Acetylsalicylic Acid Monotherapy Research Articles

The Net Clinical Outcome of Dual-Pathway Inhibition in Clinical Practice: The "Xarelto plus Acetylsalicylic Acid: Treatment Patterns and Outcomes in Patients with Atherosclerosis" Registry.

Background: In the COMPASS trial, the combination of acetylsalicylic acid (ASA) plus 2.5 mg rivaroxaban twice daily (dual-pathway inhibition, DPI) has been shown to be superior to ASA monotherapy for the reduction in ischemic major adverse cardiovascular events (MACEs, i.e., cardiovascular death, stroke, or myocardial infarction). Methods: The international XATOA registry (Xarelto plus Acetylsalicylic acid: Treatment patterns and Outcomes in patients with Atherosclerosis) is a prospective post-approval registry that investigates the cardiovascular outcomes of patients taking ASA plus 2.5 mg rivaroxaban. The aim of this pre-specified analysis was to determine the net clinical outcome (NCO), i.e., a combination of MACEs and bleeding events, of DPI in patients from daily clinical practice. Results: Among the 5615 patients, the presence of multiple risk factors resulted in an increase in the total risk of experiencing an NCO event, e.g., from 1.27% (one risk factor) to 2.18% (two risk factors) and 4.07% (three or more risk factors), respectively, with ischemic MACE representing the primary driver of bleeding complications. Conclusions: In the real-world XATOA registry, the annual rate of NCO events was low and numerically similar to those seen in the treatment group in the randomized COMPASS trial.

Efficacy and Safety of Extended Antithrombotic Therapy in Stable Coronary Artery Disease: Systematic Review of the Literature

Extended dual antithrombotic therapy, which entails the concurrent administration of acetylsalicylic acid and a P2Y12 inhibitor or anticoagulant beyond the initial 12 months of presenting with acute coronary syndrome, has been the subject of considerable research in recent years. The objective of this study was to evaluate the impact of dual antithrombotic therapy in stable coronary artery disease. We conducted a registered (PROSPERO CRD42023394771) assessing the safety and efficacy of antithrombotic therapy published over the past 20 years up to May 2021 in four databases (PubMed, EMBASE, BVSalud /LILACS, Cochrane Reviews). Using the RoB2 tool, we evaluated the risk of bias. We performed a literature search using keywords and identified 95 eligible articles, of which 23 were excluded as duplicates. After applying the inclusion and exclusion criteria, we found 29 articles for a detailed review and assessment of bias by applying the ROB2 toll, and we found that five articles had a low risk of bias. Our analysis found that extended dual antithrombotic therapy reduces ischemic cardiovascular outcomes, but it comes at the cost of an increased risk of bleeding when compared with acetylsalicylic acid monotherapy.

Contribution of ticagrelor therapy in patients with acute coronary syndrome and patients with myocardial infarction to the achievement of State Program "Health Development" target in Russia as a whole and Russian regions in 2023-2025

Aim. To evaluate the contribution ticagrelor compared with clopidogrel therapy in patients with acute coronary syndrome (ACS) and patients with myocardial infarction (MI) to achieving the State Program "Health Development" target "decrease of cardiovascular mortality" in the country as a whole and Russian regions in 2023-2025.Material and methods. In the first year of therapy, all patients over 18 years of age with a confirmed diagnosis of ACS who were indicated for dual antiplatelet therapy (DAPT) were considered as the target population. In the second and third years, therapy was continued by patients at high risk of coronary events after MI. The number of deaths that could be additionally prevented within 1 year after diagnosis using DAPT with ticagrelor compared with DAPT with clopidogrel was calculated based on the PLATO trial. For post-MI patients, the number of deaths that could be prevented in the second and third years of therapy using DAPT with ticagrelor+acetylsalicylic acid (ASA) compared with ASA monotherapy was calculated based on the PEGASUS trial. The proportion of the target "decrease of cardiovascular mortality of the population" in 2023-2025 that can be achieved by using DAPT with ticagrelor instead of clopidogrel or ASA monotherapy was calculated.Results. The use of ticagrelor as part of DAPT for patients with ACS will make it possible (compared to DAPT with clopidogrel or ASA) to contribute to achieving "decrease of cardiovascular mortality" target in the Russian Federation:in 2023 — 8,0% due to expected prevention of 4443 cardiovascular deaths,in 2024 — 30,3% due to expected prevention of 4753 cardiovascular deaths,in 2025, 5366 cardiovascular deaths can be Conclusion. The use of ticagrelor as part of DAPT for patients with ACS will contribute to achieving "decrease of cardiovascular mortality" target in the Russian Federation.

Risk of antidepressant initiation among users of cardiovascular agents and metformin. Findings from the Trøndelag Health Study (HUNT) and Norwegian Prescription Database (NorPD), Norway: Findings from the Trøndelag Health Study (HUNT) and Norwegian Prescription Database (NorPD), Norway.

Cardiovascular disease and diabetes are risk factors for depression, yet the relationship between the drug treatments for these diseases and the risk of antidepressant initiation remains unclear. This study aimed to examine possible associations between the use of angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEI), acetylsalicylic acid (ASA), beta-blockers (BB), calcium channel blockers (CCB), diuretics, or metformin and risk of antidepressant initiation. The Trøndelag Health Study (HUNT3), Norway, was linked to the Norwegian Prescription Database (NorPD). Participants with no prescriptions of cardiovascular agents, metformin, or antidepressants for at least 6 months before HUNT3 (baseline) were eligible and followed for 10 years. The exposure was the use of cardiovascular agents or metformin, defined as mono- or polytherapy from baseline to end of follow-up. The outcome was the initiation of antidepressant use, indicated by the first drug dispensation during the study period and expressed as hazard ratios (HRs) with 95% confidence intervals (CI). Among 20 227 adults aged 40-70 years at baseline, we observed different associations between cardiovascular agents or metformin and the risk of antidepressant initiation. ARBs or CCB monotherapy was associated with a lower risk of initiating antidepressant use (HR 0.70; 95%CI 0.56-0.88 and HR 0.81; 95%CI 0.61-1.06, respectively) compared to no use of any drugs included in the study (reference). Reduced risk of antidepressant initiation was among ASA or statin polytherapy users, whereas there was a small increased risk among participants on ASA monotherapy. In contrast, there was no statistical evidence of associations between ACEI, BB, diuretics, or metformin and increased or decreased risk of antidepressant initiation. Our mixed findings indicate the possibility that some cardiovascular agents may be associated with a reduced risk of initiating antidepressant use while others may not. However, bias due to the limitations of the study design is possible.

Dual pathway inhibition as compared to acetylsalicylic acid monotherapy in relation to endothelial function in peripheral artery disease, a phase IV clinical trial.

ObjectiveDual pathway inhibition (DPI) by combining acetylsalicylic acid (ASA) with low-dose rivaroxaban has been shown to reduce cardiovascular events in patients with peripheral arterial disease (PAD) when compared to ASA monotherapy. A potential explanation is that inhibition of factor Xa improves endothelial function through crosstalk between coagulation and inflammatory pathways, subsequently attenuating the occurrence of cardiovascular events. We hypothesize that the addition of rivaroxaban to ASA in PAD patients leads to improved endothelial function.DesignAn investigator-initiated, multicentre trial investigating the effect of DPI on endothelial function.MethodsPatients, diagnosed with PAD, were enrolled in two cohorts: cohort A (Rutherford I-III) and cohort B (Rutherford IV-VI). Participants received ASA monotherapy for a 4-weeks run-in period, followed by 12 weeks of DPI. Macro- and microvascular endothelial dysfunction were studied by measuring carotid artery reactivity upon sympathetic stimulus and by measuring plasma endothelin-1 concentrations, respectively. All measurements were performed during the use of ASA (baseline) and after 12 weeks of DPI.Results159 PAD patients (111 cohort A, 48 cohort B) were enrolled. Twenty patients discontinued study drugs early. Carotid artery constriction upon sympathetic stimulation at baseline (ASA) and after 12 weeks of DPI was similar in the total group, 22.0 vs. 22.7% (p = 1.000), and in the subgroups (Cohort A 22.6 vs. 23.7%, p = 1.000; cohort B 20.5 vs. 20.5%, p = 1.000), respectively. The mean concentration of plasma endothelin-1 at baseline and after 12 weeks of DPI did not differ, 1.70 ± 0.5 vs. 1.66 ± 0.64 pmol/L (p = 0.440) in the total group, 1.69 ± 0.59 vs. 1.62 ± 0.55 pmol/L in cohort A (p = 0.202), and 1.73 ± 0.53 vs. 1.77 ± 0.82 pmol/L in cohort B (p = 0.682), respectively.ConclusionMacro- and microvascular endothelial dysfunction, as reflected by carotid artery reactivity and plasma endothelin-1 concentrations, are not influenced in PAD patients by addition of low-dose rivaroxaban to ASA monotherapy for 12 weeks.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04218656.

Antithrombotic Therapy for Symptomatic Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis.

BackgroundHigh-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or acetylsalicylic acid (ASA) plus low-dose rivaroxaban is lacking. Therefore, we conducted a network meta-analysis on the effectiveness of all antithrombotic regimens studied in PAD.MethodsA systematic search was conducted to identify randomized controlled trials. The primary endpoints were major adverse cardiovascular events (MACE) and major bleedings. Secondary endpoints were major adverse limb events (MALE) and acute limb ischaemia (ALI). For each outcome, a frequentist network meta-analysis was used to compare relative risks (RRs) between medication and ASA. ASA was the universal comparator since a majority of studies used ASA as in the reference group.ResultsTwenty-four randomized controlled trials were identified including 48,759 patients. With regard to reducing MACE, clopidogrel [RR 0.78, 95% confidence interval (CI) 0.66–0.93], ticagrelor (RR 0.79, 95% CI 0.65–0.97), ASA plus ticagrelor (RR 0.79, 95% CI 0.64–0.97), and ASA plus low-dose rivaroxaban (RR 0.84, 95% CI 0.76–0.93) were more effective than ASA, and equally effective to one another. As compared to ASA, major bleedings occurred more frequently with vitamin K antagonists, rivaroxaban, ASA plus vitamin K antagonists, and ASA plus low-dose rivaroxaban. All regimens were similar to ASA concerning MALE, while ASA plus low-dose rivaroxaban was more effective in preventing ALI (RR 0.67, 95% CI 0.55–0.80). Subgroup analysis in patients undergoing peripheral revascularization revealed that ≥ 3 months after intervention, evidence of benefit regarding clopidogrel, ticagrelor, and ASA plus ticagrelor was lacking, while ASA plus low-dose rivaroxaban was more effective in preventing MACE (RR 0.87, 95% CI 0.78–0.97) and MALE (RR 0.89, 95% CI 0.81–0.97) compared to ASA. ASA plus clopidogrel was not superior to ASA in preventing MACE ≥ 3 months after revascularization. Evidence regarding antithrombotic treatment strategies within 3 months after a peripheral intervention was lacking.ConclusionClopidogrel, ticagrelor, ASA plus ticagrelor, and ASA plus low-dose rivaroxaban are superior to ASA monotherapy and equally effective to one another in preventing MACE in PAD. Of these four therapies, only ASA plus low-dose rivaroxaban provides a higher risk of major bleedings. More than 3 months after peripheral vascular intervention, ASA plus low-dose rivaroxaban is superior in preventing MACE and MALE compared to ASA but again at the cost of a higher risk of bleeding, while other treatment regimens show non-superiority. Based on the current evidence, clopidogrel may be considered the antithrombotic therapy of choice for most PAD patients, while in patients who underwent a peripheral vascular intervention, ASA plus low-dose rivaroxaban could be considered for the long-term (> 3 months) prevention of MACE and MALE.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40265-022-01756-6.

Management of blunt cerebrovascular injuries at a Canadian level 1 trauma centre: Are we meeting the grade?

Background:Untreated blunt cerebrovascular injuries (BCVIs) are associated with high rates of death and disability due to stroke. We assessed alignment of clinical practice at our centre with current recommendations for management of BCVIs and examined rates of new and recurrent in-hospital stroke.Methods:We retrospectively reviewed the BC Trauma Registry to identify all adult (age > 18 yr) patients with trauma with BCVIs at the largest level 1 trauma centre in British Columbia, Canada, from Apr. 1, 2013, to Mar. 31, 2018. We evaluated the registry, hospital databases and patient charts to assess alignment with guidelines for early initiation of appropriate antithrombotic therapy and follow-up imaging, and to ascertain short-term outcomes.Results:A total of 186 patients met the inclusion criteria. Just over half of BCVIs (97 [52.2%]) were Biffl grade 1–2. The majority of patients were treated with acetylsalicylic acid monotherapy (144/162 [88.9%]) or low-molecular-weight heparin (2/162 [1.2%]). Although guidelines recommend repeat imaging at 7–10 days to reassess the injury and guide duration of therapy, only 61/171 patients (35.7%) underwent repeat imaging within 7 days. Neuroimaging within 3 months after injury showed brain infarction in 29 patients (15.6%).Conclusion:Antithrombotic therapy was initiated in the majority of eligible patients with BCVIs, but completion of follow-up imaging and documentation of clear outpatient care plans were suboptimal. This finding shows the need for routine multidisciplinary management to facilitate standardization of care for this complex population.

American College of Gastroenterology-Canadian Association of Gastroenterology Clinical Practice Guideline: Management of Anticoagulants and Antiplatelets During Acute Gastrointestinal Bleeding and the Periendoscopic Period.

We conducted systematic reviews of predefined clinical questions and used the Grading of Recommendations, Assessment, Development and Evaluations approach to develop recommendations for the periendoscopic management of anticoagulant and antiplatelet drugs during acute gastrointestinal (GI) bleeding and the elective endoscopic setting. The following recommendations target patients presenting with acute GI bleeding: For patients on warfarin, we suggest against giving fresh frozen plasma or vitamin K; if needed, we suggest prothrombin complex concentrate (PCC) compared with fresh frozen plasma administration; for patients on direct oral anticoagulants (DOACs), we suggest against PCC administration; if on dabigatran, we suggest against the administration of idarucizumab, and if on rivaroxaban or apixaban, we suggest against andexanet alfa administration; for patients on antiplatelet agents, we suggest against platelet transfusions; and for patients on cardiac acetylsalicylic acid (ASA) for secondary prevention, we suggest against holding it, but if the ASA has been interrupted, we suggest resumption on the day hemostasis is endoscopically confirmed. The following recommendations target patients in the elective (planned) endoscopy setting: For patients on warfarin, we suggest continuation as opposed to temporary interruption (1-7 days), but if it is held for procedures with high risk of GI bleeding, we suggest against bridging anticoagulation unless the patient has a mechanical heart valve; for patients on DOACs, we suggest temporarily interrupting rather than continuing these; for patients on dual antiplatelet therapy for secondary prevention, we suggest temporary interruption of the P2Y12 receptor inhibitor while continuing ASA; and if on cardiac ASA monotherapy for secondary prevention, we suggest against its interruption. Evidence was insufficient in the following settings to permit recommendations. With acute GI bleeding in patients on warfarin, we could not recommend for or against PCC administration when compared with placebo. In the elective periprocedural endoscopy setting, we could not recommend for or against temporary interruption of the P2Y12 receptor inhibitor for patients on a single P2Y12 inhibiting agent. We were also unable to make a recommendation regarding same-day resumption of the drug vs 1-7 days after the procedure among patients prescribed anticoagulants (warfarin or DOACs) or P2Y12 receptor inhibitor drugs because of insufficient evidence.

American College of Gastroenterology-Canadian Association of Gastroenterology Clinical Practice Guideline: Management of Anticoagulants and Antiplatelets During Acute Gastrointestinal Bleeding and the Periendoscopic Period.

We conducted systematic reviews of predefined clinical questions and used the Grading of Recommendations, Assessment, Development and Evaluations approach to develop recommendations for the periendoscopic management of anticoagulant and antiplatelet drugs during acute gastrointestinal (GI) bleeding and the elective endoscopic setting. The following recommendations target patients presenting with acute GI bleeding: For patients on warfarin, we suggest against giving fresh frozen plasma or vitamin K; if needed, we suggest prothrombin complex concentrate (PCC) compared with fresh frozen plasma administration; for patients on direct oral anticoagulants (DOACs), we suggest against PCC administration; if on dabigatran, we suggest against the administration of idarucizumab, and if on rivaroxaban or apixaban, we suggest against andexanet alfa administration; for patients on antiplatelet agents, we suggest against platelet transfusions; and for patients on cardiac acetylsalicylic acid (ASA) for secondary prevention, we suggest against holding it, but if the ASA has been interrupted, we suggest resumption on the day hemostasis is endoscopically confirmed. The following recommendations target patients in the elective (planned) endoscopy setting: For patients on warfarin, we suggest continuation as opposed to temporary interruption (1–7 days), but if it is held for procedures with high risk of GI bleeding, we suggest against bridging anticoagulation unless the patient has a mechanical heart valve; for patients on DOACs, we suggest temporarily interrupting rather than continuing these; for patients on dual antiplatelet therapy for secondary prevention, we suggest temporary interruption of the P2Y12 receptor inhibitor while continuing ASA; and if on cardiac ASA monotherapy for secondary prevention, we suggest against its interruption. Evidence was insufficient in the following settings to permit recommendations. With acute GI bleeding in patients on warfarin, we could not recommend for or against PCC administration when compared with placebo. In the elective periprocedural endoscopy setting, we could not recommend for or against temporary interruption of the P2Y12 receptor inhibitor for patients on a single P2Y12 inhibiting agent. We were also unable to make a recommendation regarding same-day resumption of the drug vs 1–7 days after the procedure among patients prescribed anticoagulants (warfarin or DOACs) or P2Y12 receptor inhibitor drugs because of insufficient evidence.

Evaluation of the effect of the use of the drug ticagrelor in patients with acute coronary syndrome on achieving the target indicator “reduction of mortality from diseases of the circulatory system” in 2022-2024

Aim. To evaluate the effect of the use of the double antiplatelet therapy (DAT) with ticagrelor compared to DAT with clopidogrel and antithrombotic therapy with acetyl salicylic acid (ASA) in patients with acute coronary syndrome and patients with high coronary risk on the target indicator (CP) of the state program (GP) “Development of Healthcare” and the federal project “Fight against cardiovascular diseases” — reducing mortality from diseases of the circulatory system (BSC).Material and methods. All adult Russian patients with a diagnosis of ACS eligible for DAT were considered as the target population; in the second and third years, only patients with high coronary risk continued treatment. The calculation of the number of deaths that can be prevented using DAT ticagrelor 90 mg + ASA vs DAT of clopidogrel + ASA within 1st year from the date of diagnosis was based on the clinical efficacy data of the PLATO study. The number of deaths that can be prevented with the use of DAT ticagrelor 60 mg + ASA — instead of ASA monotherapy patients with a history of myocardial infarction was made based in the clinical efficacy results of the PEGASUS study. It was calculated what proportion of the target indicators could be achieved in 2022-24 years by using DAT with ticagrelor instead of clopidogrel or ASA monotherapy.Results. The use of DAT with ticagrelor vs DAT with clopidogrel or ASA for the treatment of patients with ACS will prevent additional 5389, 5704 and 6012 deaths in 2022-2024, that will ensure the implementation of the CP “reduction of mortality from BSC” GP “Development of healthcare” in the Russian Federation by 36,9%, 26,0% and 20,6% respectively.Conclusion. The use of DAT with ticagrelor for the treatment of patients with acute coronary syndrome ensure the implementation of the CP “reduction of mortality from BSC” GP “Development of healthcare” in the Russian Federation in 2024 by 20,6%.

Comparison of Midterm Outcomes Associated With Aspirin and Ticagrelor vs Aspirin Monotherapy After Coronary Artery Bypass Grafting for Acute Coronary Syndrome

Guidelines recommend dual antiplatelet therapy after coronary artery bypass grafting (CABG) for patients with acute coronary syndrome (ACS). However, the evidence for these recommendations is weak. To compare midterm outcomes after CABG in patients with ACS treated postoperatively with acetylsalicylic acid (ASA) and ticagrelor or with ASA monotherapy. This cohort study used merged data from several national registries of Swedish patients who were diagnosed with ACS and subsequently underwent CABG. All included patients underwent isolated CABG in Sweden between 2012 and 2017 with an ACS diagnosis less than 6 weeks before the procedure, survived 14 days after discharge from hospital, and were treated postoperatively with ASA plus ticagrelor or ASA monotherapy. A multivariable Cox regression model was used for the main analysis, and propensity score-matched models were performed as sensitivity analysis. Data were analyzed between May and September 2020. Postoperative antiplatelet treatment, defined as filled prescriptions, with either ASA and ticagrelor or ASA only. Major adverse cardiovascular events (MACE), defined as all-cause mortality, myocardial infarction, and stroke, and major bleeding, at 12 months and at the end of follow-up. A total of 6558 patients (5281 [80.5%] men; mean [SD] age at surgery, 67.6 [9.3] years) were included; 1813 (27.6%) were treated with ASA plus ticagrelor and 4745 (72.4%) were treated with ASA monotherapy. Crude MACE rate was 3.0 per 100 person years (95% CI, 2.5-3.6 per 100 person years) in the ASA plus ticagrelor group and 3.8 per 100 person years (95% CI, 3.5-4.1 per 100 person years) in the ASA group. After adjustment, there was no significant difference in MACE risk between ASA plus ticagrelor vs ASA only, neither during the first 12 months (adjusted hazard ratio [aHR], 0.84; 95% CI, 0.58-1.21; P = .34) or during total follow-up (aHR, 0.89; 95% CI, 0.71-1.11; P = .29). The use of ASA plus ticagrelor was associated with a significantly increased risk for major bleeding during the first 12 months (aHR, 1.90; 95% CI, 1.16-3.13; P = .011). Sensitivity analyses confirmed the results. In patients with ACS who survived 2 weeks after CABG, no significant difference in the risk of death or ischemic events could be demonstrated between ASA plus ticagrelor and patients treated with ASA only, while the risk for major bleeding was higher in patients treated with ASA plus ticagrelor. Sufficiently powered prospective randomized trials comparing different antiplatelet therapy strategies after CABG are warranted.

Impact of preoperative antithrombotic therapy in patients undergoing elective isolated coronary artery bypass grafting.

The objective of this retrospective study was to assess differences in clinical outcomes between patients on acetylsalicylic acid (ASA) monotherapy and patients on other antithrombotic (AT) regimens undergoing elective coronary artery bypass grafting (CABG). Patients who underwent elective isolated CABG between 2017 and 2019 at the Catharina Hospital Eindhoven were eligible for this study. The primary end points were re-exploration for bleeding and postoperative blood product transfusion. Secondary end points included 30-day mortality, in-hospital stroke, in-hospital myocardial infarction and duration of hospitalization. Propensity matching was used to compare outcomes of the main study groups (ASA vs other AT therapy) and subgroups of AT therapy (guideline adherence vs non-adherence). A total of 1068 patients were included: 710 patients on ASA monotherapy and 358 patients on other AT regimens. In the 256 matched patients in the main study groups, using AT regimens other than ASA monotherapy was associated with increased risk of re-exploration for bleeding [6.6% vs 2.0%, P = 0.017; odds ratio (OR) 3.57 (1.29-9.83)] and increased use of blood products [37.5% vs 20.3%, P < 0.001; OR 2.35 (1.58-3.49)]. In 122 matched subgroup patients, non-adherence was associated with an increased risk of re-exploration [10.7% vs 3.3%, P = 0.044; OR 3.52 (1.11-11.12)] and increased blood product use [51.6% vs 25.4%, P < 0.001; OR 3.13 (1.83-5.38)]. Secondary end points were not significantly different among the main study groups and subgroups. Preoperative use of AT therapy other than ASA monotherapy in patients who elected CABG was associated with the increased postoperative use of blood products and risk of re-exploration for bleeding; this finding was even more pronounced in non-guideline-adherent patients.

Molecular and metabolic characteristics of changes in the platelet sensitivity to antiplatelet therapy in patients with coronary artery disease before and after coronary artery bypass grafting

Aim. To study the production of reactive oxygen species (ROS) by platelets in patients with coronary artery disease (CAD) before and after coronary artery bypass grafting (CABG), depending on their sensitivity to acetylsalicylic acid (ASA) as a part of ASA monotherapy and dual antiplatelet therapy (DAPT) (ASA+clopidogrel).Material and methods. The study included 104 patients with CAD (ASA monotherapy, 64 patients; DAPT, 40 patients). From day 1 after CABG, they took 100 mg a day of enteric-coated ASA. In the DAPT group, clopidogrel was prescribed for 2-3 days after CABG. All measurements were performed before surgery, on the 1st day and days 8-10 after surgery. Control group consisted of 36 healthy donors. Resistance to ASA was determined at a level of optical platelet aggregation with arachidonic acid &gt;20% at least at one observation point. The spontaneous and ADP-induced chemiluminescence (CL) of platelets with luminol and lucigenin was assessed according to the following parameters: time to maximum intensity (Tmax), maximum intensity (Imax), area (S) under the CL curve, and the ratio of ADP-induced CL S to spontaneous CL S.Results. Throughout the study, 71 patients with CAD were sensitive to ASA (sASA) (ASA monotherapy, 46 patients; DAPT, 25 patients), three patients — resistant (rASA) (ASA monotherapy, 1; DAPT, 2). Sensitivity of other 30 patients (ASA monotherapy, 17; DAPT, 13) changed in different follow-up periods. Compared to the control group, sASA patients had increased values of platelet CL parameters throughout the study, while in the rASA group (ASA monotherapy), Tmax was higher before CABG, and in the rASA group (ASA therapy+clopidogrel), Imax and S were higher on the first day after CABG, while Imax — on days 8-10 after CABG. Compared to sASA, the values of S and Imax before CABG, Imax after CABG, as well as Imax and S on the days 8-10 after CABG in rASA (ASA monotherapy) were significantly lower, while in rASA (ASA therapy+clopidogrel), only the Tmax values were lower on the 8-10 days after CABG.Conclusion. In patients with CAD, depending on the sensitivity to ASA and antiplatelet therapy after CABG, the metabolic activity of platelets in terms of ROS production differs. In sASA patients, ROS synthesis is higher than in healthy individuals, while, in rASA patients (ASA monotherapy), platelets produce ROS levels lower than in sASA. CABG surgery and the addition of clopidogrel to ASA therapy leads to increased ROS production in rASA patients in the postoperative period.

Assessment of platelet function and resistance to aspirin and clopidogrel in patients with peripheral arterial disease undergoing percutaneous transluminal angioplasty

Introduction: Analysis of platelet function, acetylsalicylic acid (ASA) and clopidogrel resistance in patients with peripheral arterial disease (PAD) undergoing percutaneous transluminal angioplasty (PTA), the impact of procedure on this phenomenon, connection with diabetes, hypertension, smoking. Material and methods: The study included 72 patients, with a group of patients taking ASA on a permanent basis and a group of patients in whom treatment was implemented after the procedure. Patients were also divided according to the antiplatelet therapy applied, either double-therapy, or ASA monotherapy. Daily doses were 75 mg. Three methods were used for the evaluation of the platelet function: IVY bleeding time, cytometric evaluation of platelet surface antigen (CD62p and CD63) expression and hemostasis measurement by PFA-200®. Results: In the PFA-200 analysis, ASA resistance was found in 37.8% (64.7% were tobacco smokers) before surgery. Patients not taking ASA before, after PTA and first dose of ASA presented resistance in 63%. The first dose of clopidogrel after surgery was associated with resistance in 73.7%. Significant differences in the expression of CD62p and CD63 markers before and after PTA were observed. According to IVY method, aspirin resistance was found in 40% of patients permanently receiving ASA. Conclusions: Patients with PAD who undergo PTA are resistant to ASA in 40%, smoking is associated with this phenomenon. PTA increases the expression of CD62P and CD63, and thus the platelet activation, which is not adequately prevented by antiplatelet drugs at a dose of 75 mg. Dual antiplatelet therapy reduces the activation of thrombocytes more than the monotherapy of ASA.

The new Epoch of Antithrombotic Therapy in the Long-Term Prevention of a non-Cardioembolic Stroke

This article presents current opinions on the role of antithrombotic therapy in secondary prevention of cardiovascular diseases (CVD) in patients after noncardioembolic stroke or a transient ischemic attack on the background of sinus rhythm. This review analytically analyses evidence-based data on antithrombotic drugs used for this secondary prevention. Despite the fact that acetylsalicylic acid (ASA) is still a "gold standard" for prevention of noncardioembolic stroke, the search for rational combinations of antithrombotic drugs to increase the effectiveness of preventive treatment is relevant. The question whether the rivaroxaban treatment as monotherapy or in combination with ASA is more effective than the ASA monotherapy for secondary prevention of cardiovascular complications (CVC) was addressed in the COMPASS study. In that study, three regimens of antithrombotic therapy were compared in patients with stable atherosclerotic CVD: rivaroxaban (2.5 mg twice a day) in combination with ASA (100 mg/day); rivaroxaban (5 mg twice a day); and ASA (100 mg/day). Risk for development of major CVC (death, stroke, myocardial infarction (IM)) was lower (p&lt;0.001) in the rivaroxaban+ASA combination treatment group than in the ASA monotherapy group; however, the risk of major bleedings was somewhat higher. Total risk based on the definition of "pure clinical benefit" was lower for the rivaroxaban+ASA combination treatment than for the ASA monotherapy. The rivaroxaban monotherapy did not result in a significant decrease in the risk of major CVC compared to the ASA monotherapy but significantly increased the risk of major bleedings. Incidence of repeated ischemic stroke for a year was 1.1% for the combination therapy, 2.6% for the rivaroxaban therapy, and 3.4% for the ASA monotherapy with significant differences between the combination treatment group and the ASA monotherapy group (p&lt;0.01). Relative risk of repeated stroke was 67% lower for the combination therapy group compared to the ASA monotherapy group. The combination of rivaroxaban (2.5 mg twice a day) and ASA (100 mg) opens a new epoch of antithrombotic treatment for primary and secondary prevention of stroke in patients with a stable atherosclerotic CVD and sinus rhythm.

Current opportunities for secondary prevention of atherothrombotic stroke

The article is devoted to an urgent medical and social problem - secondary prevention of atherothrombotic stroke and contains current evidence on the use of combined antiplatelet and anticoagulant therapy. In the COMPASS study, the dual-pathway thrombosis inhibition scheme using rivaroxaban in combination with acetylsalicylic acid (ASA) compared with ASA monotherapy demonstrated in patients with established atherosclerotic diseases of the circulatory system, a decrease in the total risk of stroke, death from cardiovascular causes and myocardial infarction by 24%; reduced risk of recurrent stroke by 67%. The incidence of repeated ischemic stroke (IS) in the combination therapy group was 1.1% per year, in the ASA group - 3.4% per year. The total incidence of adverse outcomes included in the combined indicator «net clinical benefit» in the rivaroxaban group in combination with ASA was 20% lower than in the ASA group and confirms the advantages of combination therapy in the prevention of recurrent noncardioembolic IS.

Methods of decreasing the risk of repeat interventions in patients after arterial revascularization

Discussed in the article are the main problems related to surgical treatment of patients with peripheral artery disease, particularly taking into consideration that in the world there are from 160 to 202 million people suffering from this disease, with two thirds of such patients having signs of lesions of coronary or cerebral arteries. Vascular reconstructive interventions cannot completely eliminate the problem, since in the postoperative period there may develop cardiovascular complications related to both the limb involved as either acute or progressing chronic ischaemia and arteries of other localization (coronary, cerebral). The risk of serious cardiovascular complications in patients with a history of endured adverse ischaemic events on the part of limbs is severalfold higher. To solve these problems and decrease complications, salicylic acid is used as basic therapy. Attempts at replacing it by another drug or combined therapy with an alternative antiaggregant showed no advantages in increased risk of massive haemorrhage. On the other hand, a combination of salicylic acid with an anticoagulant at a low dose, i. e., rivaroxaban 2.5 mg twice daily as compared with acetylsalicylic acid monotherapy made it possible to significantly decrease the incidence of various cardiovascular complications in the form of myocardial infarction, stroke, adverse ischaemic events on the part of the extremity, limb amputation.

Effect of ticagrelor in patients with acute coronary syndrome on the achievement of the targets of federal project on the prevention of cardiovascular diseases: 3-year perspective estimates

Aim . To assess the additional effect of ticagrelor as part of dual antiplatelet therapy (DAPT) compared with DAPT with clopidogrel and acetylsalicylic acid (ASA) monotherapy on the achievement of goals of federal project on the prevention of cardiovascular diseases: “reduction of cardiovascular mortality” and “reduction of mortality from myocardial infarction (MI)”. Material and methods . In the first year of treatment, all adult Russian patients with documented acute coronary syndrome (ACS), who had indications for DAPT, were considered as the target population. In the second and third years, treat -ment was continued only by patients with a high risk of thrombotic events. The calculation of the number of deaths that can be prevented using DAPT with ti -cagrelor 90 mg + ASA instead of clopidogrel + ASA during the first year was based on the data of the PLATO trial. To calculate the number of deaths that can be prevented using DAPT with ticagrelor 60 mg + ASA instead of ASA monotherapy, we used the data of PEGASUS trial for patients with a history of MI within the past 2 years. Then the proportion of goals that can be achieved in 2021-2023 was calculated when using DAPT with ticagrelor instead of clopidogrel or ASA monotherapy. Results. The use of ticagrelor within DAPT for patients with ACS will allow (compared to DAPT with clopidogrel and ASA monotherapy): — to prevent an additional 5389, 5702 and 6009 deaths in 2021, 2022, and 2023, respectively, achieving the target of federal project on the prevention of cardiovascular diseases “reduction of cardiovascular mortality” by 18,4, 19,4 and 20,5%, respectively. In addition, the use of ticagrelor within DAPT for patients with ACS compared with clopidogrel or ASA monotherapy will also allow: — to prevent an additional 957, 1013 and 1067 deaths due to MI in 2021, 2022, and 2023, respectively, achieving the target of federal project on the prevention of cardiovascular diseases “reduction of mortality from MI” by 50,2%, 49,3% and 51,9%, respectively. Conclusion . The use of ticagrelor in patients with ACS will reduce cardiovascular mortality and contribute on the achievement of goals of federal project on the prevention of cardiovascular diseases.

SETAP: epidemiology and prevention of stroke and transient ischaemic attack in Czech patients with atrial fibrillation.

The aim of this study is to analyse the prevalence, epidemiology, and anticoagulation prevention of stroke or transient ischaemic attack (TIA) in Czech patients with atrial fibrillation (AF). Retrospective observational analysis of diagnoses, procedures, and treatment reported to the Czech National Registry of Reimbursed Healthcare Services between 2015 and 2018. Prevalence of AF in 2018 was 4.3% of Czech population and the prevalence of stroke/TIA in AF patients was 22.3% with annual incidence of 181.62 cases per 100 000 inhabitants. In 2018, CHA2DS2-ASc score ≥4 was present in 98% AF patients in secondary and 59% in primary prevention, respectively, while the anticoagulation treatment was used by 71-81% of them. Between 2015 and 2018, the percentage of AF patients treated with warfarin monotherapy in primary prevention decreased from 35% to 31%, with acetylsalicylic acid (ASA) monotherapy from 18% to 16% and non-vitamin K antagonist oral anticoagulants (NOACs) monotherapy increased from 7% to 11%. In secondary prevention, the percentage of warfarin monotherapy treatment decreased from 35% to 32%, with ASA monotherapy from 20% to 18% and with NOACs monotherapy increased from 9% to 15%. This study followed all Czech patients with AF. The unadjusted prevalence and incidence of AF was higher compared with other countries and 2019 European Society of Cardiology Statistics. The study identified several gaps in standard of reimbursed care. 20-30% of AF patients with other risk factors were without any prevention medication and the share of ASA monotherapy in treated patients was 16-18%.

Early dual antiplatelet therapy versus acetylsalicylic acid monotherapy after CABG: propensity score analysis addressing survival and safety outcomes

Abstract Background There is currently conflicting evidence regarding the security profile and outcomes of dual antiplatelet therapy (DAPT) in patients following coronary artery bypass grafting (CABG). Aim We aim to compare the effect of early DAPT in short and long-term survival versus acetylsalicylic acid in a monotherapy regimen (ASA). Therapy's safety was evaluated through immediate or early postoperative outcomes, with particular emphasis on the haemorrhagic. Methods Single-centre retrospective cohort study on consecutive patients undergoing 1st isolated CABG surgery in 2010. Median follow-up time was 9 years. Pre-, peri- and postoperative data was collected through clinical files and digital databases. The DAPT and ASA groups were defined considering the administration of clopidogrel plus acetylsalicylic acid and only acetylsalicylic acid, respectively, within a 24h window after CABG. T-tests and Pearson's chi-squared tests were used for group comparison. Survival analysis was performed using Kaplan-Meier curves, Log-Rank test and multivariable Cox regression. Propensity scores (PS) were estimated using a multivariable logistic regression model and included in multivariable regressions as a covariate along with DAPT. Early mortality was defined if occurred before discharge or within the 30 days following the surgery; bleeding was assessed through red blood cells' (RBC) transfusion, re-exploration of thorax and drainage. Results We included 351 patients, 81% were male, and DAPT was performed in 251 patients (72%). DAPT patients were younger (63±10 vs. 66±10 years, p=0.007) but both groups were similar regarding the cardiovascular modifiable risk factors. Kaplan-Meier curves showed similar cumulative survival between groups (75% in DAPT vs. 67% in ASA group, at 9 years of follow-up, Log-rank p=0.103), as well as the PS adjusted analysis (HR DAPT: 0.93, 95% CI: 0.57–1.51). Regarding safety outcomes, we found no differences in early mortality (two cases in the DAPT group and one in the ASA group). Total median cell-saver transfusion (300mL vs. 250mL, p=0.318) and the re-exploration of thorax due to bleeding (1.6% vs. 4% p=0.231) showed no statistical significance either. On the other hand, post-operative total median chest tube drainage was higher in the ASA group (1220mL in DAPT vs. 1300mL in ASA, p=0.043). There was also a lower frequency of DAPT patients requiring 3 or more peri and postoperative RBC transfusions (8.5% vs. 13.3% p&amp;lt;0.001 and 4.8% vs. 13%, p=0.009, respectively) and a shorter in-hospital stay following CABG (median of 7 days for DAPT and 8 days for ASA, P&amp;lt;0.001). Redo-CABG was performed in 3 patients (2 DAPT vs. 1 ASA) during follow-up. Conclusion Compared with ASA, DAPT showed a non-significant impact on long-term survival but demonstrated to be a safe option within the assessed bleeding outcomes. Further studies are needed to provide recommendations on the therapeutical strategy following CABG. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Universidade do Porto/FMUP, FSE-Fundo Social Europeu, NORTE 2020-Programa Operacional Regional do Norte, Programas Doutorais. Project NetDIAMOND, supported by ESIF under Lisbon Portugal Regional Operational Programme and National Funds through FCT