Michał Kasprzak

Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up

BACKGROUND The aim of this study was to assess antiplatelet effect of prasugrel in acute coronary syndrome (ACS) patients with high on-treatment platelet reactivity (HTPR) on clopidogrel, undergoing percutaneous coronary intervention (PCI). METHODS A prospective, platelet reactivity-guided, parallel-group, open-label study including 71 patients pretreated with clopidogrel 600 mg and assigned either to prasugrel (30 mg loading dose, 10 mg maintenance dose; n = 46) or clopidogrel (150 mg maintenance dose for 6 days and thereafter 75 mg maintenance dose; n = 25) regimen, based on vasodilator-stimulated phosphoprotein (VASP)-assessed platelet reactivity index (PRI; > 50% vs. ≤ 50%) measured next morning post-PCI. RESULTS Median PRI value after switch to prasugrel sharply declined at 24 h (70.0 [61.3-75.6] vs. 11.9 [6.8-25.7]%; p < 0.000001) and slightly but significantly rose between 24 h and 30 days (27.9 [15.5-46.8]%; p < 0.0006). In contrast, median PRI values in the clopidogrel group were similar at baseline and at 24 h (25.1 [13.7-40.2] vs. 22.0 [18.4-36.8]%; p = NS) and then modestly rose at 30 days (30.3 [20.4-45.7]%; p < 0.03). The prevalence of HTPR decreased in the prasugrel group between baseline and 24 h measurements (100.0 vs. 4.3%; p < 0.0001). Rates of patients with HTPR at 24 h and 30 days were similar in both groups, so were the tendencies in patterns of platelet inhibition evaluated with multiple electrode aggregometry as compared with the VASP assay. CONCLUSIONS Our study indicates that prasugrel overcomes HTPR on clopidogrel in the acute phase of interventionally treated ACS and maintains its antiplatelet potency in 30-day follow-up. Potential clinical benefits of personalized antiplatelet prasugrel-based therapy warrant further investigation in clinical ACS trials.

Time-related changes in determinants of antiplatelet effect of clopidogrel in patients after myocardial infarction☆

Substantial variability of antiplatelet action is an important limitation of clopidogrel. The aim of this study was to evaluate time-related changes in determinants of clopidogrel responsiveness in patients after myocardial infarction. The study population comprised 191 consecutive patients treated with primary percutaneous coronary intervention for acute myocardial infarction. Follow-up visits were scheduled at 3, 6 and 9 months after discharge. ADP-induced platelet aggregation was tested with Multiplate Analyzer. Patients with ADP-PA>46.8U were defined as clopidogrel non-responders. The prevalence of clopidogrel non-responsiveness was highest during hospitalization and at 9 month follow-up visit, while it was lowest at 3 and 6 months after myocardial infarction (P=0.004). According to multivariate analysis, platelet count, mean platelet volume, concentration of hsCRP and leukocyte count influenced ADP-induced platelet aggregation in multiple assessment points. BMI, concentrations of hemoglobin, glycated hemoglobin, and BNP, hematocrit, adherence to medication, and patient׳s age were found to be independent predictors of high on-treatment ADP-induced platelet aggregation only at a single follow-up visit. Determinants of clopidogrel responsiveness in patients after myocardial infarction change within the long-term therapy. During hospitalization and early after discharge only biological factors affect ADP-induced platelet aggregation, while non-adherence to antiplatelet therapy may be a significant factor in determining clopidogrel non-responsiveness during late follow-up visits.

ACS network-based implementation of therapeutic hypothermia for the treatment of comatose out-of-hospital cardiac arrest survivors improves clinical outcomes: the first European experience

BackgroundThere is a paucity of data regarding clinical outcomes associated with the integration of a mild therapeutic hypothermia (MTH) protocol into a regional network dedicated to treatment of patients with acute coronary syndromes (ACS). Additionally, a recent report suggests that the neurological benefits of MTH therapy in interventionally managed ACS patients resuscitated from out-of-hospital cardiac arrest (OHCA) may be potentially offset by the catastrophic occurrence of stent thrombosis. The goal of this study was to share our experience with the implementation of an MTH program using a previously established ACS network in consecutive comatose OHCA survivors undergoing interventional management due to an initial diagnosis of ACS and to assess the clinical effectiveness and safety of MTH.MethodsWe conducted a retrospective historically controlled single centre study. Hospital survival with a favourable neurological outcome (Cerebral Performance Category of 1 or 2) and all-cause in-hospital mortality were the primary and secondary efficacy end points, respectively. Occurrence of definite stent thrombosis was the primary safety end point while the development of pneumonia, presence of positive blood cultures, occurrence of probable stent thrombosis, any bleeding complications, need for red blood cell transfusion and presence of rhythm and conductions disorders during hospitalisation constituted secondary safety end points.ResultsComatose OHCA survivors (n = 32) were referred to our Department based on ECG recording transmissions and/or phone consultations or admitted from the Emergency Department. Compared with controls (n = 33), they were significantly more likely to be discharged from hospital with a favourable neurological outcome (59 vs. 27%; p < 0.05; number needed to treat [NNT] = 3.11) and experienced lower all-cause in-hospital mortality (13 vs. 55%; p < 0.05; NNT = 2.38). Rates of all safety end points were similar in patients treated with and without MTH.ConclusionsOur study indicates that a regional system of care for OHCA survivors may be successfully implemented based on an ACS network, leading to an improvement in neurological status and to a reduction of in-hospital mortality in patients treated with MTH, without any excess of complications. However, our findings should be verified in large, prospective trials.

Discrepancies in Assessment of Adherence to Antiplatelet Treatment after Myocardial Infarction

The poor response to clopidogrel is multifactorial and includes, amongst others, low patient adherence to medication. The aim of this study was to assess the reported patient adherence to treatment with clopidogrel and confront it with adherence assessed by drug availability. We evaluated determinants of adherence and its impact on platelet aggregation and clinical outcome. The study population comprised 184 patients treated with primary percutaneous coronary intervention for acute myocardial infarction. Follow-up visits were scheduled at 3, 6 and 9 months after discharge. Patient adherence to clopidogrel was defined according to self-reported drug intake and verified based on data from the National Health Fund regarding the purchase of prescribed drugs. The patients were judged as adherent when the proportion of drug availability exceeded 80%. According to drug availability, 100 (54.3%) patients were adherent and 84 (45.7%) were nonadherent. The analysis identified the following factors as predictors of low adherence (<80%): adenosine diphosphate-induced platelet aggregation (ADP-PA) during hospitalization ≤45 U, male gender and occurrence of ST-elevation myocardial infarction [(STEMI) vs. non-STEMI (NSTEMI)], while three-vessel disease was predictive of high adherence to medication. Compared with drug availability-based assessment, self-reported drug intake was significantly different: 172 (94.5%) patients reported regular and 10 (5.5%) patients reported irregular intake of clopidogrel. Clinical follow-up suggested that the self-reported nonregular clopidogrel intake may discriminate patients with a high risk of cardiovascular events. We demonstrated a huge discrepancy between the two most widely used methods for the evaluation of adherence to clopidogrel in secondary prevention treatment in patients after STEMI and NSTEMI. ADP-PA during hospitalization ≤45 U, male gender and STEMI (vs. NSTEMI) were independent predictors of nonadherence while three-vessel disease was independently predictive of adherence to treatment with clopidogrel in the investigated population.

Prediction of high risk of non-adherence to antiplatelet treatment

BACKGROUND Dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel is the standard of care for secondary prevention. Premature discontinuation of clopidogrel is associated with an increased risk of myocardial infarction (MI) or death, and greater health care expenditure. AIM To develop an objective method for identification of patients with high risk of non-adherence to clopidogrel after MI. METHODS A total of 189 patients were enrolled into a prospective, observational, single-centre study with a nine-month follow-up. Patients received a 600-mg loading dose and 75-mg maintenance dose of clopidogrel in combination with ASA doses of 300 mg and 75 mg, respectively. Adenosine diposphate-induced platelet aggregation (ADP-PA) was assessed during baseline hospitalisation and at three, six, and nine months after discharge. Adherence to medication with clopidogrel was defined as the proportion of drug availability based on data from the National Health Fund regarding prescribed drug purchases. Adherence was arbitrarily judged adequate when the proportion exceeded 80%. RESULTS According to our hypothesis, ADP-PA in non-adherent patients should be higher at follow-up visits (at least once) as compared with measurement at hospitalisation. Based on the ROC curve analysis, the optimal cut-off point equal to 4 U was defined (p < 0.0001, 95% CI 0.562-0.654; sensitivity: 60.6%, specificity: 57.1%, positive predictive value: 63.3%, negative predictive value: 54.2%). The prevalence of true adherence to medication in groups of high and low probability of adherence defined according to developed criteria amounted 60 (50.8%) and 23 (32.4%) cases, respectively (p = 0.01). CONCLUSIONS The newly developed method of objective identification of patients with high risk of non-adherence to clopidogrel after MI is easily applicable and cheap, and, despite relatively low sensitivity and specificity, it efficiently differentiates patients with regard to clinical end-points during follow-up.

Adherence to treatment assessed with the Adherence in Chronic Diseases Scale in patients after myocardial infarction

Introduction A substantial subset of patients after myocardial infarction (MI) discontinue pivotal medication early after discharge. In particular, cessation of antiplatelet treatment may lead to catastrophic ischemic events. Thus, adherence to prescribed medication in patients after MI is an issue of medical and social concern. Purpose The aim of the study was to evaluate the level of adherence to treatment using a newly developed scale in patients after MI treated with percutaneous coronary intervention. Patients and methods A single-center, prospective, observational cohort clinical study with a 6-month follow-up was performed. Patients with physical or cognitive impairment, prisoners, soldiers, and family members and coworkers of the researchers were excluded from the study. The impact of selected sociodemographic and clinical factors on adherence was evaluated in 221 patients (63 women and 158 men) aged 30 to 91 years. Results The results obtained with the Adherence in Chronic Diseases Scale (ACDS) ranged from 7 to 28 points; with the average and median scored being 23.35 and 24, respectively. The ACDS score reflects the level of adherence to prescribed medication. The high ACDS scores (>26 points) were obtained in 59 (26.7%) patients, intermediate scores (21–26 points) in 110 (49.8%) and low scores (<21 points) in 52 subjects (23.5%). Acute coronary syndrome (re-ACS) occurred in 18 (8.1%) patients during the follow-up period. The high-level adherence (ACDS score >26 points) was found in 11.1% of patients with re-ACS vs 28.4% of the remaining ones (P=0.1). Lower scores (mean ± standard deviation) in re-ACS patients were found for items 2 and 3 of the ACDS: 3.11±0.68 vs 3.45±0.73 (P=0.02) and 3.28±0.89 vs 3.64±0.64 (P=0.04), respectively. Conclusion Age and previous MI were found to be independent factors influencing adherence assessed with the ACDS.

Influence of cardiac resynchronization therapy on oxidative stress markers in patients with chronic heart failure

BACKGROUND The aim of the study was to assess changes of substances of oxidative stress in patients treated with cardiac resynchronization therapy (CRT). METHODS The study comprised 51 patients with median age of 66 years. The presence, severity, and changes of oxidative stress during CRT were assessed and expressed as malondialdehyde (MDA) concentration in plasma or in red blood cells. Antioxidant activity was assessed by the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in red blood cells. The concentration and activities were analyzed directly prior to implantation, 2-5 days after the procedure and after 6 months. Follow-up (6 months) included clinical, echocardiographic and implanted device assessments. RESULTS During the follow-up, 14% patients died. The median percentage of biventricular pacing was 99.29%. After 6 months 88% of patients improved NYHA, 12% remained as non-responders. Left ventricular ejection fraction increased from median 21.5% to 29% (p < 0.05). Left ventricular end-diastolic diameter decreased significantly from a median of 69.5 mm to 63 mm (p < 0.05). After a 6-month study, MDA plasma concentration and the activity levels of each antioxidant enzymes (CAT, SOD, GPx) showed a statistically significant reduction (p < 0.05). Changes concerning MDA concentrations in red blood cells remained statistically insignificant. CONCLUSIONS Resynchronization effect oxidative stress by reducing plasma concentration of MDA, CAT, SOD and GPX.

Acetylsalicylic acid resistance risk factors in patients with myocardial infarction

BACKGROUND Despite its commonly recognized benefits in the cardiovascular disease setting, an issue of resistance to this drug has lately emerged. The aim of this research was assessment of the phenomenon of acetylsalicylic acid (ASA) resistance and its risk factors in patients treated for myocardial infarction. METHODS This study is a post-hoc analysis of a previous prospective study with approximately 200 patients treated for myocardial infarction with a coated formulation of ASA. The population was divided into two subgroups according to the response to ASA. ASA responsiveness was assessed using the arachidonic acid-dependent platelet aggregation (ASPI-test). The measurements were performed using the technique of impedance aggregometry. RESULTS The prevalence of aspirin resistance among the study population was 6.2%. All analyzed aggregometric parameters (including ASPI-test, adenosine diphosphate dependent platelet aggregation - ADP-test, bleeding time measurement) showed significant differences between both subgroups. ASA resistant patients had higher concentrations of brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hs-CRP), leukocytes (WBC) and platelets (PLT) but lower concentrations of hemoglobin (HGB). The temporal point analysis for both subgroups showed aspirin resistance incidence peak in patients at 9 months after myocardial infarction. CONCLUSIONS The prevalence of aspirin resistance in our study population is comparable with rates reported in literature among patients with cardiovascular diseases. There is a possible relation between aspirin resistance and clopidogrel resistance. Presence did not affect the incidence of the clinical end-points.

Effectiveness of therapeutic education in patients with myocardial infarction

Introduction. Notwithstanding the development of modern diagnostic-therapeutic techniques, cardiovascular diseases still pose a grave health, social, and economic issue. Patients hospitalised for acute coronary syndrome should, in addition to establishing an optimal pharmacotherapy, be made aware of how to prevent this disease and recognise it using its typical symptoms and signs. Objective. The objective of the study was to evaluate the effectiveness of educational intervention based on educational brochures in patients with myocardial infarction with regard to socio-demographic factors and baseline patients’ knowledge. Material and methods. The single-centre, prospective, observational study was conducted in a cohort of 248 patients with myocardial infarction (women n = 72, men n = 176), hospitalised between May 2015 and July 2016. Consistently with the results of univariate analysis, multivariate analysis identified age (–3.73/10 years; p < 0.0006) and the level of education (10.37; p < 0.0001) as independent factors influencing patients’ prehospital knowledge. Results. According to multivariate analysis of the level of knowledge following the educational intervention, the only factors affecting the process of learning were age (–2.04/10 years; p < 0.03) and remaining in a steady relationship (9.7; p = 0.0003). Among factors influencing the increase of knowledge, only the level of education was of statistical significance (–6.09; p < 0.02). Conclusions. The educational brochure proved to be an effective tool for therapeutic education, allowing minimisation of the disparities between the examined groups and improvement of the breadth of patients’ knowledge.

Safety of cardiac resynchronization device implantation — retrospective analysis from high-volume centre

Aims: Cardiac resynchronization therapy (CRT) is a treatment dedicated to patients suffering from heart failure and asynchrony of systole typically due to left bundle branch block (LBBB). The aim of this study is to analyse the safety of CRT device implantation in a large single-centre group. Methods and results: The retrospective analysis of 198 patients hospitalized in the Department of Cardiology, dr A. Jurasz University Hospital no 1 in Bydgoszcz, who underwent CRT devices implantations in two consecutive years (2015–2016) has been performed. Out of 198 patients, 136 underwent implantation of CRT de novo and 62 exchange of the device. Studied procedures included implantations of 121 (89.0%) cardiac resynchronization therapy defibrillators (CRT-D) and 15 (11.0%) cardiac resynchronization therapy pacemakers (CRT-P) de novo, as procedures of exchange were excluded from statistical analysis. Collected data included: reported complications, patients’ basic clinical characteristics, comorbidities and details of implantation procedures. Development of any complication was observed in 43 patients (31.6%), out of whom 29 (21.3%) experienced one, 10 (7.4%) two and 4 (2.9%) three complications. Most of them were minor complications. Serious complications which included pneumothorax, mediastinal hematoma and cardiac tamponade were observed in 6 (4.4%) cases, there were no perioperative deaths. The occurrence of complications was significantly more frequent in females (OR , 3.45, 95% CI 1.37–8.71, p 0.008), was associated with prolonged procedure time (OR 1.11, 95% CI 1.04–1.20, p 0.003) and prolonged hospitalization time (OR 1.16, 95% CI 1.06–1.27, p 0.001). Conclusion: Overall, implantations of CRT devices are burdened with a substantial risk of complications, although the majority of them are minor and do not require subsequent surgical intervention. The risk of developing serious complications is low, accounting for 4.4%.