Regional differences in physicians' behavior and factors influencing the intensity of PCSK9 inhibitor therapy with alirocumab: a subanalysis of the ODYSSEY APPRISE study.

Background: Despite better accessibility of the effective lipid-lowering therapies, only about 20% of patients at very high cardiovascular risk achieve the low-density lipoprotein cholesterol (LDL-C) goals. There is a large disparity between European countries with worse results observed for the Central and Eastern Europe (CEE) patients. One of the main reasons for this ineffectiveness is therapeutic inertia related to the limited access to appropriate therapy and suitable dosage intensity. Thus, we aimed to compare the differences in physicians' therapeutic decisions on alirocumab dose selection, and factors affecting these in CEE countries vs. other countries included in the ODYSSEY APPRISE study. Methods: ODYSSEY APPRISE was a prospective, single-arm, phase 3b open-label (≥12 weeks to ≤30 months) study with alirocumab. Patients received 75 or 150 mg of alirocumab every 2 weeks, with dose adjustment during the study based on physician's judgment. The CEE group in the study included Czechia, Greece, Hungary, Poland, Romania, Slovakia, and Slovenia, which we compared with the other nine European countries (Austria, Belgium, Denmark, Finland, France, Germany, Italy, Spain, and Switzerland) plus Canada. Results: A total of 921 patients on alirocumab were involved [modified intention-to-treat (mITT) analysis], including 114 (12.4%) subjects from CEE countries. Therapy in CEE vs. other countries was numerically more frequently started with lower alirocumab dose (75 mg) at the first visit (74.6 vs. 68%, p = 0.16). Since week 36, the higher dose was predominantly used in CEE patients (150 mg dose in 51.6% patients), which was maintained by the end of the study. Altogether, alirocumab dose was significantly more often increased by CEE physicians (54.1 vs. 39.9%, p = 0.013). Therefore, more patients achieved LDL-C goal at the end of the study (<55 mg/dl/1.4 mmol/L and 50% reduction of LDL-C: 32.5% vs. 28.8%). The only factor significantly influencing the decision on dose of alirocumab was LDL-C level for both countries' groups (CEE: 199.2 vs. 175.3 mg/dl; p = 0.019; other: 205.9 vs. 171.6 mg/dl; p < 0.001, for 150 and 75 mg of alirocumab, respectively) which was also confirmed in multivariable analysis (OR = 1.10; 95% CI: 1.07-1.13). Conclusions: Despite larger unmet needs and regional disparities in LDL-C targets achievement in CEE countries, more physicians in this region tend to use the higher dose of alirocumab, they are more prone to increase the dose, which is associated with a higher proportion of patients reaching LDL-C goals. The only factor that significantly influences decision whether to increase or decrease the dose of alirocumab is LDL-C level.

Mitral Annular Plane Systolic Excursion (MAPSE) as a Predictor of Atrial Fibrillation Recurrence in Patients after Pulmonary Vein Isolation.

Introduction: Catheter ablation (CA) with pulmonary vein isolation (PVI) has become widely used in the past years for the treatment of atrial fibrillation (AF). Mitral annular plane systolic excursion (MAPSE) is the parameter that measures left ventricular longitudinal function, and it appears to be a good early marker of LV dysfunction. It is practically independent of poor image quality. The aim of our study was to analyse the role of echocardiographic variables, especially MAPSE in predicting the outcome of CA in patients with AF. Materials and Methods: We prospectively included 40 patients with paroxysmal and persistent AF that were referred for CA. All patients underwent radiofrequency CA with PVI. Standard transthoracic two-dimensional echocardiography was conducted one day after CA. Demographic data and the patients' characteristics were noted. The endpoint of our study was to estimate the AF recurrence rate diagnosed by ECG within 6 months of the follow-up period. Results: 40 patients, mainly male (67.5%) with an average age of 61.43 ± 8.96 years were included in our study. The majority of patients had paroxysmal AF prior to ablation (77.5%). The AF recurrence rate was 20% after 6 months of follow-up. Lateral MAPSE in the AF-free group was greater than those who relapsed (1.57 ± 0.24 vs. 1.31 ± 0.25; p = 0.012). Patients who remained AF-free after a 6-month follow-up period had a significantly smaller left ventricular volume index (LAVI) than those who relapsed (34.29 ± 6.91 ml/m2 vs. 42.90 ± 8.43 ml/m2; p = 0.05). We found a significant reverse relationship between LAVI and MAPSE (p = 0.020). Conclusion: MAPSE and LAVI present risk factors for AF recurrence, specifically reduced MAPSE and larger LAVI, are related to AF recurrence after CA. In the future, MAPSE could play a significant role when predicting the CA outcome in patients with AF.

The association between pulse wave analysis, carotid-femoral pulse wave velocity and peripheral arterial disease in patients with ischemic heart disease.

INTRODUCTION: Functional changes in peripheral arterial disease (PAD) could play a role in higher cardiovascular risk in these patients. METHODS: 123 patients who underwent elective coronary angiography were included. Ankle-brachial index (ABI) was measured and arterial stiffness parameters were derived with applanation tonometry. RESULTS: 6 patients (4.9%) had a previously known PAD (Rutherford grade I). Mean ABI was 1.04 ± 0.12, mean subendocardial viability ratio (SEVR) 166.6 ± 32.7% and mean carotid-femoral pulse wave velocity (cfPWV) 10.3 ± 2.4 m/s. Most of the patients (n = 81, 65.9%) had coronary artery disease (CAD). There was no difference in ABI among different degrees of CAD. Patients with zero- and three-vessel CAD had significantly lower values of SEVR, compared to patients with one- and two-vessel CAD (159.5 ± 32.9%/158.1 ± 31.5% vs 181.0 ± 35.2%/166.8 ± 27.8%; p = 0.048). No significant difference was observed in cfPWV values. Spearman's correlation test showed an important correlation between ABI and SEVR (r = 0.196; p = 0.037) and between ABI and cfPWV (r = - 0.320; p ≤ 0.001). Multiple regression analysis confirmed an association between cfPWV and ABI (ß = - 0.210; p = 0.003), cfPWV and mean arterial pressure (ß = 0.064; p < 0.001), cfPWV and age (ß = 0.113; p < 0.001) and between cfPWV and body mass index (BMI (ß = - 0.195; p = 0.028), but not with arterial hypertension, dyslipidemia, diabetes mellitus or smoking status. SEVR was not statistically significantly associated with ABI using the same multiple regression model. CONCLUSION: Reduced ABI was associated with increased cfPWV, but not with advanced CAD or decreased SEVR.

Acute kidney injury in patients with myocardial infarction undergoing percutaneous coronary intervention using radial versus femoral access.

BACKGROUND: Data on radial access (RA) as an independent risk factor for acute kidney injury (AKI) in myocardial infarction (MI) patients are conflicting. Our aim was to assess how RA influences the incidence of AKI in MI patients undergoing percutaneous coronary intervention (PCI). METHODS: Data from 3842 MI patients undergoing PCI at our institution from January 2011 to December 2016, of which 35.8% were performed radially, were retrospectively analyzed. A propensity-matched analysis was performed to adjust for differences in the baseline characteristics between the RA and femoral access (FA) groups. The effect of RA on the incidence of AKI was observed. RESULTS: In the unmatched cohort, AKI occurred less often in the RA group [77 (5.6%) patients in the RA group compared to 250 (10.1%) patients in the FA group; p = 0.001]. After propensity-matched adjustment, the incidence of AKI was similar in the two groups. After adjustment for potential confounders, RA was not identified as an independent predictive factor for AKI in either the unmatched or the propensity-matched cohort. Bleeding, heart failure, age ≥ 70 years, renal dysfunction, and the contrast volume/GFR ratio predicted AKI in both cohorts. Additionally, diabetes, contrast volume, and hypertension were predictive of AKI in the unmatched cohort. CONCLUSION: The access site was not independently associated with the incidence of AKI in patients with MI in both a non-matched and a propensity-matched cohort. Our study result suggests that the lower incidence of AKI in patients treated with RA in an unmatched cohort might be substantially influenced by confounding factors, especially bleeding.

Gender Related Survival Differences in ST-Elevation Myocardial Infarction Patients Treated with Primary PCI.

BACKGROUND: Data about gender as an independent risk factor for death in ST-elevation myocardial infarction (STEMI) patients is still contrasting. Aim was to assess how gender influences in-hospital and long-term all-cause mortality in STEMI patients with primary percutaneous coronary intervention (PCI) in our region. METHODS: We analysed data from 2069 STEMI patients undergoing primary PCI in our institution from January 2009-December 2014, of whom 28.9% were women. In-hospital and long-term mortality were observed in women and men. The effect of gender on in-hospital mortality was assessed by binary logistic regression modelling and by Cox regression analysis for long-term mortality. RESULTS: Women were older (68.3±61.8 vs 61.8±12.0 years; p<0.0001), with a higher prevalence of diabetes (13.7% vs 9.9%; p=0.013) and tend to be more frequently admitted in cardiogenic shock (8.4% vs 6.3%; p =0.085). They were less frequently treated with bivalirudin (15.9% vs 20.3%; p=0.022). In-hospital mortality was higher among women (14.2% vs 7.8%; p<0.0001). After adjustment, age (adjusted OR: 1.05; 95% CI: 1.03 to 1.08; p < 0.001) and cardiogenic shock at admission (adjusted OR: 24.56; 95% CI: 11.98 to 50.35; p < 0.001), but not sex (adjusted OR: 1.47; 95% CI: 0.80 to 2.71) were identified as prognostic factors of in-hospital mortality. During the median follow-up of 27 months (25th, 75th percentile: 9, 48) the mortality rate (23.6% vs 15.1%; p<0.0001) was significantly higher in women. The multivariate adjusted Cox regression model identified age (HR 1.05; 95% CI 1.04-1.07; p<0.0001), cardiogenic shock at admission (HR 6.09; 95% CI 3.78-9.81; p<0.0001), hypertension (HR 1.49; 95% CI 1.02-2.18; p<0.046), but not sex (HR 1.04; 95% CI 0.74-1.47) as independent prognostic factors of follow-up mortality. CONCLUSION: Older age and worse clinical presentation rather than gender may explain the higher mortality rate in women with STEMI undergoing primary PCI.

Deterioration of renal function at stent implantation can predict long-term outcome after stent thrombosis.

OBJECTIVES: The aim of the study was to examine the possible influence of minor deterioration of the renal function after stent implantation not fulfilling the criteria for acute kidney injury on long-term outcomes after stent thrombosis (ST). BACKGROUND: Decreased renal function (DRF) is associated with an increased risk for worse outcome after percutaneous coronary intervention. There is no data if the deterioration of renal function after stent implantation influences the prognosis after ST. If so patients with a higher risk for worse outcome after ST could be identified already at the time of stent implantation. METHODS: Data from 4824 consecutive patients treated with percutaneous coronary intervention in our center was recorded from March 2004 to April 2010. We excluded patients with acute kidney injury at stent implantation and 86 of them with ST without acute kidney injury at stent implantation were involved in the study. They were prospectively followed until December 2012 for 50.2 ± 28.1 months. Only patients with definite ST were included in the study. The Academic Research Consortium definition of ST was used. Data on death, myocardial infarction, and repeated percutaneous or operative revascularization after ST were ascertained from the hospital database, by phone or with clinical examinations. The outcomes after definite ST were compared in patients with and without deterioration of renal function after stent implantation (DRFafterSI). RESULTS: During the observational period patients with DRFafterSI had a higher mortality rate after ST than patients without DRFafterSI (35.1 vs. 10.3 %; p <0.019). The incidence of major adverse cardiac events (major adverse coronary event (MACE)-death, myocardial infarction, repeated revascularization) rate after ST was similar in both groups (66.1 % with DRFafterSI vs. 55.2 % without DRFafterSI). The prevalence of myocardial infarction was also similar in both groups (31.6 vs. 34.5 %) as was the revascularizations rate (43.9 vs. 48.3 %). Death was predicted by DRFafterSI (adjusted hazard ratio (HR) 3.96; 95 % confidence interval (CI) 1.11 to 14.10; p <0.034) and age > 75 years (adjusted HR 2.85: 95 % CI 1.12-7.30; p = 0.029). We could not find any predictor for MACE. CONCLUSIONS: Even more subtle DRFafterSI (not fulfilling the criteria for acute kidney injury) at stent implantation were associated with higher long-term mortality after ST. Especially at risk were patients older than 75 years at stent implantation. DRFafterSI and age more than 75 years pointed out the group of patients with a high risk for death after ST already at the time of stent implantation. The best treatment option for preventing ST in these patients is still to be determined. Until then, we must pay a special attention to proper patients' preparation and hydration to avoid DRFafterSI.