AimsThe currently available data indicate a drug–drug interaction between morphine and oral P2Y12 receptor inhibitors, when administered together. The aim of this trial was to assess the influence of infused morphine on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients with acute myocardial infarction.Methods and resultsIn a single-centre, randomized, double-blind trial, patients were assigned in a 1:1 ratio to receive intravenously either morphine (5 mg) or placebo, followed by a 180 mg loading dose of ticagrelor. Pharmacokinetics was determined with liquid chromatography tandem mass spectrometry and ticagrelor antiplatelet effects were measured with up to three different platelet function tests: vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode aggregometry and VerifyNow. The pharmacokinetic and pharmacodynamic assessment was performed in 70 patients (35 in each study group). Morphine lowered the total exposure to ticagrelor and its active metabolite by 36% (AUC(0–12): 6307 vs. 9791 ng h/mL; P = 0.003), and 37% (AUC(0–12): 1503 vs. 2388 ng h/mL; P = 0.008), respectively, with a concomitant delay in maximal plasma concentration of ticagrelor (4 vs. 2 h; P = 0.004). Multiple regression analysis showed that lower AUC(0–12) values for ticagrelor were independently associated with the administration of morphine (P = 0.004) and the presence of ST-segment elevation myocardial infarction (P = 0.014). All three methods of platelet reactivity assessment showed a stronger antiplatelet effect in the placebo group and a greater prevalence of high platelet reactivity in patients receiving morphine.ConclusionsMorphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction. ClinicalTrials.gov Identifier: NCT02217878.

Introduction. Patients' adherence to long-term therapies is low. It translates into reduced quality of life and significant deterioration of health economics. Identification of potential barriers of medication-related adherence is a starting point allowing implementation of more advanced interventions directed to adherence improvement. Aim. The purpose of our study was to create and validate a simple instrument used to assess patients' adherence to recommended medications. Material and methods. The Adherence Scale in Chronic Diseases is a self-reported questionnaire with 8 items and with proposed 5 sets of answers. The total score in the Adherence Scale in Chronic Diseases ranges from 0 to 32 points. Three levels of adherence were considered (low: scores of 0 to 20; medium 21 to 25; high > 26). The validation of the questionnaire was conducted in accordance with the validation procedure. Assessment of the internal consistency was performed using a-Cronbach coefficient. In order to conduct the factor analysis, we assessed: the determinant of correlation matrix, Kaiser-Mayer-Olkin (K-M-O) statistic and the Bartlett's test of sphericity. Factor analysis was conducted using principal component analysis with Oblimin rotation. The Kaiser criterion and scree plot were used in order to determine components of the questionnaire. Adherence levels were determined based on the percentiles. Results. Grand total of 413 patients with a cardiovascular disease were included in the study. The reliability and homogeneity of the questionnaire were confirmed by a-Cronbach coefficient (0.739). Factor analysis showed that in this questionnaire we can extract two components. The analysis of factor loadings indicated excluding item 2 from the questionnaire. After exclusion of the mentioned item, we repeated the validation procedure. For such a new dataset, according to the Kaiser criterion, only one component was extracted. Conclusions. The Adherence Scale in Chronic Diseases is a practical, reliable, consistent and well validated instrument for identifying specific obstacles to medication adherence. Its simplicity causes that it can be successfully applied in daily practice by health care professionals. Our survey has the potential to improve patient-health care professional communication and relationship.

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

BackgroundData from available studies suggest that the presence of ST-elevation myocardial infarction (STEMI) may be associated with delayed and attenuated ticagrelor bioavailability and effect compared with non-ST-elevation myocardial infarction (NSTEMI).MethodsIn a single-center, prospective, observational trial 73 patients with myocardial infarction (STEMI n = 49, NSTEMI n = 24) underwent a pharmacokinetic and pharmacodynamic assessment after a 180 mg ticagrelor loading dose (LD). Ticagrelor and its active metabolite (AR-C124910XX) plasma concentrations were determined with liquid chromatography tandem mass spectrometry, and their antiplatelet effect was measured with the VASP assay and multiple electrode aggregometry.ResultsDuring the first six hours after ticagrelor LD, STEMI patients had 38% and 34% lower plasma concentration of ticagrelor and AR-C124910XX, respectively, than NSTEMI (ticagrelor AUC(0–6): 2491 [344–5587] vs. 3991 [1406–9284] ng*h/mL; p = 0.038; AR-C124910XX AUC(0–6): 473 [0–924] vs. 712 [346–1616] ng*h/mL; p = 0.027). STEMI patients also required more time to achieve maximal concentration of ticagrelor (tmax: 4.0 [3.0–12.0] vs. 2.5 [2.0–6.0] h; p = 0.012). Impaired bioavailability of ticagrelor and AR-C124910XX seen in STEMI subjects was associated with diminished platelet inhibition in this group, which was most pronounced during the initial hours of treatment.ConclusionsPlasma concentrations of ticagrelor and AR-C124910XX during the first hours after ticagrelor LD were one third lower in STEMI than in NSTEMI patients. This reduced and delayed ticagrelor bioavailability was associated with weaker antiplatelet effect in STEMI.Clinical trial registrationClinicalTrials.gov identifier: NCT02602444 (November 09, 2015)