Perceptions of generic medicines and medication adherence after percutaneous coronary intervention: a prospective multicentre cohort study

Objective: To determine patient perceptions of generic medicines 2 and 6 months after percutaneous coronary intervention (PCI), and to determine whether these perceptions moderate medication adherence. Design: Prospective multicentre cohort study with repeated measures of perceptions of generic medicines and medication adherence. Setting: The CONCARDPCI study conducted at seven large referral PCI centres in Norway and Denmark between June 2017 and May 2020. Participants: A total of 3417 adults (78% men), using both generic and brand name medicines, with a mean age of 66 years (SD 11) who underwent PCI were followed up 2 and 6 months after discharge from hospital. Main outcome measures: Perceptions of generic medicines were the main outcome. The secondary outcome was medication adherence. Results: Perceptions of generic medicines were significantly more negative at 2 than at 6 months (1.10, 95% CI 0.41 to 1.79, p=0.002). Female sex (−4.21, 95% CI −6.75 to −1.71, p=0.001), older age (−0.12, 95% CI −0.23 to −0.02, p=0.020), lower education level (overall p<0.001), ethnicity (overall p=0.002), Norwegian nationality (10.27, 95% CI 8.19 to 12.40, p<0.001) and reduced self-reported health status (0.19, 95% CI 0.09 to 0.41, p=0.003) were significantly associated with negative perceptions of generic medicines. There was no evidence to suggest that perceptions of generic medicines moderate the association between sociodemographic and clinical variables and medication adherence (p≥0.077 for all covariates). Moreover, self-reported medication adherence was high, with 99% scoring at or above the Medication Adherence Report Scale midpoint at both time points. There were no substantial correlations between negative perceptions of generic medicines and medication non-adherence at 2 months (r=0.041, 95% CI 0.002 to 0.081, p=0.037) or 6 months (r=0.038, 95% CI −0.005 to 0.081, p=0.057). Conclusions: Mistrust and uncertainty about the safety and efficacy of generic medicines remains in a sizeable proportion of patients after PCI. This applies especially to those of lower socioeconomic status, older age, female sex, immigrants and those with poorer mental health. However, this study demonstrated a shift towards more positive perceptions of generic medicines in the longer term.publishedVersio

Rethinking rehabilitation after percutaneous coronary intervention: a protocol of a multicentre cohort study on continuity of care, health literacy, adherence and costs at all care levels (the CONCARD PCI )

Introduction: Percutaneous coronary intervention (PCI) aims to provide instant relief of symptoms, and improve functional capacity and prognosis in patients with coronary artery disease. Although patients may experience a quick recovery, continuity of care from hospital to home can be challenging. Within a short time span, patients must adjust their lifestyle, incorporate medications and acquire new support. Thus, CONCARDPCI will identify bottlenecks in the patient journey from a patient perspective to lay the groundwork for integrated, coherent pathways with innovative modes of healthcare delivery. The main objective of the CONCARDPCI is to investigate (1) continuity of care, (2) health literacy and self-management, (3) adherence to treatment, and (4) healthcare utilisation and costs, and to determine associations with future short and long-term health outcomes in patients after PCI. Methods and analysis: This prospective multicentre cohort study organised in four thematic projects plans to include 3000 patients. All patients undergoing PCI at seven large PCI centres based in two Nordic countries are prospectively screened for eligibility and included in a cohort with a 1-year follow-up period including data collection of patient-reported outcomes (PRO) and a further 10-year follow-up for adverse events. In addition to PROs, data are collected from patient medical records and national compulsory registries. Ethics and dissemination: Approval has been granted by the Norwegian Regional Committee for Ethics in Medical Research in Western Norway (REK 2015/57), and the Data Protection Agency in the Zealand region (REG-145-2017). Findings will be disseminated widely through peer-reviewed publications and to patients through patient organisations. Trial registration number: NCT03810612

IL-6 Receptor Inhibition by Tocilizumab Attenuated Expression of C5a Receptor 1 and 2 in Non-ST-Elevation Myocardial Infarction

Background: Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL-6 receptor (IL-6R)-antagonist tocilizumab on the expression of the anaphylatoxin receptors in whole blood from non-ST-elevation myocardial infarction (NSTEMI) patients. Separately, anaphylatoxin receptor expression in peripheral blood mononuclear cells (PBMC) from patients with different entities of CAD was investigated.Materials and Methods: NSTEMI patients were randomized to one dose of tocilizumab (n = 28) or placebo (n = 32) and observed for 6 months. Whole blood samples drawn at inclusion, at day 2, 3 and after 6 months were used for mRNA isolation. Plasma was prepared for analysis of complement activation measured as sC5b-9 by ELISA. Furthermore, patients with different CAD entities comprising stable angina pectoris (SAP, n = 22), non-ST-elevation acute coronary syndrome (NSTE-ACS, n = 21) and ST-elevation myocardial infarction (STEMI, n = 20) were included. PBMC was isolated from blood samples obtained at admission to hospital and mRNA isolated. Anaphylatoxin-receptor-expression was analyzed with qPCR using mRNA from whole blood and PBMC, respectively.Results: Our main findings were (i) Tocilizumab decreased C5aR1 and C5aR2 mRNA expression significantly (p &lt; 0.001) and substantially (&gt;50%) at day 2 and 3, whereas C3aR expression was unaffected. (ii) Tocilizumab did not affect complement activation. (iii) In analyzes of different CAD entities, C5aR1 expression was significantly increased in all CAD subgroups compared to controls with the highest level in the STEMI patients (p &lt; 0.001). For C5aR2 and C3aR the expression compared to controls were more moderate with increased expression of C5aR2 in the STEMI group (p &lt; 0.05) and C3aR in the NSTE-ACS group (p &lt; 0.05).Conclusion: Expression of C5aR1 and C5aR2 in whole blood was significantly attenuated by IL-6R-inhibition in NSTEMI patients. These receptors were significantly upregulated in PBMC CAD patients with particularly high levels of C5aR1 in STEMI patients

The impact of semi-automatic versus manually adjusted assessment of global longitudinal strain in post-myocardial infarction patients

There are unresolved questions related to the proper use of editing the region of interest (ROI) for measurements of global longitudinal strain (GLS). The purpose of the present study was to compare the semi-automatic default GLS value by the vendor's software with manually adjusted GLS and test the impact on GLS measures with different ROI widths. We selected 25 patients post myocardial infarction treated with PCI who had excellent echocardiographic recordings after 2-5 days and 3 months. The different GLS values were assessed from these 50 analyses in three steps. The semi-automatically GLS by default ROIs was compared with manually adjusted ROIs widths selected by an expert and then with manual adjustments, but with fixed ROIs being narrow, medium and wide. Their mean age was 64 (+/- 12) years, 52% had ST elevation MI and mean LVEF was 52 (+/- 4)%. Mean default GLS was - 15.3 (+/- 2.5)% with the widest ROI level selected semi-automatically in 78% of all widths. The mean expert GLS with manually adjusted ROI was - 14.7 (+/- 2.4)%, and the medium ROI level was selected by the expert in 85% of all examinations. The mean adjusted GLS, but with fixed ROIs widths was - 15.0 (+/- 2.5%)% with narrow ROI, - 14.7 (+/- 2.6)% with medium and - 13.5 (+/- 2.3)% with wide ROI width (p < 0.001 vs. default GLS). The Intra Class Coefficient Correlation between default and manually adjusted expert GLS was 0.93 (p < 0.001). The difference between the default and the manually adjusted expert GLS was neglectable. These findings may represent a simplification of the assessment of GLS that might increase its use in clinical practice. The GLS measurements with a fixed wide ROIs were significantly different from the expert measurements and indicate that a wide ROI should be avoide

Reduced inflammatory response by transcatheter, as compared to surgical aortic valve replacement

Objectives. The inflammatory response to on-pump cardiac surgery is well known. Systemic inflammatory response syndrome after transcatheter valve implantation (TAVI) has been reported. The objective of this study was to study the inflammatory response during TAVI, and compare with the response during surgical aortic valve replacement. Methods. Eighteen patients undergoing transcatheter implantation, either by a transfemoral (n = 9) or transaortal (n = 9) approach were compared with eighteen patients admitted for surgical replacement. Blood samples per- and postoperatively were analysed for C3bc, terminal complement complex, myeloperoxidase, macrophage inflammatory protein-1β, monocyte chemo-attractant peptide-1, eotaxin, IL-6 and troponin-T. All markers were measured at defined time points and the areas under the curve were compared. Results. Activation of complement, granulocytes, monocytes and eosinophils were significantly lower in the transcatheter group as compared to the surgical group (Discussion. Activation and release of inflammatory markers was significantly less during with TAVI as compared to SAVR, particularly for markers associated with extracorporeal circulation. TAVI and SAVR generated the same degree of IL-6 and troponin T, indicating that the burden on the myocardial tissue was the same

Reduced inflammatory response by transcatheter, as compared to surgical aortic valve replacement

Objectives. The inflammatory response to on-pump cardiac surgery is well known. Systemic inflammatory response syndrome after transcatheter valve implantation (TAVI) has been reported. The objective of this study was to study the inflammatory response during TAVI, and compare with the response during surgical aortic valve replacement. Methods. Eighteen patients undergoing transcatheter implantation, either by a transfemoral (n = 9) or transaortal (n = 9) approach were compared with eighteen patients admitted for surgical replacement. Blood samples per- and postoperatively were analysed for C3bc, terminal complement complex, myeloperoxidase, macrophage inflammatory protein-1β, monocyte chemo-attractant peptide-1, eotaxin, IL-6 and troponin-T. All markers were measured at defined time points and the areas under the curve were compared. Results. Activation of complement, granulocytes, monocytes and eosinophils were significantly lower in the transcatheter group as compared to the surgical group (<0.01). There was no difference in generation of troponin T and IL-6. A small difference in complement activation was observed between the transfemoral and transaortal placement of TAVI. There was no significant difference in clinical outcomes between the TAVI and surgical groups. Discussion. Activation and release of inflammatory markers was significantly less during with TAVI as compared to SAVR, particularly for markers associated with extracorporeal circulation. TAVI and SAVR generated the same degree of IL-6 and troponin T, indicating that the burden on the myocardial tissue was the same

Operative survival in patients with acute aortic disease in the era of newer oral anticoagulants

The aim of this study was the analysis of the risk associated with direct oral anticoagulants (DOACs) in patients undergoing non-elective operations on the proximal aorta due to aortic disease.Methods and resultsData from the department’s register of cardiac surgery was analysed retrospectively with emphasis on operative mortality. 135 non-elective operations for proximal aortic disease (October 2016 to 2018) were identified, of which 19 died during the first 90 days. DOAC use was the top-ranked risk factor in the univariate analysis with a HR of 9.6 (3.1 to 29), p=0.00007. Using a Cox proportional hazards model including the most relevant risk factors, the risk associated with DOAC use remained significant with a HR of 6.1 (1.4 to 26.3), p=0.015. We did not find increased risk associated with warfarin use.In patients undergoing non-elective operations on the proximal aorta due to aortic disease, the use of DOAC is associated with increased operative mortality