Combined Antithrombotic Therapy Research Articles

GDF-15 and the risk of bleeding in patients with stable CAD receiving multicomponent antithrombotic therapy: the results of the prospective REGATA register

To evaluate the prognostic value of GDF-15 in relation the development of bleeding and events in stable CAD patients, receiving combined antithrombotic therapy. The data was obtained from the prospective registry REGATA, 343 CAD patients (249 males), median age 68 [IQR 62; 75] years) were enrolled. Patients with sinus rhythm and concomitant PAD received acetylsalicylic acid in combination with rivaroxaban 2.5 mg bid (31.8%) or clopidogrel (24.8%). Other 43.4% with concomitant atrial fibrillation (AF) received direct oral anticoagulants in combination with antiplatelet therapy after elective percutaneous coronary interventions. Median follow-up was 12 months [IQR 9.0; 18.0]. The safety end point was major and clinically relevant bleedings (type 2-5) according to the BARC classification. Plasma samples for GDF-15 identification were taken at the inclusion and analyzed using ELISA assay. Frequency of BARC 2-5 bleedings was 16% (BARC 2 - 46; BARC 3 - 9; BARC 4-5 - 0), median GDF-15 level was 1185.0 pg/ml [850.0; 1680.0]. In patients with AF and concomitant MFA, the level of GDF-15 was significantly higher than in the subgroups of patients with only AF or MFA (p=0.0022). According to the quintile analysis, GDF-15 values in the top three quintiles of distribution (cut-off value >943 pg/ml) were associated with higher frequency of bleeding events: 23.2% versus 5.1%; p=0.0001. The multivariable logistic regression model demonstrated that bleeding events were independently associated with GDF-15 level>943 pg/ml (OR 2.65, 95% CI 1.11-6.30; p=0.0275), AF (OR 2.61, 95% CI 1.41-4.83; p=0.0023) and chronic kidney disease (OR 1.92, 95% CI 1.03-3.60; p=0.0401). Clinical factors determining the risk of bleeding events also determined a GDF-15 elevation. Assessment of GDF-15 level may improve bleeding risk stratification in CAD patients with concomitant AF and/or PAD receiving combined antithrombotic therapy.

Efficacy and safety of drugs in residual cardiovascular risk: A systematic review of the literature

BackgroundThe objective of this research is to evaluate the efficacy and safety of drugs in the residual risk in any of its three components: lipid, inflammatory and thrombotic risk. MethodsA systematic review was conducted of randomized clinical trials that included as a primary outcome, at least one of the conditions related to atherosclerotic cardiovascular disease. The databases used were PUBMED/MEDLINE, Scopus and ClinicalTrials.gov. The risk of bias of the studies was assessed using the Risk of Bias 2 tool. Resultsand discussion: 18 studies were included in the analysis. Half of the studies had low risk of bias or some concerns. Several drugs were effective in reducing the primary outcome: ethyl eicosapentaenoeic acid (17.2 % E-EPA versus 22 % placebo HR: 0.75; 95 % CI 0.68–0.83; p < 0.001), colchicine in stable coronary artery disease (6.8 % vs placebo 9.6 %, HR 0.59, 95 % CI 0.57–0.83; p < 0.001), Canakinumab (150 mg vs placebo ARR 15 %, HR 0.85, 95 % CI 0.74–0.98; p = 0.021) and Rivaroxaban with Aspirin in stable atherosclerotic disease (4.1 % versus aspirin 5.4 %, HR 0.76, 95 % CI 0.66–0.86, P < 0.001). Serious adverse events did not differ between study groups, except for a higher rate of bleeding with the use of combination antithrombotic therapy. ConclusionThe residual risk can be reduced through the use of different drugs that act by modifying atherogenic lipid levels, modulating inflammatory pathways and the risk of thrombosis, with an acceptable safety profile in most studies.

Omission of Antiplatelet Therapy in Patients With HeartMate 3 Left Ventricular Assist Devices: A Systematic Review and Meta-Analysis.

The HeartMate 3 (HM3) left ventricular assist device has decreased thromboembolic events and minimized the risk of pump thrombosis. However, bleeding complications due to combined antithrombotic therapy with a vitamin K antagonist (VKA) and aspirin remain high. Only limited data on the safety of VKA monotherapy in HM3 patients are available. A systematic search on the main databases was performed. Observational data and randomized trials were eligible for this analysis. As primary endpoint, we analyzed hemocompatibility-related adverse events (HRAE). As secondary endpoints, we investigated the individual components of the primary endpoint. The analysis was carried out using the odds ratio (OR) as outcome measure. A random-effects model was fitted to the data. Five manuscripts fulfilled the inclusion criteria. These trials included 785 patients (381 on VKA monotherapy, 404 on VKA and aspirin). VKA monotherapy significantly reduced HRAE (OR: 0.11 [95% confidence interval {CI}: 0.02-0.59], p = 0.01, I2 = 87%). The reduction was driven by a decrease in bleeding complications (OR: 0.12 [95% CI: 0.02-0.62], p = 0.01, I2 = 86%) without increasing the rates of thromboembolic events (OR: 0.69 [95% CI: 0.26-1.81], p = 0.45, I = 0%). Vitamin K antagonist monotherapy is associated with a significant reduction of bleeding events without increasing the risk of thromboembolic complications in HM3 patients.

A pilot study to evaluate the quality of care in oral anticoagulant and antiplatelet use in patients with permanent atrial fibrillation in Irish general practice

Abstract Aim: The aim of this pilot study is to determine the pattern of oral anticoagulant and antiplatelet use in patients with permanent atrial fibrillation (AF) in Irish general practice. Background: Worldwide, AF is the most common sustained cardiac arrhythmia in adults and poses a significant burden to patients, physicians and healthcare systems. There is a five-fold increased risk of stroke with AF, and AF-related strokes are associated with higher levels of both morbidity and mortality compared to other stroke subtypes. Thankfully, appropriate use of oral anticoagulation (OAC) for AF can reduce the risk of stroke by up to 64%. However, we know that patients are commonly undertreated with OAC, prescribed inappropriate doses of OAC and have prolonged use of an antiplatelet agent in addition to OAC without indication. Methods: A descriptive, cross-sectional observational study was undertaken. Proportionate sampling was used across 11 practices from the Ireland East practice-based research network. The general practitioners completed a report form on each patient provided by the research team by undertaking a retrospective chart review. Findings: Eleven practices participated with a total number of 1855 patients with AF. We received data on 153 patients. The main findings from this pilot project are that: 1. 11% of patients were undertreated with OAC 2. 20 % of patients were on an incorrect non-vitamin K antagonist oral anticoagulant dose 3. 28 patients (18%) were inappropriately prescribed combination antithrombotic therapy Undertreatment and underdosing of OAC expose patients to higher risk of thromboembolic events, bleeding and all-cause mortality. Prolonged combination antithrombotic therapy is associated with serious increased risk of bleeding with no additional stroke protection. This pilot project highlights several gaps between guidelines and clinical practice. By identifying these areas, we hope to develop a targeted quality improvement intervention using the electronic health records in general practice to improve the care that those with AF receive.

Efficacy of Treatment with and without Initial Clopidogrel Loading in Branch Atheromatous Disease.

Objective Despite aggressive therapeutic interventions during the acute phase of branch atheromatous disease (BAD)-type cerebral infarction, many patients, even those with a mild condition at the onset, experience neurological deterioration after hospitalization and develop serious deficits. We compared the therapeutic efficacy of multiple antithrombotic therapies for BAD between patients who received a clopidogrel loading dose (loading group; LG) and those without loading (non-loading group; NLG). Patients Between January 2019 and May 2022, patients with BAD-type cerebral infarction in the lenticulostriate artery admitted within 24 h of the onset were recruited. This study included 95 consecutive patients who received combination argatroban and dual antiplatelet therapy (aspirin and clopidogrel). Methods Patients were classified into the LG and NLG according to whether or not a loading dose of clopidogrel (300 mg) had been administered on admission. Changes in neurological severity [National Institutes of Health Stroke Scale (NIHSS) score] during the acute phase were retrospectively evaluated. Results There were 34 (36%) and 61 (64%) patients in the LG and NLG, respectively. On admission, the median NIHSS score was similar between the groups [LG: 2.5 (2-4) vs. NLG: 3 (2-4), p=0.771]. At 48 h following admission, the median NIHSS scores were 1 (0.25-4), and 2 (1-5) in the LG and NLG, respectively (p=0.045). Early neurological deterioration (END; defined as worsening of the NIHSS score by ≥4 points at 48 h after admission) occurred in 3% of LG and 20% of NLG patients (p=0.028). Conclusion Administration of a clopidogrel loading dose with combination antithrombotic therapy for BAD reduced END.

Pharmacokinetic and Pharmacogenetic Predictors of Major Bleeding Events in Patients with an Acute Coronary Syndrome and Atrial Fibrillation Receiving Combined Antithrombotic Therapy.

Objective: This study's objective was to evaluate the effects of pharmacokinetic and pharmacogenetic factors on major bleeding in patients with ACS and non-valvular AF receiving combined antithrombotic therapy consisting of rivaroxaban, clopidogrel, and aspirin as part of dual or triple therapy. Methods: A prospective observational study was conducted in two PCI centers in Moscow, the Russian Federation, from 2017 to 2018. One hundred patients with ACS and AF were enrolled. Prospective follow-ups continued for 12 months. Results: A total of 36 patients experienced bleeding events, with 10 experiencing major bleeding based on the BARC scale and 17 experiencing major bleeding based on the ISTH scale. The following predictors associated with an increased number of major bleeding events were identified: for the ISTH scale, a Css min. of rivaroxaban of >137 pg/mL (5.94 OR, (95% CI, 3.13-12.99; p < 0.004)) and carriage of the T allelic variant polymorphism ABCB1 rs4148738 (8.97 OR (95% CI, 1.48-14.49; p < 0.017)), as well as for the BARC scale (5.76 OR (95% CI, 2.36-9.87; p < 0.018)). Conclusions: Measuring residual steady-state rivaroxaban concentrations and determining the carriage of the T allelic variant polymorphism ABCB1 rs4148738 may be applicable to high-risk patients for subsequent antithrombotic therapy modification.

Experiences of Patients With Atrial Fibrillation With Combination Antithrombotic Therapy Post–Percutaneous Coronary Intervention

BackgroundUp to 30% of patients with atrial fibrillation (AF) have coronary artery disease, and many undergo percutaneous coronary intervention (PCI). In the setting of acute coronary syndrome with PCI, or high-risk elective PCI, Canadian AF guidelines recommend 1-30 days of acetylsalicylic acid, 1-12 months of clopidogrel, and oral anticoagulation (OAC) with doses that may change throughout the 12 months post-PCI. The complexity of these regimens may contribute to unplanned modifications (UPMs), increasing the risk of thrombosis and/or bleeding. We describe what happens to these patients and their antithrombotic therapy (ATT) after discharge. MethodsProspective follow-up was conducted of patients with AF requiring OAC who underwent PCI and were discharged on combination ATT. Patients were contacted at 1, 3, 6, and 12 months post-PCI. ResultsSixty-five patients were enrolled, with data at any time point available for 61 of them (94%). Of these, 44 (68%) experienced at least one UPM to ATT. In total, 105 UPMs occurred. The most common UPM was an extended duration of P2Y12 inhibitor (23 instances; 22%). The most common UPM with acetylsalicylic acid was extended (11 instances; 11%) or shortened (11 instances; 11%) duration. Thirty-nine UPMs (37%) were related to OACs; 9 (23%) were related to warfarin, and 30 (77%) were related to direct OACs. Of all patients with at least one UPM, 33 (75%) experienced bleeding. ConclusionsMore than 2 in 3 patients with AF undergoing PCI experienced a UPM to their ATT. This study underscores the challenges of combination ATT for patients and clinicians alike, emphasizing the need for patient support after discharge.

Implementation of a Patient Questionnaire in Community Pharmacies to Improve Care for Patients Using Combined Antithrombotic Therapy: A Qualitative Study.

For several indications or combinations of indications the use of more than one antithrombotic agent is required. The duration of combined antithrombotic therapy depends on indication and patient characteristics. This study investigated the use of an antithrombotic questionnaire tool that had been developed for pharmacists to detect patients with possible incorrect combined antithrombotic therapy. The objective of this study was to identify potential barriers and facilitators that could influence the implementation of the developed antithrombotic questionnaire tool in daily community pharmacy practice. A qualitative study was conducted at 10 Dutch community pharmacies in which the antithrombotic questionnaire tool had been used with 82 patients. Semi-structured interviews were conducted with pharmacy staff who used the antithrombotic questionnaire tool. The interview questions to identify barriers and facilitators were based on the Consolidated Framework for Implementation Research. The interview data were analysed using a deductive thematic analysis. Ten staff members from nine different pharmacies were interviewed. Facilitators for implementation were that the questionnaire was easily adaptable and easy to use, as well as the relative short duration to administer the questionnaire. A possible barrier for using the questionnaire was a lower priority for using the questionnaire at moments when the workload was high. The pharmacists estimated that the questionnaire could be used for 70-80% of the patient population and they thought that it was a useful addition to regular medication surveillance. The antithrombotic questionnaire tool can be easily implemented in pharmacy practice. To implement the tool, the focus should be on integrating its use into daily activities. Pharmacists can use this tool in addition to regular medication surveillance to improve medication safety in patients who use combined antithrombotic therapy.

Stroke Risk and Antithrombotic Treatment During Follow-up of Patients With Ischemic Stroke and Cortical Superficial Siderosis.

In patients with ischemic stroke (IS) or transient ischemic attack (TIA) and cortical superficial siderosis (cSS), there are few data regarding the risk of future cerebrovascular events and also about the benefits and safety of antithrombotic drugs for secondary prevention. We investigated the associations of cSS and stroke risk in patients with recent IS or TIA. We retrospectively analyzed the Microbleeds International Collaborative Network (MICON) database. We selected patients with IS or TIA from cohorts who had MRI-assessed cSS, available data on antithrombotic treatments, recurrent cerebrovascular events (intracranial hemorrhage [ICrH], IS, or any stroke [ICrH or IS]), and mortality. We calculated incidence rates (IRs) and performed univariable and multivariable Cox regression analyses. Of 12,669 patients (mean age 70.4 ± 12.3 years, 57.3% men), cSS was detected in 273 (2.2%) patients. During a mean follow-up of 24 ± 17 months, IS was more frequent than ICrH in both cSS (IR 57.1 vs 14.6 per 1,000 patient-years) and non-cSS (33.7 vs 6.3 per 1,000 patient-years) groups. Compared with the non-cSS group, cSS was associated with any stroke on multivariable analysis {IR 83 vs 42 per 1,000 patient-years, adjusted hazard ratio [HR] for cSS 1.62 (95% CI: 1.14-2.28; p = 0.006)}. This association was not significant in subgroups of patients treated with antiplatelet drugs (n = 6,554) or with anticoagulants (n = 4,044). Patients with cSS who were treated with both antiplatelet drugs and anticoagulants (n = 1,569) had a higher incidence of ICrH (IR 107.5 vs 4.9 per 1,000 patient-years, adjusted HR 13.26; 95% CI: 2.90-60.63; p = 0.001) and of any stroke (IR 198.8 vs 34.7 per 1,000 patient-years, adjusted HR 5.03; 95% CI: 2.03-12.44; p < 0.001) compared with the non-cSS group. Patients with IS or TIA with cSS are at increased risk of stroke (ICrH or IS) during follow-up; the risk of IS exceeds that of ICrH for patients receiving antiplatelet or anticoagulant treatment alone, but the risk of ICrH exceeds that of IS in patients receiving both treatments. The findings suggest that either antiplatelet or anticoagulant treatment alone should not be avoided in patients with cSS, but combined antithrombotic therapy might be hazardous. Our findings need to be confirmed by randomized clinical trials.

Prevalence of H. pylori among patients undergoing coronary angiography (The HP-DAPT prevalence study)

Helicobacter pylori (H. pylori) screening and treatment is recommended for patients on chronic aspirin (ASA) therapy to reduce the risk of gastrointestinal bleeding. Coronary artery disease patients requiring combination antithrombotic therapy (dual antiplatelet therapy; DAPT, or dual pathway inhibition; DPI) are at an even higher risk of GI bleeding. Therefore, we aimed to evaluate the prevalence of H. pylori among patients referred for angiography and likely to receive DAPT or DPI. This single-center prospective observational study recruited patients undergoing coronary angiography and with the possibility of requiring DAPT or DPI. All included patients underwent H. pylori serology testing. Multivariable logistic regression was performed to determine predictors of seropositivity. 195 patients were included in the analysis. Mean age was 67 years, 50% had known prior CAD, and 49% underwent coronary intervention. H. pylori serology was positive in 36%. Chronic kidney disease (odds ratio [OR] 2.76; 95% confidence interval [CI] 1.24 to 6.15; p = 0.01) and chronic obstructive pulmonary disease (OR 2.52; 95% CI 1.14 to 5.55; p = 0.02) history were independent predictors of H. pylori seropositivity. Given the clinically significant prevalence of H. pylori seropositivity among patients referred for angiography, systematic screening strategies and eradication of H. pylori could significantly reduce the incidence of GI bleeding in patients requiring DAPT or DPI.

Experience with the use of combination antithrombotic therapy in a patient with acute coronary syndrome and underlying severe coronavirus infection

The paper presents the experience of treating a patient with acute coronary syndrome without ST segment elevation and underlying severe novel coronavirus infection (COVID-19) complicated by polysegmental viral pneumonia and significant respiratory events. Emphasis has been placed on the use of antithrombotic therapy after endovascular treatment. A 56-year-old patient underwent respiratory support (non-invasive face mask lung ventilation followed by high-flow oxygenation), urgent diagnostic coronary angiography followed by percutaneous coronary intervention (balloon angioplasty and stenting of the right coronary artery and anterior interventricular artery). In addition to the etiopathogenetic therapy for coronavirus infection, the patient received combination antithrombotic therapy, including acetylsalicylic acid, prasugrel, FRaMon monoclonal antibodies (single exposure, intraoperatively), sodium enoxaparin. The therapy resulted in normalization of hemodynamic parameters, stable normothermia, absence of catarrhal events, improvement of exercise tolerance. A chest ultrasound imaging showed consolidation events, inflammatory markers significantly decreased, circulatory deficiency events were compensated, anginal pains did not recur. On the 20th day of hospitalization, the patient was discharged home with outpatient follow-up. The use of potent antiplatelet agents such as prasugrel or ticagrelor combined with IIb/IIIa receptor inhibitors and prolonged anticoagulant therapy can potentially improve the outcome of the disease in acute coronary syndrome with underlying severe coronavirus infection. In the presented clinical example, the use of aggressive approaches to the antithrombotic therapy did not lead to the development of significant hemorrhagic or other complications.

Current approaches to the selection of acetylsalicylic acid dosage forms in cardiology

The article is devoted to modern approaches to the selection of optimal dosage forms of acetylsalicylic acid (ASA), which ensure high bioavailability of ASA drugs. The relevance of improving the tactics of ASA use for both primary and secondary prevention of cardiovascular diseases is discussed. Changes in the role of ASA in the prevention of cardiovascular disease complications are discussed, including as part of combined antithrombotic therapy, including ASA and either P2Y12 inhibitor or low-dose rivaroxaban. Evidence is presented that has led to doubts about the sufficient bioavailability of the enteric form of ASA, as well as the predictability of the response to therapy. A separate part of the article is devoted to the safety of different forms of ASA, in particular - the effect on the mucosa of the small intestine. The results of clinical studies evaluating the effect of ASA intake in enteric-soluble and buffered forms on the small intestinal mucosa and the risk of bleeding are presented. In addition, the problem of decreased effectiveness of ASA intake in overweight or obese individuals is considered. The article provides information on ongoing randomized trials to assess the effectiveness of increasing the frequency of ASA intake, as well as the effectiveness of chronopharmacological approaches to optimize the use of ASA. The analysis performed leads it to conclude that the buffer form can now be considered the preferred acetylsalicylic acid (ASA) dosage form, which, on the one hand, exerts a less pronounced effect on the gastric and small intestinal mucosa, and on the other hand, ensures high bioavailability, as well as minimal variability of treatment response.

How to optimize treatment in patients with different forms of coronary artery disease

Coronary artery disease (CAD) retains top positions in terms of morbidity and mortality both in our country and many countries of the world. CAD takes many acute and chronic clinical forms and can be observed in patients with various cardiac and extracardiac pathologies. The therapy should be personalized to improve the prognosis for each patient with CAD. The COMPASS trial showed that administration of rivaroxaban at a dose of 2.5 mg twice daily combined with a longterm use of acetylsalicylic acid is reasonable in patients with stable coronary artery disease, a high risk of thrombotic complications and a low risk of bleeding to prevent the development of atherothrombotic cardiovascular events. The clinical benefit of this combination therapy is especially high in patients with diabetes mellitus. Once the percutaneous coronary intervention (PCI) is performed in a patient with CAD and atrial fibrillation (AF), we face the task to minimize the risk of atherothrombotic events, including the possibility of stent thrombosis, and the development of ischemic stroke, given the increased risk of bleeding due to such therapy. The results of PIONEER AF-PCI trial have become the grounds for recommendation of rivaroxaban 15 mg as part of combination antithrombotic therapy for this group of patients with AF. An option to add rivaroxaban to therapy may be considered in the presence of sinus rhythm in patients with reduced left ventricular ejection fraction and high thromboembolic risk to reduce the incidence of neurological events, as was shown in the COMMANDER HF trial. So there is a wealth of evidence that rivaroxaban may be used as an important component of the combination therapy of patients with CAD in a variety of clinical situations.

Management of combined oral antithrombotic therapy by an antithrombotic stewardship program: A prospective study.

Antithrombotic management initiatives could prevent inappropriate prescribing and improve patient outcomes especially in patients on combined antithrombotic therapy. To investigate this, a multidisciplinary antithrombotic stewardship program (ASP) was implemented in our hospital. The primary aim of this study was to determine the efficacy of this ASP by assessing the number of patients on combined antithrombotic therapy for whom one or more interventions were needed. A prospective cohort study in a large teaching hospital was conducted. Hospitalized patients were included who received combined antithrombotic therapy in which an oral anticoagulant was combined with one (double therapy) or two (triple therapy) platelet aggregation inhibitors. The ASP proactively evaluated the appropriateness of this combined antithrombotic therapy. If needed, ASP improved the concerned therapy. Each improvement measurement recommended by the ASP was counted as one intervention. A total of 460 patients were included over a period of 12 months. Of these, 251 (54.6%) patients required at least one intervention from the ASP. The most common interventions were: (1) to define and document the maximum duration of the combined antithrombotic therapy needed instead of lifetime use of the combination (65.5%), (2) to discontinue antithrombotic therapy as the proper indication was lacking (19.4%), and (3) to adjust the dosage (8.1%). An intervention was needed in more than half of the patients on combined antithrombotic therapy. Implementation of a dedicated ASP evaluating combined antithrombotic therapy improves the use and safety of antithrombotic medication.

Influence of Clinically Significant Genes on Antiplatelet Effect of Clopidogrel and Clinical Outcomes in Patients with Acute Coronary Syndrome and Atrial Fibrillation

Introduction: The interindividual variability of the antiplatelet effect of clopidogrel is determined by multiple clinical and genetic factors. A lot of genotype-oriented studies have concentrated on the impact of CYP2C19 gene polymorphisms on platelet aggregation in patients receiving clopidogrel. However, the influence of this polymorphism may be only 12–20%, so other genetic markers should also be investigated. The aim of this work was to study the impact of carriage of CES1, PON1, ABCG2, CYP4F2, CYP3A4, IGTB3, P2Y12, PEAR1, and B4GALT2 polymorphisms on antiplatelet effect of clopidogrel and clinical outcomes in patients with acute coronary syndrome (ACS) and atrial fibrillation (AF). Methods: 103 patients who underwent ACS with or without percutaneous coronary intervention and concomitant nonvalvular AF were included in an open multicenter prospective study to assess efficacy and safety of combined antithrombotic therapy. The study assessed the frequency of different primary clinical outcomes (incidence of major bleeding, hospital mortality, cardiovascular mortality, stroke and transient ischemic attacks (TIAs), renal mortality) and secondary outcomes (resistance to therapy – high residual platelet reactivity, excessive platelet suppression). Residual platelet reactivity was examined using the VerifyNow system (Accumetrics, Latham, NY, USA). Results: None of the studied genetic markers had no statistically significant effect on the antiaggregant response to clopidogrel in patients with ACS and AF. However, CYP4F2 C(Val433Met) T, PEAR1 rs41273215 C>T were statistically significantly associated with an increased frequency of bleeding on antithrombotic therapy. B4GALT2 rs1061781 was statistically significantly associated with increased frequency of strokes and TIA. Conclusion: In our study, we determined that carriers of CYP4F2 gene polymorphisms C(Val433Met)T, PEAR1 rs41273215 C>T (CT+TT) were associated with lower safety of antithrombotic therapy in patients with ACS and AF. And, the B4GALT2 rs1061781 gene polymorphism was associated with a greater risk of insufficient efficacy of the therapy. The data obtained in our study may improve the understanding of the effect of less studied genetic markers on the efficacy and safety of antithrombotic therapy in patients with ACS and AF.

Koroner Aterosklerozda CagA Pozitif Helicobacter pylori Enfeksiyonu: Lenfosit Sayısının Ortalama Trombosit Hacmine Oranının Tanısal Değeri

Aim: Potent combined and long-term antithrombotic therapies that predispose to gastric injury are the mainstay of treatment in acute coronary syndromes (ACS). Severe chronic gastric mucosal inflammation due to the Helicobacter Pylori (H. pylori) infection was shown to be associated with higher peripheral blood lymphocytes and lower blood mean platelet volume (MPV) levels. We aimed to investigate the discriminative usefulness of blood lymphocyte to MPV ratio as a simple premise marker for CagA positive H. Pylori infection before the required advanced diagnostic tests in patients with coronary arterial disease (CAD). Materials and Methods: A total of 293 patients’ who had undergone elective and urgent coronary angiography due to CAD were included in the study. Serologic H. pylori infection status and hematological parameters were determined. Two groups were compared according to CagA serology status. Confounding factors were adjusted by propensity score matching and multivariate logistic regression analysis. Results: Rates of ACS, male gender, diabetes mellitus, family history of CAD, current smoking and lymphocyte to MPV ratio were higher in seropositive patients according to seronegative patients (p &amp;lt; 0.05). The ROC curve analysis showed that the lymphocyte to MPV ratio at a cut-off point of 165 had 71% sensitivity and 60% specificity for discriminating patients with positive H. pylori serology (AUC = 0.71, p &amp;lt; 0.0001). Lymphocyte to MPV ratio was independently associated with positive H. Pylori serology. Conclusion: Lymphocyte to MPV ratio can be helpful for discriminating CagA positive H pylori infected CAD patients requiring advanced confirmatory tests.

Growth differentiation factor-15 and plasminogen activator inhibitor-1 are possible predictors of cardiovascular events in atrial fibrillation patients after elective PCI

Abstract Introduction Patients (pts) with AF (atrial fibrillation), undergoing elective PCI (percutaneous coronary intervention), receiving combined antithrombotic therapy (AT) have high risk of stroke/systemic embolism, coronary events and bleedings. Minimizing the duration of combined AT is the main way to improve the safety of treatment. However, due to the high risk of thrombotic events, patient stratification is necessary. Biomarkers of high risk cardiovascular events (CVE) could be the rational reason to prolong combined AT for some pts. The search for them is relevant. There is data on relationship between growth differentiation factor-15 (GDF-15) level, plasminogen activator inhibitor-1 (PAI-1) level and adverse CVE. Purpose To investigate the prognostic value of GDF-15 and PAI-1 levels in AF pts after elective PCI during 1 year follow up. Methods 150 pts (104 males), aged 70.8±8.5 years, with AF after elective PCI were enrolled in the prospective study. All pts received direct oral anticoagulants and double (89.3%) or single (10.7%) antiplatelet therapy. Median duration of follow up period was 11.5 months [IQR 8.0; 12.0]. Efficacy endpoint of the study was the sum of CVE: ACS (acute coronary syndrome), ischemic stroke (IS), VTE (venous thrombotic events), cardiovascular death and need for unplanned PCI. Plasma samples for GDF-15 and PAI-1 were taken before PCI and analyzed using ELISA. Results AF pts receiving combined AT demonstrated high thrombotic risk (CHA2DS2-VASc, Med 5 [IQR 4; 6]), high rate of comorbidity (index Charlson, Med 7 [IQR 5; 9]). Frequency of CVE during follow up period was 16% (ACS 2; fatal IS 2; VTE 2, include 1 fatal pulmonary embolism; cardiovascular death 2; pts needed an unplanned PCI 16). Median GDF-15 level was 1270 pg/ml [IQR 953; 1778]. Median PAI-1 level was 10.15 U/ml [6,3; 17,0]. By linear correlation analysis (r=0.24; p=0.0037) and by regression model (F-ratio 157.4, p&amp;lt;0.0001) GFD-15 and PAI-1 are exhibited a relation. According to ROC analysis GDF-15 level &amp;gt;1191 pg/ml (sensitivity 83.0, specifity 50.0) and PAI-1 level &amp;gt;13.2 U/ml (sensitivity 58.3, specifity 68.6) increases the probability of the development of CVE (AUC=0.647, p=0.0076, CI 0.565–0.723; AUC=0.652, p=0.0135, CI 0.569–0.728 respectively). Kaplan-Meier curves demonstrated significant difference in CVE free survival between the patients with GDF-15 level &amp;gt; and ≤1191 pg/ml (75.9% and 94.0% respectively, p=0.0032 [HR 4.36, CI 1.50–7.48]); and with PAI-1 level &amp;gt; and ≤13.2 U/ml (74% and 89% respectively, p=0.0112 [HR 2.73, CI 1.28–6.98]). The multivariable Cox regression model demonstrated that GDF-15 (p=0.0363) and PAI-1 (p=0.0074), were independently associated with an increased risk of CVE (op=0.0022). Conclusions GDF-15 and PAI-1 are correlated, and they are new markers of CVE in AF pts after elective PCI. Funding Acknowledgement Type of funding sources: None.

Use of biomedical photonics for in vivo and in vitro assessment of haemostasis and microcirculation in patients on antithrombotic therapy

Abstract Background Antithrombotic therapy in patients with cardiovascular disease requires rapid translation of laboratory assessment of haemorrheological parameters in clinical cardiology practice. Both antiplatelet and anticoagulant agents, especially when used in combination, can potentially increase the risk of severe bleeding. The precise balance between thrombosis and hemorrhage is therefore pivotal to ensure optimal treatment results. Purpose To develop simple and reliable methods to control the haemorheological properties of the blood and to assess the risk of potential bleeding. Methods We assessed platelet aggregation parameters measured in vitro by laser aggregometry and optical trapping techniques in blood samples of 131 patients with coronary artery disease. Additionally, blood rheology and microcirculation parameters were assessed in vivo in the nail-fold area using the digital capillaroscopy system. Results We found a statistically significant correlation between the number of aggregated blood cells in vitro and the presence of aggregates in the blood capillaries in vivo. A significant correlation was also observed between red blood cells (RBC) aggregation time in vitro and capillary flow velocity in vivo. The most severe deterioration of the rheological properties was found in patients with diffuse atherosclerotic disease receiving combined antithrombotic therapy. Interestingly, optical examination of soft tissues surrounding the capillaries of the nail-fold area revealed the presence of micro-hemorrhages in patients with history of hemorrhagic complications on antithrombotic therapy (Fig. 1). Conclusion Novel methods of biomedical photonics applied for in vivo and in vitro assessment of the blood haemorrheological properties can provide important additional information on microcirculation parameters and optimize treatment in patients on antithrombotic therapy. Funding Acknowledgement Type of funding sources: None. In vivo nail-fold digital capillaroscopy

ATRIAL FIBRILLATION PATIENTS' EXPERIENCES WITH COMBINATION ANTITHROMBOTIC THERAPY POST-PERCUTANEOUS CORONARY INTERVENTION

BACKGROUND Up to 30% of patients with atrial fibrillation (AF) have coronary artery disease (CAD). Many undergo percutaneous coronary intervention (PCI), requiring antithrombotic therapy (ATT) with acetylsalicylic acid (ASA) and a P2Y12 inhibitor to prevent stent thrombosis, combined with warfarin or a direct oral anticoagulant (DOAC) for stroke prevention (triple therapy). In the setting of acute coronary syndrome (ACS) with PCI, or elective PCI with high-risk features, Canadian AF guidelines recommend limiting ASA to 30 days post-PCI, as continuation of triple therapy beyond 30 days results in increased bleeding without reduction in ischemic outcomes. They also recommend 1-12 months of clopidogrel, and oral anticoagulation with doses that may change through the 12 months post-PCI. The complexity of these regimens may contribute to unintended modifications, increasing the risk of thrombosis and/or bleeding. Our goal was to describe patient experiences with combination ATT, including unplanned modifications, after discharge from acute care. METHODS AND RESULTS This is a prospective, observational study of patients with documented AF requiring OAC, who underwent PCI and were discharged on combination ATT. Patients were contacted at 1-, 3-, 6-, and 12-months post-PCI. Fifty-eight patients have been enrolled (January 2020-April 2021) with data from at least 1 time point available for 55 patients (Table 1). Of these, 31 (56.4%) experienced at least one unplanned modification to ATT and 15 (27.3%) experienced more than one. Forty-five (81.8%) of the 55 patients were discharged with a plan for triple therapy. In 18 patients (40.0%), the original plan was to stop ASA at 1-month post-PCI; 7 (38.9%) did not stop as directed. Nine patients (20.0%) had ASA stopped prior to the intended stop date by a prescriber. Of the 31 patients with at least one modification, 9 (29.0%) experienced a modification to clopidogrel which was a prolonged duration in 5 patients; prescriber-driven in 2. Eighteen (58.1%) patients experienced modifications related to oral anticoagulants; 4 in 10 (40.0%) warfarin-treated patients and 14 in 45 (31.1%) DOAC-treated patients. Of all patients with at least one modification, 15 (48.4%) experienced a bleeding event that was either a reason for, or due to, an unplanned ATT modification. CONCLUSION More than 1 in 2 patients with AF undergoing PCI experienced an unplanned modification to their ATT and half of those were associated with bleeding. This underscores the challenges of managing combination ATT for patients and clinicians alike and emphasizes the need for follow up and patient support after discharge. Up to 30% of patients with atrial fibrillation (AF) have coronary artery disease (CAD). Many undergo percutaneous coronary intervention (PCI), requiring antithrombotic therapy (ATT) with acetylsalicylic acid (ASA) and a P2Y12 inhibitor to prevent stent thrombosis, combined with warfarin or a direct oral anticoagulant (DOAC) for stroke prevention (triple therapy). In the setting of acute coronary syndrome (ACS) with PCI, or elective PCI with high-risk features, Canadian AF guidelines recommend limiting ASA to 30 days post-PCI, as continuation of triple therapy beyond 30 days results in increased bleeding without reduction in ischemic outcomes. They also recommend 1-12 months of clopidogrel, and oral anticoagulation with doses that may change through the 12 months post-PCI. The complexity of these regimens may contribute to unintended modifications, increasing the risk of thrombosis and/or bleeding. Our goal was to describe patient experiences with combination ATT, including unplanned modifications, after discharge from acute care. This is a prospective, observational study of patients with documented AF requiring OAC, who underwent PCI and were discharged on combination ATT. Patients were contacted at 1-, 3-, 6-, and 12-months post-PCI. Fifty-eight patients have been enrolled (January 2020-April 2021) with data from at least 1 time point available for 55 patients (Table 1). Of these, 31 (56.4%) experienced at least one unplanned modification to ATT and 15 (27.3%) experienced more than one. Forty-five (81.8%) of the 55 patients were discharged with a plan for triple therapy. In 18 patients (40.0%), the original plan was to stop ASA at 1-month post-PCI; 7 (38.9%) did not stop as directed. Nine patients (20.0%) had ASA stopped prior to the intended stop date by a prescriber. Of the 31 patients with at least one modification, 9 (29.0%) experienced a modification to clopidogrel which was a prolonged duration in 5 patients; prescriber-driven in 2. Eighteen (58.1%) patients experienced modifications related to oral anticoagulants; 4 in 10 (40.0%) warfarin-treated patients and 14 in 45 (31.1%) DOAC-treated patients. Of all patients with at least one modification, 15 (48.4%) experienced a bleeding event that was either a reason for, or due to, an unplanned ATT modification. More than 1 in 2 patients with AF undergoing PCI experienced an unplanned modification to their ATT and half of those were associated with bleeding. This underscores the challenges of managing combination ATT for patients and clinicians alike and emphasizes the need for follow up and patient support after discharge.

Antithrombotic Management for Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

Comprehensive protection of a patient with atrial fibrillation (AF) should not only reduce the risk of stroke and systemic embolism, but also reduce the risk coronary events and ensure high adherence to treatment. In accordance with consensus document issued by the European Heart Rhythm Association, European Society of Cardiology, European Association of Percutaneous Cardiovascular Interventions, as well as with other recent Russian Society of Cardiology Guidelines, the management of antithrombotic therapy of patients with AF undergoing percutaneous coronary intervention (PCI) requires that multiple and interconnected issues. The review article addresses questions about duration of initial triple antithrombotic therapy (TAT), selection of P2Y12 inhibitor, choice of oral anticoagulant to be combined with antiplatelet therapy, intensity of oral anticoagulation throughout combination therapy, and choice of oral anticoagulant for indefinite therapy. In general, it is recommended to refuse the routine use of TAT for most patients. Accordingly, for patients who need both anticoagulant and antiplatelet therapy, it is strongly recommended that the default strategy after recent PCI is a double antithrombotic therapy consisting of an anticoagulant and one antiplatelet, preferably from the group of P2Y12 inhibitors. When conducting combined antithrombotic therapy, preference should be given to clopidogrel compared to other, more powerful P2Y12 inhibitors and direct oral anticoagulant (DOAC) instead of vitamin K antagonists. The primary choice of DOAC in patients with AF who have undergone PCI should be carried out taking into account such factors as individual risk of stroke and bleeding, adherence to treatment, concomitant diseases, pharmacological characteristics and evidence base of a specific DOAC, taking other medications, etc. The pharmacokinetic features of rivaroxaban, which create the possibility of its single administration, the evidence base for reducing coronary risks in various variants of the course of coronary heart disease, determines the special positions of the drug for the comprehensive protection of patients with AF after PCI.