Risk and time preferences in individuals with lifestyle-related and non-lifestyle-related cardiovascular diseases: a pilot study.

OBJECTIVES: To (1) pilot a study of behavioural characterisation based on risk and time preferences in clinically well-characterised individuals, (2) assess the distribution of preferences in this population and (3) explore differences in preferences between individuals with 'lifestyle-related' (LS) and 'non-lifestyle-related' (NLS) cardiovascular diseases. DESIGN: Cross-sectional study with an economic online experiment to collect risk and time preferences, a detailed clinical characterisation and a sociodemographic and lifestyle survey. A definition of LS and NLS groups was developed. SETTING: Specialist outpatient clinics of the clinic for cardiology and pneumology of the University Hospital Düsseldorf and patients from a cardiology practice in Düsseldorf. PARTICIPANTS: A total of 74 individuals with cardiovascular diseases. OUTCOMES: Risk and time preferences. RESULTS: The implementation of the study process, including participant recruitment and data collection, ran smoothly. The medical checklist, the survey and the time preference instrument were well received. However, the conceptual understanding of the risk preference instrument resulted in inconsistent choices for many participants (47%). The remaining individuals were more risk averse (27%) than risk seeking (16%) and risk neutral (10%). Individuals in our sample were also more impatient (49%) than patient (42%). The participant classification showed that 65% belonged to the LS group, 19% to the NLS group and 16% could not be assigned (unclear allocation to lifestyle (ULS) group). Excluding the ULS group, we show that individuals in the LS group were more risk seeking, and unexpectedly, more patient than those in the NLS group. CONCLUSIONS: The process of the pilot study and its results can be used as a basis for the design of the main study. The differences in risk and time preferences between the LS and NLS groups provide us with a novel hypothesis for unhealthy behaviours: individuals never give up a bad habit, they simply postpone the latter, which can be tested alongside other additional research questions.

A comparison of conventional and advanced 3D imaging techniques for percutaneous left atrial appendage closure.

Background: Understanding complex cardiac anatomy is essential for percutaneous left atrial appendage (LAA) closure. Conventional multi-slice computed tomography (MSCT) and transesophageal echocardiography (TEE) are now supported by advanced 3D printing and virtual reality (VR) techniques for three-dimensional visualization of volumetric data sets. This study aimed to investigate their added value for LAA closure procedures. Methods: Ten patients scheduled for interventional LAA closure were evaluated with MSCT and TEE. Patient-specific 3D printings and VR models were fabricated based on MSCT data. Ten cardiologists then comparatively assessed LAA anatomy and its procedure relevant surrounding structures with all four imaging modalities and rated their procedural utility on a 5-point Likert scale questionnaire (from 1 = strongly agree to 5 = strongly disagree). Results: Device sizing was rated highest in MSCT (MSCT: 1.9 ± 0.8; TEE: 2.6 ± 0.9; 3D printing: 2.5 ± 1.0; VR: 2.5 ± 1.1; p < 0.01); TEE, VR, and 3D printing were superior in the visualization of the Fossa ovalis compared to MSCT (MSCT: 3.3 ± 1.4; TEE: 2.2 ± 1.3; 3D printing: 2.2 ± 1.4; VR: 1.9 ± 1.3; all p < 0.01). The major strength of VR and 3D printing techniques was a superior depth perception (VR: 1.6 ± 0.5; 3D printing: 1.8 ± 0.4; TEE: 2.9 ± 0.7; MSCT: 2.6 ± 0.8; p < 0.01). The visualization of extracardiac structures was rated less accurate in TEE than MSCT (TEE: 2.6 ± 0.9; MSCT: 1.9 ± 0.8, p < 0.01). However, 3D printing and VR insufficiently visualized extracardiac structures in the present study. Conclusion: A true 3D visualization in VR or 3D printing provides an additional value in the evaluation of the LAA for the planning of percutaneous closure. In particular, the superior perception of depth was seen as a strength of a 3D visualization. This may contribute to a better overall understanding of the anatomy. Clinical studies are needed to evaluate whether a more comprehensive understanding through advanced multimodal imaging of patient-specific anatomy using VR may translate into improved procedural outcomes.

Assessing the potential for precision medicine in body weight reduction with regard to type 2 diabetes mellitus therapies: A meta-regression analysis of 120 randomized controlled trials.

AIMS: To assess the potential for precision medicine in type 2 diabetes by quantifying the variability of body weight as response to pharmacological treatment and to identify predictors which could explain this variability. METHODS: We used randomized clinical trials (RCTs) comparing glucose-lowering drugs (including but not limited to sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and thiazolidinediones) to placebo from four recent systematic reviews. RCTs reporting on body weight after treatment to allow for calculation of its logarithmic standard deviation (log[SD], i.e., treatment response heterogeneity) in verum (i.e., treatment) and placebo groups were included. Meta-regression analyses were performed with respect to variability of body weight after treatment and potential predictors. RESULTS: A total of 120 RCTs with a total of 43 663 participants were analysed. A slightly larger treatment response heterogeneity was shown in the verum groups, with a median log(SD) of 2.83 compared to 2.79 from placebo. After full adjustment in the meta-regression model, the difference in body weight log(SD) was -0.026 (95% confidence interval -0.044; 0.008), with greater variability in the placebo groups. Scatterplots did not show any slope divergence (i.e., interaction) between clinical predictors and the respective treatment (verum or placebo). CONCLUSIONS: We found no major treatment response heterogeneity in RCTs of glucose-lowering drugs for body weight reduction in type 2 diabetes. The precision medicine approach may thus be of limited value in this setting.

Absolute treatment effects of novel antidiabetic drugs on a composite renal outcome: meta-analysis of digitalized individual patient data.

BACKGROUND: Absolute treatment benefits-expressed as numbers needed to treat-of the glucose lowering and cardiovascular drugs, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose transporter 2 (SGLT2) inhibitors on renal outcomes remain uncertain. With the present meta-analysis of digitalized individual patient data, we aimed to display and compare numbers needed to treat of both drugs on a composite renal outcome. METHODS: From Kaplan-Meier plots of major cardiovascular outcome trials of GLP-1 receptor agonists and SGLT2 inhibitors vs. placebo, we digitalized individual patient time-to-event information on composite renal outcomes with WebPlotDigitizer 4.2; numbers needed to treat from individual cardiovascular outcome trials were estimated using parametric Weibull regression models and compared to original data. Random-effects meta-analysis generated meta-numbers needed to treat with 95% confidence intervals (CI). RESULTS: Twelve cardiovascular outcome trials (three for GLP-1 receptor agonists, nine for SGLT2 inhibitors) comprising 90,865 participants were included. Eight trials were conducted in primary type 2 diabetes populations, two in a primary heart failure and two in a primary chronic kidney disease population. Mean estimated glomerular filtration rate at baseline ranged between 37.3 and 85.3 ml/min/1.73 m2. Meta-analyses estimated meta-numbers needed to treat of 85 (95% CI 60; 145) for GLP-1 receptor agonists and 104 (95% CI 81; 147) for SGLT2 inhibitors for the composite renal outcome at the overall median follow-up time of 36 months. CONCLUSION: The present meta-analysis of digitalized individual patient data revealed moderate and similar absolute treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors compared to placebo for a composite renal outcome.

Risk-adjusted management in catheterization procedures for non-ST-segment elevation myocardial infarction: A standard operating procedure pilot study.

BACKGROUND: The effects of standardized risk-adjusted periprocedural management of cardiac catheterization procedures in Non-ST segment elevation myocardial infarction (NSTEMI) remain unknown. We implemented a standard operating procedure (SOP) specifying risk assessment (RA, using National Cardiovascular Data Registry (NCDR) risk models) and risk-adjusted management (RM, e.g. intensified monitoring) in 2018 and aimed to investigate staff SOP adherence and associations with patient outcomes. METHODS AND RESULTS: All 430 invasively managed NSTEMI patients (mean age 72y; 70.9% male) in 2018 were analyzed for staff SOP adherence and in-hospital clinical outcomes. 207 patients (48.1%; RM+) received both RA and RM; 92 patients (21.4%; RM-) received RA but no RM; 131 patients (30.5%; RA-) received neither RA nor RM. Lower staff adherence to RA was associated with emergency settings (51.9% (RA-) vs. 22.1% (RA+); p<0.01), presentation in cardiogenic shock (17.6% (RA-) vs. 6.4% (RA+); p<0.01) and invasive mechanical ventilation (12.2% (RA-) vs. 3.3% (RA+); p<0.01). Early sheath removal (87.9% (RM+) vs. 56.5% (RM-); p<0.01) and intensified monitoring (p<0.01) were more frequent in the RM+ group. All-cause mortality was not different (1.4% (RM+) vs. 4.3% (RM-); p=0.13), but there were fewer major bleeding events with associated with RM (2.4% (RM+) vs. 12% (RM-); p<0.01), which remained independently associated with RM in a multivariate logistic regression model correcting for confounders (p<0.01). CONCLUSION: In an all-comer patient cohort with NSTEMI, staff adherence to risk-adjusted periprocedural management was independently associated with fewer major bleeding events. Staff adherence to SOP-specified risk assessment was frequently neglected in more critical clinical situations.

Knowledge of HbA1c and LDL-C treatment goals, subjective level of disease-related information and information needs in patients with atherosclerotic cardiovascular disease.

BACKGROUND/HYPOTHESIS: Risk factor control of diabetes mellitus (DM) and especially dyslipidemia remains unsatisfactory in patients with atherosclerotic cardiovascular disease (ASCVD). We aimed to analyze the knowledge of low-density lipoprotein cholesterol (LDL-C) and glycated hemoglobin (HbA1c) treatment goals, subjective level of information, and information needs in very high-risk patients with ASCVD. METHODS: ASCVD patients (n = 210; 75 ± 9 years; 71.4% male; 89.5% coronary disease) with DM (96.7% type 2) completed a questionnaire assessing knowledge of HbA1c and LDL-C treatment goals and subjective level of information and information needs on disease-related topics of DM and ASCVD. Serum LDL-C and HbA1c were measured. RESULTS: HbA1c goal (<7.0% in 60.6%) was attained more frequently than LDL-C goal (<70 mg/dl in 39.9%; p < .01). Significantly more participants named the correct goal for HbA1c compared to LDL-C (52.9% vs. 2.4%; p < .01). Subjective levels of information were higher and information needs were lower for DM than for ASCVD (p < .01 for all topics). No associations of knowledge of treatment goals and level of information with the attainment of treatment goals for HbA1c and LDL-C were found. However, in multivariate regression, higher levels of education were associated with knowledge of treatment goals (HbA1c: odds ratio [OR] 1.32, 95% confidence interval [CI] 1.01-1.72, p = .04; LDL-C: OR 2.32, 95% CI 1.07-5.03; p = .03). CONCLUSION: In very high-risk patients with ASCVD, a deficit of knowledge of treatment goals to control dyslipidemia exists when compared to DM, patients felt significantly better informed for topics of DM than for ASCVD and display higher information needs for topics of ASCVD.

Meta-analysed numbers needed to treat of novel antidiabetic drugs for cardiovascular outcomes.

AIMS: Absolute treatment effects-i.e. numbers needed to treat (NNTs)-of novel antidiabetic drugs for cardiovascular outcomes have not been comprehensively evaluated. We aimed to perform a meta-analysis of digitalized individual patient outcomes to display and compare absolute treatment effects. METHODS AND RESULTS: Individual patient time-to-event information from Kaplan-Meier plots of cardiovascular mortality (CM) and/or hospitalization for heart failure (HHF) endpoints from cardiovascular outcome trials (CVOTs) evaluating dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium glucose transporter 2 (SGLT2) inhibitors vs. placebo were digitalized using WebPlotDigitizer 4.2 and the R code of Guyot et al.; Weibull regression models were generated, validated, and used to estimate NNT for individual trials; random-effects meta-analysis generated Meta-NNT with 95% confidence intervals. Sixteen CVOTs reported time-to-event information (14 in primary diabetes and 2 in primary heart failure populations). Thirteen studies including 96 860 patients were meta-analysed for CM: At the median follow-up of 30 months, Meta-NNTs were 178 (64 to ∞ to -223) for DPP-4 inhibitors, 261 (158 to 745) for GLP-1 receptor agonists, and 118 (68 to 435) for SGLT2 inhibitors. Ten studies including 96 128 patients were meta-analysed for HHF: At the median follow-up of 29 months, estimated Meta-NNTs were -644 (229 to ∞ to -134) for DPP-4 inhibitors, 441 (184 to ∞ to -1100) for GLP-1 receptor agonists, and 126 (91 to 208) for SGLT2 inhibitors. SGLT2 inhibitors were especially effective for HHF in primary heart failure populations [Meta-NNT 25 (19 to 39)] vs. primary diabetes populations [Meta-NNT 233 (167 to 385)] at 16 months of follow-up. CONCLUSIONS: We found only modest treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors for CM and HHF in primary type 2 diabetes mellitus populations. In primary heart failure populations, SGLT2 inhibitor benefits were substantial and comparable in efficacy to established heart failure medication.

Process Standardization in High-Risk Coronary Interventions is Associated With Quality of Care Measures.

BACKGROUND: Patient safety is one of the most important issues in healthcare. High-risk percutaneous coronary interventions (HR-PCIs) offer well-established treatment options for patients with complex coronary artery disease and multiple comorbidities. Whether process standardization using standard operating procedure (SOP) management and checklists improves HR-PCI is still unknown. METHODS AND RESULTS: This retrospective study analyzed procedural characteristics, in-hospital outcomes, and length of hospital stay in patients who received HR-PCI in a German heart center 12 months before the introduction of process standardization using SOP management-the SOP (-) group-and after the introduction of process standardization using SOP management-the SOP (+) group. A total of 192 patients were included, with 77 patients in the SOP (-) group and 115 patients in the SOP (+) group. The mean age in the SOP (-) group was 72.0 ± 10.2 years and 81.8% were male; mean age in the SOP (+) group was 75.2 ± 10.4 years and 68.7% were male. Acute kidney events were significantly lower in the SOP (+) group than in the SOP (-) group (7.0% vs 10.4%; P=.04). Bleeding was the most common adverse event and significantly lower in the SOP (+) group than in the SOP (-) group (13.1% vs 31.2%, respectively; P<.01). There were trends toward shorter length of hospital stay in the SOP (+) group compared with the SOP (-) group (9.3 ± 6.4 days vs 10.9 ± 7.3 days, respectively; P=.10) and days of hospital stay in the intensive care unit (3.7 ± 4.0 days vs 4.7 ± 4.3 days; P=.07). SOP management was independently associated with shorter length of hospital stay in multivariate regression analysis. CONCLUSION: This retrospective study shows significantly better quality of care measures after the introduction of process standardization techniques using SOP management in HRPCIs, with a lower risk of adverse outcomes and shorter length of hospital stay.

Clinical efficacy and safety outcomes of bempedoic acid for LDL-C lowering therapy in patients at high cardiovascular risk: a systematic review and meta-analysis.

OBJECTIVES: Bempedoic acid (BA) is a novel oral low-density lipoprotein cholesterol lowering drug. This systematic review and meta-analysis aims to assess efficacy and safety for clinical outcomes in high cardiovascular (CV) risk patients. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Embase, ClinicalTrials.gov, Clinical Trial Results and the American College of Cardiology web site were searched. STUDY SELECTION: Randomised controlled trials (RCTs) of BA versus placebo in high CV risk patients reporting clinical outcomes were included. MAIN OUTCOMES AND MEASURES: Primary efficacy outcomes were major adverse cardiovascular events (MACE), all-cause mortality, CV mortality and non-fatal myocardial infarction (MI). Safety outcomes included new onset or worsening of diabetes mellitus (DM), muscular disorders, gout and worsening of renal function. RESULTS: Six RCTs with a total of 3956 patients and follow-ups of four to 52 weeks were identified. Heterogeneity mainly derived from differing follow-up duration and baseline CV risk. No difference in MACE (OR 0.84; 95% CI 0.61 to 1.15), all-cause mortality (OR 2.37; CI 0.80 to 6.99) and CV mortality (OR 1.66; CI 0.45 to 6.04) for BA versus placebo was observed. BA showed beneficial trends for non-fatal MI (OR 0.57; CI 0.32 to 1.00) and was associated with a lower risk of new-onset or worsening of DM (OR 0.68; CI 0.49 to 0.94), but higher risk of gout (OR 3.29; CI 1.28 to 8.46) and a trend for muscular disorders (OR 2.60; CI 1.15 to 5.91) and worsening of renal function (OR 4.24; CI 0.98 to 18.39). CONCLUSION: BA in high CV risk patients showed no significant effects on major CV outcomes in short-term follow-up. Unfavourable effects on muscular disorders, renal function and gout sound a note of caution. Hence, further studies with longer term follow-up in carefully selected populations are needed to clarify the risk/benefit ratio of this novel therapy.

National Cardiovascular Data Registry-Acute Kidney Injury (NCDR) vs. Mehran risk models for prediction of contrast-induced nephropathy and need for dialysis after coronary angiography in a German patient cohort.

BACKGROUND: Contrast-induced nephropathy (CIN) is a major adverse event in patients undergoing coronary angiography. The Mehran risk model is the gold-standard for CIN risk prediction. However, its performance in comparison to more contemporary National Cardiovascular Data Registry-Acute Kidney Injury (NCDR-AKI) risk models remains unknown. We aimed to compare both in this study. METHODS AND RESULTS: Predictions of Mehran and NCDR-AKI risk models and clinical events of CIN and need for dialysis were assessed in a total of 2067 patients undergoing coronary angiography with or without percutaneous coronary intervention. Risk models were compared regarding discrimination (receiver operating characteristic analysis), net reclassification improvement (NRI) and calibration (graphical and statistical analysis). The NCDR risk model showed superior risk discrimination for predicting CIN (NCDR c-index 0.75, 95% CI 0.72-0.78; vs. Mehran c-index 0.69, 95% CI 0.66-0.72, p < 0.01), and continuous NRI (0.22; 95% CI 0.12-0.32; p < 0.01) compared to the Mehran model. The NCDR risk model tended to underestimate the risk of CIN, while the Mehran model was more evenly calibrated. For the prediction of need for dialysis, NCDR-AKI-D also discriminated risk better (c-index 0.85, 95% CI 0.79-0.91; vs. Mehran c-index 0.75, 95% CI 0.66-0.84; pNCDRvsMehran < 0.01), but continuous NRI showed no benefit and calibration analysis revealed an underestimation of dialysis risk. CONCLUSION: In German patients undergoing coronary angiography, the modern NCDR risk model for predicting contrast-induced nephropathy showed superior discrimination compared to the Mehran model while showing less accurate calibration. Results for the outcome 'need for dialysis' were equivocal.

Modern NCDR and ACTION risk models outperform the GRACE model for prediction of in-hospital mortality in acute coronary syndrome in a German cohort.

BACKGROUND AND PURPOSE: Risk prediction with the Global Registry of Acute Coronary Events (GRACE) risk model is guideline-recommended in acute coronary syndrome (ACS) patients. However, the performance of more contemporary scores derived from ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and National Cardiovascular Data (NCDR) registries remains incompletely understood. We aimed to compare these models in German ACS patients. METHODS AND RESULTS: A total of 1567 patients with (Non-)ST-segment elevation myocardial infarction (NSTEMI: 1002 patients, STEMI: 565 patients) undergoing invasive management at University Hospital Düsseldorf (Germany) from 2014 to 2018 were included. Overall in-hospital mortality was 7.5% (NSTEMI 3.7%, STEMI 14.5%). Parameters for calculation of GRACE 1.0, GRACE 2.0, ACTION and NCDR risk models and in-hospital mortality were assessed and risk model performance was compared. The GRACE 1.0 risk model for prediction of in-hospital mortality discriminated risk superior (c-index 0.84) to its successor GRACE 2.0 (c-index 0.79, pGRACE1.0vsGRACE2.0 = 0.0008). The NCDR model performed best in discrimination of risk in ACS overall (c-index 0.89; pACTIONvsNCDR < 0.0001; pGRACEvsNCDR < 0.0001) and showed superior performance compared to GRACE in NSTEMI and STEMI subgroups (pGRACEvsNCDR both < 0.02). ACTION and GRACE risk models performed comparable to each other (both c-index 0.84, pGRACEvsACTION = 0.68), with advantages for ACTION in NSTEMI patients (c-index 0.87 vs. 0.84 (GRACE); pGRACEvsACTION = 0.02). ACTION and GRACE 2.0 showed the most accurate calibration of all models. CONCLUSIONS: In a contemporary German patient population with ACS, modern NCDR and ACTION risk models showed superior performance in prediction of in-hospital mortality compared to the gold-standard GRACE model.

Uninterrupted anticoagulation during catheter ablation for atrial fibrillation: no difference in major bleeding and stroke between direct oral anticoagulants and vitamin K antagonists in an updated meta-analysis of randomised controlled trials.

BACKGROUND: Periprocedural uninterrupted anticoagulation for catheter ablation of atrial fibrillation (AF) became standard after positive results of vitamin K antagonist (VKA) trials. Previous studies of uninterrupted direct oral anticoagulants (DOACs) vs. VKA have given controversial results. We thus aimed to elucidate the risk/benefit ratio of uninterrupted DOAC vs. VKA during catheter ablation of AF in an updated meta-analysis of randomised controlled trials (RCTs). METHODS: Online databases were searched for RCTs comparing uninterrupted DOAC to VKA in patients undergoing catheter ablation of AF. Data from retrieved studies were analysed in a comprehensive meta-analysis. Primary safety outcome was major bleeding; primary efficacy outcome was stroke or transient ischaemic attack (TIA). Secondary outcomes included a composite of major bleeding and stroke or TIA, minor bleeding, acute cerebral lesions on magnetic resonance imaging (MRI), and mortality. RESULTS: Six eligible RCTs comprising 2,369 patients were included. There were no significant differences in DOAC vs. VKA concerning the rates of major bleeding (2.2% vs. 3.8%; odds ratio (OR) 0.69, 95% confidence interval (CI) 0.30-1.56; p = .37) and stroke or TIA (0.2% vs. 0.2%; OR 0.97, CI 0.20-4.72; p = .97). Pooled meta-analysis of secondary outcomes revealed no significant differences (OR 0.73, p = .49 for composite of major bleeding and stroke or TIA; OR 1.08, p = .52 for minor bleeding; OR 1.12, p = .59 for acute cerebral lesions on MRI; and OR 0.60, p = .64 for all-cause mortality). CONCLUSION: Our meta-analysis suggests that uninterrupted DOAC is not superior to VKA in patients undergoing catheter ablation of AF with comparable rates of major bleeding and stroke.

Kidney function stratified outcomes of percutaneous left atrial appendage occlusion in patients with atrial fibrillation and high bleeding risk.

Background: Patients with chronic kidney disease (CKD) and atrial fibrillation have increased risks for stroke and bleeding under oral anticoagulation (OAC). We investigated an alternative therapy of percutaneous left atrial appendage occlusion (LAAO) in CKD patients in this study.Methods: Consecutive patients undergoing LAAO were included in a retrospective analysis and stratified for kidney function into CKD/Non-CKD groups (cutoff eGFR 60 ml/min). Procedural characteristics, in-hospital and follow-up events were analysed and compared between groups.Results: LAAO was performed in 146 patients (81 CKD; 65 Non-CKD), mean follow-up was 391 days. Groups differed in eGFR (40.1 (CKD) vs. 75.1 (Non-CKD) ml/min) and CHA2DS2VASc scores (4.65 ± 1.3 (CKD) vs. 4.06 ± 1.4 (Non-CKD)). Procedural success was 98.6%, contrast-induced acute kidney injury was significantly more frequent in CKD patients (11.1% vs. 0%; p = .004). Follow-up mortality was higher in CKD (10.5/100 PY vs. 4.2/100 PY; p = .156). Follow-up stroke rates were 2.3/100 (CKD) patient-years (PY) and 1.4/100 PY (Non-CKD) (p = 1.000), corresponding to a relative risk reduction (RRR) of 60% (all), 68% (CKD) and 71% (Non-CKD) compared to expected stroke rates. Follow-up major bleeding rates were 3.5/100 PY (CKD) and 4.2/100 PY (Non-CKD), corresponding to RRR of 57% (all), 61% (CKD) and 53% (Non-CKD) compared to OAC.Conclusions: Left atrial appendage occlusion shows comparable efficacy for stroke and bleeding prevention in CKD and Non-CKD patients. CKD patients experience more adverse events during follow-up and a significantly increased risk for periprocedural contrast-induced acute kidney injury.

Validation of National Cardiovascular Data Registry risk models for mortality, bleeding and acute kidney injury in interventional cardiology at a German Heart Center.

BACKGROUND AND PURPOSE: The National Cardiovascular Data Registry (NCDR) risk scores for mortality, bleeding and acute kidney injury (AKI) are accurate outcome predictors of coronary catheterization procedures in North American populations. However, their application in German clinical practice remained elusive and we thus aimed to verify their use. METHODS: NCDR scores for mortality, bleeding and AKI and corresponding clinical outcomes were retrospectively assessed in patients undergoing catheterization for ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) or for elective coronary procedures at a German Heart Center from 2014 to 2017. Risk model performance was assessed using receiver-operating-characteristic curves (discrimination) and graphical analysis/logistic regression (calibration). RESULTS: A total of 1637 patients were included, procedures were performed for STEMI (565 patients, 34.5%), NSTEMI (572 patients, 34.9%) and elective purposes (500 patients, 30.5%); 6% (13% of STEMI and 5% of NSTEMI patients) presented in cardiogenic shock and 3% with resuscitated cardiac arrest. Radial access was used in 38% of procedures and cross-over was necessary in 5%; PCI was performed in 60% of procedures. In-hospital mortality was 6.3% (STEMI 14.5%; NSTEMI 3.7%; elective 0%) and major bleedings occurred in 5.6% (STEMI 10.6%; NSTEMI 5.4%; elective 0.2%); AKI was detected in 18.1% of patients (STEMI 23.7%; NSTEMI 27.3%; elective 1.4%), amounting to KDIGO stage I/II/III in 11.5%/3.5%/3.2%. NCDR risk models discriminated very well for mortality [AUC 0.93 with 95% confidence interval (CI) 0.91-0.95] and well for major bleeding (AUC 0.82, CI 0.78-0.86) and any AKI (AUC 0.83, CI 0.81-0.86). Discrimination in the subgroup of patients with PCI was comparable (mortality: AUC 0.90; major bleeding: AUC 0.78; any AKI: AUC 0.79). However, calibration showed considerable underestimation of mortality and AKI in high-risk patients, while major bleeding was consistently overestimated (Hosmer-Lemeshow p < 0.02 for all outcomes). CONCLUSIONS: The NCDR risk models showed excellent performance in discriminating high-risk from low-risk patients in contemporary German interventional cardiology. Model calibration for adverse event probability prediction, however, is limited and demands recalibration, especially in high-risk patients.

Routine Glycoprotein IIb/IIIa Inhibitor Therapy in ST-Segment Elevation Myocardial Infarction: A Meta-analysis.

BACKGROUND: Guidelines recommend adjunct glycoprotein IIb/IIIa inhibitors (GPIs) only in selected patients with acute ST-segment elevation myocardial infarction (STEMI). This study aimed to evaluate routine GPI use in STEMI treated with primary percutaneous coronary intervention. METHODS: Online databases were searched for randomized controlled trials of routine GPI vs control therapy in STEMI. Data from retrieved studies were abstracted and evaluated in a comprehensive meta-analysis. Twenty-one randomized controlled trials with 8585 patients were included: 10 trials randomized tirofiban, 9 abciximab, 1 trial eptifibatide, and 1 trial used abciximab+tirofiban; only 1 trial used dual antiplatelet therapy with prasugrel/ticagrelor. RESULTS: Routine GPI use was associated with a significant reduction in all-cause mortality at 30 days (2.4% [GPI] vs 3.2%; risk ratio [RR], 0.72; P = 0.01) and 6 months (3.7% vs 4.8%; RR, 0.76; P = 0.02), and a reduction in recurrent myocardial infarction (1.1% vs 2.1%; RR, 0.55; P = 0.0006), repeat revascularization (2.5% vs 4.1%; RR, 0.63; P = 0.0001), thrombolysis in myocardial infarction flow <3 after percutaneous coronary intervention (5.4% vs 8.2%; RR, 0.61; P < 0.0001), and ischemic stroke (RR, 0.42; P = 0.04). Major (4.7% vs 3.4%; RR, 1.35; P = 0.005) and minor bleedings (7.2% vs 5.1%; RR, 1.39; P = 0.006) but not intracranial bleedings (0.1% vs 0%; RR, 2.7; P = 0.37) were significantly increased under routine GPI. CONCLUSIONS: Routine GPI administration in STEMI resulted in a reduction in mortality, driven by reductions in recurrent ischemic events-however predominantly in pre-prasugrel/ticagrelor trials. Trials with contemporary STEMI management are needed to confirm these findings.

Endovascular Thrombectomy as a Means to Improve Survival in Acute Ischemic Stroke: A Meta-analysis.

Importance: Although endovascular thrombectomy (EVT) in acute ischemic stroke is recommended by guidelines to improve functional recovery, thus far there are insufficient data on its association with mortality. Objective: To identify guideline-relevant trials of EVT vs medical therapy reporting 90-day mortality and perform a meta-analysis. Data Sources: All randomized clinical trials cited for recommendations on EVT vs medical therapy in the latest 2018 American Stroke Association/American Heart Association guidelines. Study Selection: Ten American Stroke Association/American Heart Association guideline-relevant randomized clinical trials of EVT vs medical therapy were selected for inclusion. Two EVT trials were excluded owing to infrequent use of EVT. Data Extraction and Synthesis: Data were abstracted by 2 independent investigators and double-checked by 4 others. Singular study data were integrated using the Cochran-Mantel-Haenszel method and a random-effects model to compute summary statistics of risk ratios (RR) with 95% CIs. Main Outcomes and Measures: Risk of 90-day mortality and 90-day intracranial hemorrhage was analyzed; sensitivity analyses were performed in early-window EVT trials (which included patients from the onset of symptoms onward) vs late-window EVT trials (which included patients from 6 hours after onset of symptoms onward). Results: In 10 trials with 2313 patients, EVT significantly reduced the risk for 90-day mortality by 3.7% compared with medical therapy (15.0% vs 18.7%; RR, 0.81; 95% CI, 0.68-0.98; P = .03). Trends were similar in early-window (RR, 0.83; 95% CI, 0.67-1.01; P = .06) and late-window trials only (RR, 0.76; 95% CI, 0.41-1.40; P = .38). There was no difference in the risk for intracranial hemorrhage in EVT vs medical therapy (4.2% vs 4.0%; RR, 1.11; 95% CI, 0.71-1.72; P = .65). Limitations of the studies include trial protocol heterogeneity and bias originating from prematurely terminated trials. Conclusions and Relevance: This meta-analysis of all evidence on EVT cited in the 2018 American Stroke Association/American Heart Association guidelines shows significant benefits for survival during the first 90 days after acute ischemic stroke compared with medical therapy alone.

Antiplatelet effects of aspirin and clopidogrel after left atrial appendage (LAA) occluder implantation.

BACKGROUND: The optimal antithrombotic strategy after interventional left atrial appendage closure (LAAC) is controversial. Dual antiplatelet therapy with aspirin and clopidogrel is the most frequently used regiment. However, pharmacodynamic response to antiplatelet medication differs significantly between individuals. Therefore, we aimed to analyse pharmacodynamic response to aspirin and clopidogrel after LAAC. METHODS: In this study, we included 129 patients undergoing interventional LAAC. Primary end point was pharmacodynamic response to antiplatelet medication. Platelet reactivity was measured by light transmittance aggregometry and vasodilator stimulated protein phosphorylation assay. Secondary endpoints were TIMI bleeding events and MACCE during hospital course and one-year follow-up. RESULTS: Insufficient pharmacodynamic response (high on-treatment platelet reactivity - HTPR) to clopidogrel occurred in 67 patients (52%); HTPR to aspirin in 15 patients (12%); low on-treatment platelet reactivity - LTPR - to clopidogrel in 13 patients (10%). No occluder thrombosis or stroke occurred during one year follow-up. Pharmacodynamic response to antiplatelet medication was not associated with MACCE. However, the incidence of TIMI minor bleeding was increased in patients with LTPR to clopidogrel. CONCLUSIONS: Impaired clopidogrel antiplatelet effects were very frequent in patients after LAAC. No stroke or occluder thrombosis occurred. Patients with LTPR to clopidogrel showed more minor bleeding events. Therefore, this hypothesis generating pilot study raises the question if clopidogrel early after LAAC is needed. This question should be addressed in large scale trials.

Patent foramen ovale closure or medical therapy for cryptogenic ischemic stroke: an updated meta-analysis of randomized controlled trials.

BACKGROUND: Previous randomized controlled trials (RCT) failed to demonstrate benefits of patent foramen ovale (PFO) closure (PFO-C) over medical therapy (MT) for secondary prevention of cryptogenic ischemic stroke. Three recently published RCTs, however, turned out positive for PFO-C and warrant an updated meta-analysis. METHODS: Data from all available RCTs on PFO-C vs. MT for secondary prevention of cryptogenic ischemic stroke up until October 2017 were abstracted and analyzed in a comprehensive meta-analysis. Clinical efficacy outcomes were recurrent stroke, recurrent TIA, and their combination; safety outcomes were mortality, major bleeding, venous thromboembolism (VTE), and new-onset atrial fibrillation/flutter (NOAF). RESULTS: Five trials including a total of 3440 patients were included in the meta-analysis. PFO-C significantly reduced recurrent stroke [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.19-0.90; p = 0.03] and the combination of recurrent stroke + TIA (OR 0.53, CI 0.36-0.80; p = 0.002) compared to MT; recurrent TIA alone showed no differences (OR 0.77; CI 0.51-1.14; p = 0.19). NOAF was significantly more frequent after PFO-C (OR 5.75, CI 3.09-10.70; p < 0.00001). Mortality (OR 0.80, CI 0.39-1.67), major bleeding (OR 0.96, CI 0.48-1.92), and VTE (OR 2.45, CI 0.75-7.99) remained neutral. Trials with superior patient selection for PFO-C showed advantageous results compared to MT. CONCLUSIONS: PFO-C after cryptogenic ischemic stroke is safe and effective to reduce the risk of recurrent stroke and recurrent stroke + TIA, albeit with an increased risk for NOAF.