Impact of sex on outcomes associated with polyvascular disease in patients after PCI.

BACKGROUND: Atherosclerosis in more than one vs. one arterial bed is associated with increased risk for major adverse cardiovascular events (MACE). This study aimed to determine whether the risk of post percutaneous coronary intervention (PCI) MACE associated with polyvascular disease (PVD) differs by sex. METHODS: We analyzed 18,721 patients undergoing PCI at a tertiary-care center between 2012-2019. Polyvascular disease was defined as history of peripheral artery and/or cerebrovascular disease. The primary endpoint was MACE, a composite of all-cause death, myocardial infarction, or stroke at 1 year. Multivariate Cox regression was used to adjust for differences in baseline risk between patients with PVD vs. coronary artery disease (CAD) alone and interaction testing was used to assess risk modification by sex. RESULTS: Women represented 29.2% (N=5,467) of the cohort and were more likely to have PVD than men (21.7% vs. 16.1%; p<0.001). Among both sexes, patients with PVD were older with higher prevalence of comorbidities and cardiovascular risk factors. Women with PVD had the highest MACE rate (10.0%), followed by men with PVD (7.2%), women with CAD alone (5.0%), and men with CAD alone (3.6%). Adjusted analyses revealed similar relative MACE risk associated with PVD vs. CAD alone in women and men (adjusted hazard ratio [aHR] 1.54, 95% confidence interval [CI] 1.20-1.99; p<0.001 and aHR 1.31, 95% CI 1.06-1.62; p=0.014, respectively; p-interaction=0.460). CONCLUSION: Women and men derive similar excess risk of MACE from PVD after PCI. The heightened risk associated with PVD needs to be addressed with maximized use of secondary prevention in both sexes.

Left Atrial Appendage Closure Compared With Oral Anticoagulants for Patients With Atrial Fibrillation: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Percutaneous left atrial appendage closure (LAAC) has been suggested as an alternative to long-term oral anticoagulation for nonvalvular atrial fibrillation, but comparative data remain scarce. We aimed to assess ischemic and bleeding outcomes of LAAC compared with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) for the prevention of cardioembolic events in patients with atrial fibrillation. METHODS AND RESULTS: Embase and MEDLINE were searched for randomized trials comparing LAAC, VKAs, and DOACs. The primary efficacy end point was any stroke or systemic embolism. Treatment effects were calculated from a network meta-analysis and ranked according to the surface under the cumulative ranking curve. Seven trials and 73 199 patients were included. The risk of the primary end point was not statistically different between LAAC versus VKAs (odds ratio [OR], 0.92 [95% CI, 0.62-1.50]) and LAAC versus DOACs (OR, 1.11 [95% CI, 0.71-1.73]). LAAC and DOACs resulted in similar risk of major or minor (OR, 0.93 [95% CI, 0.61-1.42]) and major bleeding (OR, 0.92 [95% CI, 0.58-1.46]); however, after exclusion of procedural bleeding, bleeding risk was significantly lower in those undergoing LAAC. Both LAAC and DOACs reduced the risk of all-cause death  compared with VKAs (LAAC versus VKAs: OR, 0.70 [95% CI, 0.53-0.91]; DOACs versus VKAs: OR, 0.90 [95% CI, 0.85-0.95], respectively). DOACs ranked as the best treatment for stroke or systemic embolism prevention (66.9%) and LAAC for reducing major bleeding (63.9%) and death (96.4%). CONCLUSIONS: As a nonpharmacological alternative to oral anticoagulation for atrial fibrillation, LAAC showed similar efficacy and safety compared with VKAs or DOACs. Prospective confirmation from larger studies is warranted.

Change in left ventricular function and outcomes following high-risk percutaneous coronary intervention with Impella-guided hemodynamic support.

Introduction: High-risk percutaneous coronary interventions (HRPCI) are a potential treatment option for patients with reduced left ventricular ejection fraction (LVEF) and coronary artery disease. The extent to which such intervention is coupled with improvement in LVEF and associated with favorable outcomes is unknown. Methods: We aimed to characterize the incidence and correlates of LVEF improvement after Impella-guided HRPCI, and compare clinical outcomes in patients with versus without LVEF improvement. Data on consecutive patients undergoing Impella-guided HRPCI from a single center registry were analyzed. LVEF-improvement was defined as an absolute increase of LVEF of ≥10% measured at ≥30-days after intervention. The primary outcome was a composite of all-cause death, myocardial infarction or target vessel revascularization within 1-year. Results: Out of 161 consecutive patients undergoing Impella-guided HRPCI from June 2008 to December 2017, 43% (n = 70) demonstrated LVEF-improvement (baseline LVEF of 25.09 ± 6.19 to 33.30 ± 11.98 post intervention). Patients without LVEF-improvement had higher frequency of previous MI (61.5% vs. 37.1%, p = 0.0021), Q-waves on ECG (17.6% vs. 5.7%, p = 0.024) and higher SYNTAX scores (30.8 ± 17.6 vs. 25.2 ± 12.2; p = 0.043). After correction of these confounders by multivariable analysis, no significant differences were found regarding the composite endpoint in patients with versus without LVEF-improvement (34.9% vs. 38.3%; p = 0.48). Discussion: In this single-center retrospective analysis, we report the following findings. First, LVEF improvement of at least 10% was documented in over 40% of patients undergoing Impella supported high-risk PCI. Second, a history of MI, Q-waves on admission ECG, and higher baseline SYNTAX scores were independent correlates of no LVEF improvement. Third, one year rates of adverse CV events were substantial and did not vary by the presence or absence of LVEF improvement Prospective studies with longer follow-up are needed to elucidate the impact of LVEF improvement on clinical outcomes.

Demystifying the Contemporary Role of 12-Month Dual Antiplatelet Therapy After Acute Coronary Syndrome.

For almost two decades, 12-month dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) has been the only class I recommendation on DAPT in American and European guidelines, which has resulted in 12-month durations of DAPT therapy being the most frequently implemented in ACS patients undergoing percutaneous coronary intervention (PCI) across the globe. Twelve-month DAPT was initially grounded in the results of the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, which, by design, studied DAPT versus no DAPT rather than the optimal DAPT duration. The average DAPT duration in this study was 9 months, not 12 months. Subsequent ACS studies, which were not designed to assess DAPT duration, rather its composition (aspirin with prasugrel or ticagrelor compared with clopidogrel) were further interpreted as supportive evidence for 12-month DAPT duration. In these studies, the median DAPT duration was 9 or 15 months for ticagrelor and prasugrel, respectively. Several subsequent studies questioned the 12-month regimen and suggested that DAPT duration should either be fewer than 12 months in patients at high bleeding risk or more than 12 months in patients at high ischemic risk who can safely tolerate the treatment. Bleeding, rather than ischemic risk assessment, has emerged as a treatment modifier for maximizing the net clinical benefit of DAPT, due to excessive bleeding and no clear benefit of prolonged treatment regimens in high bleeding risk patients. Multiple DAPT de-escalation treatment strategies, including switching from prasugrel or ticagrelor to clopidogrel, reducing the dose of prasugrel or ticagrelor, and shortening DAPT duration while maintaining monotherapy with ticagrelor, have been consistently shown to reduce bleeding without increasing fatal or nonfatal cardiovascular or cerebral ischemic risks compared with 12-month DAPT. However, 12-month DAPT remains the only class-I DAPT recommendation for patients with ACS despite the lack of prospectively established evidence, leading to unnecessary and potentially harmful overtreatment in many patients. It is time for clinical practice and guideline recommendations to be updated to reflect the totality of the evidence regarding the optimal DAPT duration in ACS.

Predictors of outcomes after PCI with incomplete revascularization: Impact of CTO and LAD vessel.

BACKGROUND: Incomplete revascularization (ICR) after percutaneous coronary intervention (PCI) is associated with mortality and morbidity. AIM: We sought to investigate whether ICR in the left anterior descending artery (LAD) is worse than ICR of the right coronary artery (RCA) or left circumflex artery (LCX); and whether ICR in patients with a chronic total occlusion (CTO) is worse than in those without. METHODS: In the RIVER-PCI trial, 2651 patients with ICR after PCI were randomly assigned to ranolazine or placebo. Angiograms were assessed at an independent core laboratory in 2501 patients (94.3%). The primary endpoint was the composite of ischemia-driven revascularization or hospitalization. RESULTS: A total of 1664 patients (66.5%) had ICR involving the LAD, whereas 837 (33.5%) had ICR limited to the RCA or LCX. At median follow-up of 643 days, the primary endpoint occurred in 26.9% versus 26.5% of patients (adjusted HR [aHR]: 1.03, 95% confidence interval [CI]: 0.88-1.21). A nonrecanalized CTO was present in 854 patients (34.1%) with ICR after PCI. The primary endpoint occurred in 28.6% versus 25.9% of ICR patients with versus without a CTO (aHR: 1.10, 95% CI: 0.94-1.29). However, patients with a CTO had higher rates of ischemia-driven hospitalization without revascularization (aHR: 1.27, 95% CI: 1.04-1.56), heart failure hospitalization (aHR: 2.69, 95% CI: 1.61-4.59) and myocardial infarction (aHR: 1.46, 95% CI: 1.11-1.92) compared with those without. CONCLUSIONS: The 2-year prognosis was similar in post-PCI patients with ICR whether the LAD was versus was not involved. ICR patients with a CTO had more frequent hospitalizations for ischemia and myocardial infarctions compared with those without.

A Patch Wearable Cardioverter-Defibrillator for Patients at Risk of Sudden Cardiac Arrest.

BACKGROUND: For many patients, sudden cardiac arrest (SCA) risk is elevated temporarily. Wearable cardioverter-defibrillators (WCDs) can monitor and treat SCA during these temporary periods. Traditional WCDs can be uncomfortable, require frequent maintenance, and cannot be used when showering, resulting in poor compliance and avoidable SCA deaths. The Jewel is a novel, water-resistant patch-wearable cardioverter-defibrillator (P-WCD) with a machine learning detection algorithm designed to improve compliance and protection against SCA. OBJECTIVES: This study aims to demonstrate the safety and clinical effectiveness of a novel P-WCD. METHODS: The Jewel IDE Study, a prospective, single-arm study conducted at 30 U.S. sites, enrolled patients at SCA risk due to ventricular tachycardia/ventricular fibrillation who were not candidates for or refused an implantable defibrillator. The primary safety endpoint was <15% patients with clinically significant cutaneous adverse device effects and the primary effectiveness endpoint was <2 inappropriate shocks/100 patient-months. Secondary endpoints were ≥1 successful ventricular tachycardia/ventricular fibrillation conversion and wear time compliance of >14.1 h/d. RESULTS: A total of 305 patients (mean age: 57.9 years; 30.2% female, 27.9% non-White) were enrolled, of which 290 had available device data. The clinically significant cutaneous adverse device effect rate was 2.30% (upper 1-sided 98% CI: 4.80); none were severe. No device-related deaths or serious adverse events were reported. The inappropriate shock rate was 0.36/100 patient-months (upper 1-sided 98% CI: 1.53). Of 11 shocks in 9 patients, 9 shocks were adjudicated to be appropriate. Eight of 9 shocks were successful with a single shock. Median wear time compliance was 23.5 (20.7-23.9) h/d. CONCLUSIONS: The novel P-WCD is a safe and effective WCD with high patient compliance. There were no deaths due to noncompliance and a high number of successful conversions (Jewel IDE study [A Clinical Evaluation of the Jewel P-WCD in Subjects at High Risk for Sudden Cardiac Arrest]; NCT05201495).

Risk Factors of Ischemic Stroke in Patients With Atrial Fibrillation After Transcatheter Aortic Valve Implantation from the Randomized ENVISAGE-TAVI AF Trial.

In patients with prevalent or incident atrial fibrillation (AF) after successful transcatheter aortic valve implantation (TAVI) enrolled in the EdoxabaN Versus standard of care and theIr effectS on clinical outcomes in pAtients havinG undergonE Transcatheter Aortic Valve Implantation - in Atrial Fibrillation (ENVISAGE-TAVI AF) trial, the incidence of ischemic stroke (IS) and any stroke was numerically less in the edoxaban group than in the vitamin K antagonist (VKA) group. The present study aimed to identify risk factors associated with IS in an on-treatment subanalysis in patients from ENVISAGE-TAVI AF who received ≥1 dose of edoxaban or VKA. Baseline patient characteristics were compared in patients with and those without IS. Numerical variables were compared using a 1-way analysis of variance; categorical variables were compared using Fisher's exact test. Stepwise Cox regression determined patient characteristics associated with the first IS event. Of 1,377 patients, 41 (3.0%) experienced an IS, and 1,336 (97.0%) did not; baseline demographics and clinical characteristics were well balanced between groups. Most ISs occurred within 180 days of TAVI for edoxaban (57.9%) and VKA (68.2%). The rate of IS was 2.0/100 person-years for edoxaban versus 2.7/100 person-years for VKA. Independently associated with IS were history of systemic embolic events (hazard ratio 2.96, 95% confidence interval 1.26 to 7.00, p = 0.01) and pre-TAVI use of VKAs (hazard ratio 2.17, 95% confidence interval 1.12 to 4.20, p = 0.02). In conclusion, although the overall incidence of IS was small for patients with AF on edoxaban or VKA after successful TAVI, patients with a history of systemic embolic events or pre-TAVI use of VKAs may be at greater risk of IS after TAVI.

P2Y12 Inhibitor Monotherapy After Short DAPT in Acute Coronary Syndrome: A Systematic Review and Meta-analysis.

BACKGROUND: P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) may balance ischemic and bleeding risks in patients with acute coronary syndrome (ACS). However, it remains uncertain how different P2Y12 inhibitors used as monotherapy affect outcomes. METHODS: Randomized controlled trials comparing P2Y12 inhibitor monotherapy after a short course of DAPT (≤3 months) versus 12-month DAPT in ACS were included. The primary endpoint was major adverse cardiovascular events (MACE). All analyses included an interaction term for the P2Y12 inhibitor used as monotherapy. Trial sequential analysis were run to explore whether the effect estimate of each outcomes may be affected by further studies. RESULTS: Seven trials encompassing 27,284 ACS patients were included. Compared with 12-month DAPT, P2Y12 inhibitor monotherapy after a short course of DAPT was associated with no difference in MACE (OR 0.92, 95% CI 0.76-1.12) and a significant reduction in net adverse clinical events (NACE) (OR 0.75; 95% CI 0.60-0.94), any bleeding (OR 0.54, 95% CI 0.43-0.66) and major bleeding (OR 0.47, 95% CI 0.37-0.60). Significant interactions for subgroup difference between ticagrelor and clopidogrel monotherapy were found for MACE (pint=0.016), all-cause death (pint=0.042), NACE (pint=0.018), and myocardial infarction (pint=0.028). Trial sequential analysis showed conclusive evidence of improved NACE with ticagrelor, but not with clopidogrel monotherapy, compared with standard DAPT. CONCLUSIONS: In patients with ACS, P2Y12 inhibitor monotherapy after short DAPT halves bleeding without increasing ischemic events compared with standard DAPT. Ticagrelor, but not clopidogrel monotherapy, reduced MACE, NACE and mortality compared with standard DAPT, supporting its use after aspirin discontinuation. Protocol registration: This study is registered in PROSPERO (CRD42023494797).

Mortality After Procedural or Spontaneous Myocardial Infarction.

BACKGROUND: It remains unclear whether procedural myocardial infarction (pMI) and spontaneous myocardial infarction (spMI) have a similar impact on prognosis. OBJECTIVES: The aim of this study was to assess mortality after pMI and spMI. METHODS: Patients with chronic coronary syndrome (CCS) and baseline troponin ≤1× the upper reference level (URL) or with acute spMI who underwent percutaneous coronary intervention (PCI) were included. PMI was defined as post-PCI troponin increase >1× URL in patients with CCS. SpMI comprised any acute coronary syndrome with elevated troponin. The 1-year risk of all-cause death was assessed after pMI and spMI across 3 strata of troponin elevation (>1-5×, >5-35×, and >35× URL), with CCS patients having post-PCI troponin ≤1× URL as a reference group. Conventional troponin I was measured using the Architect methodology (Abbott). RESULTS: Among 10,707 patients undergoing PCI from 2012 to 2020, 8,515 patients presented with CCS and 2,192 with spMI. Among CCS patients, 913 (10.7%) had pMI. Troponin peaks >1-5×, >5-35×, and >35× URL were observed in 53%, 41%, and 6% of patients with pMI, and in 24%, 38%, and 37% of patients with spMI, respectively. Mortality at 1 year was higher after pMI (7.7%; adjusted HR: 4.40; 95% CI: 1.59-12.2), and spMI (8.5%; adjusted HR: 7.57; 95% CI: 5.44-10.5) with troponin peak >35× URL compared with no-MI (1.4%). Mortality was also increased after spMI with troponin peak >1-5× or >5-35× URL. CONCLUSIONS: Mortality at 1 year was significantly increased after pMI and spMI with troponin peak >35× URL, whereas for troponin levels ≤35× only spMI had a relevant impact on mortality.

Pathophysiology of Preeclampsia-Induced Vascular Dysfunction and Implications for Subclinical Myocardial Damage and Heart Failure.

Tragically, preeclampsia is a leading cause of pregnancy-related complications and is linked to a heightened risk for morbid and fatal cardiovascular disease (CVD) outcomes. Although the mechanism connecting preeclampsia to CVD risk has yet to be fully elucidated, evidence suggests distinct pathways of early and late preeclampsia with shared CV risk factors but with profound differences in perinatal and postpartum risk to the mother and infant. In early preeclampsia, <34 weeks of gestation, systemic vascular dysfunction contributes to near-term subclinical myocardial damage. Hypertrophy and diastolic abnormalities persist postpartum and contribute to early onset heart failure (HF). This HF risk remains elevated decades later and contributes to premature death. Black women are at the highest risk of preeclampsia and HF. These findings support closer monitoring of women postpartum, especially for those with early and severe preeclampsia to control chronic hypertension and reduce the potentially preventable sequelae of heightened CVD and HF risk.

Geographic Mapping of Gender Disparities in Authorship of Cardiovascular Literature.

BACKGROUND: Women in cardiology experience considerable gender disparities in publications, which hinders their career advancements to higher faculty and senior leadership positions. However, the extent of these disparities across different types of cardiovascular literature is not well understood. OBJECTIVES: We investigated gender differences in authorship across various cardiovascular publications over a decade and examined geographic variations in the representation of women authors. METHODS: All papers published from January 1, 2010, to December 31, 2019, in 4 major cardiovascular journals (Journal of the American College of Cardiology, European Heart Journal, Journal of the American Medical Association Cardiology, and Nature Reviews Cardiology) were reviewed. RESULTS: Of the 18,535 papers with 111,562 authors, 20.6% of the authors were women, and 47.7% of the papers had no women authors. Over 10 years, the proportion of women authors remained low (20.7% in 2010 to 21.4% in 2019), with the lowest proportion in editorial papers (14.8%) and the highest in research papers (21.8%). More women as first (34.6%) and last (47.6%) authors were affiliated with institutions in the United States compared with other countries. The proportion of women middle-order authors was higher on papers with women as first authors (29.4% vs 20.5%) or last authors (30.6% vs 21.3%), compared with papers with men as first or last authors, respectively. CONCLUSIONS: Over the past decade, the proportion of women authors across all article types in major cardiovascular journals remained low. A call to action is needed to promote women in cardiology and provide them with equitable opportunities.

One-Month Versus Three-Month Dual-Antiplatelet Therapy in High Bleeding Risk Patients With Chronic Kidney Disease.

Shortening the duration of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) was shown to be effective and safe in patients at high bleeding risk (HBR). We aimed to investigate the effect of 1 versus 3-month DAPT on outcomes after drug-eluting stent in HBR patients with or without chronic kidney disease (CKD). Data from 3 prospective single-arm studies (XIENCE Short DAPT Program) enrolling HBR patients after successful coronary implantation of cobalt-chromium everolimus-eluting stent (XIENCE, Abbott) were analyzed. Subjects were eligible for DAPT discontinuation at 1 or 3 months if free from ischemic events. The primary end point was all-cause death or any myocardial infarction. The key secondary end point was Bleeding Academic Research Consortium Type 2 to 5 bleeding. Outcomes were assessed from 1 to 12 months after PCI. CKD was defined as baseline creatinine clearance <60 ml/min. Of 3,286 patients, 1,432 (43.6%) had CKD. One-month versus 3-month DAPT was associated with a similar 12-month risk of the primary outcome irrespective of CKD status (CKD: 9.5% vs 10.9%, adjusted hazard ratio 0.86, 95% confidence interval 0.60 to 1.22; no-CKD: 6.6% vs 5.6%, adjusted hazard ratio 1.15, 95% confidence interval 0.77 to 1.73; p interaction 0.299). Bleeding Academic Research Consortium 2 to 5 bleeding rates were numerically but not significantly lower with 1-month versus 3-month DAPT in both CKD (9.9% vs 12%) and no-CKD (6.4% vs 9.0%) patients. In conclusion, in HBR patients, 1-month versus 3-month DAPT was associated with a similar risk of ischemic complications and a trend toward fewer bleeding events at 12 months after PCI, irrespective of CKD status.

Inflammatory risk and clinical outcomes according to polyvascular atherosclerotic disease status in patients undergoing PCI.

BACKGROUND: Individuals suffering from polyvascular atherosclerotic disease (PolyVD) face a higher likelihood of adverse cardiovascular events. Additionally, inflammation, assessed by high-sensitivity C-reactive protein (hsCRP), affects residual risk following percutaneous coronary intervention (PCI). We aimed to explore the interplay between PolyVD and hsCRP in terms of clinical outcomes after PCI. METHODS: Patients undergoing PCI for chronic coronary disease at a tertiary center between January 2012 and February 2020 were included for the current analysis. PolyVD was defined by additional history of cerebrovascular and/or peripheral artery disease. HsCRP levels were defined as elevated when the measured baseline concentration was > 3 mg/L. The primary outcome of interest was major adverse cardiovascular events (MACE), a composite of all-cause mortality, spontaneous MI, or target vessel revascularization. RESULTS: Overall, 10,359 participants were included in the current study, with 17.4% affected by PolyVD and 82.6% included in the non-PolyVD subgroup. Patients with PolyVD had higher hsCRP levels than those without. Among the PolyVD group, a larger proportion (33.6%) exhibited elevated hsCRP compared to the non-PolyVD group (24.7%). Patients with both PolyVD and elevated hsCRP levels had significantly higher adverse event rates than all other subgroups at 1-year follow-up. Furthermore, an independent association between elevated hsCRP and MACE was observed within the PolyVD population, while this was not the case for individuals without PolyVD. CONCLUSION: A residual risk of adverse outcomes after PCI linked to inflammation appears to be present among individuals with PolyVD. This could help define further target populations for anti-inflammatory treatment options.

Antithrombotic Strategies According to Age: Insights from the AUGUSTUS Trial.

OBJECTIVE: We aimed to evaluate the safety and efficacy of antithrombotic strategies by age in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention in AUGUSTUS. METHODS: Patients were stratified into 3 age groups: <65, 65-74, and ≥75 years. Outcomes of interest were major or clinically relevant non-major bleeding, major bleeding, death or rehospitalization, and ischemic events. Treatment effects of apixaban vs. vitamin K antagonist (VKA) and aspirin vs. placebo were assessed across age groups using Cox models. RESULTS: Of 4614 patients, 1267 (27.5%) were <65, 1802 (39.0%) were 65-74, and 1545 (33.5%) were ≥75 years. Apixaban was associated with lower rates of major or clinically relevant non-major bleeding than VKA (<65: HR 0.69 [0.47-1.00]; 65-74: HR 0.57 [0.43-0.75]; ≥75: HR 0.81 [0.63-1.04]). Death or hospitalization occurred less often with apixaban, regardless of age. No differences were observed in rates of ischemic events between apixaban and VKA according to age. Aspirin was associated with higher rates of bleeding than placebo (<65: HR 1.67 [1.15-2.43]; 65-74: HR 2.32 [1.73-3.10]; ≥75: HR 1.69 [1.31-2.19]). Rates of death or rehospitalization and ischemic events were similar among patients receiving aspirin or placebo across age groups. CONCLUSIONS: Apixaban was associated with greater absolute reduction in bleeding than VKA in older age groups, reflecting their higher hemorrhagic risk. Aspirin increased bleeding in all age groups vs. placebo. Our findings support the use of apixaban plus a purinergic receptor P2Y12(P2Y12) inhibitor without aspirin in patients with atrial fibrillation and recent acute coronary syndrome/percutaneous coronary intervention, regardless of age.

IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial.

Inflammation mediated by interleukin-6 (IL-6) is strongly associated with cardiovascular risk. Here we evaluated clazakizumab, a monoclonal antibody targeting the IL-6 ligand, in a phase 2b dose-finding study. Adults with cardiovascular disease and/or diabetes receiving maintenance dialysis with high-sensitivity C-reactive protein (hs-CRP) ≥ 2 mg l-1 at baseline were randomized to receive clazakizumab (2.5 mg, 5 mg or 10 mg, n = 32 per dose group) or placebo (n = 31) every 4 weeks. The primary endpoint was the change from baseline in hs-CRP to week 12, expressed as the geometric mean ratio. Clazakizumab treatment signficantly reduced serum hs-CRP concentrations at week 12 by 86%, 90% and 92% relative to placebo in patients randomized to 2.5 mg, 5 mg or 10 mg clazakizumab, respectively (all P < 0.0001), meeting the primary outcome. With regard to secondary endpoints, clazakizumab treatment reduced serum fibrinogen, amyloid A, secretory phospholipase A2, and lipoprotein(a) concentrations, as well as increased mean serum albumin concentrations at 12 weeks, relative to placebo. The proportion of patients who achieved hs-CRP < 2.0 mg l-1 was 79%, 82% and 79% in the 2.5 mg, 5 mg and 10 mg clazakizumab groups, respectively, compared with 0% of placebo-treated patients. With regard to safety, no cases of sustained grade 3 or 4 thrombocytopenia or neutropenia were observed. Serious infections were seen with similar frequency in the placebo, clazakizumab 2.5 mg and clazakizumab 5 mg groups, but were numerically more frequent in the clazakizumab 10 mg group. The results of this trial indicate that in patients receiving maintenance dialysis, clazakizumab reduced inflammatory biomarkers associated with cardiovascular events. ClinicalTrials.gov registration: NCT05485961 .

Outcomes Following Percutaneous Coronary Intervention in Patients With Multivessel Disease Who Were Recommended for But Declined Coronary Artery Bypass Graft Surgery.

BACKGROUND: Patients may prefer percutaneous coronary intervention (PCI) over coronary artery bypass graft (CABG) surgery, despite heart team recommendations. The outcomes in such patients have not been examined. We sought to examine the results of PCI in patients who were recommended for but declined CABG. METHODS AND RESULTS: Consecutive patients with stable ischemic heart disease and unprotected left main or 3-vessel disease or Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery score >22 who underwent PCI after heart team review between 2013 and 2020 were included. Patients were categorized into 3 groups according to heart team recommendations on the basis of appropriate use criteria: (1) PCI-recommended; (2) CABG-eligible but refused CABG (CABG-refusal); and (3) CABG-ineligible. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. The study included 3687 patients undergoing PCI (PCI-recommended, n=1718 [46.6%]), CABG-refusal (n=1595 [43.3%]), and CABG-ineligible (n=374 [10.1%]). Clinical and procedural risk increased across the 3 groups, with the highest comorbidity burden in CABG-ineligible patients. Composite events within 1 year after PCI occurred in 55 (4.1%), 91 (7.0%), and 41 (14.8%) of patients in the PCI-recommended, CABG-refusal, and CABG-ineligible groups, respectively. After multivariable adjustment, the risk of the primary composite outcome was significantly higher in the CABG-refusal (hazard ratio [HR], 1.67 [95% CI, 1.08-3.56]; P=0.02) and CABG-ineligible patients (HR, 3.26 [95% CI, 1.28-3.65]; P=0.004) groups compared with the reference PCI-recommended group, driven by increased death and stroke. CONCLUSIONS: Cardiovascular event rates after PCI were significantly higher in patients with multivessel disease who declined or were ineligible for CABG. Our findings provide real-world data to inform shared decision-making discussions.

Impact of Polyvascular Disease in Patients Undergoing Unprotected Left Main Percutaneous Coronary Intervention.

Percutaneous coronary intervention (PCI) has demonstrated its safety and efficacy in treating left main (LM) coronary artery disease (CAD) in select patients. Polyvascular disease (PolyVD) is associated with adverse events in all-comers with CAD. However, there is little data examining the interplay between PolyVD and LM-PCI, which we sought to investigate in a retrospective single-center study. We included patients who underwent unprotected LM-PCI at a tertiary center from 2012 to 2019. The study population was stratified based on the presence or absence of PolyVD (i.e., medical history of cerebrovascular and/or peripheral artery disease in addition to LM-CAD). The primary outcome was major adverse cardiovascular events (MACE) combining all-cause mortality and spontaneous myocardial infarction within 1 year after index PCI. Overall, 869 patients were included, and 23.8% of the population had PolyVD. Subjects with PolyVD were older and had a greater burden of co-morbidities. After 1-year follow-up, PolyVD patients exhibited significantly higher rates of both MACE (22.8% vs 9.4%, p <0.001) and bleeding events compared with those without PolyVD. MACE was primarily driven by an increase in all-cause mortality (18.3% vs 7.1%, p <0.001). Results persisted after adjusting for confounders. In conclusion, in patients who underwent LM-PCI, the presence of PolyVD is linked to an increased risk of MACE and bleeding after 1 year of follow-up, which highlights the vulnerability of this population.

Obicetrapib on top of maximally tolerated lipid-modifying therapies in participants with or at high risk for atherosclerotic cardiovascular disease: rationale and designs of BROADWAY and BROOKLYN.

BACKGROUND: Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events. METHODS AND RESULTS: BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed to examine the efficacy, safety, and tolerability of obicetrapib as an adjunct to dietary intervention and maximally tolerated lipid-modifying therapies in participants with a history of ASCVD and/or underlying HeFH whose LDL-C is not adequately controlled. The primary efficacy endpoint was the percent change in LDL-C from baseline to day 84. Other endpoints included changes in Apo B, non-HDL-C, HDL-C, Apo A1, Lp(a), and triglycerides in addition to parameters evaluating safety, tolerability, and pharmacokinetics. BROADWAY also included an adjudicated assessment of major adverse cardiovascular events, measurements of glucose homeostasis, and an ambulatory blood pressure monitoring substudy. A total of 2,532 participants were randomized in BROADWAY and 354 in BROOKLYN to receive obicetrapib 10 mg or placebo (2:1) for 365 days with follow-up through 35 days after the last dose. Results from both trials are anticipated in 2024. CONCLUSION: These trials will provide safety and efficacy data to support the potential use of obicetrapib among patients with ASCVD or HeFH with elevated LDL-C for whom existing therapies are not sufficiently effective or well-tolerated.