrival; however, malnourished patients significantly decreased to 91 (31.4%) during the convalescence period (p < 0.01). The incidence rates of mortality and primary composite endpoints were significantly higher in the malnourished group than in the well-nourished group both on arrival and during the convalescence period (All p < 0.05). Nutrition guidance significantly improved GNRI in a group of patients who were undernourished (94.7 vs. 91.0, p < 0.01). Malnourished patients on admission who received nutritional guidance showed similar all-cause mortality with well-nourished patients, whereas malnourished patients without receiving nutritional guidance demonstrated significantly worse compared to the others (p = 0.03). The assessment of GNRI during the convalescence period is a useful risk predictor for patients with AMI. Nutritional guidance may improve the prognoses of patients with poor nutritional status.

Prognostic value of a novel artificial intelligence-based coronary computed tomography angiography-derived ischemia algorithm for patients with suspected coronary artery disease

Abstract Introduction Coronary computed tomography angiography (CCTA) has emerged as the first-line, non-invasive imaging tool to detect coronary artery disease (CAD) in patients with low to intermediate pre-test probability of CAD. However, CCTA cannot directly assess the presence of ischemia, which may lead to further downstream testing. A novel artificial-intelligence (AI)-based algorithm, comprising a machine-learned method that leverages atherosclerosis and vascular morphology features to determine vessel-level coronary ischemia from CCTA images, may be useful in this regard. Purpose We aimed to investigate the prognostic value of the AI-based ischemia algorithm for clinical events among symptomatic patients with suspected CAD referred for CCTA. Methods The AI-based ischemia algorithm was calculated by analysts blinded for patient characteristics and clinical outcomes using CCTA data from patients with suspected CAD who underwent clinically indicated CCTA at a large tertiary care center from February 2007 to December 2016. The primary endpoint was the composite of death, myocardial infarction (MI), and unstable angina pectoris (uAP) throughout a median follow-up of 8.1 years (IQR 6.0-9.6). Secondary endpoints were the association between the AI-based ischemia algorithm and the primary endpoint among patients with no/non-obstructive (i.e. ≤50%) CAD vs. obstructive (i.e. &amp;gt;50% stenosis) CAD in CCTA. Results 1574 patients were evaluated by the AI-based ischemia algorithm and 1540 were analyzable. Patients with positive AI-based ischemia findings (30.4%, n=468) had a significantly higher crude rate of the primary endpoint as compared to patients with negative AI-based ischemia findings (69.6%, n=1072) (HR 2.37, 95% CI 1.80-3.11, p&amp;lt;0.001), driven by higher rates of all endpoint composites (death: HR 1.48, 95% CI 1.13-2.22, p=0.007; MI: HR 5.42, 95% CI 3.10-9.49, p&amp;lt;0.001; uAP: HR 6.76, 95% CI 3.01-15.20, p&amp;lt;0.001). Results were consistent after adjusting for clinical confounders (age, sex, diabetes mellitus, smoking, hypertension, dyslipidemia, BMI&amp;gt;25 kg/m2, CAD family history) (primary endpoint: HR 1.66, 95% CI 1.24-2.22, p=0.001). Positive AI-based ischemia findings were associated with a significantly higher rate of the primary endpoint among patients with no/non-obstructive CAD in CCTA (n=1001/1487) (HR 2.56, 95% CI 1.53-4.27, p&amp;lt;0.001), but not among those with anatomically obstructive CAD in CCTA (n=486/1487) (HR 1.08, 95% CI 0.70-1.66, p=0.715). Conclusions A novel AI-based CCTA-derived ischemia algorithm was associated with a 1.7-fold increased adjusted rate of long-term death, MI, or uAP. This AI-based ischemia algorithm may be helpful to improve risk stratification, especially among patients with normal/non-obstructive CCTA.Kaplan Meier CCTA ≤50% and &amp;gt;50% stenosis

Long-term outcome after upgrade to cardiac resynchronization therapy: A propensity score-matched analysis.

Cardiac resynchronization therapy (CRT) is a cornerstone in the management of chronic heart failure in patients with a broad or paced QRS. However, data on long-term outcome after upgrade to CRT are scarce. This international, multicentre retrospective registry included 2275 patients who underwent a de novo or upgrade CRT implantation with a mean follow-up of 3.6 ± 2.7 years. The primary composite endpoint included all-cause mortality, heart transplantation, or ventricular assist device implantation. The secondary endpoint was first heart failure admission. Multivariable Cox regression and propensity score matching (PSM) analyses were performed. Patients who underwent CRT upgrade (n = 605, 26.6%) were less likely female (19.7% vs. 28.8%, p < 0.001), more often had ischeemic cardiomyopathy (49.8% vs. 40.2%, p < 0.001), and had worse renal function (median estimated glomerular filtration rate 50.3 ml/min/1.73 m2 [35.8-69.5] vs. 59.9 ml/min/1.73 m2 [43.0-76.5], p < 0.001). The incidence rate of the composite endpoint was 10.8%/year after CRT upgrade versus 7.1%/year for de novo implantations (p < 0.001). PSM for the primary endpoint resulted in 488 pairs. After propensity score matching, upgrade to CRT was associated with a higher chance to reach the composite endpoint (multivariable hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.08-1.70), for both upgrade from pacemaker (multivariable HR 1.33, 95% CI 1.03-1.70) and implantable cardioverter-defibrillator (ICD) (multivariable HR 1.40, 95% CI 1.01-1.95). PSM for the secondary endpoint resulted in 277 pairs. After PSM, upgrade to CRT was associated with a higher chance for heart failure admission (HR 1.74, 95% CI 1.26-2.41). In this retrospective analysis, the outcome of patients who underwent upgrades to CRT differed significantly from patients who underwent de novo CRT implantation, particularly for upgrades from ICD. Importantly, this difference in outcome does not imply a causal relation between therapy and outcome but rather a difference between two different patient populations.

Intravascular ultrasonography guided percuatneous coronary intervention with everolimus-eluting stents or bypass surgery for multivessel coronary artery disease: post-hoc analysis of the BEST study

Abstract Background Previous studies suggested that intravascular ultrasonography (IVUS)-guided percutaneous coronary intervention (PCI) improved clinical outcomes compared with coronary angiography (CAG)-guided PCI in complex coronary artery disease. Objectives We compared long-term clinical outcomes of IVUS-guided PCI with everolimus-eluting stent and coronary-artery bypass grafting (CABG) in multivessel coronary disease (MVD). Methods Among 880 patients with MVD enrolled in the BEST Extended Follow-up study, 333 patients underwent IVUS-guided PCI and 131 patients underwent CAG-guided PCI, which were compared with 401patients underwent CABG. The primary endpoint was the composite of death from any cause, myocardial infarction, or target-vessel revascularization during a median follow-up of 11.8 years (interquartile range, 10.6 to 12.5 years). Results During an extended follow-up, primary endpoint occurred in 75 patients (22.8%) in the IVUS-guided PCI group, in 58 patients (44.38%) in the CAG-guided PCI group, and in 95 patients (24.0%) in the CABG group. Compared with the CABG group, the IVUS-guided PCI group had a similar rate of primary endpoint (adjusted hazard ratio [HR], 1.013; 95% confidence interval [CI], 0.747-1.374; P=0.93), whereas the CAG-guided PCI group had a significantly higher risk of clinical events (adjusted HR, 2.231; 95% CI, 1.582-3.145; P&amp;lt;0.001). Similarly, whereas the IVUS-guided PCI group had similar rate (adjusted HR, 0.845; 95% CI, 0.605-1.181; P=0.324), the CAG guided PCI group had the significantly higher rate of the safety composite of death, stroke and myocardial infarction (adjusted HR, 2.016; 95% CI, 1.405-2.895; P&amp;lt;0.001) compared with the CABG group. However, both IVUS- and CAG-guided PCI groups had significantly higher rate of any repeat revascularization than CABG group. Conclusions In patients with MVD, IVUS-guided PCI appeared to be an safe and effective alternative to CABG. This study advocated the routine use of intravascular imaging during PCI for MVD.KM curve of outcomesPrimary and secondary outcome

DOACs or warfarin use in morbidly obese patients (BMI &amp;gt; 40 kg/m2) on anticoagulant therapy? : a systematic review and meta-analysis

Abstract Introduction Current guidelines and consensus statements have advised against the use of direct oral anticoagulants (DOACs) for morbidly obese patients (BMI &amp;gt; 40 kg/m2), indicating warfarin as the first-line treatment. Purpose Our aim was to systematically review and examine the effectiveness and safety of DOACs compared to warfarin in patients with BMI &amp;gt; 40 kg/m2 and atrial fibrillation (AF) or venous thromboembolism (VTE). Methods This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies comparing the effectiveness and safety of DOACs and Warfarin in extremely obese patients. The primary outcome was the incidence of the composite endpoint (stroke, systemic embolism, myocardial infarction, or all-cause mortality), ii) stroke/systematic embolism (SE) and, iii) VTE. Secondary endpoints referred to major and minor bleeding events. Results This meta-analysis comprised 16 studies and 114,999 morbidly obese patients with AF or VTE on oral anticoagulation therapy (48,937 on DOACs vs. 65,080 on Warfarin). The DOAC use was significantly associated with lower all-cause mortality and major bleeding rates compared to the warfarin group [risk ratio= 0.66; 95% confidence interval: 0.53, 0.81; p = 0.03; I2 = 60%, RR: 0.78 (95% CI: 0.6-1.01, p &amp;lt;0.01, I2 = 85%)]. Although the rates of composite endpoint, stroke/SE and VTE were lower in the DOAC group, no statistically significant difference was observed [RR: 0.88 (95% CI: 0.7-1.12, p &amp;lt;0.01, I2 = 86%), RR: 0.92; (95% CI: 0.63-1.35, p &amp;lt;0.01, I2 = 86%), RR: 0.72; (95% CI: 0.46-1.15, p &amp;lt;0.01, I2 = 91%)], indicating no-superiority of Warfarin compared to DOAC use. The rates of minor bleeding events, hemorrhagic stroke and ischemic stroke were lower in the DOAC compared to warfarin groups [RR: 0.78 (95% CI: 0.56-1.10, p &amp;lt;0.01, I2 = 80%), RR: 0.56 (95% CI: 0.26-1.21, p &amp;lt;0.01, I2 = 86%), RR: 0.87; (95% CI: 0.6-1.24, p &amp;lt;0.01, I2 = 81%)]. The same trend favoring DOACs over Warfarin in all the assessed endpoints was observed in the subgroup analysis when results adjusted for the anticoagulation indication (AF or VTE). Conclusions Our findings are of paramount importance indicating, firstly, the non-superiority of Warfarin compared to DOAC use, and secondly, a significantly better profile of DOACs in terms of safety and effectiveness in morbidly obese patients with BMI &amp;gt; 40 kg/m2 in all the assessed endpoints. The findings may aid in the endeavor to enhance the upcoming recommendations for the management of this subgroup.

Effectiveness and safety of bempedoic acid in routine clinical practice: 1-year follow-up snapshot of the MILOS German cohort

Abstract Background Low-density lipoprotein cholesterol (LDL-C) has an established role in the development of atherosclerotic cardiovascular disease. The 2019 ESC/EAS dyslipidaemia guidelines recommended more intensive treatment goals, however, many patients do not reach them. Bempedoic acid (BA) is a first-in-class ATP citrate lyase inhibitor that lowers LDL-C levels. There is limited data on the use of BA and BA + ezetimibe (EZE) fixed-dose combination (FDC) in clinical practice. Purpose The purpose of this snapshot of 1-year follow-up data from the MILOS study is to evaluate the effectiveness and safety of BA and its FDC in routine clinical practice in Germany. Methods MILOS is a European, prospective, observational, non-interventional study in adult patients with primary hypercholesterolaemia or mixed dyslipidaemia. Patients were recruited from 126 sites in Germany between January 2021 and January 2022, and are followed up for 1–2 years after baseline measurements. Here, we summarise 1-year follow-up data from a snapshot taken on January 13th, 2023. Results Of 992 patients enrolled in Germany, 714 had either completed their 1-year follow-up or discontinued the study prematurely, and 524 of these 714 patients attended their 1-year follow-up visit. For this snapshot, 714 patients are used when determining cardiovascular (CV) outcomes and safety endpoints, and 524 patients are used when reporting efficacy data. The overall mean (SD) age of the population (n=524) was 64.7 (10.0) years, and 60.7% were male. Patients treated with BA/BA+EZE FDC had an overall mean LDL-C level of 2.18 mmol/L (84.1 mg/dL) at 1 year compared with 3.20 mmol/L (123.6 mg/dL) pre-treatment, representing a mean relative LDL-C reduction of 27.3%. Overall, 25.8% (135/524) of patients had reached their LDL-C goal after 1 year of treatment compared with 4.0% (21/524) pre-treatment (Figure 1A and 1B). The overall incidence rate of the composite endpoint of major adverse cardiovascular event (4-component MACE) including CV death, non-fatal myocardial infarction, non-fatal stroke, and coronary revascularisation (n=714) was 3.36%. At 1-year follow-up, 19% (136/714) of patients had an adverse drug reaction (ADR) suspected to be related to BA/BA+EZE FDC, and 0.8% (6/714) had serious ADRs, as deemed by the investigator. Conclusion This snapshot analysis of 1-year follow-up data suggests that the addition of BA to other lipid-lowering therapies increases the proportion of patients at LDL-C goal by ∼6-fold in the observed cohort. The safety and tolerability profile of bempedoic acid are in line with data from randomised controlled trials.

Safety and efficacy of protamine administration for prevention of bleeding complications in patients with recent PCI undergoing TAVR

Abstract Background Despite major advances, TAVR is still associated with vascular and bleeding complications, that have an impact on mortality. Recent studies have shown that heparin antagonization using protamine resulted in lower bleeding rates in patients undergoing TAVR as compared to those without heparin reversal. However, there are only limited data on the safety of protamine regarding thromboembolic complications including in-stent thrombosis in TAVR patients who have had a recent PCI. Accordingly, daily practice varies between Centers. Purpose The aim of this multicentre study was to evaluate the safety and efficacy of protamine administration in patients who have had a recent PCI undergoing subsequent TAVR. Methods Our study included 1838 patients undergoing TAVI between 2017 and 2020. Of the patients included, 173 (9.4%) had a recent PCI (≤30 days), 319 (17.4%) had an intermediately (≥30 days) and 303 (16.5%) a previously performed PCI (≥6 months). Standardized vascular access management included the use of preclosure devices and PTA or implantation of a stent-graft, if necessary. The primary endpoint was a composite of one-year mortality and myocardial infarction at 30 days. Secondary endpoints included 30-day mortality and VARC-3-defined complications. Results The overall study population had a mean age of 81.1±6.2 years. Among patients with recent PCI, 134 (77.5%) patients received protamine for heparin reversal during the TAVR procedure. In the group of patients with intermediately and previously performed PCI 258 (80.9%) and 249 (82.2%) patients received protamine, respectively. In the recent PCI group, the occurrence of the primary endpoint was comparable between patients with protamine administration (24.6%) as compared to patients without heparin reversal (30.8%, p=0.53, Figure 1). Similarly, among patients with intermediately as well as previously performed PCI, the rates of the primary endpoint were comparable irrespective of protamine administration (20.1 vs 16.4%, p=0.59; 17.3 vs 27.7%, p=0.08, respectively, Figure 2). Moreover, among all three groups, the incidence of myocardial infarction at 30 days after TAVR was low and comparable between patients with and without heparin reversal (p&amp;gt;0.50). Overall, protamine administration was associated with decreased life-threatening bleeding (3.2 vs 9.4%, p&amp;lt;0.01) and major vascular complications (4.4 vs 7.9%, p=.02). Regarding safety endpoints, no overall differences were observed in the incidence of stroke between patients with and without protamine administration (1.5 vs 2.9%, p=0.13). Conclusion Protamine administration during the TAVR procedure did not increase the rate of myocardial infarction or one-year mortality in patients who have had a recently or intermediately performed PCI. Overall, heparin reversal using protamine resulted in significantly lower rates of life-threatening bleeding and major vascular complications, without increasing the incidence of stroke.Figure 1Figure 2

Optimal medical management vs. percutaneous coronary intervention for patients with stable angina: from nation-wide Korean Insurance data

Abstract Background To investigate whether percutaneous coronary intervention (PCI) on top of optimal medical therapy (OMT) is superior to OMT only in patients with stable angina. Methods We enrolled patients with stable angina from 2005-2010 using the Korean national Insurance data. 68621 patients were candidate with stable angina and finally 5673 patients in PCI plus OMT and 5673 in OMT were selected with 1:1 propensity matching. Results Primary endpoint, a composite of myocardial infarction (MI), stroke, cardiac death and revascularization was significantly more common in PCI than in OMT group, 13.5/1000 vs. 11.5/1000 person year with HR, 1.182(1.059-1.319) (P=0.0027). Individual outcome rate of MI, revascularization and cardiac death was higher in PCI group then in OMT group , 2.9 vs. 2. (HR [1.376 1.085-1.744], p=0.0085), 30.3 vs. 8.1 (HR 3.638 [3.269-4.049], p&amp;lt;0.001) and 4.8 vs 3.4/1000 person year (HR 1.397 [1.155-1.69], p=0.0006) respectively. No difference was found in stroke rate. In subgroup analysis same trend of more rate of event in PCI group was detected. Conclusions PCI was associated with higher rate of primary endpoint of MI, stroke, cardiac death as compared to OMT only in patients with stable angina.Primary endpoint between PCI vs. OMT

Impact of the antiplatelet strategy following patent foramen ovale percutaneous closure

Abstract Background Temporary dual antiplatelet therapy (DAPT) is recommended following patent foramen ovale (PFO) percutaneous closure although its benefit, compared to single antiplatelet therapy (SAPT), has not been demonstrated in this setting. Objective We aimed at assessing outcomes following PFO closure according to the antiplatelet strategy at discharge. Methods The ambispective AIR-FORCE cohort included consecutive patients from 7 centers in France and Canada undergoing PFO closure and discharged without anticoagulation. Patients treated in French and Canadian centers were mostly discharged with DAPT and SAPT, respectively. The primary endpoint was the composite of death, stroke, transient ischemic attack, peripheral embolism, myocardial infarction, or BARC type ≥2 bleeding with up to 5 years of follow-up. The impact of the antiplatelet strategy on outcomes was evaluated with a marginal Cox model (cluster analyses per country) with inverse probability weighting according to propensity score. Results A total of 1,532 patients were included from 2001 to 2022, of whom 599 (39.1%) were discharged with SAPT and 933 (60.9%) with DAPT, for ≤3 months in 894/923 (96.9%) cases (Table 1). After a median follow-up of 2.4[1.1-4.4] years, a total of 58 events were observed. In the weighted analysis the rate of the primary endpoint up to 5 years was 7.8% in the SAPT strategy and 7.3% in the DAPT strategy (weighted hazard ratio 1.04, 95% confidence interval 0.59-1.83) (Figure 1). Results were consistent in a sensitivity analysis. Conclusion The strategy of antiplatelet strategy following PFO closure did not seem to impact clinical outcomes, thus challenging the current recommendations of temporary DAPT.Table 1.Baseline characteristicsFigure 1.Central illustration