High residual platelet reactivity during dual antiplatelet therapy, found by optical aggregometry and the rate of atherothrombotic complications after coronary artery stenting in patients with ischemic heart disease in clinical practice

Aim. To study the prevalence of high residual platelet reactivity (HRPR) during the dual antiplatelet therapy (DAT) with acetylsalicylic acid (ASA) and clopidogrel by optical aggregometry in patients with ischemic heart disease (IHD) after percutaneous transluminal coronary angioplasty (PTCA) in clinical practice, as well as to determine its value for the prediction of clinical course and outcome of disease.Material and methods. Patients after PTCA and during DAT were included into the study. Evaluation of the functional activity of platelets by optical aggregometry was performed in all patients at baseline. Resistance to ASA, clopidogrel and DAT were detected. Endpoints included cases of repeated atherothrombotic events (sudden cardiac death, myocardial infarction, unstable angina, ischemic stroke, stent thrombosis). Adherence to therapy was evaluated by Morisky-Green test.Results. 97 patients were included into the final analysis. The risk of myocardial infarction or unstable angina pectoris in the ASA-resistant patients was significantly higher than this in the DAT-sensitive patients [relative risk (RR)=7.68; 95% confidence interval (CI) 2.8-20.54; p=0.045]. Maximum RR for stent thrombosis was in clopidogrel-resistant (RR=7.1; 95% CI 1.41-35.82; p=0.0485) and DAT-resistant patients (RR=12.8; 95% CI 4.5-36.38; p=0.0491), compared with patients with a sensitivity to antiplatelet therapy. DAT-resistance was associated with a higher RR of the combined endpoint, compared with the sensitivity to antiplatelet therapy (RR=10.24; 95% CI 3.96-26.5; p=0.046]), and have a tendency to association with increased risk of combined endpoint compared with isolated ASA-resistance (RR=1.3; 95% CI 0.68-2.6; p=0.081).Conclusion. HRPR during DAT is common in clinical practice in patients with ischemic heart disease after PTCA. Routine use of optical aggregometry in DAT may help to identify patients with an increased risk of thrombotic events in the postoperative period and to assign them an alternative antiplatelet therapy

RISK OF REPEATED THROMBOTIC EVENTS IN PATIENTS SURVIVED ACUTE CORONARY SYNDROME AND HAVING LABORATORY PROVEN RESISTANCE TO ACETYLSALICYLIC ACID

Aim. To evaluate risk of repeated atherothrombotic events in patients survived acute coronary syndrome (ACS) and having poorly reduced platelet aggregation (proven by optical aggregometry) in response to acetylsalicylic acid (ASA) therapy.Material and methods. 200 patients with ACS (aged 56,6±9,2 y.o.) were included in the study. Platelet functional activity during ASA therapy was evaluated with laser aggregometer. ASA resistance was defined if the summarizing index of platelet aggregation (induced with ADP, 5 mμml/l) was 50% or higher during ASA therapy. Observation period was 18±6 months. Atherothrombotic events (unstable angina, myocardial infarction, stroke, cardiovascular death) were considered.Results. Lack ASA response rate was about 12%. Totally 22 repeated atherothrombotic events were registered: 5,6% among ASA sensitive patients and 50% - among ASA resistant patients. Repeated atherothrombotic events were registered in ASA resistance patients during first 14 days. ASA sensitive patients showed repeated atherothrombotic events in some months after ACS. The relative risk of cardiovascular event in ASA resistance patients was 8,92 (CI 95% 4,39; 17,84 р=0,05).Conclusion. The high level of the induced platelet aggregation (proven by laser aggregometry) points to high risk of repeated atherothrombotic events in patients with ACS

Intrahospital switch of the P2Y12 inhibitors in patients with ST segment elevation myocardial infarction in ‘real-life’ clinical practice: the effect on the functional activity of thrombocytes and thrombocytopoiesis, prognostic value

Aim. To assess the P2Y12 inhibitors switch in patients ST segment elevation myocardial infarction (STEMI) in real-life’ clinical practice, evaluate the functional activity of thrombocytes and thrombocytopoiesis and determine the clinical and prognostic value of P2Y12 inhibitors switch in the framework of dual antiplatelet therapy in patients with STEMI.Material and methods. We conducted local, stratified, prospective study in which were involved 101 patients, hospitalized no later than 12hours after the STEMI manifestation. The antiplatelet therapy (APT), prescribed by the physicians at the pre-hospital and inpatient phases of treatment, was analyzed. Functional activity of thrombocytes, levels of thrombopoietin (THPO), stromal cell-derived factor 1 (SDF1) and thrombopoietic receptor (MPL) were investigated. The minimum observation period was 2 years. Death and repeated hospitalizations due to cardiovascular causes were monitored.Results. P2Y12 inhibitors were switched in 32,7% of patients with STEMI. In the hospital, clopidogrel, which was prescribed at the prehospital phase, was replaced with ticagrelor (early APT escalation) — 22,8%. Patients with early APT escalation by the seventh day had significantly greater inhibition of platelet aggregation activity parameters (slope of the aggregation curve, latent aggregation time and area under the aggregation curve). Activation of the collagen-induced platelet aggregation was detected. With the early escalation of APT, the THPO level was statistically significantly higher, both on the second and on the 7th day measurements: 256,2 (209,0; 396,8) pg/ml vs 137,5 (105,7; 179,1) pg/ml (p=0,000) and 283,4 (228,9; 334,3) pg/ml vs 226,5 (163,2; 287,3) pg/ml (p=0,045), respectively. The frequency of reaching the combined endpoint (death + re-hospitalization) was 7,9% in patients who had a P2Y12 switch, and 28,1% in patients who did not change the P2Y12 blocker.Conclusion. In actual clinical practice, patients with STEMI had the most frequent early APT escalation, which was characterized by a more significant suppression of adenosine diphosphate-induced platelet aggregation and secretion than in patients without P2Y12 inhibitors switch, but with activation of collagen-induced aggregation. An increase in thrombocytogenesis was revealed in early replacement of clopidogrel by ticagrelor. Intrahospital replacement of the P2Y12 inhibitor in patients with STEMI was accompanied by a decrease in the two-year death risk and repeated hospitalizations

RISK OF RECURRENT THROMBOTIC EVENTS IN PATIENTS WITH ACUTE CORONARY SYNDROME AND HIGH PLASMA LEVELS OF D-DIMER

Aim. To study the association of plasma D-dimer levels and the risk of thrombotic events in patients hospitalised with acute coronary syndrome (ACS).Material and methods. The study included 70 patients, aged 34-88 years, who were admitted to the Acute Coronary Care Unit with the ACS diagnosis.Results. During the follow-up period, thrombotic events were registered in 12 patients (17%). Three patients with myocardial infarction (MI) suffered recurrent MI. Nine patients were rehospitalised with the unstable angina (UA) diagnosis. All participants were divided into quartiles by the levels of D-dimer (25% percentile 136 ng/ml; median 1250 ng/ml; and 75% percentile 2930 ng/ml). High plasma levels of D-dimer (third quartile) were associated with a 1,5-fold increase in the risk of recurrent thrombotic events among ACS patients.Conclusion. In ACS patients, plasma D-dimer levels could be regarded as one of the additional risk factors of thrombotic events

Features and main problems of treating patients with high and very high cardiovascular risk with statins in real clinical practice (according to the data of the “PRIORITET” research)

Aim. To determine the features and main problems of statin therapy, as well as assess the possibility of achieving the target level of lipid pattern in patients with high and very high cardiovascular risk (CVR) in real clinical practice.Material and methods. The design of the “PRIORITET” observational program is an open observational study. Patients with high and very high CVR were divided into 3 groups in accordance with the initial data: (1) not taking statins, (2) taking statins, but not reaching the target low-density lipoprotein cholesterol (LDL-C) level, (3) taking statins with the achievement of the target LDL-C level, which is justified in replacing the statin inside the class — adverse effects (AE), high price, etc. Within 12 weeks 3 visits of patients to hospitals were carried out: baseline visit (B0), visit 1 month after the study initiation (B1) and visit 3 months after the study initiation (B3). The choice of atorvastatin or rosuvastatin was assessed by the doctors.Results. Groups 1, 2 and 3 included 112, 170 and 16 people, respectively. At B0, 145 (48,7%) patients were prescribed atorvastatin, and 153 (51,3%) — rosuvastatin. Three people dropped out of the study to B3, 295 patients completed the program. Lipid pattern of 285 patients were analyzed: 121 (41%) people (101 with very high CVR and 20 with high CVR) achieved the target LDL-C level, the remaining 164 (59%) patients (CVR — 156 and 8, respectively) — no. The most pronounced dynamics of LDL=C level was revealed in group 1, the differences between group 1 and groups 2 and 3 are highly statistically significant (p<0,0001). There were no differences in the frequency of reaching the target LDL-C level between patients taking atorvastatin or rosuvastatin. The target level of LDL-C (p=0,003) in the treatment of rosuvastatin in patients with high CVR was reached significantly more often than in patients with very high CVR. Also 3 non-serious AEs were reported. On average, in 9% of cases, reaching the target level of LDL-С during visits B1 and B3 was wrong interpreted by the attending physicians.Conclusion. The main problems of statin therapy in real clinical practice are the wrong interpretation of reaching the target level of LDL-C, inertness of doctors in titrating of statins doses and achieving the target level of lipid pattern. It may be the cause of reduced efficiency and deterioration of lipid-lowering therapy results in patients with high and very high CVR. The results of the “PRIORITET” study demonstrated the possibility of improving the practice of statins use and its accordance with clinical guidelines.Skibitsky V. V. on behalf of the working group of the “PRIORITET” researchWorking Group of the “PRIORITET” study: Voronina V. P. (Moscow), Zelenova T. I. (Moscow), Sladkova T.A. (Moscow), Alekseeva A. I. (Tula), Barabanova T. Yu. (Tula), Zotova A. S. (Tula), Kolomeitseva T. M. (Tula), Prikhod’ko T. N. (Tula), Pazelt E. A. (Nizhny Novgorod), Khramushev N. Yu. (Nizhny Novgorod), Skibitsky A. V. (Krasnodar), Alekseeva V. V. (Saratov), Lazareva E. V. (Saratov)

Adherence to Statins Therapy of High and Very High Cardiovascular Risk Patients in Real Clinical Practice: Diagnostics and Possible Ways to Solve the Problem (According to the PRIORITY Observational Study)

Aim. To study adherence to treatment with generic statins prescribed to patients with high and very high cardiovascular risk in routine clinical practice, as well as the possible impact of educational training of doctors on compliance with clinical guidelines and changes in patient adherence to treatment. Material and methods. The study was prospective, with educational training for physicians on the main provisions of current clinical guidelines prior to the program. It included 3 visits over 12 weeks: inclusion visit (V0), and visits after 1 and 3 months of follow-up (V1 and V3). The use of generic atorvastatin or rosuvastatin was recommended for all patients. To assess adherence the following surveys were used: medical survey (all visits), the original questionnaire to assess the potential and the actual commitment to taking statins and the causes of non-adherence, and the Morisky-Green 8-question test (visits V0 and V3) to evaluate overall adherence to drug treatment. The patients who started the drug taking according to the medical recommendations and continued it during the study were considered as adherents. Patients who started but stopped taking the drug for 12 weeks were considered as partially non-adherent. Patients who refused to take the recommended statin were considered as non-adherents. The prescribed doses of statins and medical tactics in the titration of doses, as well as the achievement of the target level of low-density lipoprotein cholesterol (LDL cholesterol) were evaluated. Results. 112 (37.5%) of the 298 patients with baseline indications for taking statins did not take these drugs. According to the medical survey at V0 a total of 286 (96%) patients were potential adherents to medical recommendations; at V3 262 (88%) patients were adherent to statin treatment; 34 patients were partially non-adherent, 1 – was non-adherent, and 1 – dropped out of the study immediately after V0. According to the original questionnaire, potential adherence was assessed in 281 patients: 244 (86.8%) were potentially adherent, 37 (13.2%) – partially non-adherent. At V3, out of 294 patients who filled in the original questionnaire, 260 (88.5%) were adherent, 26 (8.8%) – partly non-adherent, 8 (2.7%) – nonadherent. The Morisky-Green questionnaire was filled in by 292 patients: at V0, 106 patients (36.3%) had treatment adherence, non-adherence – 186 patients (63.7%). By V3, an increase in total adherence was found: 159 patients (54.5%) were adherent, and 133 (45.5%) – non-adherent. The lipid profile was evaluated in 231 patients in V1 and in 285 ones – in V3. The target LDL cholesterol level was reached by V1 in 47 (20.3%) patients, and in 184 (79.7%) patients – was not. Dose titration occurred in 56 patients. By V3, 121 (42.4%) patients reached the target level of LDL cholesterol, and 164 – did not. The results of the lipid profile analysis were erroneously interpreted in 21 patients. Conclusion The results of the medical survey and the original questionnaire for assessing adherence predominantly coincided. The Morisky-Green test does not accurately reflect patients' commitment to taking a particular drug. Clinical inertness of doctors in the titration of statin doses and achievement of target LDL cholesterol levels were found as well as erroneous interpretation of the LDL cholesterol level. Educational trainings for doctors had a positive effect on the implementation of clinical guidelines, and also contributed to increasing patient adherence to medical recommendations

Edoxaban versus warfarin in patients with atrial fibrillation

Contains fulltext : 125374.pdf (publisher's version ) (Open Access)BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)