Review of the Ticagrelor Trials Evidence Base.

Ticagrelor is a platelet P2Y12 receptor inhibitor approved for use in patients with acute coronary syndromes, coronary artery disease, and low-moderate risk acute ischemic stroke or high-risk transient ischemic attack. Clinical trials have evaluated the efficacy and safety of ticagrelor on ischemic and bleeding outcomes for different indications and with varying treatment approaches. As a result, there is a large body of clinical evidence demonstrating different degrees of net clinical benefit compared with other platelet inhibitor drugs based on indication, patient characteristics, clinical presentation, treatment duration, and other factors. We provide a review of the major trials of ticagrelor in the context of other randomized trials of clopidogrel and prasugrel to organize the volume of available information, elevate corroborating and conflicting data, and identify potential gaps as areas for further exploration of optimal antiplatelet treatment.

The role of serum lipid in predicting coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease: a cohort study.

OBJECTIVE: To assess the predictive value of the serum lipid profile for initial intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: This retrospective cohort study enrolled patients with KD and divided them into IVIG-responsive and IVIG-resistant groups. They were also stratified based on the presence of CALs (CALs and non-CALs groups). Clinical, echocardiographic and biochemical values were evaluated. A subgroup analysis was performed on complete and incomplete KD. Predictors of initial IVIG resistance and CALs were determined by multivariate logistic regression analysis. RESULTS: A total of 649 KD patients were enrolled: 151 had CALs and 76 had initial IVIG resistance. Low-density lipoprotein cholesterol (LDL-C) was significantly lower in the IVIG-resistant group than in the IVIG-responsive group. LDL-C and apolipoprotein (Apo) B were significantly lower in the CALs group compared with the non-CALs group. Multivariate logistic regression failed to identify the serum lipid profile (LDL-C, Apo A or Apo B) as an independent risk factor for initial IVIG resistance or CALs in KD patients. CONCLUSION: KD patients might have dyslipidaemia in the acute phase, but the serum lipid profile might not be suitable as a single predictor for initial IVIG resistance or CALs.

[Effect of statins on severity of coronary artery lesion and clinical prognosis in patients with coronary heart disease].

OBJECTIVE: To investigate the effect of statins on the severity of coronary artery lesion in patients with coronary heart disease, and to analyze the risk factors of clinical prognosis. METHODS: A retrospective cohort study was conducted. The clinical data of 156 patients with coronary heart disease and completed the second re-examination of coronary CT angiography (CCTA) who were admitted to the department of cardiovascular medicine of Peking University People's Hospital from January 2017 to December 2021 were collected. According to whether they took statins regularly according to the doctor's instructions after being diagnosed with coronary heart disease based on the first CCTA examination, the patients were divided into statin group and non-statin group, and the clinical characteristics of the two groups and the results of the second re-examination of CCTA were compared and analyzed. According to whether the patients had major adverse cardiovascular and cerebrovascular events (MACCE) within 3-5 years after diagnosis of coronary heart disease, the patients were divided into MACCE group and non-MACCE group, and the clinical characteristics of the two groups were compared and analyzed. Multivariate Logistic regression analysis was used to screen the risk factors related to the adverse prognosis (occurrence of MACCE) of patients with coronary heart disease. RESULTS: (1) A total of 156 patients with coronary heart disease were enrolled, including 113 patients (72.44%) in the statin group and 43 patients (27.56%) in the non-statin group. Except for low density lipoprotein (LDL) and serum creatinine (SCr), there was no significant difference in gender, age, body mass index (BMI), basic diseases, smoking history, the first CCTA display of coronary artery lesions and plaque characteristics, the interval between the two CCTA and other laboratory indicators between the two groups. Compared with the non-statin group, the statin group had a significant reduction in the overall increase rate of coronary artery stenosis score (Gensini score) in the CCTA re-examination and the incidence of MACCE [Gensini score increase rate: 25.66% (29/113) vs. 46.51% (20/43), incidence of MACCE: 9.73% (11/113) vs. 30.23% (13/43), both P < 0.05]. (2) Among 156 patients with coronary heart disease, 24 cases (15.38%) experienced MACCE within 3-5 years after diagnosis, while 132 cases (84.62%) did not experience MACCE. The proportion of patients in the MACCE group who regularly took statins after diagnosis was significantly lower than that in the non-MACCE group [45.83% (11/24) vs. 77.27% (102/132), P < 0.01], and D-dimer and glycosylated hemoglobin (HbA1c) were significantly higher than those in the non-MACCE group [D-dimer (µg/L): 148.50 (101.25, 314.75) vs. 88.10 (59.03, 132.12), HbA1c: 6.45% (6.20%, 7.93%) vs. 6.10% (5.81%, 6.92%), both P < 0.05]. Compared with the non-MACCE group, in the first CCTA examination of patients in the MACCE group, the total percentage of atheroma volume (PAV), fibrous-fat PAV, necrotic core PAV and Gensini score were significantly increased [total PAV: 43.05% (29.19%, 60.60%) vs. 24.57% (16.94%, 39.09%), fibrous-fat PAV: 18.61% (8.48%, 26.44%) vs. 6.81% (4.16%, 12.57%), necrotic core PAV: 5.96% (2.98%, 8.71%) vs. 2.29% (1.47%, 4.36%), Gensini score: 30.25 (23.50, 38.30) vs. 19.50 (13.20, 31.10), all P < 0.05]. Multivariate Logistic regression analysis showed that regular use of statins [odds ratio (OR) = 0.282, 95% confidence interval (95%CI) was 0.110-0.727, P = 0.008], D-dimer (OR = 1.011, 95%CI was 1.005-1.017, P < 0.001), necrotic core PAV (OR = 1.323, 95%CI was 1.120-1.563, P = 0.001) and Gensini score (OR = 1.038, 95%CI was 1.004-1.073, P = 0.028) were independent risk factors for MACCE within 3-5 years after diagnosis in patients with coronary heart disease. CONCLUSIONS: For patients with coronary heart disease, D-dimer, necrotic core PAV, and Gensini scores should be closely monitored. Statins can effectively alleviate the severity of coronary artery disease and reduce the occurrence of MACCE in patients with coronary artery disease.

Therapeutic peptides for coronary artery diseases: in silico methods and current perspectives.

Many drug formulations containing small active molecules are used for the treatment of coronary artery disease, which affects a significant part of the world's population. However, the inadequate profile of these molecules in terms of therapeutic efficacy has led to the therapeutic use of protein and peptide-based biomolecules with superior properties, such as target-specific affinity and low immunogenicity, in critical diseases. Protein‒protein interactions, as a consequence of advances in molecular techniques with strategies involving the combined use of in silico methods, have enabled the design of therapeutic peptides to reach an advanced dimension. In particular, with the advantages provided by protein/peptide structural modeling, molecular docking for the study of their interactions, molecular dynamics simulations for their interactions under physiological conditions and machine learning techniques that can work in combination with all these, significant progress has been made in approaches to developing therapeutic peptides that can modulate the development and progression of coronary artery diseases. In this scope, this review discusses in silico methods for the development of peptide therapeutics for the treatment of coronary artery disease and strategies for identifying the molecular mechanisms that can be modulated by these designs and provides a comprehensive perspective for future studies.

Antithrombotic therapy for stable coronary artery disease and atrial fibrillation in patients with and without revascularisation: the AFIRE trial.

BACKGROUND: The Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial demonstrated non-inferior efficacy endpoints for rivaroxaban monotherapy versus combination therapy (rivaroxaban plus a single antiplatelet) and superior safety endpoints in patients with atrial fibrillation and stable coronary artery disease. AIMS: This post hoc analysis investigated whether the AFIRE trial results reflected the presence or absence of prior revascularisation. METHODS: Among 2,215 patients, 1,697 (76.6%) had previously undergone revascularisation, and the remaining 518 (23.4%) had not undergone prior revascularisation. The primary efficacy endpoint was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularisation, or death from any cause, while the primary safety endpoint was major bleeding. RESULTS: In 1,697 patients with prior revascularisation, the efficacy and safety endpoints were superior for monotherapy versus combination therapy (efficacy: hazard ratio [HR] 0.62, 95% confidence interval [CI]: 0.45-0.85; p=0.003; safety: HR 0.62, 95% CI: 0.39-0.98; p=0.042). Among 518 without prior revascularisation, there were no significant differences in endpoints (efficacy: HR 1.19, 95% CI: 0.67-2.12; p=0.554; safety: HR 0.47, 95% CI: 0.18-1.26; p=0.134). There was borderline interaction of the efficacy endpoints (p=0.055) between two treatments. The safety benefit of monotherapy on any bleeding was significant in patients without prior revascularisation (HR 0.59, 95% CI: 0.38-0.93; p=0.022). CONCLUSIONS: In high-risk thrombosis patients with a history of prior revascularisation, rivaroxaban monotherapy versus combination therapy demonstrated favourable safety and efficacy outcomes.

The clinical value of ß-blockers in patients with stable angina.

Stable angina, one manifestation of chronic coronary syndrome (CCS), is characterised by intermittent episodes of insufficient blood supply to the myocardium, provoking symptoms of myocardial ischaemia, particularly chest pain. These attacks usually occur during exercise or stress. Anti-ischaemic drugs are the mainstay of pharmacologic management of CCS with symptoms of angina. ß-blockers reduce heart rate and myocardial contractility, thus reducing myocardial oxygen consumption. These drugs have been shown to ameliorate the frequency of anginal attacks and to improve exercise capacity in these patients. Current management guidelines include ß-blockers as a first-line management option for most patients with CCS and symptoms of myocardial ischaemia, alongside dihydropyridine calcium channel blockers (CCB). The presence of comorbid angina and heart failure is a strong indication for starting with a ß-blocker. ß-blockers are also useful in the management of angina symptoms accompanied by a high heart rate, hypertension (with or without a renin-angiotensin-aldosterone-system [RAS] blocker or CCB), or microvascular angina (with a RAS blocker and a statin). A ß-blocker is not suitable for a patient with low heart rate (<50 bpm), although use of a ß-blocker may be supported by a pacemaker if the ß-blocker is strongly indicated) and should be used at a low dose only in patients with low blood pressure.

The role of hydrogen in the prevention and treatment of coronary atherosclerotic heart disease.

Coronary atherosclerotic heart disease (CHD) is a primary cardiovascular disease caused by atherosclerosis (AS), which is characterized by chronic inflammation and lipid oxidative deposition. Molecular hydrogen (H2) is an effective anti-inflammatory agent and has potential to ameliorate glycolipid metabolism disorders, which is believed to exert beneficial effects on the prevention and treatment of CHD. It is suggested that H2 reduces inflammation in CHD by regulating multiple pathways, including NF-κB inflammatory pathway, pyroptosis, mitophagy, endoplasmic reticulum (ER) stress, and Nrf2 antioxidant pathway. Additionally, H2 may improve glycolipid metabolism by mediation of PI3K and AMPK signalling pathways, contributing to inhibition of the occurrence and development of CHD. This review elaborates pathogenesis of CHD and evaluates the role of H2 in CHD. Moreover, possible molecular mechanisms have been discussed and speculated, aiming to provide more strategies and directions for subsequent studies of H2 in CHD.

Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction.

BACKGROUND: Cardiovascular events frequently recur after acute myocardial infarction, and low cholesterol efflux - a process mediated by apolipoprotein A1, which is the main protein in high-density lipoprotein - has been associated with an increased risk of cardiovascular events. CSL112 is human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity. Whether infusions of CSL112 can reduce the risk of recurrent cardiovascular events after acute myocardial infarction is unclear. METHODS: We conducted an international, double-blind, placebo-controlled trial involving patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors. Patients were randomly assigned to receive either four weekly infusions of 6 g of CSL112 or matching placebo, with the first infusion administered within 5 days after the first medical contact for the acute myocardial infarction. The primary end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes from randomization through 90 days of follow-up. RESULTS: A total of 18,219 patients were included in the trial (9112 in the CSL112 group and 9107 in the placebo group). There was no significant difference between the groups in the risk of a primary end-point event at 90 days of follow-up (439 patients [4.8%] in the CSL112 group vs. 472 patients [5.2%] in the placebo group; hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.05; P = 0.24), at 180 days of follow-up (622 patients [6.9%] vs. 683 patients [7.6%]; hazard ratio, 0.91; 95% CI, 0.81 to 1.01), or at 365 days of follow-up (885 patients [9.8%] vs. 944 patients [10.5%]; hazard ratio, 0.93; 95% CI, 0.85 to 1.02). The percentage of patients with adverse events was similar in the two groups; a higher number of hypersensitivity events was reported in the CSL112 group. CONCLUSIONS: Among patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors, four weekly infusions of CSL112 did not result in a lower risk of myocardial infarction, stroke, or death from cardiovascular causes than placebo through 90 days. (Funded by CSL Behring; AEGIS-II ClinicalTrials.gov number, NCT03473223.).

Colchicine for the Prevention of Cardiovascular Disease: Potential Global Implementation.

PURPOSE OF REVIEW: Targeting traditional cardiovascular risk factors is effective in reducing recurrent cardiovascular events, yet the presence of residual cardiovascular risk due to underlying systemic inflammation is a largely unaddressed opportunity. This review aims to comprehensively assess the evolving role of colchicine as a therapeutic approach targeting residual inflammatory risk in the context of those with coronary artery disease (CAD). RECENT FINDINGS: Inflammation plays a significant role in promoting atherosclerosis, and targeting anti-inflammatory pathways has the potential to decrease cardiovascular events. Low-dose colchicine (0.5 mg/day orally), when added to guideline-directed medical care for CAD, safely decreases major adverse cardiovascular events (MACE) by 31% in stable atherosclerosis patients and 23% in those after recent myocardial infarctions. Meta-analyses of recent randomized control trials further support both the efficacy and safety of colchicine, particularly when added to other standard cardiovascular therapies, including statin therapy. The European Society of Cardiology and other national guidelines endorse the use of low-dose colchicine in patients across the spectrum of CAD. Recently, colchicine was FDA-approved in the United States as the first anti-inflammatory therapy for the reduction of cardiovascular events. In a period of a rising incidence of CAD across the globe, colchicine represents a unique opportunity to decrease MACE due to its large magnitude of benefits and general affordability. However, challenges with drug interactions must be addressed, especially in those regions where HIV, hepatitis, and tuberculosis are prevalent. Colchicine is safe and effective at reducing cardiovascular events across a broad spectrum of coronary syndromes. The ability to simultaneously target traditional risk factors and mitigate residual inflammatory risk marks a substantial advancement in cardiovascular prevention strategies, heralding a new era in the global battle against CAD.

Association between metformin treatment and coronary artery inflammation based on pericoronary adipose tissue attenuation in type 2 diabetes mellitus patients.

Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients. The role of metformin in reducing cardiovascular events is well-established, but its effect on coronary artery inflammation in T2DM patients is still unclear. In this study, we evaluated 547 T2DM patients who underwent coronary computed tomography angiography (CCTA) at Wuhan Central Hospital. Using propensity score matching, we compared the attenuation of pericoronary adipose tissue (PCAT), an imaging marker of coronary artery inflammation, between patients treated with and without metformin. Multiple linear regression models were used to analyze the influence of metformin on PCAT attenuation. The results of the propensity-matched analysis showed that patients on metformin therapy had significantly lower PCAT attenuation, indicating reduced coronary inflammation. Specifically, the PCAT attenuation in the left anterior descending artery (LAD) and right coronary artery (RCA) was lower in the metformin group compared to the non-metformin group. Metformin use was independently associated with decreased LAD-PCAT attenuation in the multivariate regression analysis. The association of metformin with PCAT attenuation differed significantly in populations analyzed in subgroups of patients with obesity and chronic kidney disease. In conclusion, our study shows a preliminary signal that metformin therapy may be associated with decreased coronary artery inflammation in T2DM patients, as indicated by PCAT attenuation on CCTA. And this correlation may vary depending on the patient population. This initial finding suggests that PCAT attenuation could be potentially used as an imaging biomarker to monitor the anti-inflammatory effects of medication.

Meta-Analysis of Randomized Trials: Efficacy and Safety of Colchicine for Secondary Prevention of Cardiovascular Disease.

Background: Colchicine has shown potential cardioprotective effects owing to its broad anti-inflammatory properties. We performed a meta-analysis to assess its safety and efficacy in secondary prevention in patients with established coronary artery disease (CAD). Methods: We searched Ovid Healthstar, MEDLINE, and Embase (inception to May 2022) for randomized controlled trials (RCTs) evaluating the cardiovascular effects of colchicine compared with placebo or usual care in patients with CAD. Study-level data on efficacy and safety outcomes were pooled using the Peto method. The primary outcome was the composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke. Results: A total of 8 RCTs were included with a follow-up duration of ≥1 month, comprising a total of 12,151 patients. Compared with placebo or usual care, colchicine was associated with a significant risk reduction in the primary outcome (odds ratio (OR) 0.70, 95% CI 0.60 to 0.83, P < 0.0001; I2 = 52%). Risks of MI (OR 0.75, 95% CI 0.62 to 0.91, P = 0.003; I2 = 33%), stroke (OR 0.47, 95% CI 0.30 to 0.74, P = 0.001; I2 = 0%), and unplanned coronary revascularization (OR 0.67, 95% CI 0.55 to 0.82, P = 0.0001; I2 = 58%) were all reduced in the colchicine group. Rates of CV and all-cause mortality did not differ between the two groups, but there was an increase in noncardiac deaths with colchicine (OR 1.54, 95% CI 1.10 to 2.15, P = 0.01; I2 = 51%). The occurrence of all other adverse events was similar between the two groups, including GI reactions (OR 1.06, 95% CI 0.94 to 1.20, P = 0.35; I2 = 42%) and infections (OR 1.04, 95% CI 0.84 to 1.28, P = 0.74; I2 = 53%). Conclusions: Colchicine therapy may reduce the risk of future cardiovascular events in patients with established CAD; however, there remains a concern about non-CV mortality. Further trials are underway that will shed light on non-CV mortality and colchicine NCT03048825, and NCT02898610.

Levels of adherence to treatment, illness perception and acceptance of illness in patients with coronary artery disease - descriptive and correlational study.

BACKGROUND: Understanding the disease and its acceptance significantly influence adherence to prescribed medications, a critical aspect in managing coronary artery disease (CAD). This study is designed to explore the multifaceted factors influencing medication adherence specifically in CAD patients. Of particular interest is investigating the interconnectedness between medication adherence, the perception of illness, and the level of acceptance of the illness itself among these individuals. METHODS: This cross-sectional study involved 280 confirmed CAD patients who were selected through a convenience sampling method adhering to predefined inclusion criteria. The study was conducted between March and September 2023. Three primary parameters-medication adherence, illness perception, and acceptance of illness-were evaluated using standardized tools: The Morisky Medication Adherence Scale-8, Illness Perception Questionnaire-Brief, and Acceptance of Illness Scale. Statistical analyses using SPSS (version 25) were used to analyze the data. RESULTS: Patients had moderate illness perception (51.82 ± 7.58) and low acceptance to illness (16.98 ± 4.75), and 61.8 of them adhered to their medication regimen. A positive relationship between acceptance of illness and medication adherence (r = 0.435, p-value < 0.01) was found. Level of education, type of drug and marital status had significantly impact on medication adherence, and gender, level of education, intention to stop drug and marital status were associated with acceptance of illness (p < 0.05). CONCLUSION: These results underscore the pivotal role of medication adherence in CAD management. Future interventions should target improving illness perception and acceptance of illness among CAD patients to enhance their overall adherence to prescribed medications and ultimately improve disease management.

Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI randomized clinical trial substudy.

BACKGROUND AND AIMS: The effects of protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on endothelial function as assessed by flow-mediated dilation (FMD) in patients with acute myocardial infarction (AMI) are unknown. Therefore, we aimed to investigate the effects of the PCSK9 inhibitor alirocumab added to high-intensity statin on FMD, and its association with coronary atherosclerosis in non-infarct related arteries using intracoronary intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT). METHODS: This was a pre-specified substudy among patients recruited at Bern University Hospital, Switzerland, for the randomized-controlled, double-blind, PACMAN-AMI trial, which compared the effects of biweekly alirocumab 150 mg vs. placebo added to rosuvastatin. Brachial artery FMD was measured at 4 and 52 weeks, and intracoronary imaging at baseline and 52 weeks. RESULTS: 139/173 patients completed the substudy. There was no difference in FMD at 52 weeks in the alirocumab (n = 68, 5.44 ± 2.24%) versus placebo (n = 71, 5.45 ± 2.19%) group (difference = -0.21%, 95% CI -0.77 to 0.35, p = 0.47). FMD improved throughout 52 weeks in both groups similarly (p < 0.001). There was a significant association between 4 weeks FMD and baseline plaque burden (IVUS) (n = 139, slope = -1.00, p = 0.006), but not with lipid pool (NIRS) (n = 139, slope = -7.36, p = 0.32), or fibrous cap thickness (OCT) (n = 81, slope = -1.57, p = 0.62). CONCLUSIONS: Among patients with AMI, the addition of alirocumab did not result in further improvement of FMD as compared to 52 weeks secondary preventative medical therapy including high-intensity statin therapy. FMD was significantly associated with coronary plaque burden at baseline, but not with lipid pool or fibrous cap thickness.

Rationale for the Inclusion of ß-Blockers Among Major Antihypertensive Drugs in the 2023 European Society of Hypertension Guidelines.

We address the reasons why, unlike other guidelines, in the 2023 guidelines of the European Society of Hypertension ß-blockers (BBs) have been regarded as major drugs for the treatment of hypertension, at the same level as diuretics, calcium channel blockers, and blockers of the renin-angiotensin system. We argue that BBs, (1) reduce blood pressure (the main factor responsible for treatment-related protection) not less than other drugs, (2) reduce pooled cardiovascular outcomes and mortality in placebo-controlled trials, in which there has also been a sizeable reduction of all major cause-specific cardiovascular outcomes, (3) have been associated with a lower global cardiovascular protection in 2 but not in several other comparison trials, in which the protective effect of BBs versus the other major drugs has been similar or even greater, with a slightly smaller or no difference of global benefit in large trial meta-analyses and a similar protective effect when comparisons extend to BBs in combination versus other drug combinations. We mention the large number of cardiac and other comorbidities for which BBs are elective drugs, and we express criticism against the exclusion of BBs because of their lower protective effect against stroke in comparison trials, because, for still uncertain reasons, differences in protection against cause-specific events (stroke, heart failure, and coronary disease) have been reported for other major drugs. These partial data cannot replace global benefits as the main deciding factor for drug choice, also because in the general hypertensive population whether and which type of event might occur is unknown.

Assessment of Aspirin and Clopidogrel Resistance in Patients Undergoing Cardiovascular Surgery: A Single-Center Cross-Sectional Study

Objective: We aimed to investigate antiplatelet drug resistance utilizing light transmission-lumiaggregometry (LT-LA) and the Platelet Function Analyzer-100 (PFA-100) in patients undergoing cardiovascular surgery. Materials and Methods: The study included 60 patients diagnosed with stable coronary artery disease and peripheral vascular diseases that required surgery. Participants were divided into three groups: patients receiving aspirin (ASA) (n=21), patients receiving clopidogrel (CLO) (n=19), and patients receiving dual therapy (ASA+CLO) (n=20). Aggregation and secretion tests by LT-LA and closure time by the PFA-100 were used to measure antiplatelet drug resistance. Results: Based on the adenosine diphosphate (ADP)-induced aggregation test, 43% of patients were resistant to ASA, 22% to CLO, and 15% to dual therapy. Diabetes, hypertension, and hyperlipidemia were the most commonly identified comorbid disorders. In patients with comorbid risk factors, the median value of platelet aggregation response to ADP was significantly higher in the ASA group than in the CLO and dual therapy groups (p=0.0001). In patients receiving ASA monotherapy, the maximum amplitude of aggregation response to platelet agonists was ≥70% in 43% of patients for ADP and 28% for collagen by LT-LA. Elevated ADP (≥0.29 nmol) and collagen (≥0.41 nmol)-induced adenosine triphosphate release were found by LT-LA in 66% of patients utilizing an ADP agonist and 80% of patients using a collagen agonist undergoing ASA therapy. Closure times obtained with the PFA-100 were normal in 28% of patients using collagen-ADP cartridges and 62% of patients using collagen-epinephrine (CEPI) cartridges who received ASA. Recurrent thrombosis and bleeding were observed in 12 (20%) patients with cardiovascular disease. Three of these individuals (25%) showed ASA resistance with normal responses to ADP-induced aggregation (≥70%) and secretion (≥0.29 nmol), as well as normal CEPI closure times. Conclusion: Our findings suggest that antiplatelet drug monitoring by LT-LA and PFA-100 may be useful for high-risk and complicated cardiovascular patients.

Role of interleukin 6 signaling pathway in the anti-inflammatory effects of statins on coronary artery disease: Evidence from Mendelian randomization analysis.

BACKGROUND: Statins are currently widely used in the prevention of coronary artery disease (CAD) primarily for lipid-lowering with a potential anti-inflammatory effect. However, it is not clear if their potential anti-inflammatory effects are mediated through the interleukin 6 (IL-6) signaling pathway. METHODS: Using the Mendelian randomization (MR) approach followed by multivariable MR analyses, we examined the extent to which the effects of statins on CAD might be mediated through the IL-6 signaling pathway. RESULTS: Our observations showed that HMG-CoA reductase, using LDL levels as a proxy, had a significant effect on upstream IL-6 (ßMR = 0.47, P-IVW = 0.01) and nominally significant effects on IL-6RA (ßMR = 0.22, P-IVW = 0.047) and APOB (ßMR = 0.82, P-IVW = 1.8 × 10-33). While the IL-6 signaling cascade (IL-6RA ßMR = -0.06, P-IVW = 3.45 × 10-20 and IL-6 ßMR = -0.03, P-IVW = 0.09) and the anti-inflammatory effect of HMG-CoA reductase (ßMR = -0.31, P-IVW = 0.01) was found to influence the risk of CAD, the multivariable MR (MVMR) model indicated that the anti-inflammatory effect of HMG-CoA reductase is not likely to be mediated through the IL-6 signaling cascade, including APOB and IL-6RA (MVMRß = 0.23, P = 0.688). CONCLUSIONS: Our findings suggest that statins may use inflammatory mechanisms independent of the IL-6 signaling pathway to prevent CAD. This result could potentially affect the definition of the target population for statin use.