Population Pharmacokinetic Analysis of Bisoprolol in Patients With Acute Coronary Syndrome.

To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed ß1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625-7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS.

Efficiency of chewable toothbrush in reduction of dental plaque in students.

BACKGROUND: Besides classical and electrical toothbrushes market offers tooth brushes that can be chewed, like chewing gums. The aim of this study was to show the effectiveness of chewable toothbrush versus a conventional brush in the students' population. METHODS: The prospective study included 346 students. For this research, we used a e-questionnaire for "smart" phones, that students completed outside the dental office. Respondents are divided into two groups: control group used conventional toothbrushes, respondents from the tested group used chewable toothbrush. For assessment of accumulation of the plaque we used TQHI index. For testing statistical hypotheses, the following were used: t-test for two independent samples and analysis of the variance of repeated measurements. RESULTS: Before brushing teeth, the average TQHI value for chewable brushes is 2.8 ± 0.3, while conventional is 2.7 ± 0.3, which is not a statistically significant difference (p = 0.448). After brushing teeth, the average TQHI value for chewable brushes is 2.0 ± 0.1, while conventional 2.0 ± 0.3, which is also not statistically significant (p = 0.729). Observing the index of the plaque values on the tooth surfaces in the upper jaw, in both groups, there was a statistically significant change in the amount of plaque in time (p < 0.001). There is a statistically significant interaction between groups and changes in the amount of plaque in the observed period (p = 0.013). CONCLUSIONS: The fact that there is no significant difference in the effectiveness of the tested brushes indicates the benefits of using chewable toothbrushes in order to reduce plaque, primarily in the inability to use conventional brushes.

Randomised evaluation of a novel biodegradable polymer-based sirolimus-eluting stent in ST-segment elevation myocardial infarction: the MASTER study.

AIMS: The MASTER study was designed to compare the performance of a new biodegradable polymer sirolimus-eluting stent (BP-SES) with a bare metal stent (BMS) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: The study was a prospective, randomised (3:1), controlled, single-blind multicentre trial that enrolled 500 STEMI patients within 24 hours of symptom onset during 2013-2015. Three hundred and seventy-five patients were treated with BP-SES and 125 with BMS. One hundred and four (104) randomised patients underwent angiographic follow-up at six months. The primary clinical endpoint was target vessel failure (TVF), defined as cardiac death, MI not clearly attributable to a non-target vessel, or clinically driven target vessel revascularisation (TVR) at 12 months. The primary angiographic endpoint was in-stent late lumen loss (LLL) at six months in the angiographic cohort. The major secondary endpoint for safety was a composite of all-cause death, recurrent MI, unplanned infarct-related artery revascularisation, stroke, definite stent thrombosis (ST) or major bleeding at one month. At 12 months, TVF had occurred in 6.1% of BP-SES and 14.4% of BMS patients (pnon-inferiority=0.0004), mainly driven by a higher rate of repeat revascularisation in BMS patients. The safety endpoint occurred in 3.5% of BP-SES and 7.2% of BMS patients (p=0.127). In-stent LLL demonstrated the superiority (p=0.0125) of BP-SES (0.09±0.43 mm) over BMS (0.79±0.67 mm). CONCLUSIONS: The study showed clinical non-inferiority and angiographic superiority of BP-SES versus a comparator BMS, suggesting that this novel DES may be a potential treatment option in STEMI.

Prevalence of renal dysfunction and its influence on functional capacity in elderly patients with stable chronic heart failure.

BACKGROUND/AIM: Chronic heart failure (CHF) is highly prevalent and constitutes an important public health problem around the world. In spite of a large number of pharmacological agents that successfully decrease mortality in CHF, the effects on exercise tolerance and quality of life are modest. Renal dysfunction is extremely common in patients with CHF and it is strongly related not only to increased mortality and morbidity but to a significant decrease in exercise tolerance, as well. The aim of our study was to investigate the prevalence and influence of the renal dysfunction on functional capacity in the elderly CHF patients. METHODS: We included 127 patients aged over 65 years in a stable phase of CHF. The diagnosis of heart failure was based on the latest diagnostic principles of the European Society of Cardiology. The estimated glomerular filtration rate (eGRF) was determined by the abbreviated modification of diet in renal disease (MDRD2) formula, and patients were categorized using the kidney disease outcomes quality initiative (K/DOQI) classification system. Functional capacity was determined by the 6 minute walking test (6MWT). RESULTS: Among 127 patients, 90 were men. The average age was 72.5 +/- 4.99 years and left ventricular ejection fraction (LVEF) was 40.22 +/- 9.89%. The average duration of CHF was 3.79 +/- 4.84 years. Ninty three (73.2%) patients were in New York Heart Association (NYHA) class II and 34 (26.8%) in NYHA class III. Normal renal function (eGFR > or = 90 mL/min) had 8.9% of participants, 57.8% had eGFR between 60-89 mL/min (stage 2 or mild reduction in GFR according to K/DOQI classification), 32.2% had eGFR between 30-59 mL/min (stage 3 or moderate reduction in GFR) and 1.1% had eGFR between 15-29 mL/min (stage 4 or severe reduction in GFR). We found statistically significant correlation between eGFR and 6 minute walking distance (6MWD) (r = 0.390, p < 0.001), LVEF (r = 0.268, p < 0.05), NYHA class (p = -0.269, p < 0.05) and age (r = 0.214, p < 0.05). In multiple regression analysis only patients' age was a predictor of decreased 6MWD < 300 m (OR = 0.8736, CI = 0.7804 - 0.9781, p < 0.05). CONCLUSION: Renal dysfunction is highly prevalent in the elderly CHF patients. It is associated with decreased functional capacity and therefore with poor prognosis. This study corroborates the use of eGFR not only as a powerful predictor of mortality in CHF, but also as an indicator of the functional capacity of cardiopulmonary system. However, clinicians underestimate a serial measurement of eGFR while it should be the part of a routine evaluation performed in every patient with CHF, particularly in the elderly population.

Life-saving percutaneous coronary interventions on the unprotected left main coronary artery in patients with acute coronary syndrome in the catheterization laboratory without cardiosurgical back-up.

INTRODUCTION: The optimal revascularization strategy for unprotected left main coronary disease (ULMCD) is the subject of ongoing debate and patients with ULMCD still represent a challenge for interventionalist, especially in the setting of an acute coronary syndome (ACS). CASE REPORT: We presented two cases of percutaneous treatment of ULMCD in the settings of ACS (ST Segment Myocardial Infarction and Non ST Segment Myocardial Infarction--STEMI and NSTEMI) in a catheterization laboratory without back-up of cardiosurgical department. Both patients were hemodynamically unstable with clinical signs of cardiogenic shock. Coronary angiography revealed left main thromobosis and using intra-aortic balloon pump as hemodynamic support primary angioplasty procedures were performed. Immediately after the procedures the patients hemodynamically improved and remained stable till discharge from hospital. CONCLUSION: Percutaneous coronary intervention (PCI) has become the most common strategy of revascularization in ACS patients with ULMCD and is generally preferred in patients with multiple comorbidities and/or in very unstable patients. In cases with no cardiosurgical departments PCI is an inevitable, bail-out, life saving procedure.

Successful retrieval of an unexpanded coronary stent from the left main coronary artery during primary percutaneous coronary intervention.

INTRODUCTION: Dislodgement and embolization of the new generation of coronary stents before their deployment are rare but could constitute a very serious complication. CASE OUTLINE: We report a case of a stent dislodgement into the left main coronary artery during the primary coronary intervention of infarct related left circumflex artery in a patient with acute myocardial infarction. The dislodged and unexpanded bare-metal stent FlexMaster 3.0x19 mm (Abbot Vascular) was stranded and bended in the left main coronary artery (LMCA), probably by the tip of the guiding catheter, but stayed over the guidewire. It was successfully retrieved using a low-profile Ryujin 1.25x15 balloon catheter (Terumo) that was passed through the stent, inflated and then pulled back into the guiding catheter. After that, the whole system was withdrawn through the 6 F arterial sheath via the transfemoral approach. After repeated cannulation via the 6F arterial sheath, additional BMW and ATW guidewires were introduced into the posterolateral and obtuse marginal branches and a bare-metal stent Driver (Medtronic Cardiovascular Inc) 3.0x18 mm was implanted in the target lesion. CONCLUSION: Stent dislodgement is a rare but potentially life-threatening complication of the percutaneous coronary intervention. This incident occurring in the LMCA in particular during an acute myocardial infarction requires to be urgently resolved. The avoidance of rough manipulation with the guiding catheter and delivery system may help in preventing this kind of complications.