Anticoagulation in the Management of Acute Pulmonary Embolism-A Review.

Venous thromboembolism (VTE) is a very frequent cardiovascular entity that encompasses deep vein thrombosis and pulmonary embolism (PE). This last entity represents a major cause of cardiovascular morbidity and mortality. The incidence of PE and the rate of PE-related morbidity significantly increase with age, race, and underlying medical conditions, such as malignancy. Given the recent advances in diagnostic strategies and algorithms, patients can be risk assessed and treated promptly to avoid disease progression. Anticoagulation is the mainstay of treatment for acute PE that is not hemodynamically unstable. Direct oral anticoagulants, such as apixaban, rivaroxaban, or edoxaban, are currently the preferred agents for the treatment of patients who present with acute PE or for long-term treatment. Treatment duration should be continued for at least 3 months, and all patients should be assessed for extended duration of therapy based on the precipitating factors that led to the development of the VTE. Novel anticoagulant agents targeting factor XI/XIa are currently being investigated in phases 2 and 3 clinical trials, representing an attractive option in anticoagulation therapies in patients with VTE. For hemodynamically unstable patients, systemic thrombolysis is the treatment of choice, and it may also be of benefit-in reduced dose-for patients with intermediate to high risk who are at risk of hemodynamic collapse.

After stent implantation for ACS, ticagrelor monotherapy after <1 mo of DAPT vs. 12 mo of DAPT improved 1-y net clinical benefit.

SOURCE CITATION: Hong SJ, Lee SJ, Suh Y, et al; T-PASS (Ticagrelor Monotherapy in Patients Treated With New-Generation Drug-Eluting Stents for Acute Coronary Syndrome) Investigators. Stopping aspirin within 1 month after stenting for ticagrelor monotherapy in acute coronary syndrome: the T-PASS randomized noninferiority trial. Circulation. 2024;149:562-573. 37878786.

Autoimmune Rheumatic Diseases and Outcomes Following Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.

Autoimmune Rheumatic Diseases (AIRDs) are associated with increased cardiovascular mortality. However, the post-percutaneous coronary intervention (PCI) outcomes in this population present a research gap, given the limited and discordant findings in existing studies. We conducted a systematic review and meta-analysis to assess the relationship between AIRDs and clinical outcomes after PCI; 9 studies with 7,027,270 patients (126,914 with AIRD, 6,900,356 without AIRD) were included. The AIRD cohort was characterized by an older age, a predominantly female demographic, and a greater prevalence of hypertension and diabetes mellitus. Over a mean follow-up period of 4.6 ± 3.5 years, AIRD patients demonstrated significantly higher odds of all-cause mortality (odds ratio (OR) 1.45, 95% CI: 1.25-1.78, P < .001) and major adverse cardiovascular events (MACE) (OR 1.63, 95% CI: 1.01-2.62, P = .04) compared with non-AIRD patients. Sensitivity analysis using adjusted estimates, confirmed the higher all-cause mortality (hazard ratio 1.32, 95% CI: 1.05-1.64, P = .01). Patients with rheumatoid arthritis had a significantly elevated odds of all-cause mortality (OR 1.50, 95% CI: 1.27-1.77) and MACE (OR 1.18, 95% CI: 1.14-1.21). Our study demonstrated an association between AIRDs and suboptimal long-term outcomes post-PCI. Prospective studies are warranted to explore the risk factors of unfavorable prognoses in patients with AIRDs.

Insights Into Differences in Pulmonary Hemodynamics in Hispanic Patients With Pulmonary Arterial Hypertension.

Background: Emerging data suggest that Hispanic patients with pulmonary arterial hypertension (PAH) exhibit improved survival rates compared to individuals of other ethnicities with similar baseline hemodynamics. However, the underlying reasons for this survival advantage remain unclear. This study focused on comparing pulmonary hemodynamics in Hispanic and non-Hispanic PAH patients and how these differences may contribute to varied clinical outcomes. Methods: A retrospective analysis of right heart catheterization data was conducted on a treatment-naive PAH patient cohort from a single center. Results: Over a 10-year period, a total of 226 PAH patients were identified, of which 138 (61%) were Hispanic and 88 (39%) were non-Hispanic. Hispanic patients presented with lower pulmonary artery pressures, lower pulmonary vascular resistance, and exhibited significantly higher pulmonary arterial compliance (PAc). Hispanic patients had better 5-year survival rates. Conclusions: This study highlights the importance of exploring phenotypic differences in ethnically diverse PAH cohorts.

Fluorenyl-tethered N-heterocyclic carbene (NHC): an exclusive C-donor ligand for heteroleptic calcium and strontium chemistry.

Exclusive C-donating ligands are rarely used with kinetically labile heavier alkaline earths (Ca, Sr, Ba). We report herein the aptitude of a combination of NHC with fluorenyl connected by a flexible -(CH2)2- linker as a ligand support for heteroleptic Ca- and Sr-N(SiMe3)2 and iodides. The Ca-N(SiMe3)2 complex even catalyzes the intramolecular hydroamination of aminoalkenes to showcase the effectiveness of this ligand framework.

Gender Differences in the Short and Long-Term Outcomes Following Rotational Atherectomy: A Meta-Analysis.

Rotational atherectomy (RA) is used to address complex calcified coronary lesions but data regarding the association between gender and outcomes of patients who underwent RA remain uncertain. We aimed to investigate the short- and long-term outcomes of patients who underwent RA based on gender. A systematic literature search was performed in PubMed, Embase, and Cochrane databases from its inception until August 2023 for relevant studies. Endpoints were pooled using the DerSimonian and Laird random-effects model as odd ratios (OR) with 95% confidence intervals (CIs). A total of 7 studies with 8,490 patients (2,565 women and 5,925 men) who underwent RA were included in the study. In terms of periprocedural outcomes, women had a higher risk of in-hospital mortality (OR 2.00, 95% CI 1.08 to 3.68, p = 0.03), coronary dissection (OR 1.80, 95% CI 1.05 to 3.10, p = 0.03), coronary perforation (OR 1.96, 95% CI 1.19 to 3.23, p = 0.01), and stroke (OR 4.22, 95% CI 1.06 to 16.82, p = 0.04) than men. There were no significant differences between women and men in terms of major adverse cardiovascular events (OR 1.43, 95% CI 0.69 to 2.94, p = 0.33), myocardial infarction (OR 1.35, 95% CI 0.87 to 2.08, p = 0.18), bleeding (OR 1.71, 95% CI 0.88 to 3.30, p = 0.11), and cardiac tamponade (OR 2.30, 95% CI 0.45 to 11.68, p = 0.32). Over a follow-up period of 3 years, the results of meta-analysis showed that women had a higher risk of all-cause mortality (OR 1.45, 95% CI 1.19 to 1.77, p <0.001), long-term major adverse cardiovascular events (OR 1.38, 95% CI 1.10 to 1.74, p = 0.01), and long-term stroke (OR 3.41, 95% CI 1.63 to 7.17, p <0.001). The risk of long-term myocardial infarction was found to be similar between both genders (OR 1.45, 95% CI 0.95 to 2.22, p = 0.09). In conclusion, female gender is associated with adverse periprocedural and long-term outcome after RA. Women consistently demonstrated higher risk of in-hospital mortality, coronary dissection, coronary perforation, and stroke in the periprocedural period. Long-term follow-up further highlighted a heightened risk for women in terms of all-cause mortality and stroke.

In acute MI and anemia, restrictive vs. liberal transfusion did not differ for a composite of recurrent MI or death at 30 d.

SOURCE CITATION: Carson JL, Brooks MM, Hebert PC, et al; MINT Investigators. Restrictive or liberal transfusion strategy in myocardial infarction and anemia. N Engl J Med. 2023;389:2446-2456. 37952133.

Statins and Venous Thromboembolic Disease - Where are we Now?

Classical risk factors for atherosclerosis also play a role in the pathogenesis of venous thromboembolism (VTE). Low-density lipoprotein cholesterol has prothrombotic and endothelium- deteriorating effects which are not limited to the arterial system. The association between hypercholesterolemia and VTE has been established, but the benefits of statins in the prevention of VTE assessed by observation studies seemed equivocal. The large, randomized trial Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) recorded the occurrence of VTE as a protocol-specified endpoint and reported a reduced incidence of VTE among subjects taking 20 mg of rosuvastatin daily vs placebo (hazard ratio 0.57; 95% confidence interval 0.37-0.86; p=0.007). Similar results were confirmed by meta-analyses of observation studies and randomized trials. Recently, a Mendelian randomization study that took the presence of gene variants coding for less efficient hydroxymethyl-glutaryl coenzyme A reductase activity as a proxy for statin treatment, confirmed a small, but significant negative association between the score of selected genetic polymorphisms and the incidence of VTE. However, since the protective effects of statins are limited, they should not be substituted for guideline-recommended VTE prophylaxis or anticoagulation treatment.

Flexible NHC-aryloxido aluminum complex and its zwitterionic imidazolium aluminate precursor in ring-opening polymerization of ε-caprolactone.

Anionic donor-functionalized NHC (N-heterocyclic carbene) complexes of Al are rare. We report one such case here, an NHC-aryloxido AlMe2 complex [Al(L)Me2] (2), following a stepwise synthesis from the proligand [HO-4,6-tBu2-C6H2-2-CH2{CH(NCHCHNAr)}]Br [LH2Br; Ar = 2,6-iPr2-C6H3 (Dipp)] and AlMe3via the zwitterionic intermediate [Al(LH)Me2Br] (1). The ligand's flexibility in 2 is evident from the conformational fluxionality revealed by VT-1H NMR spectroscopic analysis. The ∠O-Al-C (ca. 100.5°) bite angle is also wider than the ∠O-Ti-C (ca. 80.6°) as seen in our recently reported Ti complex [Ti(L)(NMe2)2Br]. DFT analysis showed that the CNHC-Al bond is significantly ionic, as is the CNHC-Ti bond. Both 1 and 2 are active in the ring-opening polymerization (ROP) of ε-caprolactone (CL). 2, similar to [Ti(L)(NMe2)2Br], exhibits bifunctional MLC-type monomer activation, but only at an elevated temperature. However, the 2/BnOH combination is catalytically active at room temperature, likely through a zwitterionic [Al(LH)Me2(OBn)]. The 1/BnOH combination follows a similar mechanism but surprisingly at a faster rate.

Evaluation of Four Validated Risk Scores to Predict Outcomes in Hispanic Patients With Acute Pulmonary Embolism.

Risk stratification plays an essential role in the management of acute pulmonary embolism (PE). Several risk scores have been studied to support risk stratification and management. While ethnic differences in acute PE risk factors exist, current risk scores lack validation for Hispanic patients. Therefore, the present study retrospectively investigated the performance of the pulmonary embolism severity index (PESI), simplified PESI (sPESI), the European Society of Cardiology risk assessment (ESC), and the Bova score, to predict 30-day mortality in Hispanic patients presenting with an acute PE. Among 437 patients admitted with acute PE, 30-day mortality was 10.8%; 30-day mortality in low-risk groups ranged from 0% (sPESI, ESC) to 0.2% (PESI, Bova), and 3.0% (Bova) to 5.7% (PESI) in the highest risk groups, respectively. All four scores produced statistically significant discrimination between different risk strata. However, no single scoring system was able to identify all patients with 30-day mortality. The findings of the present study suggest that PESI, sPESI, ESC, and Bova scores provide important information about 30-day mortality in Hispanic in-patients presenting with acute PE. However, additional clinical information could further improve predictability that is not provided by a single scoring system.

Reduced-Dose Thrombolysis in Acute Pulmonary Embolism A Systematic Review.

Pulmonary embolism (PE) is the third-leading cause of cardiovascular mortality and the second-leading cause of death in cancer patients. The clinical efficacy of thrombolysis for acute PE has been proven, yet the therapeutic window seems narrow, and the optimal dosing for pharmaceutical reperfusion therapy has not been established. Higher doses of systemic thrombolysis inevitably associated with an incremental increase in major bleeding risk. To date, there is no high-quality evidence regarding dosing and infusion rates of thrombolytic agents to treat acute PE. Most clinical trials have focused on thrombolysis compared with anticoagulation alone, but dose-finding studies are lacking. Evidence is now emerging that lower-dose thrombolytic administered through a peripheral vein is efficacious in accelerating thrombolysis in the central pulmonary artery and preventing acute right heart failure, with reduced risk for major bleeding. The present review will systematically summarize the current evidence of low-dose thrombolysis in acute PE.

Factor XI/XIa inhibitors for the prevention and treatment of venous and arterial thromboembolism: A narrative review.

During the past decade, direct oral anticoagulants (DOACs) have advanced and simplified the prevention and treatment of venous thromboembolism (VTE). However, there remains a high incidence of bleeds, which calls for agents that have a reduced risk of bleeding. Factor XI (FXI) deficiency is associated with lower rates of venous thrombosis and stroke compared to the general population with a lower risk of bleeding. In conjunction with this, phase 2 studies have demonstrated safety and the potential for reduced thrombotic events with FXI inhibitors as compared to currently available medications. The aim of this review is to summarize key data on the clinical pharmacology of FXI, the latest developments in clinical trials of FXI inhibitors, and to describe the efficacy and safety profiles of FXI inhibitors for the prevention of venous and arterial thromboembolism.

2-Anilidomethylpyridine-Derived Three-Coordinate Zinc Hydride: The Journey Unveils Anilide Backbone's Reactive Nature.

Low-coordinate heteroleptic zinc hydrides are catalytically important but rare and synthetically challenging. We herein report three-coordinate monomeric zinc hydride on a 2-anilidomethylpyridine framework (NNL). The synthetic success comes through systematically screening a few different routes from different precursors. During the process, the ligand's anilide backbone interestingly appears to be more reactive than Zn's terminal site to electrophilic Lewis and Brønsted acids. The proligand NNLH reacts with [Zn{N(SiMe3)2}2] and ZnEt2 to give [(NNL)ZnA] (A = N(SiMe3)2 (1), Et(2)). Both are inert to PhSiH3 and H2 but react with HBpin only through the internal Zn-Nanilide bond to give the borylated ligand NNLBpin (3). The reactions of 1 and 2 with Ph3EOH (E = C, Si) afford a series of divergent compounds like [(NNLH)Zn(OSiPh3)2] (4), [Zn3(OSiPh3)4Et2] (5), and [EtZn(OCPh3)] (6). But in all cases, it is invariably the Zn-Nanilide bond protonated by the -OH with equal or higher preference than the terminal Zn-N or Zn-C bonds. A DFT analysis rationalizes the origin of such a reactivity pattern. Realizing that an acid-free route might be the key, reacting [(NNL)Li] with ZnBr2 gives [(NNL)Zn(µ-Br)]2 (7), which on successively treating with KOSiPh3 and PhSiH3 gives the desired [(NNL)ZnH] (8) as a three-coordinate monomer with a terminal Zn-H bond. Estimating the ligand steric in 8 shows the openness in Zn's coordination sphere, a desired criterion for efficient catalysis. This and a positive influence of the pyridyl sidearm is reflected in 8's superior activity in hydroborating PhC(O)Me by HBpin in comparison to Jones' two-coordinate anilido zinc hydride.

Lipoprotein (a) as a Biomarker for Cardiovascular Diseases and Potential New Therapies to Mitigate Risk.

BACKGROUND: Lipoprotein (a) [Lp(a)] is a molecule that induces inflammation of the blood vessels, atherogenesis, valvular calcification, and thrombosis. METHODS: We review the available evidence that suggests that high Lp(a) levels are associated with a persisting risk for atherosclerotic cardiovascular diseases despite optimization of established risk factors, including low-density lipoprotein cholesterol (LDL-C) levels. OBSERVATIONS: Approximately a quarter of the world population have Lp(a) levels of >50 mg/dL (125 nmol/L), a level associated with elevated cardiovascular risk. Lifestyle modification, statins, and ezetimibe do not effectively lower Lp(a) levels, while proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors and niacin only lower Lp(a) levels modestly. We describe clinical studies suggesting that gene silencing therapeutics, such as small interfering RNA (siRNA) and antisense oligonucleotide targeting Lp(a), offer a targeted approach with the potential for safe and robust Lp(a)- lowering with only a few doses (3-4) per year. Prospective randomized phase 3 studies are ongoing to validate safety, effectiveness in improving hard clinical outcomes, and tolerability to assess these therapies. CONCLUSION: Several emerging treatments with robust Lp(a)-lowering effects may significantly lower atherosclerotic cardiovascular risk.