Secondary Prevention Of Cardiovascular Events Research Articles

PMU91 Heterogeneity of Patient Preferences for Low-Dose Aspirin Treatment - Evidence from a Discrete Choice Experiment in Italy

Low-dose aspirin (LDA; 100mg), indicated as an antiplatelet for prevention of cardiovascular (CV) events, has been found to have preventative effect on colorectal cancer (CRC). This study assessed heterogeneity in patient preferences for efficacy including CV and CRC prevention, as well as safety outcomes associated with LDA in primary and secondary prevention of CV events in Italy. Individuals in Italy eligible for LDA treatment completed a discrete choice experiment (DCE) to elicit preferences for LDA benefits (myocardial infarction prevention, ischaemic stroke and CRC) and risks (gastrointestinal bleeding, peptic ulcer, intracranial bleeding and severe allergic reaction). Participants were divided into primary prevention cohort (PPC) and secondary prevention cohort (SPC) which were analysed separately using latent class logit models. A total of 1,005 participants completed the DCE of whom 49% were in PPC. Mean age was 62.4 years and most respondents were overweight (mean body mass index=26.6 kg/m2) with low education (76%). The best fit was a 4-class model for the PPC and a 3-class model for the SPC. A class of patients (26% of PPC), characterized by having a type 2 diabetes and current use of LDA, especially valued myocardial infarction (relative attribute importance [RAI]=35%) and ischaemic stroke (RAI=29%) whereas a class of patients (18.3% of PPC), characterized by younger age and a low propensity of having type 2 diabetes and past use of blood pressure lowering drug, tended to value CRC prevention (RAI=25%). A class of patients (37% of SPC), characterized by relatively younger age, having a smoking history, being physically inactive and having many CV comorbidities, tended to value intracranial hemorrhage (RAI=31%) and gastrointestinal bleeding (RAI=31%). Italian patients have heterogenous preferences for benefits and risks of LDA. There exists a strong relationship between patients' characteristics like age, LDA use, CV comorbidities, and treatment preferences.

Icosapent Ethyl - More than Just a Fish Tale?

Icosapent ethyl (Vascepa®) is a purified preparation of the omega-3 fatty acid eicosapentaenoic acid, which is marketed by Amarin Pharma. The product was initially approved by the U.S. Food and Drug Administration for the use of a high dose (4 g/day) in the treatment of hypertriglyceridemia. On the basis of the results of the REDUCE-IT trial, the agency later granted a label extension to include the additional indication of a reduction in risk of cardiovascular events in persons with serum triglyceride levels 150 mg/dl or greater and established cardiovascular disease or diabetes. Data supporting the efficacy of omega-3 fatty acids in the prevention of cardiovascular disease have been inconsistent and controversial. The story of the development of icosapent ethyl has been fraught with challenges, including the invalidation of six core patents on the product, and recently, the completion of a new clinical trial, STRENGTH, that directly contradicts REDUCE-IT and calls into question whether icosapent ethyl is actually effective in the secondary prevention of cardiovascular events. This article traces the course of the development of this fascinating product and discusses lessons that can be learned from its complex history, which is still continuing to unfold.

Ex vivo synergistic effects of apixaban with dual anti-platelet therapy (DAPT) in lowering platelet reactivity and thrombin generation (SEARCH)

Abstract Direct oral anticoagulants such as apixaban are increasingly being evaluated clinically for the secondary prevention of cardiovascular events; however, their effects on platelet function in combination with dual anti-platelet therapy (DAPT) have not been fully investigated. The purpose of this translational, in vitro study was to determine if apixaban via inhibition of thrombin generation exhibits synergistic activity with DAPT to reduce platelet reactivity. Consented subjects with a prior history (<12 mo) of ACS on DAPT regime with aspirin and clopidogrel (n=15; DAPT-C) or aspirin and ticagrelor (n=15; DAPT-T) were recruited, along with the age-matched healthy subjects as controls. Enrolled DAPT subjects had taken their prescribed regimen >7 days prior to blood collection. Platelet-rich plasma from TSC anticoagulated blood was prepared and treated in vitro with nothing, a carrier control or apixaban (40, 90 and 220 ng/mL). The range of 40 to 220 ng/mL brackets the expected apixaban exposure at steady state with all three approved regimens with the 40 ng/mL treatment corresponding to <5th percentile for the 2.5 mg bid dose, the 90 ng/mL corresponding to Cmax after the 2.5 mg bid or to Cmin after the 5 mg bid dose, and the 220 ng/mL corresponding to the Cmax after 10 mg bid dose. Platelet aggregation was measured by light transmission aggregometry (LTA) with tissue factor (TF) as agonist. Platelet p-selectin expression was measured by flow cytometry and thrombin generation was quantified. TF agonist was chosen to evaluate endogenous thrombin effects via Factor Xa activation (fXa). The CaCl2 concentration in the TF was titrated in the presence of peptide GPRP which minimized fibrin generation. The baseline maximal aggregation (MA) response was similar for both DAPT-T and DAPT-C (64%). Compared to DAPT alone, 90 and 220 ng/mL apixaban treatments decreased MA from 64% to 36% and 17% in the DAPT-T group and from 64% to 28% and 9% in the DAPT-C group (p<0.009), respectively. Platelet P-selectin expression decreased by 53% in the DAPT-T group with 220 ng/mL apixaban treatment (p<0.02) and in the DAPT-C group by 70% and 76% with 90 and 220 ng/mL apixaban treatment (p<0.004), respectively, compared to DAPT alone. Apixaban treatment (90 and 220 ng/mL) significantly increased thrombin generation lag time and time-to-peak results and significantly decreased peak thrombin in both DAPT groups (p<0.05). ACS patients on a DAPT regimen were susceptible to thrombin-mediated platelet activation via fXa. Apixaban treatment in vitro caused a larger reduction in thrombin-mediated platelet activation in the clopidogrel group compared to the ticagrelor group, consistent with ticagrelor having a more potent anti-platelet effect compared to clopidogrel. The in vitro addition of apixaban that corresponded to currently approved dosing regimens and at plasma drug levels routinely achieved demonstrated synergy with DAPT to reduce platelet reactivity and thrombin generation. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Bristol-Myers Squibb

Successful lifestyle modification in older patients with coronary artery disease: results from the RESPONSE-2 trial

Abstract Introduction Interventions to reduce lifestyle-related risk factors (LRFs) such as overweight, physical inactivity and smoking are effective in the secondary prevention of cardiovascular events. However, evidence of the effects of lifestyle-related secondary prevention programmes in older patients with coronary artery disease (CAD) is less conclusive than in younger patients. Purpose To compare the treatment effect on lifestyle-related risk factors (LRFs) in older (≥65 years) versus younger (<65 years) patients with CAD in The Randomised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists 2 (RESPONSE-2) trial. Methods The RESPONSE-2 trial was a community-based lifestyle intervention trial (N=824) comparing nurse-coordinated referral to a comprehensive set of three lifestyle interventions (physical activity, weight reduction and/or smoking cessation) to care as usual. The primary outcome was the proportion of patients with improvement at 12 months follow-up (N=711) in at least 1 LRF (without deterioration in the other LRFs). In the current analysis, we assessed if the overall beneficial treatment effect of the RESPONSE-2 intervention varied by age. Results At baseline, older patients (n=245, 69.2±3.9) had significantly more serious cardiovascular risk profiles and comorbidities (hypertension, diabetes mellitus and peripheral artery disease) than younger patients (n=579, 53.7±3.9). The overall treatment effect did not vary by age (OR overall 1.67, 95% CI 1.22 - 2.31). However, older patients were more likely to achieve ≥5% weight loss (OR old 5.58, 95% CI 2.77–11.26 vs. OR young 1.57, 95% CI 0.98 - 2.49, P interaction=0.003) and younger patients were more likely to show non-improved individual LRFs (OR old 0.38, 95% CI 0.22–0.67 vs. OR young 0.88, 95% CI 0.61–1.26, P interaction=0.01). Conclusion Despite more serious cardiovascular risk profiles and comorbidities among older patients, nurse-coordinated referral to community-based lifestyle interventions was at least as successful in improving LRFs in older as in younger patients. Higher age alone should not be a reason to withhold lifestyle interventions in patients with CAD. LRFs at 12 months follow-up Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The RESPONSE-2 trial was sponsored by Weight Watchers International, Inc. (New York, New York) and Philips Consumer Lifestyle (the Netherlands). This work was also supported by the Netherlands Organisation for Scientific Research (NWO) to PJ.

Persistence and cardiovascular outcomes with ramipril, atorvastatin, ASA as a single pill compared to the multi pill combination. A subanalysis of the START study, a claims data analysis

Abstract Background/Introduction Large randomized clinical trials have shown the efficacy of aspirin (ASA), angiotensin converting enzyme inhibitors (ACEI) and statins (S) in secondary prevention. However, adherence to medication is low in patients suffering from a cardiovascular event and decreases with each additional tablet. Therefore, a single pill (SP) approach is considered to increase drug persistence and decrease cardiovascular events in this patient population. Purpose Data that show an advantage for a SP regimen containing ASA, ACEI, and S compared to the identical loose combination (LC) regarding persistence, and clinical outcomes under conditions of daily practise in one study are missing. We conducted the START study to answer these questions. A subset, in which we anlysed data from patients in secondary prevention is presented here. Methods The START study was a retrospective, non-interventional analysis of an anonymised claims dataset covering patients suffering from cardiovascular diseases insured by the German AOK PLUS public health insurance in the years 2012–2017. Patients at age ≥18 years with an indication for the use of a combination treatment in cardiovascular disorders – including the use of ASA, ramipril, and atorvastatin - in a SP or identical LC were followed up to 1 year. After 1:1-Propensity Score Matching (PSM) persistence (defined as redemption of prescription with a lack >60 days) and clinical outcomes were compared using non-parametric tests. Results Before PSM, 564,941 patients had a cardiovascular event in the medical history, 427,046 suffered from coronary artery disease. 275 received the three substances described above as SP, 6,662 as LC. After PSM, data from 211 patients were suitable for further analysis in each group. Baseline characteristics were comparable between SP and LC groups. Persistence to treatment was significant lower in the LC group (Hazard Ratio, HR, 0.25 [95% CI 0.19–0.34], p<0.001). 8 clinical outcomes were analysed. Lower Incidence Rate Ratio (IRR) was found in the SP group for myocardial infarction (IRR 0.46; 95% CI 0.07–2.36), stroke (IRR 0.51; 95% CI 0.04–4.46), transitory ischemic attac (IRR 0.77; 95% CI 0.01–60.12), coronary artery disease (IRR 0.60; 95% CI 0.25–1.43), and all cause mortality (IRR 0.38; 95% CI 0.06–1.79). All cause hospitalisation was significant lower in the SP group (IRR 0.58; 95% CI 0.47–0.72; p<0.001). Conclusion The number of patients receiving a SP regimen in secondary prevention was relatively low. However, persistence to medication was significantly higher in the SP group. In addition, a tendency for a lower IRR was also observed for cardiovascular events and all cause mortality in the SP group. The results of our analysis support the use of a SP regimen in secondary prevention of cardiovascular events. Funding Acknowledgement Type of funding source: None

Efficacy and Safety of PCSK9 Inhibitors in Hypercholesterolemia Associated With Refractory Nephrotic Syndrome

IntroductionTreatment of hypercholesterolemia in refractory nephrotic syndrome remains a therapeutic challenge. There is not enough evidence supporting the efficacy of statins, and these drugs can be associated with an increased incidence of adverse effects. Herein we summarize our clinical experience with 12 patients suffering from refractory nephrotic syndrome with associated vascular disease and uncontrolled hypercholesterolemia despite treatment with statins who were treated with proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors.MethodsTwelve adult patients with primary nephrotic syndrome refractory to multiple lines of immunosuppressive treatment who suffered from clinical atheromatous vascular disease were treated with PCSK9 inhibitors according to the prescription guidelines for secondary prevention of cardiovascular events. Eight patients with refractory nephrotic syndrome without vascular disease treated with atorvastatin comprised the control group.ResultsFour weeks after treatment with PCSK9 inhibitors, a statistically significant decrease in total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels was observed without significant changes in serum albumin levels or proteinuria. The mean LDL-C decrease was 36.8% ± 4.9% mmol/L at 4 weeks and remained unchanged throughout the follow-up period. In the control group, there were no significant changes in the levels of total cholesterol or LDL-C during the follow-up period. At the diagnosis of nephrotic syndrome, plasma PCSK9 levels were 334 ± 40 ng/mL and correlated significantly with serum LDL-C levels (r = 0.49, P = 0.023). Six months after starting treatment with PCSK9 inhibitors, plasma PCSK9 levels were significantly reduced to values of 190 ± 36 ng/mL (P = 0.001) with a mean relative reduction of 42.3% ± 12.6%. No local adverse effects were seen at the injection site and no significant changes were seen in the levels of transaminase, creatine phosphokinase, or aldolase.ConclusionPCSK9 inhibitors may be an effective and safe alternative for the treatment of hypercholesterolemia associated with refractory nephrotic syndrome.

Inclisiran as Adjunct Lipid-Lowering Therapy for Patients with Cardiovascular Disease: A Cost-Effectiveness Analysis

Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9 (PCSK9). The comparison of inclisiran with statin versus statin alone in the ORION-10 trial demonstrated significant reductions in low-density lipoprotein cholesterol (LDL-C). Our study explored whether the use of inclisiran with statin versus statin alone for secondary prevention of cardiovascular events is cost effective from the Australian healthcare perspective, based on the price of currently available PCSK9 inhibitors. A Markov model was developed based on the ORION-10 trial to model outcomes and costs incurred by patients over a lifetime analysis. The three health states were 'alive with cardiovascular disease (CVD)', 'alive with recurrent CVD', and 'dead'. Cost and utilities were estimated from published sources. The cost of inclisiran was estimated from the annual cost of evolocumab, a PCSK9 inhibitor currently available in Australia (AU$6334, based on 2020 data). Outcomes of interest were incremental cost-effectiveness ratios (ICERs) in terms of cost per quality-adjusted life-year (QALY) and cost per year of life saved (YoLS). All costs, QALYs and YoLS were discounted at 5% per annum in line with Australian standards. Among 1000 subjects followed-up over a lifetime analysis, inclisiran with statin compared with statin alone prevented 235 non-fatal myocardial infarctions (NFMIs; 151 NFMI and 84 repeat NFMI cases) and 114 coronary revascularisation cases, and increased years of life by 0.549 (discounted) and QALYs by 0.468 (discounted). At an annual price of AU$6334, the net marginal cost was AU$58,965 per person. The above values equated to ICERs of AU$107,402 per YoLS and AU$125,732 per QALY gained. Assuming a willingness-to-pay threshold of AU$50,000, inclisiran would have to be priced 60% lower than other available PCSK9 inhibitors to be considered cost effective. As an adjunct therapy to statin treatment in those who have persistently elevated LDL-C despite optimal statin therapy, inclisiran is effective in reducing cardiovascular events in patients with atherosclerotic CVD. Inclisiran is not cost effective from the Australian healthcare perspective, assuming acquisition costs of current PCSK9 inhibitors. The cost of inclisiran would have to be 60% lower than that of evolocumab.

Reasons for non-vaccination against influenza among older adults with hypertension in Brazil: a cross-sectional study.

The aim of this study was to estimate the prevalence of non-vaccination against influenza among Brazilian older adults with systemic arterial hypertension and determine the main reasons for non-adherence. A cross-sectional study was conducted using data from older adults (≥ 60 years of age) with hypertension who participated in the 2013 National Health Survey and reported not having been vaccinated against flu over the previous 12 months (n = 1,295). The analyses were performed using the Stata 14.0 software. The data were weighted because of the sampling design. An estimated 3,026,080 older adults with hypertension had not received a flu vaccine over the 12 months prior to the survey (22.6%). No significant associations were found with sex, age group or schooling. The prevalence of unvaccinated older adults was lower in the southern and southeastern regions of Brazil than in the northern and northeastern regions, even after adjusting for age. The prevalence was higher among individuals without private health insurance. The main reasons for non-vaccination were fear of a reaction, rarely having the flu and not believing in the protection of the vaccine. The present findings underscore the need for healthcare professionals to explain to the population the benefits of the vaccine for preventing severe influenza (protective effect and possible reactions) and for secondary prevention of cardiovascular events. Increasing the prevalence of vaccination in older adults with hypertension and other cardiovascular diseases is of fundamental importance within the realm of public health as a strategy for reducing occurrences of complications and deaths associated with influenza.

Bempedoic Acid: A New Drug for an Old Problem.

To review the pharmacology, pharmacokinetics, safety, and efficacy of bempedoic acid for low-density lipoprotein cholesterol (LDL-C) reduction. A PubMed search was conducted from January 2000 to June 15, 2020, using the keyword bempedoic acid for phase III clinical trials published in the English language. Articles related to the Food and Drug Administration (FDA) approval of bempedoic acid and other trials relating to the safety and efficacy of this drug were included. The findings from this review show that bempedoic acid is a safe and effective option for lowering LDL-C levels in patients requiring LDL-C lowering for primary or secondary prevention of cardiovascular events. Statin therapy remains the mainstay of treatment for both primary and secondary prevention. However, many patients cannot tolerate statin therapy because of statin-associated muscle symptoms. Bempedoic acid may be a reasonable adjunct for LDL-C reduction, though further evaluation of cardiovascular outcomes with bempedoic acid in this population is needed. The recent FDA approval of bempedoic acid offers an additional option for lowering LDL-C levels in patients with atherosclerotic cardiovascular disease or heterozygous familial hyperlipidemia. Additional data regarding effect on long-term cardiovascular outcomes with bempedoic acid are currently being studied.

Sex differences in flow cytometry–based platelet reactivity in stable outpatients suspected of myocardial ischemia

BackgroundAntiplatelet therapy is the mainstay of secondary prevention of cardiovascular events. Studies suggest that women do not obtain equal therapeutic benefit from antiplatelet therapy compared with men. The link between sex differences in platelet biology and response to antiplatelet therapies is unclear. We therefore investigated the role of sex differences in platelet reactivity in a cohort of outpatients with chest pain, in response to treatment with antiplatelet agents. MethodsPlatelet reactivity was measured in 382 randomly selected patients participating in the Myocardial Ischemia Detection by Circulating Biomarkers (MYOMARKER) study, an observational cohort study of outpatients suspected of myocardial ischemia. In all patients, blood was collected during diagnostic workup, and platelet reactivity was assessed with a flow cytometry–based platelet activation test that quantifies both platelet degranulation (P‐selectin expression) and platelet aggregation (fibrinogen binding to integrin αIIbβ3) in whole blood. ResultsPlatelet reactivity was higher in women compared with men when activated with protease activating receptor 1–activating peptide SFLLRN (PAR1‐AP) and adenosine 5′‐phosphate (ADP), independent of age, basal activation status, estimated glomerular filtration rate < 60, platelet count, statin use, the use of P2Y12 inhibitors, or the use of aspirin. P2Y12 inhibitor use strongly reduced fibrinogen binding after stimulation with PAR1‐AP, but only slightly reduced platelet P‐selectin expression. Calculation of the relative inhibition in P2Y12 users indicated 62% inhibition of the response toward ADP. Stratified analysis showed that women (n = 14) using P2Y12 inhibitors showed less inhibition of fibrinogen binding after PAR1‐AP stimulation than men (n = 38) using P2Y12 inhibitors. ConclusionsThese findings call for further study of differential effects of P2Y12 inhibitors in women with suspected myocardial ischemia.

STATIN TREATMENT PATTERNS AMONG PATIENTS WITH ACUTE MYOCARDIAL INFARCTION IN AN INTEGRATED HEALTHCARE SYSTEM

Lipid lowering therapy, particularly use of high-intensity statins (HIS) is vital for secondary prevention of cardiovascular events, after acute myocardial infarction (AMI). However, physician prescription patterns for HIS are not well documented in the real-world setting in post-AMI patients. We

DIPEPTIDYL PEPTIDASE-4 INHIBITORS WERE ASSOCIATED WITH THE REDUCED LONG-TERM RISK OF ADVERSE CARDIOVASCULAR EVENTS IN JAPANESE DIABETIC PATIENTS FOLLOWING PERCUTANEOUS CORONARY INTERVENTION

Although dipeptidyl-peptidase-4 inhibitors (DPP4i) are one of the most popular antidiabetic agents worldwide, major randomized trials of DPP4i have failed to demonstrate the benefit of DPP4i to reduce the risk of adverse cardiovascular events in secondary prevention. This retrospective analysis

Antithrombotic agents for primary and secondary prevention of cardiovascular events in patients with end-stage renal disease on chronic hemodialysis

Background and aimsCardiovascular disease (CVD) is common in patients with end-stage renal disease (ESRD) on hemodialysis (HD). However, antithrombotic therapy to prevent CVD increases the risk of bleeding. We aimed to investigate the prevalence of CVD and the practice patterns of antithrombotic agents in patients with ESRD on HD. MethodsIn a cross-sectional population based cohort of chronic HD patients (n = 626) from Vienna, Austria, the medical histories of patients and use of antithrombotic treatment were recorded, and the distribution of antithrombotic therapies for primary (n = 260, 41.5%) or secondary (n = 366, 58.5%) prevention of CVD was analyzed. ResultsSingle antiplatelet therapy (SAPT) was used in 234 patients (37.4%), dual antiplatelet (DAPT) in 50 (8.0%), combination of anticoagulation and antiplatelet in 59 (9.4%), anticoagulation monotherapy in 78 (12.5%), and no antithrombotics in 205 patients (32.7%). The prevalence of CVD was 58.5%. In primary CVD prevention, 23.5% (n = 61) of patients were treated with SAPT. For secondary prevention, SAPT was used in 173 (47.3%), DAPT in 49 (13.4%), and dual antithrombotic therapies in 50 patients (13.7%), while 55 (15.0%) patients received no antithrombotics. Age (odds ratio [OR] per 1 year increase 0.96, 95%CI 0.94–0.99, p = 0.004) and hereditary nephropathy (OR 4.13, 95%CI 1.08–15.78, p = 0.038) were independently associated with the absence of antithrombotic therapy in secondary CVD prevention. ConclusionThe majority of patients did not receive antithrombotic therapy for primary prevention. Only 15% did not receive antithrombotic agents in the secondary prevention setting. The net-clinical benefit of antithrombotic therapy in ESRD needs to be determined.

Effect of Lifestyle Changes after Percutaneous Coronary Intervention on Revascularization.

Objective Whether optimal cardiovascular health metrics may reduce the risk of cardiovascular events in secondary prevention is uncertain. The study was conducted to evaluate the influence of lifestyle changes on clinical outcomes among the subjects underwent percutaneous coronary intervention (PCI). Methods The study group consists of 17,099 consecutive PCI patients. We recorded data on subject lifestyle behavior changes after their procedure. Patients were categorized as ideal, intermediate, or poor CV health according to a modified Life's Simple 7 score (on body mass, smoking, physical activity, diet, cholesterol, blood pressure, and glucose). Multivariable COX regression was used to evaluate the association between CV health and revascularization event. We also tested the impact of cumulative cardiovascular health score on reoccurrence of cardiovascular event. Results During a 3-year median follow-up, 1,583 revascularization events were identified. The observed revascularization rate was 8.0%, 9.3%, and 10.6% in the group of patients with optimal (a modified Life's Simple 7 score of 11–14), average (score = 9 or 10), or inadequate (less or equal than 8) CV health, respectively. After multivariable analysis, the adjusted hazard ratios were 0.83 (95% CI: 0.73–0.94) and 0.89 (95% CI: 0.79–0.99) for patients with optimal and average lifestyle changes comparing with the inadequate tertile (P for trend = 0.003). In addition, each unit increase in above metrics was associated with a decrease risk of revascularization (HR, 0.96; 95% confidence interval, 0.93–0.98; P for trend = 0.003). In addition, each unit increase in above metrics was associated with a decrease risk of revascularization (HR, 0.96; 95% confidence interval, 0.93–0.98; Conclusion Ideal CV health related to lower incidence of cardiovascular events, even after the percutaneous coronary intervention. Revascularization can be reduced by lifestyle changes. The cardiovascular health metrics could be extrapolated to secondary prevention and need for further validation.

EZETYMIB JAKO LECZENIE DYSLIPIDEMII W PRZEWLEKŁEJ CHOROBIE NEREK

Cardiovascular disease is the leading cause of death among patients with chronic kidney disease (CKD). Primary and secondary prevention of cardiovascular events is one of the major CKD patients' treatment targets. Dyslipidaemia is the important modifiable risk factor in general population. Each 1.0 mmol reduction in LDL cholesterol with statins reduces annual rate of heart attack, coronary revascularization or ischemic stroke by 20% leading to 10% reduction of all-cause mortality. Adding ezetimibe, an inhibitor of intestinal lipids absorption, further reduces LDL cholesterol by 20%. Optimal lipid lowering treatment for CKD patients remains unclear. Cardiovascular risk reduction observed with statins therapy decreases together with a progression of the disease, moreover patients with advanced CKD treated with high doses of statins have an increased risk of adverse events. These patients might benefit from adding ezetimibe to moderate dose statin therapy for prevention of cardiovascular events.

Antithrombotic therapy and revascularisation strategies in people with diabetes and coronary artery disease.

Diabetes mellitus, largely type 2, affects nearly 10% of the global adult population according to the World Health Organization. Diabetes is an independent risk factor for atherosclerotic cardiovascular diseases, including coronary artery disease. Diabetes patients experience a two to three-fold increased incidence of coronary artery disease, despite improved metabolic control and management of other cardiovascular risk factors. Platelet abnormalities and activation as well as reduced antiplatelet drug responsiveness characterise diabetes mellitus. Mechanisms linking diabetes to platelet and vascular abnormalities, atherogenesis and atherosclerotic cardiovascular disease are still only partially known, highlighting the unique complexity of the pro-atherogenic clinical scenario and its treatment. Consistently, a higher residual cardiovascular risk characterises patients with diabetes compared with those without, in spite of improved antiplatelet and antithrombotic treatment combinations. Randomised clinical trials aimed at optimising antiplatelet treatment specifically in patients with diabetes are lacking, both in acute and chronic coronary artery disease settings. Thus, patients with diabetes are treated with regimens validated in studies including only variable proportions of diabetes patients. Myocardial revascularisation appears to confer a comparable relative benefit between diabetes patients and patients without diabetes, and generally coronary artery bypass grafting has a better outcome in diabetes mellitus versus peripheral coronary intervention. New glucose-lowering drugs have been shown to reduce the incidence of major cardiovascular events in secondary prevention. Type 1 diabetes mellitus remains less explored than type 2 in this context. Diabetes-tailored antithrombotic strategies in acute and chronic coronary artery disease remain an unmet clinical need, requiring ad-hoc trials and precision pharmacological strategies.

Genetic markers of risk for ST-elevated myocardial infarction

Aim. To identify genetic markers of risk for ST-elevated myocardial infarction (STEMI). Material and methods . The study included 210 patients (119 men, 91 women) with STEMI, hospitalized from December 21, 2016 to June 16, 2017 The average age of men was 55,5±9,5 years, women — 57,5±9,1 years. The diagnosis of STEMI was verified according to the criteria of the European Society of Cardiology (2015, 2017). During hospitalization, patients underwent clinical and instrumental examination, stipulated by medical care standards and clinical guidelines We also conducted a genetic study of single nucleotide polymorphisms (SNPs), which showed their association with the risk of coronary artery disease (CAD) and acute myocardial infarction (AMI) according to the GWAS: rs2820315 of the LMOD1 gene (Leiomodin 1, mapped on chromosome 1), rs9349379 of the PHACTR1 gene (regulator 1 of actin and phosphotase, localized on chromosome 6p241), rs867186 of the PROCR gene (Protein C receptor, located on chromosome 20q11.22), rsi1799883 of the FABP2 gene (Fatty acid-binding protein 2, located on chromosome 4q26). Statistical data analysis was performed using the SPSS 170.5 software package and authorial odds ratio (OR) calculator. Results. Carriage of the CC genotype of rs2820315 polymorphism of the LMOD gene is associated with an increased risk of STEMI by 1,87 times (95% CI 1,2862,722, p=0,016). Carriers of the CT genotype of rs2820315 polymorphism have a reduced risk of STEMI (OR 0,633; 95% CI 0,436-0,918, p=0,016). Conclusion. In order to identify risk groups for STEMI development, the study of the rs2820315 polymorphism of the LMOD gene is recommended. This will define the high-risk group for STEMI for developing of personalized programs for primary and secondary prevention of cardiovascular events in practical health care, which will contribute to reducing of STEMI mortality.

PCV29 COST-EFFECTIVENESS OF CORONARY AND PERIPHERAL ARTERY DISEASE TREATMENTS

Many individuals with coronary (CAD) or peripheral artery disease (PAD) experience cardiovascular events (CVE) irrespective of acetylsalicylic acid (ASA) use. Thus, improvements to the secondary prevention of CVE are needed. We evaluated the cost-effectiveness of CAD/PAD treatments in the secondary prevention of CVEs and applied Patients-Interventions-Comparator-Outcomes-Setting-Time-Effects-Perspective-Sensitivity analysis (PICOSTEPS) structural reporting framework. Myocardial infarction, ischaemic stroke, haemorrhagic stroke, acute limb ischaemia, amputation, major non-fatal extracranial bleed and various CVE-related and other reasons for death were included in a Markov model setting among a cohort consisting of stable CAD or symptomatic PAD patients. Effects of interventions in the secondary prevention of CVEs were incorporated from COMPASS trial. Primary outcome was 3% per year discounted incremental cost-effectiveness ratio (ICER), given as year 2019 payer cost per quality-adjusted life-year (QALY) gained in Finnish setting over lifetime horizon. Effects covered Finnish mortality, health-related quality of life and direct costs from health care payer perspective. Costs per life-year gained (LYG), cost-effectiveness tables and acceptability frontiers (CEAF) were the secondary outcomes. Probabilistic and deterministic sensitivity analyses were done. In comparison to ASA, rivaroxaban resulted to the highest modelled amount of discounted QALYs gained (0.395) and LYGs (0.469) among the interventions, and its modelled average additional costs were €1,229. Rivaroxaban had an ICER of €4,742/QALY versus ASA (€3,114/QALY in probabilistic analysis). Rivaroxaban had 98% probability of cost-effectiveness with the very plausible willingness-to-pay of €25,254/QALY gained. The primary result was robust based on the sensitivity analyses. Rivaroxaban was cost-effective in modelled comparisons among stable CAD or symptomatic PAD patients. Starting from July 2019, rivaroxaban is also reimbursed as restricted in the respective indication in Finland.

The prescription of direct oral anticoagulants in the elderly: An observational study of 19 798 Ambulatory subjects

Direct oral anticoagulants (DOACs) are increasingly prescribed to elderly people, but the epidemiologic data for this population remains scarce. We compared the elderly population taking DOACs and those not taking DOACs (noDOAC). We included individuals over 75years old, affiliated to Mutualité Sociale Agricole of Burgundy (a French regional health insurance agency), who had been refunded for a prescribed DOAC between 1st and 30th September 2017. The DAOC group (DAOCG) and noDOAC group (noDOACG) were compared in terms of demographic conditions, registered chronic diseases (RCD), and number and types of prescribed drugs. In the DOACG, we compared the type of prescribing physician and laboratory monitoring for novel prescriptions (initial) and prescription refills (≥ 3months). Of the 19798 included patients, 1518 (7.7%) were prescribed DAOCs and 18280 (92.3%) were not. Mean and median age was 85years in the 2 groups (DOACG and noDOACG). In the DOACG, there were more men (50% vs 40.2%), more RCD (88.9% vs 68.7%) and more drugs per prescription (6±2.8 vs 5±2.9) (All P<.01). The DOACG also took more antihypertensive drugs. The most commonly prescribed DOACs were apixaban (42.9%) followed by rivaroxaban (38.4%) and dabigatran (18.6%). Complete blood count, serum creatinine and coagulation function tests were requested for 69.4%, 75% and 22.2%, respectively, of patients prescribed DAOCs. The DOACG had more RCD and drugs per prescription than the noDOACG; routine laboratory monitoring was insufficient. What's known Platelet aggregation inhibitors (low-dose) are recommended for secondary prevention of cardiovascular events in patients suffering from symptomatic atherosclerosis. The main risk of this treatment is bleeding. What's new A prescription for platelet aggregation inhibitors was found in 34% of geriatric inpatients in this prospective study. Compliance to guidelines was better for symptomatic peripheral artery disease than for primary prevention in accordance with recent publications. Geriatric comorbidities had no impact on the prescription of platelet aggregation inhibitors. Underuse of platelet aggregation inhibitors was observed in 11.3% of cases and overuse in 13.7% of cases.

IL-1β and Statin Treatment in Patients with Myocardial Infarction and Diabetic Cardiomyopathy.

Statins are effective lipid-lowering drugs with a good safety profile that have become, over the years, the first-line therapy for patients with dyslipidemia and a real cornerstone of cardiovascular (CV) preventive therapy. Thanks to both cholesterol-related and “pleiotropic” effects, statins have a beneficial impact against CV diseases. In particular, by reducing lipids and inflammation statins, they can influence the pathogenesis of both myocardial infarction and diabetic cardiomyopathy. Among inflammatory mediators involved in these diseases, interleukin (IL)-1β is a pro-inflammatory cytokine that recently been shown to be an effective target in secondary prevention of CV events. Statins are largely prescribed to patients with myocardial infarction and diabetes, but their effects on IL-1β synthesis and release remain to be fully characterized. Of interest, preliminary studies even report IL-1β secretion to rise after treatment with statins, with a potential impact on the inflammatory microenvironment and glycemic control. Here, we will summarize evidence of the role of statins in the prevention and treatment of myocardial infarction and diabetic cardiomyopathy. In accordance with the dual lipid-lowering and anti-inflammatory effect of these drugs and in light of the important results achieved by IL-1β inhibition through canakinumab in CV secondary prevention, we will dissect the current evidence linking statins with IL-1β and outline the possible benefits of a potential double treatment with statins and canakinumab.