Acetylsalicylic Acid In Patients Research Articles

A study of the comparative effectiveness of dual antiplatelet therapy and a combination of acetylsalicylic acid with colchicine in patients in the acute period of “minor” ischemic atherothrombotic stroke during hospitalization. Interim analysis of data from the «COLCHIDA» study

Influence on inflammation is currently becoming a priority target for the prevention of recurrent atherothrombotic events, including stroke. In 2022, we planned the KOLCHIDA study, a two-center, prospective, randomized, open-label, controlled clinical trial with endpoint assessment (ClinicalTrials.gov identifier: NCT06102720). The purpose of this study is to conduct a comparative assessment of the clinical effectiveness of dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel and the combination of ASA with colchicine in patients in the acute period of “minor” ischemic atherothrombotic stroke. The purpose of this publication is to present the basic concept of the protocol, its design and the first intermediate results. Material and methods. The intervention consisted of colchicine 0.5 mg/day in addition to ASA versus dual antiplatelet therapy (DAPT) in patients with non-severe ischemic stroke. 31 patients were included in the colchicine and ASA group, and 34 patients were included in the DAPT group. Results. In the comparison group, 7 (20.6%) recurrent non-fatal strokes were recorded, in contrast to the colchicine group, where acute vascular events were recorded in only two patients (6.5%) [RRR 2.2, NNT = 7, χ2 = 2, 9, p = 0.09]. There were no clinically significant bleeding or other adverse events in both groups. Conclusion. Interim results of the study indicate possible confirmation of the hypothesis that anti-inflammatory therapy with low doses of colchicine in combination with standard therapy is not inferior to the combination of ASA and clopidogrel, and perhaps more effectively reduces the number of early neurological deteriorations and recurrent ischemic strokes in patients in the acute period of mild atherothrombotic stroke with equal security profile.

Postgenomic aspects of resistance to acetylsalicylic acid in patients with coronary artery disease

Aim. To study the expression level of the P-selectin gene (SELP) mRNA and the level of intercellular interaction in patients with coronary artery disease (CAD) before and after coronary artery bypass grafting (CABG) in patients with resistance to acetylsalicylic acid (ASA).Material and methods. The study included 65 patients with CAD who were scheduled to CABG. SELP expression, the platelet-leucocyte aggregate level, and the level of P-selectin expression on aggregates were determined in all participants. Resistance to ASA was defined as platelet aggregation with arachidonic acid ≥20% in at least one sample. All studies were performed before and on the 8th-10th day after CABG.Results. Among patients, 29,4% (n=30) were resistant to ASA (ASA-R) at least at one point, while 7,8% (n=8) acquired resistance after CABG. ASA-R had a higher level of SELP (0,41 [0,28; 0,48] vs 0,32 [0,23; 0,39], p=0,037), absolute content of monocyte-platelet aggregates (24,70 [9,69; 39,90] vs 10,15 [5,27; 30,63], p=0,037) and relative amount of platelet-platelet CD62P aggregates (7,37% [3,43; 35,49] vs 4,84% [0,90; 9,63], p=0,045). A negative correlation was found between SELP expression and the relative content of monocyte-platelet aggregates (ρ=-0,349, p=0,013) on days 8-10 after CABG. Mmultivariate regression analysis found that the level of SELP gene mRNA expression is a predictor of ASA resistance before CABG (odds ratio 404,48; 95% confidence interval 1,68-97461,63).Conclusion. Increased SELP expression is associated with an increase in platelet aggregation activity, which contributes to an insufficient platelet response to antithrombotic therapy in patients with CABG. The level of SELP gene mRNA expression can be considered as a predictor of ASA resistance.

Long-term combined antiplatelet therapy for secondary prevention of noncardioembolic stroke

Introduction. The high risk of recurrent ischemic events after non-cardioembolic ischemic stroke(IS), the prevalence of which is 25% of all strokes in the Russian Federation, determines the need to search for effective and safe secondary prevention strategies.Аim. The study was to evaluate the efficacy and safety of a combination of ADP receptor inhibitors (dipyridamole) with acetylsalicylic acid in patients with ischemic stroke (IS) in the secondary prevention of noncardioembolic stroke.Materials and methods. 229 patients in the early recovery period of noncardioembolic IS (139 women, 90 men), with an average age of 59.0 ± 5.7 years were included in the study. The duration of IS was 54.4 ± 6.1 days. All patients received a multimodal medical rehabilitation (MMR) program. Long-term double antiplatelet therapy with acetylsalicylic acid (ASA) 75 mg per day and dipyridamole at a daily dose of 225 mg divided into 3 doses were prescribed to all the patients. The neurological and neuropsychological status of the patient, quality of life and hemorheological parameters were assessed initially (T0), after MMR (T1, 6 weeks) and 12 months after IS(T2).Results. Motor and coordination indicators of patients as well as the cognitive and emotional parameters were significantly (p < 0,05) improved due to MMR technology. These were confirmed by the dynamics of the corresponding scales. The prescribed double antiplatelet therapy did not cause significant adverse events and worsening of the patients’ well-being both during the MMR process and during the observation period. The combination of ASA with dipyridamole was well tolerated. At the end of the study, recurrent IS, myocardial infarctions, and fatal bleeding were not recorded. In 5.2% patients with severe risks of cardiovascular complications there was occurred TIA. The effectiveness of the dual antiplatelet therapy was confirmed by a decrease in the level of platelet aggregation (p < 0,05).Conclusions. The high effectiveness of secondary prevention of IS with a combination of ASA and dipyridamole with good tolerability and safety in patients after IS has been shown.

Bleeding in patients on concurrent treatment with a selective serotonin reuptake inhibitor (SSRI) and low-dose acetylsalicylic acid (ASA) compared with SSRI or low-dose ASA alone-A systematic review and meta-analysis.

The aim of this study was to systematically review whether concurrent treatment with an SSRI and low-dose ASA increases the risk of bleeding compared with treatment with an SSRI alone or ASA alone. Medline, Embase, the Cochrane Library, PsycINFO and Web of Science (from database inception to January 2023) were searched according to PICO: P = patients on treatment with an SSRI and/or low-dose ASA; I = intervention: SSRI + ASA; C = comparison: ASA or SSRI alone; O = outcomes: bleeding/major bleeding. The included articles were assessed using checklists. Studies without major risk of bias formed the basis for the conclusions. Extracted data were pooled using random-effects meta-analyses. Certainty of evidence was assessed according to GRADE. Twenty-four studies met the PICO and were included. One randomized and six nonrandomized studies were assessed not to have major risk of bias. Regarding SSRI + ASA vs. ASA only, the pooled hazard ratio of three nonrandomized studies (n = 38 467) was 1.37 (95% confidence interval: 1.10; 1.70; I2= 0%), and the pooled odds ratio of two nonrandomized studies (n = 28296) was 0.95 (0.77; 1.19; I2= 0%). Regarding SSRI + ASA vs. SSRI only, the randomized controlled trial (n = 1048) reported a hazard ratio of 1.82 (0.66; 5.02), the hazard ratio being 1.60 (1.24; 2.06) for ASA vs. placebo in patients without SSRI treatment; and one nonrandomized controlled study (n = 18 920) reported an incidence rate ratio of 1.03 (0.96; 1.12). The compiled evidence was too uncertain to support an interaction when an SSRI is added to low-dose ASA. Low-dose ASA added to an SSRI may imply an increased risk of bleeding primarily attributable to the initiation of ASA.

Feasibility and comparability of different platelet function tests in acute stroke with or without prior antiplatelet therapy.

The clinical course of ischemic and hemorrhagic strokes can be influenced by the coagulation status of individual patients. The prior use of antiplatelet therapy (APT) such as acetylsalicylic acid (ASA) or P2Y12-antagonists has been inconsistently described as possibly increasing the risk of hemorrhagic transformation or expansion. Since clinical studies describing prior use of antiplatelet medication are overwhelmingly lacking specific functional tests, we aimed to implement testing in routine stroke care. We used fluorescence-activated cell sorting (FACS) with antibodies against CD61 for thrombocyte identification and CD62p or platelet activation complex-1 (PAC-1) to determine platelet activation. Aggregometry and automated platelet functioning analyzer (PFA-200) were employed to test thrombocyte reactivity. FACS and aggregometry samples were stimulated in vitro with arachidonic acid (AA) and adenosine diphosphate (ADP) to measure increase in CD62p-/PAC-1-expression or aggregation, respectively. Between February and July 2023, 20 blood samples (n = 11 ischemic strokes; n = 7 hemorrhagic strokes; n = 2 controls) were acquired and analyzed within 24 h of symptom onset. N = 11 patients had taken ASA, n = 8 patients no APT and n = 1 ASA+clopidogrel. ASA intake compared to no APT was associated with lower CD62p expression after stimulation with AA on FACS analysis (median 15.8% [interquartile range {IQR} 12.6-37.2%] vs. 40.1% [IQR 20.3-56.3%]; p = 0.020), lower platelet aggregation (9.0% [IQR 7.0-12.0%] vs. 88.5% [IQR 11.8-92.0%]; p = 0.015) and longer time to plug formation with PFA-200 (248.0 s [IQR 157.0-297] vs. 121.5 s [IQR 99.8-174.3]; p = 0.027). Significant correlations were noted between AA-induced CD62p expression and aggregometry analysis (n = 18; ρ = 0.714; p < 0.001) as well as a negative correlation between CD62p increase and PFA clot formation time (n = 18; ρ = -0.613; p = 0.007). Sensitivity for ASA intake was highest for PFA (81.8% for values ≥155.5 s). The combination of ASA + clopidogrel also affected ADP-induced CD62p and PAC-1 expression. In the clinical setting it is feasible to use differentiated platelet analytics to determine alterations caused by antiplatelet therapy. Among the tests under investigation, PFA-200 showed the highest sensitivity for the intake of ASA in stroke patients. FACS analysis on the other hand might be able to provide a more nuanced approach to altered platelet reactivity.

Плейотропные эффекты ацетилсалициловой кислоты

Currently, researchers are investigating new mechanisms of action and potential applications of acetylsalicylic acid (ASA). This article summarizes recent studies on the use of ASA for primary prevention of cardiovascular complications (CVC), cancer, and chronic obstructive pulmonary disease (COPD) in progressive chronic kidney disease (CKD). The article discusses the efficacy and safety of ASA in patients with diabetes, COPD, CKD, and subclinical atherosclerosis of brachiocephalic arteries. ASA is a promising tool for primary prevention of CVC and progression of COPD and its complications, as well as malignant diseases. The safety profile of ASA is also addressed. The optimal dosage form of ASA that is both effective and safe is an important factor that should be considered when prescribing ASA for long-term use. Enteric-coated ASA is now widely used due to its diminished negative effect on gastrointestinal mucosa and improved safety. KEYWORDS: primary prevention, acetylsalicylic acid, antiplatelet therapy, cardiovascular complications, chronic kidney disease, chronic obstructive pulmonary disease, diabetes FOR CITATION: Smirnova M.D. Pleiotropic effects of acetylsalicylic acid. Russian Medical Inquiry. 2024;8(1):31–36 (in Russ.). DOI: 10.32364/2587-6821-2024-8-1-5.

The improvement of endothelial function by inhibition of platelet activity using acetylsalicylic acid in patients with arterial hypertension

In accordance with modern ideas about the pathogenesis of thrombotic complications of cardiovascular diseases (myocardial infarction, stroke), it should be noted that platelets and platelet humoral factors play a key role in the development of thrombosis. Activated platelets are able to activate both endotheliocytes and pro-inflammatory cells - monocytes/macrophages, which take a direct part in the formation and progression of atherosclerotic plaque. The purpose of the study is to investigate the potential improvement of endothelial function through the inhibition of platelet activity using acetylsalicylic acid in patients with arterial hypertension and established atherosclerotic cardiovascular diseases. Materials and methods. We enrolled 41 patients with arterial hypertension and established atherosclerotic cardiovascular diseases in our study. The participants were divided into two groups. Group 1 comprised 20 patients who were already taking acetylsalicylic acid (ASA) before the study, while Group 2 consisted of 21 patients who had not received ASA before participating. During the 6-month study period, patients from both groups received ASA (75 mg once a day) as part of their basic therapy, which included antihypertensive and statin therapy. Platelet activity was assessed in all patients before the study and at the final stage by determining the expression of glycoproteins GPIIb-IIIa and P-selectin on their surface. Additionally, the content of endothelial progenitor cells (phenotype CD45-CD31+CD133+) and desquamated endothelial cells (phenotype CD45-CD31+CD133-) in the blood was analyzed using flow cytometry. ELISA was employed to measure the content of C-reactive protein, cytokines TNF-α and IL-10, as well as asymmetric dimethylarginine (ADMA) in the blood. Finally, all patients underwent a test with flow-dependent vasodilation of the brachial artery. Results. In patients who did not receive ASA before the study, there was a higher level of platelet activity in peripheral blood flow, along with signs of more pronounced endothelial dysfunction compared to those who received it. After 6 months of taking ASA alongside standard antihypertensive therapy, the activation level of circulating blood platelets decreased in both groups. Specifically, in patients of group 1, the expression level of CD41 (GPIIb) decreased by 31.8 % (p &lt; 0.01), and CD61 (GPIIIa) decreased by 15.2 % (p &lt; 0.01). In group 2 patients, the suppression of platelet activity was even more pronounced, with the expression level of CD41 (GPIIb) decreasing by 55.2 % (p &lt; 0.001), and CD61 (GPIIIa) decreasing by 27.5 % (p &lt; 0.05). Furthermore, in patients of group 1, the percentage of platelets carrying P-selectin on the surface decreased by 78.1 % (p &lt; 0.01). In group 2, the number of such platelets also significantly decreased by 42.5 % (p &lt; 0.05). The number of progenitor cells of endothelial cells in the circulating blood increased significantly in both groups, showing a 3-fold increase in patients of group 1 (p &lt; 0.001) and a 2.3-fold increase in patients of group 2 ( p&lt; 0.001). In patients of both groups, a significant 2-fold increase in the endothelium-dependent vasodilatation index was observed (p &lt; 0.01). At the end of the study, there was a decrease in the blood level of CRP by 12.2 % and 18.8 %, and pro-inflammatory cytokine TNF-α decreased by 50% and 57 %, respectively, in patients of groups 1 and 2 (p &lt; 0.001). Conclusion. The reduction in blood platelet activity triggered by ASA in patients with arterial hypertension and atherosclerotic cardiovascular diseases was associated with notable alterations in the intensity of systemic inflammation and the restoration of endothelial functions. These findings suggest a potential therapeutic role for ASA in modulating both platelet function and endothelial health in individuals with these conditions.

Antiplatelet effect of acetylsalicylic acid in patients early after cardiac valve surgery: comparative investigation of the impairment of platelet inhibition by dipyrone versus acetaminophen

Abstract Background Low-dose acetylsalicylic acid (ASA) is recommended in current guidelines for a period of 3 months after surgical implantation of a bioprosthesis in aortic position or after surgical repair of the mitral valve. Dipyrone (D; metamizole) and acetaminophen (A; paracetamol) are frequently used non-opioid analgesics after surgery. The active metabolite of dipyrone (4-methylaminoantipyrine) is a reversible inhibitor of cyclooxygenase-1 and an interaction with the antiplatelet effect of ASA in more than 50 % of patients has been reported. Material and methods We enrolled 162 patients scheduled for cardiac surgery in this prospective investigator-initiated clinical study. Patients were randomized at day 1 after surgery to either 4 x 1g dipyrone iv/day or 4 x 1g acetaminophen iv/day. All patients were on ASA 100 mg daily (200 mg at day 1). The primary endpoint was the proportion of patients with adequate antiplatelet response to ASA assessed via determination of thromboxane B2 in platelet rich plasma after stimulation with arachidonic acid (AA) at day 4/5 after surgery (cutpoint ≤209.8 ng/ml thromboxane B2). Key secondary endpoints comprised platelet reactivity assessed by light transmission aggregometry [LTA] and by multiple electrode impedance aggregometry [MEIA]. Results 15 patients dropped out of the study. Thus, data from 71 patients randomized to dipyrone and 76 patients randomized to acetaminophen were available for data analysis. Patients had a mean age of 66.5±7.6 years and 97 were male and 50 female. Aortic valve was replaced in 92 patients, 54 underwent mitral valve reconstruction and combined surgery was performed in a single patient. The primary endpoint analyzed at day 4/5 after surgery is shown in the Figure. The proportion of non-responders was 12.5% (D) and 3.0% (A), respectively. Platelet reactivity at day 4/5 after surgery was assessed after stimulation with arachidonic acid by LTA or MEIA. No statistically significant difference between the treatment strata was determined in both assays: Maximum aggregation in LTA was 5.0% (median; 95% confidence interval [95% CI]: 4.0 - 8.0%) in D+ASA and 6.0% (95% CI: 5.0 - 11.0%) in A+ASA (p=0.528) and MEIA AUC was 345.5 AU*min (95% CI: 268.0 - 419.0) in D+ASA and 276.5 AU*min (95% CI: 241.0 - 330.0) in A+ASA (p=0.098). Plasma concentrations of MAA in patients treated with dipyrone were higher in patients identified as responders to ASA (86.6 µM; 95% CI: 67.9 - 102.4 µM) compared to non-responders (31.0 µM; 95% CI: 2.9 – 146.7 µM; p=0.0147). Summary and conclusion The proportion of non-responders to ASA is higher in patients treated with dipyrone compared to acetaminophen. The proportion of non-responders in the dipyrone-treated group in our study is substantially lower than reported in previous studies. High plasma concentrations of MAA in responders may contribute to enhanced inhibition of COX-1 in patients treated with dipyrone.

Rapid desensitization to acetylsalicylic acid in patients with ischemic heart disease: 10-year experience of a portuguese allergy department.

Introduction. Managing Acetylsalicylic Acid (ASA) hypersensitivity (HS) in patients with ischemic heart disease (IHD) is a challenge. Data on Rapid Desensitization (RD) to ASA is scarce. We aimed to report the outcomes of our 10-year experience with RD to ASA. Methods. Retrospective, observational, single-center study of patients with ASA HS and suspected IHD who underwent RD to ASA between March 2009 and February 2019. Results. Fifty patients were included. ASA HS presentation ranged from urticaria (56%) to anaphylaxis (32%). Regarding cardiologic diagnoses, 40 patients (80%) had acute coronary syndrome and 10 (20%) stable angina. The majority of patients (N = 36.72%) underwent percutaneous coronary intervention. RD to ASA was successful in all patients. Two patients presented a mild HS reaction during the RD, which was promptly treated, and subsequent daily doses of ASA 100 mg were tolerated. Conclusions. In our cohort, RD to ASA in patients with ASA HS and IHD was very effective and safe.

Pharmacoeconomic analysis of antithrombotic therapy in patients with acute coronary syndrome and patients with atrial fibrillation who underwent percutaneous coronary intervention

Objective: to assess the clinical and economic feasibility of ticagrelor in combination with acetylsalicylic acid (ASA) in comparison with clopidogrel in combination with ASA in patients with acute coronary syndrome (ACS), including both those who underwent, and those who did not undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG); and new oral anticoagulants (NOACs) in combination with clopidogrel in comparison with warfarin in combination with clopidogrel and ASA in patients with atrial fibrillation (AF) who underwent PCI; to identify the impact of the above strategies of antithrombotic therapy on the targets of the State Health Care Program of the Russian Federation (RF) “Development of Health Care” and the Federal Project “Cardiovascular Diseases Control”.Material and methods. The clinical and economic study (CES) of ticagrelor in combination with ASA in ACS patients was based on a costbenefit analysis. A combined model, including a decision tree and Markov model was developed. The horizon period of the analysis was 5 years. Quality-adjusted life year (QALY) was used as an efficiency criterion and only the direct medical costs associated with the conditions identified in the modeling were taken into account. A discount rate of 5% was taken into account during the CES. The application of NOACs in combination with clopidogrel was studied in the CES using a cost minimization analysis considering the costs per patient characterized by the presence of AF regardless of the presence of ACS and a history of PCI.Results. We used a decision tree and Markov modeling in adult patients with ACS, who had or had not undergone PCI or CABG, in the horizon period of 5 years considering the discount rate of the added quality-adjusted life year (incremental cost-effectiveness ratio (ICER) per QALY). The result for ticagrelor in combination with ASA compared to clopidogrel in combination with ASA was 605,199 rubles, which was significantly lower than the willingness-to-pay threshold (2,235,201 rubles). Assessment of the impact of the therapy regimen including ticagrelor in combination with ASA on the target indicators of the State Health Care Program of the RF “Development of Healthcare” and the Federal Project “Cardiovascular Diseases Control” showed that the use of this therapy regimen will reduce mortality from myocardial infarction (MI) and cardiovascular causes by 2.45 cases per 100 thousand population provided that 100% of patients with MI and unstable angina in the RF are transferred from clopidogrel + ASA scheme to ticagrelor + ASA. The potential contribution of ticagrelor in combination with ASA compared to clopidogrel in combination with ASA in patients with ACS in achieving the target reduction of mortality from circulatory diseases will be 6.48% by 2023. In all simulated scenarios, in the group of patients with AF who had undergone PCI, pharmacotherapy regimens containing NOACs (dabigatran etexilate, rivaroxaban, apixaban) were more costly than therapy regimens containing warfarin (with not significantly different effectiveness).Conclusion. The results of the evaluation of clinical and economic feasibility of antiplatelet therapy strategies demonstrated the costeffectiveness of ticagrelor in combination with ASA compared to clopidogrel in combination with ASA in patients with ACS, including those who had undergone PCI or CABG and those who had not. The strategy of ticagrelor + ASA showed a favorable effect on the rates of mortality from MI, as well as from circulatory diseases. The results of the clinical and economic evaluation of the four strategies of antithrombotic drug therapy in patients with AF who had undergone PCI showed higher costs of the regimens containing NOACs with a presumed zero effect on the mortality from circulatory diseases.

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.

USPSTF concludes daily aspirin may hurt more than help, especially for older adults

USPSTF concludes daily aspirin may hurt more than help, especially for older adults

Antiplatelet agents and anticoagulants for hypertension.

The main complications of elevated systemic blood pressure (BP), coronary heart disease, ischaemic stroke,and peripheral vascular disease, are related to thrombosis rather than haemorrhage.Therefore, it is important to investigate if antithrombotic therapy may be useful in preventing thrombosis-related complications in patients with elevated BP. To conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with elevated BP, including elevations in systolic or diastolic BP alone or together. To assess the effects of antiplatelet agents on total deaths or major thrombotic events or both in these patients versus placebo or other active treatment. To assess the effects of oral anticoagulants on total deaths or major thromboembolic events or both in these patients versus placebo or other active treatment. The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to January 2021: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 12), Ovid MEDLINE (from 1946), and Ovid Embase (from 1974). The World Health Organization International Clinical Trials Registry Platform and the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) were searched for ongoing trials. SELECTION CRITERIA: RCTs in patients with elevated BPwere included if they were ≥ 3 months in duration and compared antithrombotic therapy with control or other active treatment. Two review authors independently extracted data for inclusion criteria, our prespecified outcomes, and sources of bias. They assessed the risks and benefits of antiplatelet agents and anticoagulants by calculating odds ratios (OR), accompanied by the 95% confidence intervals (CI). They assessed risks of bias and applied GRADE criteria. MAIN RESULTS: Six trials (61,015 patients) met the inclusion criteria and wereincluded in this review. Four trials were primaryprevention (41,695 patients; HOT, JPAD, JPPP, and TPT), and two secondary prevention (19,320 patients, CAPRIE and Huynh). Four trials (HOT, JPAD, JPPP, and TPT) were placebo-controlled and two studies (CAPRIE and Huynh) included active comparators. Four studies compared acetylsalicylic acid (ASA) versus placebo and foundno evidence of a difference for all-cause mortality (OR 0.97, 95% CI 0.87 to 1.08; 3 studies, 35,794 participants; low-certainty evidence). We found no evidence of a difference for cardiovascular mortality (OR 0.98, 95% CI 0.82 to 1.17; 3 studies, 35,794 participants; low-certainty evidence). ASA reduced the risk of all non-fatal cardiovascular events (OR 0.63, 95% CI 0.45 to 0.87; 1 study (missing data in 3 studies), 2540 participants; low-certainty evidence) and the risk of all cardiovascular events (OR 0.86, 95% CI 0.77 to 0.96; 3 studies, 35,794 participants; low-certainty evidence). ASA increased the risk of major bleeding events (OR 1.77, 95% CI 1.34 to 2.32; 2 studies, 21,330 participants; high-certainty evidence). One study (CAPRIE; ASA versus clopidogrel) included patients diagnosed with hypertension (mean age 62.5 years, 72% males, 95% Caucasians, mean follow-up: 1.91 years). It showedno evidence of a difference for all-cause mortality (OR 1.02, 95% CI 0.91 to 1.15; 1 study, 19,143 participants; high-certainty evidence) andfor cardiovascularmortality (OR 1.08, 95% CI 0.94to 1.26; 1 study, 19,143 participants; high-certainty evidence). ASA probably reducedthe risk of non-fatal cardiovascular events (OR 1.10, 95% CI 1.00 to 1.22; 1 study, 19,143 participants; high-certainty evidence) and the risk of all cardiovascular events (OR 1.08, 95% CI 1.00 to 1.17; 1 study,19,143 participants; high-certainty evidence) when compared to clopidogrel. Clopidogrelincreasedthe risk of major bleeding events when compared to ASA(OR 1.35, 95% CI 1.14 to 1.61; 1 study, 19,143 participants; high-certainty evidence). In one study (Huynh; ASA verus warfarin) patients with unstable angina or non-ST-segment elevation myocardial infarction, with prior coronary artery bypass grafting (CABG) were included (mean age 68 years, 79.8% males, mean follow-up: 1.1 year). There was no evidence of a difference for all-cause mortality (OR 0.98, 95% CI 0.06 to 16.12; 1 study, 91 participants; low-certainty evidence). Cardiovascular mortality,non-fatal cardiovascular events, and all cardiovascular events were not available. There was no evidence of a difference for major bleeding events(OR 0.13, 95% CI 0.01to 2.60; 1 study, 91 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There is no evidence that antiplatelet therapymodifies mortalityin patients with elevated BP for primary prevention. ASA reduced the risk ofcardiovascular events and increased the risk of major bleeding events. Antiplatelet therapy with ASA probably reducesthe risk of non-fatal andall cardiovascular events when compared to clopidogrel. Clopidogrelincreasesthe risk of major bleeding events compared to ASA in patients with elevated BP for secondary prevention. There is no evidence that warfarin modifies mortality in patients with elevated BP for secondary prevention. The benefits and harms of the newer drugs glycoprotein IIb/IIIa inhibitors, clopidogrel, prasugrel, ticagrelor, and non-vitamin K antagonist oral anticoagulants for patients with high BPhave not been studied in clinical trials. Further RCTsof antithrombotic therapy including newer agents and complete documentation of all benefits and harms are required in patients with elevated BP.

P1071: IMPACT OF ACETYLSALICYLIC ACID DOSAGE ON INCIDENCE OF THROMBOSIS AND MORTALITY IN PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS.

Background: Bcr/abl – negative myeloproliferative neoplasms (MPN) are associated with a higher risk of thrombosis and higher vascular mortality. Acetylsalicylic acid (ASA) used in prevention decreases risk of vascular events in patients with MPN. There is some evidence that ASA in dose 100 mg once daily results in incomplete inhibition of a platelet function over the whole 24-hour interval in most patients with essential thrombocythemia (ET). High on-treatment reactivity (HOTR) was corrected with dosing ASA twice daily. Evidence of clinical consequences of these findings has been missing. Aims: Authors compared thrombosis incidence, mortality and safety among cohorts of MPN patients with adequate on-treatment reactivity (AOTR) on ASA dosed once daily, twice daily and patients with HOTR. Methods: Response to ASA in patients with MPN was evaluated by a platelet light transmission aggregometry induced by arachidonic acid. AOTR was defined as maximal amplitude up to 20% just before the next dose of ASA. In patients with HOTR, ASA dosing was changed to twice daily with a dose from 50 mg step by step up to 150 mg till AOTR was reached. A few patients didn´t change their doses at their own decision despite HOTR. The patients were regularly followed-up. Incidence of thrombosis, adverse events and mortality were compared among the cohorts. Results: The platelet aggregation was tested in 69 patients with MPN on ASA. Patients with ET, polycythemia vera (PV), primary myelofibrosis, post-PV plus post-ET myelofibrosis and MPN not otherwise specified presented 16, 42, 36, 5 and 1%, respectively. The adequate responses (AOTR) were found in 57 (83%), cohort 1. The insufficient responses were found in 12 persons (17%), in 30% of patients on an enterosolvent form of ASA. In these 12 patients the dose of ASA was changed to 2x50mg in 4 and to 2x100mg in 1 patient (cohort 2) and remained unchanged in seven (cohort 3). There were no differences in frequency of risk factors besides higher frequency of diabetes mellitus in group 3 compared to group 1 (p=0,021). Non-adherence to regular administration of ASA was found in 10% of patients. The follow-up was 36,8 months. All-cause mortality was higher in the cohort 3 compared to the cohort 1 (p=0,009), see fig. 1, but thrombotic episodes incidence not. The cohort 2 had not different incidence of both thrombotic episodes and deaths compared to the cohort 1. No proximal gastrointestinal bleeding and other gastropathies occurred. There was no bleeding episode on ASA in dose of 2x50mg daily. A non-severe bleeding dependant on any ASA dose were found. Repeated measurement of platelet aggregation was done in 29 patients in median 49,5 months after previous measurements. There was no statistically significant difference of adequate/high platelet reactivity on ASA between the first and the last measurement. Image:Summary/Conclusion: The frequency of MPN patients with higher platelet reactivity on ASA was lower than in the most data in literature. Correction of an ASA dosage to twice daily reaching AOTR resulted in lower mortality. Other studies are required to confirm these data. Initial dose 2x50mg seems to be effective and safer than higher dosage. The long-term reproducibility of platelet aggregation testing results was preserved.

Acetylsalicylic acid use is associated with reduced risk of out-of-hospital cardiac arrest in the general population: Real-world data from a population-based study.

AimActivated blood platelet products facilitate myocardial intracellular Ca2+ overload, thereby provoking afterdepolarizations and increasing susceptibility of ischemic myocardium to ventricular fibrillation (VF). These effects are counteracted in vitro by acetylsalicylic acid (ASA), but no prior study investigated whether ASA is associated with decreased out-of-hospital cardiac arrest (OHCA) risk on a population level. Therefore, we studied whether ASA and other antiplatelet drugs (carbasalate calcium, clopidogrel) are associated with decreased risk of OHCA.MethodsWe conducted a population-based case-control study among individuals (772 OHCA-cases with documented VT/VF, 2444 non-OHCA-controls) who had used antiplatelet drugs in the year before index-date (OHCA-date), and studied the association between current antiplatelet drug use and OHCA-risk with multivariable logistic regression analysis.ResultsASA use was associated with reduced OHCA-risk (adjusted odds ratio (ORadj) 0.6 [0.5–0.8]), and more so in women (ORadj 0.3 [0.2–0.6]) than in men (ORadj 0.7 [0.5–0.95], Pinteraction 0.021). Carbasalate calcium was associated with decreased OHCA-risk in women (ORadj 0.5 [0.3–0.9]), but not in men (ORadj 1.3 [0.96–1.7], Pinteraction 0.005). Clopidogrel was not associated with reduction in OHCA-risk. Risk reduction associated with ASA in patients with OHCA was similar in the presence of acute myocardial infarction (AMI) (ORadj 0.6 [0.4–0.9]) and in the absence of AMI (ORadj 0.7 [0.4–1.2]).ConclusionASA use was associated with reduced OHCA-risk in both sexes, and more so in women, while carbasalate calcium only protected women. Clopidogrel was not associated with reduced OHCA-risk.

Predictors of Recurrent Stroke After Embolic Stroke of Undetermined Source in the RE-SPECT ESUS Trial.

BackgroundWe sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS).Methods and ResultsWe applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE‐SPECT ESUS (Randomized, Double‐Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow‐up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83–2.82]), creatinine clearance <50 mL/min (HR, 1.69 [95% CI, 1.23–2.32]), male sex (HR, 1.60 [95% CI, 1.27–2.02]), and CHA2DS2‐VASc ≥4 (HR, 1.55 [95% CI, 1.15–2.08] and HR, 1.66 [95% CI, 1.21–2.26] for scores of 4 and ≥5, respectively) versus CHA2DS2‐VASc of 2 to 3, were independent predictors for recurrent stroke.ConclusionsIn RE‐SPECT ESUS trial, expected risk factors previously linked to other common stroke causes were associated with stroke recurrence. These data help define high‐risk groups for subsequent stroke that may be useful for clinicians and for researchers designing trials among patients with ESUS.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.

Antithrombotische Therapie bei Diabetes mellitus

Cardiovascular disease (CVD) is the leading cause of death in patients with diabetes mellitus (DM) and despite modern therapeutic strategies, patients with DM have at least a two-fold increased risk of cardiovascular events. The prothrombotic state in patients with DM is associated with multiple determinants such as platelet alterations and endothelial dysfunction. Thus, proper antithrombotic strategies to reduce the risk of CVD in this population are critical. Recently, the COMPASS trial showed a net clinical benefit of the combination therapy of low-dose rivaroxaban plus acetylsalicylic acid, called dual antithrombotic therapy (DAT), when compared to acetylsalicylic acid in patients with chronic vascular disease (either peripheral artery disease [PAD] or chronic coronary syndrome [CCS]) and DM, even when it comes to all-cause mortality. Therefore, guidelines currently advise to evaluate DAT or dual antiplatelet therapy (DAPT) for high-risk patients with DM.

Features of the reactive oxygen species production by platelets and neutrophils in the formation of an insufficient response to acetylsalicylic acid in patients with coronary heart disease after coronary bypass surgery

Background. Aspirin resistance can lead to thrombosis. Platelets interact with neutrophils in the focus of atherosclerotic damage. The levels of synthesis of reactive oxygen species (ROS) characterize their functional potential. Platelet resistance to acetylsalicylic acid (ASA) can affect the synthesis of ROS.Objective. To reveal the features of ROS synthesis by platelets and neutrophils in patients with coronary heart disease (CHD) after coronary artery bypass grafting (CABG) depending on sensitivity to ASA and antiplatelet therapy.Design and methods. There were 104 patients with CHD and 36 healthy donors. Patients stopped receiving antiplatelet agents 5 days before CABG, ASA was prescribed after surgery, patients on dual antiplatelet therapy (DAT) clopidogrel were added to ASA for 2–3 days. Resistance to ASA was determined at a level of platelet aggregation with arachidonic acid ≥ 20 %. The ROS synthesis levels were examined by the chemiluminescent method (CL).Results. 31.7 % of patients were resistant to ASA (rASA). In ASA-sensitive patients (sASA), CL values were increased. In rASA on DAT, CL parameters were increased, but did not differ from sASA. In the sASA and rASA groups on ASA therapy, correlations between neutrophil and platelet CL parameters were revealed.Conclusion. The presence or absence of interaction between platelets and neutrophils at the level of receptors and/or microvesicles can lead to platelet resistance to ASA in patients with coronary artery disease. Sometimes, this effect could be compensated by DAT.

The Impact of Combination Therapy with Rivaroxaban and Acetylsalicylic Acid in Patients with Coronary Heart Disease on the Achievement of the Target for Reducing Mortality from Cardiovascular Diseases of the Federal Project "Fight against Cardiovascular Diseases"

Aim. To assess the outcomes of combination therapy with rivaroxaban and acetylsalicylic acid (ASA) in patients with stable coronary artery disease (CAD) and a high risk of thrombotic events on the set targets of Ministry of Health for reduction of cardiovascular mortality in Russia.Material and methods. The development of the model for analysis in MS Excel included the following stages: calculation of the population of patients with stable CAD who can be treated with combination therapy (rivaroxaban and ASA); calculation of the number of deaths due to cardiovascular disease (CVD), number of strokes and myocardial infarction (MI) in the current scenario (patients receive monotherapy with ASA) and simulated scenario (some patients switch from monotherapy to combination therapy); estimation the impact of the number of avoided cases of deaths due to combination therapy on set target for reducing CVD mortality in 2024 year; sensitivity analysis to assess the sustainability of outcomes.Results. Total number of eligible patients for combination therapy was estimated as 1.08 million patients. Based on the simulation results, it was determined that with the reallocation of patients from monotherapy with ASA to combination therapy with rivaroxaban and ASA, the number of avoided deaths in 2022 will be 973 cases, in 2023 – 1,622 cases, in 2024 – 3,245 cases, which will make it possible to reach 6.7%, 7.4% and 11.1% of the set target for reduction of mortality from CVD in the respective years. In addition, the gradual reallocation of patients from monotherapy to combination therapy might decrease the cases of stroke and MI in 973 and 649 cases by 2022, 1,622 and 1,082 cases by 2023, and 3 245 and 2 163 cases by 2024 year, respectively. Sensitivity analysis showed that outcomes are sustainable.Conclusion. The use of combination therapy of rivaroxaban and ASA in patients with stable CAD and high thrombotic risk will allow to achieve up to 11.1% of the set target for reduction of mortality from CVD by 2024 in Russia and can also potentially impact on another set target for reduction mortality from cerebrovascular diseases by reducing the number of strokes. Thereby, this therapy can be considered for drug provision programmes for patients with stable CAD and high thrombotic risk to fulfill the goals to reduce mortality from CVD.

Low-dose ticagrelor with or without acetylsalicylic acid in patients with acute coronary syndrome: Rationale and design of the ELECTRA-SIRIO 2 trial.

Low-dose ticagrelor with or without acetylsalicylic acid in patients with acute coronary syndrome: Rationale and design of the ELECTRA-SIRIO 2 trial.