A systematic review on the role of bivalirudin in patients undergoing percutaneous coronary interventions: primus inter pares or a falling star?

Intracoronary thrombosis triggered by ruptured or eroded atherosclerotic plaques constitutes the predominant underlying cause of acute coronary syndromes (ACS). Thrombin is considered a central enzyme in hemostasis and thrombosis, and a well-established target for anticoagulant therapies. Bivalirudin was introduced in the clinical practice as a promising, reversible, direct thrombin inhibitor with a predictable anticoagulant effect. Initial randomized clinical trials demonstrated that bivalirudin compared with heparin on top of a glycoprotein IIb/IIIa inhibitor was associated with a significant reduction of major bleeding and favorable net clinical outcomes in patients undergoing percutaneous coronary interventions (PCI). The HORIZON-AMI trial even indicated mortality benefit in bivalirudin-treated patients. Thereby, the 2011 and 2012 European Society of Cardiology Guidelines on the management of non-ST-segment elevation ACS and ST-segment elevation myocardial infarction positioned bivalirudin as the anticoagulant of choice in the PCI setting. Further randomized studies, better reflecting routine clinical practice, revealed significantly increased rates of stent thrombosis and myocardial infarction in the bivalirudin arm. Additionally, these findings were corroborated in the subsequent meta-analyses. Speculations that excessive occurrence of stent thrombosis and myocardial infarction may be caused by too short duration of post PCI bivalirudin infusion did not find confirmation in the latest MATRIX trial. In this systematic review, we aim to assess the efficacy and safety of bivalirudin therapy in patients undergoing PCI and to formulate recommendations on the bivalirudin use for clinicians. In our opinion, the research evidence and pharmacoeconomic considerations strongly support the use of bivalirudin in PCI patients at high risk of bleeding complications, while in other situations old and inexpensive UFH or enoxaparin remain the first line antithrombotic drugs

Ocena czynności śródbłonka naczyniowego - gdzie jesteśmy, dokąd zmierzamy?

Śródbłonek naczyniowy odgrywa niezwykle istotną rolę w organizmie. Pojedyncza warstwa komórek wyścielająca ścianę naczyń wydziela wiele substancji o działaniu wazoaktywnym, wpływającym na procesy krzepnięcia i fibrynolizy, biorących udział w regulacji procesów zapalnych, a także w oddziaływaniach między komórkami i ścianą naczyń. Dysfunkcja śródbłonka naczyniowego wyrażająca się zaburzeniem tych złożonych procesów odgrywa zasadniczą rolę w patogenezie miażdżycy. Obecnie dysponujemy biochemicznymi i fizycznymi metodami umożliwiającymi ocenę czynności śródbłonka naczyniowego. Oznaczenie biodostępności tlenku azotu, stężenia czynnika von Willebranda lub cząstek adhezyjnych koreluje z występowaniem czynników ryzyka chorób sercowo-naczyniowych. Wśród metod fizycznych uznaną metodą oceny funkcji śródbłonka jest określenie stopnia rozszerzenia tętnicy ramiennej po uprzedniej okluzji mankietem manometru tętnic przedramienia lub proksymalnej części ramienia (FMD). Stosuje się również techniki oceniające sztywność naczyń (PWA, PWV). Pośrednią metodą oceny dysfunkcji śródbłonka jest określenie grubości błony środkowej i błony wewnętrznej tętnicy szyjnej (IMT). Zwiększenie grubości tego kompleksu koreluje z dysfunkcją endotelium. Duże nadzieje pokłada się w nowej metodzie oceniającej czynność śródbłonka w odpowiedzi na reaktywne przekrwienie (RH-PAT). Metody fizyczne, zwłaszcza nieinwazyjne, są kluczowe dla wczesnej identyfikacji osób zagrożonych wystąpieniem zdarzeń sercowo-naczyniowych, dlatego konieczny jest dalszy ich rozwój. (Folia Cardiologica Excerpta 2010; 5, 5: 292-297

Impact of health education on adherence to clopidogrel and clinical effectiveness of antiplatelet treatment in patients after myocardial infarction

Non-adherence rates to antiplatelet drugs in patients with acute myocardial infarction (AMI) range from 13% to 60%. We aimed to evaluate whether individual health education can improve adherence to treatment with clopidogrel in patients after AMI. This was a prospective, single-center, randomized clinical trial with a 12-month follow-up. Patients with AMI treated with percutaneous coronary intervention (PCI) were enrolled. The primary endpoint was defined as non-adherence to clopidogrel during follow-up (drug availability ≤ 80%). Secondary endpoints included platelet function assessment, adverse cardiovascular (CV) events (CV death, PCI for ACS, unscheduled CV hospitalization). There were 191 patients enrolled in the study and divided into two groups: the individual education (IE) group (100 patients) and the standard treatment (ST) group (91 patients). Adherence to the treatment with clopidogrel based on the data from the National Health Fund did not differ significantly between the IE and ST groups [76.7% (30.7–99.7%) v. 84.4% (46.5–99.7%); p = 0.25]. There was a substantial difference in the prevalence of unscheduled CV hospitalizations between both groups, IE and ST respectively [22 (22.0%) v. 10 (11.0%); p = 0.042]. The rate of CV death and ACS treated with PCI during follow-up was low and did not differ between groups. In conclusion, the program of individual health education did not improve adherence to treatment with clopidogrel. The expected benefits of medication are not achievable at current levels of adherence. The self-reported adherence assessment is unreliable and cannot be used for effective treatment guidance

Impact of ticagrelor administration strategy on its pharmacokinetics and pharmacodynamics in patients with unstable angina pectoris: a protocol of a randomized study

Introduction. Dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor constitutes an essential part of the management of patients with acute coronary syndromes (ACS). Based on the favorable results of the PLATO trial, ticagrelor is currently recommended as the first line P2Y12 receptor inhibitor in a broad spectrum of ACS patients. According to the recently published data, several conditions, including concurrent analgesia with morphine and clinical presentation as an ACS, may alter ticagrelor absorption and its antiplatelet effect. Therefore, the goal of the present study was to investigate pharmacokinetics and pharmacodynamics of new ticagrelor administration strategies aimed to overcome limitations of the standard ticagrelor loading regimen. Methods/design. The study is designed as a phase IV, single center, randomized, investigator-initiated, parallel-group, open-label, interventional study comparing the influence of various ticagrelor administration strategies on its pharmacokinetics and pharmacodynamics. Patients with unstable angina pectoris will be randomized in a 1:1:1 ratio into one of three arms, each receiving a 180 mg ticagrelor loading dose (LD). Ticagrelor administration strategies comprise: 1) pulverized ticagrelor administered sublingually, 2) pulverized ticagrelor in 10 mL suspension in tap water administered orally and 3) integral ticagrelor tablets administered orally. An internal pilot study including 30 (10 in each of the arms) is planned in order to determine the final sample size. The primary endpoint of the trial is time (tmax) required for ticagrelor and its active metabolite AR-C124900XX to reach maximum plasma concentration within time frame of six hours after administration of ticagrelor LD. The secondary endpoints include ticagrelor and AR-C124900XX maximum plasma concentration, area under the plasma concentration-time curve for ticagrelor and AR-C124900XX (AUC 0–6h) and platelet reactivity assessed with Multiple Electrode Aggregometry using the Multiplate™ Analyzer prior to and within time frame of six hours following ticagrelor LD. Discussion. This study is expected to provide essential evidence-based data on the impact of ticagrelor administration strategy on its pharmacokinetics and pharmacodynamics in patients with unstable angina pectoris. Hopefully, based on its results, further clinical outcome-powered trials on new ticagrelor administration strategies will be designed and conducted.

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

Value of C-Reactive Protein as a Risk Factor for Acute Coronary Syndrome: A Comparison with Apolipoprotein Concentrations and Lipid Profile

Objective. To investigate whether assessment of C-reactive protein (CRP) and apolipoproteins, besides the traditional lipid profile, enhances the assessment process for the risk of acute coronary syndrome (ACS). Methods. The study group consisted of 220 consecutive patients admitted to hospital within the first 6 hours from the onset of chest pain. Patients were diagnosed with unstable angina (n = 96), non-ST-elevation myocardial infarction (NSTEMI; n = 57), or ST-elevation myocardial infarction (STEMI; n = 67). ACS patients were compared with 116 healthy volunteers in a case-control study. The serum was assayed on admission for CRP, apolipoproteins ApoAI and ApoB100, and lipid parameters. Results. The highest concentrations of CRP were found in NSTEMI and STEMI, with a median value four-fold higher in ACS patients than in controls (P < 0.0001). Only CRP significantly increased the probability of ACS development (adjusted odds ratio for a 1 mg/L increase 1.90; 95% confidence interval [CI] 1.34–2.89) and explained 90% of the variation for ACS development. Similarly, we demonstrated the highest diagnostic accuracy for CRP among all investigated markers (area under the curve 0.80; 95% CI 0.75–0.85). Conclusions. Our study indicates that CRP superiorly to apolipoproteins and lipid profile facilitates the risk stratification for ACS occurrence

The readiness for hospital discharge of patients after acute myocardial infarction: a new self-reported questionnaire

Introduction. Medical care providers are responsible for adequate preparation of patients for discharge from the hospital. The purpose of this study was to validate a new self-reported questionnaire assessing the readiness of patients for hospital discharge. Methods. The Readiness for Hospital Discharge after Myocardial Infarction Scale (RHD MIS) was validated in 201 patients, 57 (29%) females and 144 (71%) males (mean age 63.3 ± 11.3), hospitalised due to myocardial infarction. Results. For the considered 23 items the a-Cronbach coefficient was 0.789, indicating a high level of reliability and homogeneity of the questionnaire. The RHD MIS fulfilled the assumption of factor analysis: the determinant of correlation matrix was 0.001, Kaiser-Mayer-Olkin (K-M-O) statistic was 0.723, and the Bartlett’ test of sphericity was statistically significant. The analysis of internal consistency of the three areas confirm the rightness of the distinguishing of three subscales. Answers to each item were assigned a score from 0 to 3. The highest total score is 69 points. The total score of the scale and total scores of the subscales have skewed distributions and statistically significant results of Shapiro-Wilk test (p &lt; 0.001). The scoring less than 44 points for the entire questionnaire indicates low readiness, obtaining between 44 and 57 points indicates medium readiness, and scores over 57 points are classified as high readiness for discharge from hospital. Conclusions. The validation procedure revealed that RHD MIS is a reliable and homogeneous tool to measure the readiness of patients for hospital discharge. The set of items divided into three subscales allows subjective and objective evaluation of the patient’s knowledge and expectations. Further investigation is needed to assess the potential impact of RHD MIS scoring on long-term outcome

Variability of prasugrel antiplatelet effect in patients with acute coronary syndrome

Background. Many reports have demonstrated excessive variability in response to clopidogrel, the most commonly used P2Y12 receptor antagonist. Clopidogrel resistant patients are at increased risk of cardiovascular (CV) events. Prasugrel is a new P2Y12 inhibitor that provides greater and faster platelet inhibition and reduces CV events more effectively than clopidogrel. The aim of this study was to evaluate the variability and efficacy of prasugrel antiplatelet activity in patients presenting with acute coronary syndrome (ACS). Materials and methods. The study was designed as a prospective, single-center, non-randomized, observational trial. Platelet reactivity (PR) was assessed with the VeryfyNow assay three times during hospitalization in forty-two patients undergoing percutaneous coronary intervention (PCI) for ACS and treated with standard doses of prasugrel. Results. Platelet aggregation with prasugrel displayed relatively high variability. The platelet aggregation was lowest on the 3rd day of the treatment at 4 p.m. and was significantly different from the measurements obtained on the 3rd and 4th day in the morning (6.0 v. 8.5 U; p = 0.0005 and 6.0 v. 36.5 U; p &lt; 0.00001, respectively), with the latter two differing significantly from each other (p = 0.002). All participants were successfully treated with prasugrel achieving PR &lt; 208 PRU in each measurement, whereas 42.9–80.9% (depending on sampling point) of patients presented very low platelet activity. The subgroups of stable and persistent low PR included a higher percentage of active smokers (73.3 v. 40.7%; p = 0.04 and 80.0 v. 43.8%; p = 0.04, respectively). Conclusions. Prasugrel treatment is associated with high variability of PR. Nonetheless, prasugrel is a highly effective antiplatelet drug. Active smoking may predispose to strong and stable on-prasugrel platelet inhibition.

Mild therapeutic hypothermia for patients with acute coronary syndrome and cardiac arrest treated with percutaneous coronary intervention (UNICORN). The design and rationale for the prospective, observational, multicenter study

Introduction. Cardiac arrest constitutes the most frequent reason for sudden death in developed countries. Out-of-hospital cardiac arrest (OHCA) survivors are at high risk of death or neurologic deficits. The existing data regarding effectiveness and safety of mild therapeutic hypothermia (MTH) for treatment of OHCA survivors are inconsistent and ambiguous. Moreover, a uniform protocol of treatment by means of MTH is lacking. Methods. The UNICORN study is a phase IV, prospective, international, multi-centre, observational study designed to assess the effectiveness of MTH in patients after OHCA with shockable rhythm presenting with acute coronary syndrome (ACS). The trial is expected to include up to 500 patients. Depending on the availability of MTH in each study centre, besides the routine treatment of ACS in OHCA survivors, patients will either undergo MTH according to a uniform protocol or will not undergo MTH (250 patients per group). The primary end-point of the study is all cause mortality at 180 days after enrolment. Secondary end-points include: neurological outcome at discharge, stent thrombosis at 30 days, bleeding according to the BARC criteria, infectious complications at 180 days, and rhythm and conduction disorders at 180 days. Ethics and dissemination. The study received approval from the Local Ethics Committee to conduct the study (Komisja Bioetyczna Uniwersytetu Mikołaja Kopernika w Toruniu przy Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy; study approval reference number KB 615/2015). The study results will be disseminated through conference presentations and publications in peer-reviewed journals. Trial registration. ClinicalTrials.gov identifier: NCT02611934 (18 November 2015).