Abstract The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

BACKGROUND Atherosclerotic cardiovascular diseases (ASCVD) are still the leading cause of morbidity and mortality in Bosnia and Herzegovina. Elevated LDL-cholesterol is established as a strong marker of cardiovascular risk. Some researchers believe that measuring triglyceride levels gives a good assessment of the residual risk for ASCVD besides the measurement of LDL-cholesterol. OBJECTIVE The aim of this study was to evaluate the overall prevalence of major risk factors for ASCVD, lipid profile and 10-year fatal cardiovascular risk using the HeartSCORE scoring system. Further we want to evaluate the prevalence and relationship between elevated triglyceride levels and high 10-year fatal cardiovascular risk calculated as a HeartSCORE. METHODS This is a cross-sectional study conducted on 832 volunteers aged between 40 and 65 years without a diagnosis of diabetes and without known preexisting cardiovascular disease, as a part of the preventive program conducted at the Familly Medicine office. Data were collected for ASCVD risk factors and lipid panel (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides). 10-year fatal cardiovascular risk was calculated using the HeartSCORE scoring system for countries with high CV risk. RESULTS Among 832 participants included, 565 (67.9%) were female, and 267 (32.1%) were male. We found high prevalence of hypertension (27.7%), obesity (32.2%), and smoking (36.2%). All lipid parameters, except HDL-C, were not optimal. Only 17.4% of participants had normal estimated HeartSCORE risk, while more than one-third (33.9%) had high or very high estimated HeartSCORE risk. Although we found a higher percentage of participants with elevated triglycerides in groups with higher HeartScore, there was a very weak positive correlation between values of triglycerides and the 10-year risk of a fatal cardiovascular event (r= 0.249, p= 0.000). CONCLUSION High prevalence of major known risk factors and high estimated HeartSCORE risk indicate a high overall risk for ASCVD in the sample. The proportion of participants with elevated triglycerides was increased in patients with high HeartSCORE risk what implicates importance of trygliceride measurement.

Abstract Aims Long-term, placebo-controlled cholesterol-lowering trials have demonstrated legacy effects (clinical benefits that persist or emerge after trial end). It is unknown whether legacy effects follow a short period of very low low-density lipoprotein cholesterol (LDL-C) levels achieved with statin plus proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. Methods and results In 18 924 patients with recent acute coronary syndrome, the ODYSSEY OUTCOMES trial compared the PCSK9 inhibitor alirocumab with placebo, each added to high-intensity or maximum-tolerated statin therapy. Patients with two consecutive LDL-C levels <0.39 mmol/L (15 mg/dL) on alirocumab had blinded placebo substitution for the remainder of the trial with continued statin treatment. In post hoc analyses, major adverse cardiovascular events (MACE) in these patients were compared to MACE in propensity score–matched patients from the placebo group with similar baseline characteristics and study medication adherence. In the alirocumab group, 730 patients had blinded placebo substitution at a median of 8.3 months from randomization, after a median of 6.0 months with LDL-C <0.39 mmol/L. They were matched to 1460 placebo patients. Both groups had lower baseline LDL-C and lipoprotein(a) and better study medication adherence than those of the overall cohort. Over a median follow-up of 2.8 years, MACE occurred in 47 (6.4%) alirocumab patients with limited-duration, very low achieved LDL-C vs. 122 (8.4%) matched placebo patients (treatment hazard ratio 0.72; 95% confidence interval 0.51, 0.997; P = 0.047). Conclusion A short period of LDL-C levels <0.39 mmol/L achieved with statin and alirocumab, followed by statin monotherapy, was associated with a lower risk of MACE than statin monotherapy throughout the observation period. Clinical benefit persisted for several years. Trial registration ClinicalTrials.gov NCT01663402

Aim To evaluate the efficacy (rate of recanalization) of therapy with novel oral anticoagulants (NOAC; rivaroxaban, apixaban) compared to conventional treatment (low molecular weight heparin - LMWH and vitamin K antagonist) in the treatment of deep vein thrombosis (DVT) of the proximal segments of lower extremities. Methods The first group consisted of patients diagnosed with DVT and treated with NOAC (n = 100), while the second group consisted of patients diagnosed with DVT, who were treated by conventional treatment (low molecular weight heparin and vitamin K antagonists) (n = 100). In the first group, NOAC was included in the initial treatment. Patients in the second group were treated with LMWH for four days, and on the fifth day vitamin K antagonist was included in therapy, international ratio (INR) was titrated to therapeutic values (2.0-3.0), and then low molecular weight heparin was excluded from the therapy. Results There was a statistically significant difference in the estimated values of free lumen of the blood vessel between the examined groups after 30 days (p=0.0001), after 90 days (p=0.0001) and after 180 days (p=0.0001). After 180 days, the average free lumen values in the NOAC group were 85% (81-89%), which was significantly higher than the free lumen values in the second group, 73% (69-79%). Conclusion The use of NOAC represents more efficient treatment of DVT comparing to vitamin K antagonists.

AIMS European guidelines set low-density lipoprotein cholesterol (LDL-C) treatment goals <1.4 mmol/L after acute coronary syndrome (ACS), and <1.0 mmol/L for patients with recurrent cardiovascular events ≤2 years. Many ACS patients do not achieve these goals on statin alone. We examined actual goal achievement with alirocumab and projected achievement with ezetimibe, either added to optimized statin therapy. METHODS AND RESULTS The ODYSSEY OUTCOMES trial (NCT01663402) compared alirocumab with placebo in 18,924 patients with recent ACS and hyperlipidaemia despite high-intensity or maximum-tolerated statin therapy. This subanalysis comprised 17,589 patients with LDL-C ≥1.4 mmol/L at baseline who did not receive ezetimibe treatment. High-intensity statin treatment was used in 88.8%. Median (interquartile range) baseline LDL-C was 2.3 (1.9-2.7) mmol/L. With alirocumab, 94.6% of patients achieved LDL-C <1.4 mmol/L at ≥1 post-baseline measurement vs. 17.3% with placebo. Among 2236 patients with a previous cardiovascular event within 2 years (before the qualifying ACS), 85.2% vs. 3.5%, respectively, achieved LDL-C <1.0 mmol/L. Among patients not treated with ezetimibe, we projected that its use would have achieved LDL-C <1.4 and <1.0 mmol/L in 10.6% and 0%, respectively at baseline (assuming 18 ± 3% reduction of LDL-C). CONCLUSION Among patients with recent ACS and LDL-C ≥1.4 mmol/L despite optimized statin therapy, addition of alirocumab allowed 94.6% to achieve the 2019 European guideline LDL-C goal <1.4 mmol/L, and 85.2% of those with recurrent cardiovascular events to achieve <1.0 mmol/L. In contrast, addition of ezetimibe to optimized statin therapy was projected to achieve LDL-C <1.4 mmol/L in only 10.6% of patients at baseline.

Aim To investigate the benefit of high-dose lipophilic statin therapy on cardiac remodelling, function and progression of heart failure (HF) in patients with ischemic heart disease. Methods A total of 80 patients with ischemic HF diagnosis were followed during 6 months, and they were divided in two groups. First group (n=40) was treated by high-dose lipophilic statin therapy (atorvastatin 40 mg) and conventional therapy for HF, while the second group (n=40) had no atorvastatin in the therapy. Results In the beginning of study, from all of the observed parameters, only the ratio of flow rates in early and late diastole (E/A ratio) differed between the test groups (p=0.007). After six months, a statistically significant increase in left ventricular end-diastolic diameter (LVIDD) in patients who had not been treated with atorvastatin was found. In the patients treated with atorvastatin, there was a significant reduction in basal right ventricle diameter in diastole and systole (p<0.001 and p<0.001, respectively), and in tricuspid annular plane systolic excursion (TAPSE) (p<0.001); there was a reduction in LVIDD (p<0.001), and an increase of ejection fraction of the left ventricle according to Teicholtz and Simpson (p<0.001 and p<0.001, respectively). Also, there was an increase of deceleration time of early diastolic velocity (DTE) (p<0.05) and a decrease of isovolumic relaxation time (IVRT) (p<0.001). Conclusion The reduction in the right and left ventricle diameters was noted after the six-month atorvastatin therapy. Atorvastatin in the therapy resulted in increased EFLV and better systolic function and should be a part of a therapeutic modality of HF.

BACKGROUND European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V in primary care was carried out by the European Society of Cardiology EURObservational Research Programme in 2016-2018. The main objective was to determine whether the 2016 Joint European Societies' guidelines on cardiovascular disease prevention in people at high cardiovascular risk have been implemented in clinical practice. METHODS The method used was a cross-sectional survey in 78 centres from 16 European countries. Patients without a history of atherosclerotic cardiovascular disease either started on blood pressure and/or lipid and/or glucose lowering treatments were identified and interviewed ≥ 6 months after the start of medication. RESULTS A total of 3562 medical records were reviewed and 2759 patients (57.6% women; mean age 59.0 ± 11.6 years) interviewed (interview rate 70.0%). The risk factor control was poor with 18.1% of patients being smokers, 43.5% obese (body mass index ≥30 kg/m2) and 63.8% centrally obese (waist circumference ≥88 cm for women, ≥102 cm for men). Of patients on blood pressure lowering medication 47.0% reached the target of <140/90 mm Hg (<140/85 mm Hg in people with diabetes). Among treated dyslipidaemic patients only 46.9% attained low density lipoprotein-cholesterol target of <2.6 mmol/l. Among people treated for type 2 diabetes mellitus, 65.2% achieved the HbA1c target of <7.0%. CONCLUSION The primary care arm of the EUROASPIRE V survey revealed that large proportions of people at high cardiovascular disease risk have unhealthy lifestyles and inadequate control of blood pressure, lipids and diabetes. Thus, the potential to reduce the risk of future cardiovascular disease throughout Europe by improved preventive cardiology programmes is substantial.