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Abstract: Atherosclerotic cardiovascular diseases remain the leading cause of morbidity and mortality worldwide despite all efforts made towards their management. Other than targeting the traditional risk factors for their development, scientific interest has been shifted towards epigenetic regulation, with microRNAs (miRs) being at the forefront. MiR-126, in particular, has been extensively studied in the context of cardiovascular diseases. Downregulated expression of this miR has been associated with highly prevalent cardiovascular risk factors such as arterial hypertension and diabetes mellitus. At the same time, its diagnostic and prognostic capability concerning coronary artery disease is still under investigation, with up-to-date data pointing towards a dysregulated expression in a stable disease state and acute myocardial infarction. Moreover, a lower expression of miR-126 may indicate a higher disease complexity, as well as an increased risk for future major adverse cardiac and cerebrovascular events. Ultimately, overexpression of miR-126 may emerge as a novel therapeutic target in atherosclerotic cardiovascular diseases due to its potential in promoting therapeutic angiogenesis and anti-inflammatory effects. However, the existing challenges in miR therapeutics need to be resolved before translation to clinical practice.

Background: MicroRNAs modify protein expression at the post-transcriptional level, and their circulating levels may help identify the underlying molecular pathways. Objective: The purpose of this study was to assess the differential expression of microRNAs related to myocardial cell energy substrate, autophagy, and ischaemia in chronic and acute heart failure (HF). Methods: In this case-control study, we studied 19 patients with acute HF (AHF) and 19 patients with chronic HF (CHF). Basic demographic and clinical characteristics were collected from the patients upon arrival, at 48 hours, and at 120 hours. Blood samples for microRNAs measurements (miR-22, -92a, and -499), B-type natriuretic peptide (BNP), C reactive protein, and high sensitivity cardiac troponin I, were collected at all study points. In this study, we included subjects with a left ventricular ejection fraction of Results: At baseline, circulating miR-22 levels were 1.9-fold higher (p Conclusions: MicroRNAs -22, -92a, and -499 are differentially expressed in chronic and acute HF subjects. MicroRNA signatures are also differentially expressed up to the discharge of the patients. These findings may have important implications for diagnosis, progression, and treatment of patients with chronic and acute heart failure.

Although evidence indicates the association of lipoprotein(a) [Lp(a)] with atherosclerosis, the link with calcific aortic valve disease (CAVD) is unclear. This systematic review and meta-analysis explores the connection between Lp(a) and aortic valve calcification and stenosis (AVS). We included all relevant studies, indexed in eight databases, up to February 2023. A total of 44 studies (163 139 subjects) were included, with 16 of them being further meta-analysed. Despite considerable heterogeneity, most studies support the relationship between Lp(a) and CAVD, especially in younger populations, with evidence of early aortic valve micro-calcification in elevated-Lp(a) populations. The quantitative synthesis showed higher Lp(a) levels, by 22.63 nmol/L (95% CI: 9.98–35.27), for patients with AVS, while meta-regressing the data revealed smaller Lp(a) differences for older populations with a higher proportion of females. The meta-analysis of eight studies providing genetic data, revealed that the minor alleles of both rs10455872 and rs3798220 LPA gene loci were associated with higher risk for AVS (pooled odds ratio 1.42; 95% CI: 1.34–1.50 and 1.27; 95% CI: 1.09–1.48, respectively). Importantly, high-Lp(a) individuals displayed not only faster AVS progression, by a mean difference of 0.09 m/s/year (95% CI: 0.09–0.09), but also a higher risk of serious adverse outcomes, including death (pooled hazard ratio 1.39; 95% CI: 1.01–1.90). These summary findings highlight the effect of Lp(a) on CAVD initiation, progression and outcomes, and support the early onset of Lp(a)-related subclinical lesions before clinical evidence.

Background: In recent years much research has been devoted to the deployment of biomarkers in the field of heart failure. Objectives: To study the potential of post-transcriptional regulation by microRNAs on the diagnosis, management and therapy of heart failure. Methods: Literature search focus on the role of microRNAs in heart failure. Results: MicroRNAs are expressed and regulated in the course of the pathological manifestations of heart failure (HF). This wide and uncharted area of genetic imprints consisting of small non-coding RNA molecule is upregulated and released into the bloodstream from organs under certain conditions and or stress. The use of genetically based strategies for the management of HF has gained great interest in the field of biomedical science because they can be used as biomarkers providing information regarding cardiac status and function. They also appear as promising tools with therapeutic potential because of their ability to induce changes at the cellular level without creating alterations in the gene sequence. In addition, with the advances in genomic sequencing, quantification and synthesis in technologies of microRNAs identification as well as the growing knowledge of the biology of miRNAs and their involvement in HF, it is expected to favorably affect the prognosis of HF patients. Conclusion: MicroRNAs are involved in the regulation of multibiological processes involved in the progress of heart failure. More studies are needed to achieve a clinical valuable implementation of microRNAs in the management of HF.

Introduction This study compares the incidence of vascular complications and other major outcomes between patients undergoing transcatheter aortic valve implantation, with and without a standardized preoperative vascular surgeon consultation. Methods This retrospective study evaluated all patients scheduled for transcatheter aortic valve implantation during a five-year period at a Hellenic University Hospital. Two main periods were evaluated: Group A (early period (2014–2015), without a standardized preoperative vascular surgeon consultation) and Group B (late period (2016–2018), with a standardized preoperative vascular surgeon consultation). All vascular complications as well as other major outcomes (early death, stroke, myocardial infarction, and treatment) were recorded. Univariate and multivariate analyses were also conducted. Results Overall, 382 transcatheter aortic valve implantation procedures were conducted (Group A: n = 115; duration = 19 months; Group B: n = 267; duration = 41 months). Overall, 58 vascular complications were recorded (21 patients in Group A and 37 patients in Group B (18.3% versus 13.9%; P = 0.279)). However, vascular complications that necessitated a vascular surgeon’s interference were more frequent during the first period (13% versus 4.9%; P = 0.009). Among patients with a vascular complication, early mortality was higher during the first period (14.3% versus 0%; P = 0.034) although stroke and myocardial infarction rates were similar. Age >80 years (OR = 1.856 [1.134–3.452]; P = 0.03) and preoperative vascular surgeon consultation (OR = 0.345 [0.132–0.756]; P = 0.015) were the only independent predictors for vascular complications. Conclusions A standardized preoperative evaluation by a vascular surgeon may decrease the risk for vascular complications that necessitate a repair as well as early mortality among patients undergoing transcatheter aortic valve implantation procedures.

Background Peripheral arterial disease caused mainly by atherosclerosis portent significant morbidity, adverse prognosis and mortality, with localized treatment approaches aiming at symptom alleviation and improvement of circulation. Recently, scientific interest has been shifted towards epigenomics, with microRNAs appearing as a future therapeutic target in ischemic cardiovascular diseases due to their potential in regulating angiogenesis. Purpose We investigated the pro-angiogenic effect of miRNA-126 mimic in an in vivo model of hind limb ischemia. Methods Ten-week-old male C57Bl/6 mice (n=20) were subjected to left femoral artery ligation and were treated with microRNA-126 mimic at a dose of 5mg/kg (Group A, n=10) or 0.2ml normal saline (Group B, n=10) on days 1, 3 and 7. Laser Doppler imaging was performed to verify successful ligation on day 0 and to evaluate differences in the ischemic-to-normal (I/N) hind limb perfusion ratio on day 7 and 28. Muscle tissue expression of microRNA-126 and vascular endothelial growth factor (VEGF) was determined via PCR. Results Following microRNA-126 mimic administration in Group A subjects, we noted a qualitative and quantitative stepwise increase in I/N hind limb perfusion ratio [Day 0: 0.354 (0.276, 0.455) vs. Day 8: 0.775 (0.700, 0.844) vs. Day 28: 0.681 (0.660, 0.896), p=0.001] (Figure 1, Panels A and B). In Group B a stepwise increase of lesser magnitude was observed in I/N hind limb perfusion ratio [Day 0: 0.267 (0.164, 0.383) vs. Day 8: 0.400 (0.338, 0.418) vs. Day 28: 0.539 (0.483, 0.603), p=0.074]. Importantly, over time changes of I/N hind limb perfusion ratio were significantly higher in group A compared to group B (p for interaction=0.005) (Figure 1, Panel B). Muscle tissue expression of microRNA-126 in the ischemic hind limb of Group A was 350-fold lower compared to the ischemic hind limb of Group B (p Conclusion MicroRNA-126 mimic delivery in the ischemic hind limb of mice can accelerate vascular perfusion recovery via angiogenesis, which is mediated by VEGF expression. Funding Acknowledgement Type of funding sources: None. Figure 1

We systematically reviewed the literature regarding the impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on vascular function, including endothelial function and arterial stiffness, as predictors of atherosclerosis progression and cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). We searched PubMed in order to identify clinical trials that investigated the effect of DPP-4i on vascular function in patients with T2DM when compared with placebo. Although 168 articles were initially found, only 6 studies (total 324 patients) investigated the effect of DPP-4i in comparison with placebo, specifically linagliptin and sitagliptin, and satisfied the inclusion criteria. There are scarce data to indicate that linagliptin may enhance endothelial function and exert a slight beneficial effect on arterial wall properties. Sitagliptin seems to have a neutral effect on these variables. Further trials are needed to elucidate the topic. The standards of reporting were in accordance with the PRISMA guidelines.

BACKGROUND AND AIMS We compared the clinical outcome of diabetic versus nondiabetic patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the GReek AntiPlatElet (GRAPE) registry. PATIENTS AND METHODS GRAPE is a prospective observational study, focusing on contemporary antiplatelet use in moderate-risk to high-risk ACS patients receiving PCI. Major adverse cardiovascular events (MACE), (composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and bleeding events (Bleeding Academic Research Consortium definition) at 1 year of follow-up were analyzed using propensity score adjustment. A subanalysis according to diabetes mellitus (DM) status was performed. RESULTS Out of 2047 registered patients, 469 (22.9%) were diabetic. Complete 1-year follow-up was available in 95.1% of patients. MACE occurred in 12.2 and 7.2% of those patients with and without DM, respectively [adjusted hazard ratio (HR), 95% confidence interval (CI)=1.27 (0.89-1.79), P=0.2]. Observed BARC type ≥3 bleeding risk was not higher in diabetic patients: adjusted HR (95% CI)=1.20 (0.79-1.84). In the subgroup of clopidogrel-treated patients (N=238), MACE rate was significantly higher in diabetic compared with nondiabetic cohort [13.4 vs. 9%, adjusted HR (95% CI)=1.68 (1.07-2.64), P=0.03]. In the subgroup of ticagrelor-treated or prasugrel-treated patients (N=228), MACE rate did not differ significantly between diabetic and nondiabetic patients: 9.6 versus 5%, adjusted HR (95% CI)=1.35 (0.77-2.37), P=0.38. CONCLUSION In 'real-life' ACS undergoing PCI, diabetic patients have higher - although not significantly - MACE rate and no difference in bleeding events. This difference in MACE was significant among clopidogrel-treated patients, whereas when newer antiplatelet agents were used the negative impact of DM on ischemic events was eliminated.

Transcatheter aortic valve implantation (TAVI) has become the mainstay for high-risk or inoperable patients with symptomatic aortic valve stenosis, and research regarding the use of transcatheter valves in intermediate or low-risk patients is currently ongoing. The aim of this article is to provide comprehensive insight into the anesthetic management of patients undergoing TAVI and to highlight possible gaps in the current knowledge. One important procedural characteristic that is imperative to consider is the type of anesthesia being used and its possible complications. Increasingly, experienced centers have changed from general anesthesia with endotracheal intubation to local anesthesia with sedation, especially when the transfemoral access route is used for TAVI. There is still debate regarding what type of anesthesia should be used in the procedure, and the lack of randomized data makes it even more challenging for the operators.

Essentials The comparative efficacy and safety of antiplatelet agents in ‘real life’ is not clear. We recruited acute coronary syndrome patients receiving percutaneous coronary intervention. At 1-year follow-up, prasugrel offers better anti-ischemic protection than clopidogrel. Prasugrel and ticagrelor are accompanied by more frequent bleeding events. SummaryBackground The comparative efficacy and safety of antiplatelet treatment outside randomized trials is not clear. Objectives To investigate long-term efficacy and safety in ‘real-life’ acute coronary syndrome (ACS) patients treated by percutaneous coronary intervention (PCI) with contemporary use of clopidogrel, prasugrel and ticagrelor. Methods In a prospective, observational, multicenter cohort study, 2047 patients were recruited into the GReek AntiPlatElet (GRAPE) Registry and were followed-up for 1 year for major adverse cardiovascular events (MACE, a composite of death, non-fatal myocardial infarction, urgent revascularization and stroke) and bleeding events (Bleeding Academic Research Consortium [BARC] classification). Results Exposure to clopidogrel, prasugrel and ticagrelor by PCI occurred in 959, 363 and 717 patients, respectively. After adjustment, the rate of MACE (primary outcome endpoint) was lower in prasugrel-treated patients (4.4%) than in clopidogrel-treated patients (10.1%) (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.30–0.91), although not significantly different between ticagrelor (6.8%) and clopidogrel groups (HR, 0.78; 95% CI, 0.54–1.12). Any type of BARC-classified bleeding (secondary outcome endpoint) was more frequent in prasugrel-treated patients (51.2%) than in clopidogrel-treated patients (37.6%) (HR, 1.61; 95% CI, 1.33–1.95) and more frequent in ticagrelor-treated patients (56.9%) than in clopidogrel-treated patients (HR, 1.81; 95% CI, 1.55–2.10). An adjusted comparison between prasugrel and ticagrelor-treated groups did not reveal differences in any outcome measure. After adjustment, the death rate was more reduced by novel agents in comparison with clopidogrel (2.9% vs. 6.2%). Conclusions In ACS/PCI patients, prasugrel offered better anti-ischemic protection than clopidogrel, whereas use of both novel agents is accompanied by more frequent bleeding events.

Aims Data on the clinical impact of gender in ‘real life’ acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), receiving clopidogrel, prasugrel or ticagrelor are limited. We aimed to investigate sex-based differences in clinical outcome of those patients. Methods In a prospective, observational, multicenter, cohort study 2047 patients were recruited into the GReekAntiPlatElet (GRAPE) Registry and were followed-up until 1 year for major adverse cardiovascular events (MACE, composite of death, non fatal myocardial infarction,urgent revascularization and stroke) and bleeding events [Bleeding Academic Research Consortium (BARC) classification]. Results Women (n=360, 17.6%) were more frequently administered clopidogrel (rather than novel P2Y12 receptor antagonists) at PCI hospital and at discharge. MACE occurred in 9.2% and 8.1% of women and men, respectively and did not differ significantly by gender. Rate of observed bleeding BARC any type was 57.2% and 44.4% in women and men, respectively. Following adjustment, only differences in BARC any type and BARC type 1 events remained significant, with higher rates observed between women: hazard ratio (95% confidence interval)1.51(1.23-1.85) and 1.58(1.27-1.96), respectively, p

In ‘real life’ acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and receiving contemporary antiplatelet treatment, data on dyspnea occurrence and impact on persistence with treatment are scarce. In a prospective, multicenter, cohort study, ACS patients undergoing PCI were recruited into the GReekAntiPlatElet (GRAPE) registry. During 1-year follow up, overall, 249/1989 (12.5%) patients reported dyspnea, more frequently at 1-month and decreasing thereafter. Multivariate analysis showed that ticagrelor administration (n = 738) at discharge was associated with the occurrence of dyspnea: Odds ratio 2.46 (95% confidence interval, CI, 1.87–3.25), p < 0.001. Older age, lower hematocrit, and prior bleeding event were also associated with dyspnea reports. Persistence, switching, and cessation rates were 68.3%, 20.9%, and 10.8% vs 76.7%, 12.5%, and 10.9% among patients reporting dyspnea compared with those who did not, p for trend = 0.002. In conclusion, in ACS patients undergoing PCI and treated with a P2Y12 receptor antagonist, dyspnea occurs commonly, particularly when ticagrelor is administered. Non-persistence with antiplatelet agents at discharge is more frequently observed among dyspnea-reporters.

Objective. - Using intracoronary ultrasound we studied the anatomical characteristics and the pulsatile changes of the coronary arterial wall of ectatic coronary arteries in patients with atherosclerotic coronary artery disease who underwent percutaneous transluminal coronary angioplasty. Methods and results. - Three study groups were formed according to the characteristics of the coronary segments, (a) group CES, coronary segments with ectasia, n = 10, (b) group NES, normal coronary segments adjacent to ectatic sites, n = 10 and (c) group NAS, normal coronary segments adjacent to atherosclerotic sites, n = 30. Pulsatile changes was dined as CSL s y s t -CSLA d i a /CSLA d i a x 100. Coronary segments with ectasia (CES group) had significantly thinner media than the NAS group. Furthermore, increased vessel wall pulsatile changes were found in the ectatic segments. Conclusions. - Atherosclerotic ectatic coronary segments reveal diminished media thickness and increased coronary arterial wall pulsatile changes, which may be Indicative of a mechanically and structurally weak artery prone to aneurysm formation.

Regular physical activity has been associated with less severity of an acute coronary syndrome (ACS), lower in-hospital mortality rates, and an improved short term prognosis. This study evaluated the relationship between physical activity status and the development of left ventricular systolic dysfunction (LVSD) according to inflammation and sex in elderly patients who had had an ACS.We analyzed prospectively collected data from 355 male (age 74 ± 6 years) and 137 female (76 ± 6 years) patients who were hospitalized with an ACS. LVSD was evaluated by echocardiography on the 5th day of hospitalization and physical activity status was assessed by a self-reported questionnaire. Inflammatory response was evaluated by measuring C-reactive protein levels. Logistic regression models were applied to evaluate the effect of physical activity status on the development of LVSD and inflammatory response at entry.Physical inactivity had a higher prevalence in women who developed LVSD than in the female patients with preserved systolic function (46% vs. 20%, p=0.02). There was a significant positive association between physical activity levels and ejection fraction in women (p=0.06), but not in men (p=0.30). Multiadjusted logistic regression showed that women who were physically active had 76% lower odds (95%CI: 1-94%) of developing LVSD compared to their sedentary counterparts. Furthermore, physical activity was inversely associated with C-reactive protein levels in both sexes (p=0.08).Long-term involvement in a physically active lifestyle seems to confer further cardio-protection by reducing the inflammatory response and preserving left ventricular systolic function in elderly female, but not male patients with an ACS.

A 65 year old man was transferred to our cath lab for primary PCI about two hours after the onset of pain in the context of acute, anterior myocardial infarction. Thrombus aspiration of the proximal LAD and balloon angioplasty with a DES implantation were performed. After a few days, although the patient was under treatment with unfractioned heparin, he sustained a transient ischemic attack. The echocardiographic study revealed a large, mobile, protruding thrombus in the apex. Four days later, the patient complained of mild abdominal pain with a gradual deterioration. Abdominal CT scan revealed embolism of the superior mesenteric artery and urgent embolectomy was scheduled.

Aims. We evaluated the interaction effect between depressive symptoms and dietary habits on 30-day development of cardiovascular disease (CVD) (death or rehospitalization) in elderly, acute coronary syndrome (ACS) survivors.Methods. During 2006–2008, we recorded 277 nonfatal, consecutive ACS admissions (75 ± 6 years, 70% males, 70% had diagnosis of myocardial infarction) with complete 30-day follow-up. Assessment of recent depressive symptoms was based on the CES-D scale. Among sociodemographic, bioclinical, lifestyle characteristics, the MedDietScore that assesses the inherent characteristics of the Mediterranean diet was applied.Results. 22% of the ACS pts developed a CVD event during the first 30 days (14.8% rehospitalization and 9.4% death). Patients in the upper tertile of the CES-D scale (i.e., >18) had higher incidence of CVD events as compared with those in the lowest tertile (21% versus 8%, ). Multiple logistic regression analysis revealed that 1-unit increase in CES-D was associated with 4% higher odds (95% CI 1.008–1.076, ) of CVD events; however, when MedDietScore was entered in the model, CES-D lost its significance ().Conclusion. Short-term depressive symptoms are related to a worsen 30-day prognosis of ACS patients; however, this relationship was mediated by Mediterranean diet adherence.

Two techniques for correcting malpositioning occurring during percutaneous aortic valve replacement (PAVR) with the CoreValve ReValving™ System are described in this article. The "Removing and Reinserting Technique" was used in 2 patients, in whom the prosthesis was positioned too high. The "Snare Technique" was used in 1 patient, in whom the prosthesis was implanted too low. In all patients the aortic valve prosthesis was successfully re-implanted.

Introduction: Coronary artery bypass grafting (CABG) with left internal mammary artery (LIMA) and percutaneous transluminal coronary angioplasty (PCI) with drug eluting stent (DES) implantation are both effective to treat ischemic heart disease. In the current study we evaluated the long term results of the two methods in patients (pts) with isolated proximal left anterior descending artery lesion (pLAD), suffering from chronic stable angina (CSA). Methods: We included 280 pts, 170 with DES implantation and 110 with LIMA grafting. Primary end points were the occurrence of major adverse cardiac events (MACE), defined as: Death, myocardial infarction and target vessel revascularization (TVR). Secondary end-points included the length of hospitalization, in-hospital complications and the recurrence of chest pain. Pts were followed-up clinically. Results: Mean follow-up period was two years (midrange, one to three years). MACE was 5.29% in the DES group and 2.72% in the surgical group (p=0.37). TVR was 3.52% after PCI and 0% after CABG (p=0.08). The event-free survival curve was similar between the two groups (Figure ). More in-hospital complications were observed in the surgical group compared with the PCI group (16.36% vs. 1.17%, respectively, p=0.01). Recurrent angina was 4.11% in the DES group and 6.36% in CABG group (p = 0.41). Conclusions : In the current study the two procedures had similar long-term results, even though the surgical approach was associated with increased in-hospital complications and longer hospitalization. Therefore, both revascularization modalities can be used to treat pLAD lesions in pts with CSA.

Using intracoronary ultrasound we studied the anatomical characteristics and the pulsatile changes of the coronary arterial wall of ectatic coronary arteries in patients with atherosclerotic coronary artery disease who underwent percutaneous transluminal coronary angioplasty.Three study groups were formed according to the characteristics of the coronary segments, (a) group CES, coronary segments with ectasia, n = 10, (b) group NES, normal coronary segments adjacent to ectatic sites, n = 10 and (c) group NAS, normal coronary segments adjacent to atherosclerotic sites, n = 30. Pulsatile changes was defined as CSLA(syst)-CSLA(dia)/CSLA(dia) x 100. Coronary segments with ectasia (CES group) had significantly thinner media than the NAS group. Furthermore, increased vessel wall pulsatile changes were found in the ectatic segments.Atherosclerotic ectatic coronary segments reveal diminished media thickness and increased coronary arterial wall pulsatile changes, which may be indicative of a mechanically and structurally weak artery prone to aneurysm formation.

Background P2Y12 inhibitor switching has appeared in clinical practice as a consequence of prasugrel and ticagrelor availability, apart from clopidogrel, for use in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods In the context of the GReek AntiPlatelet REgistry (GRAPE) we assessed the prevalence, predictive factors and short-term outcome of in-hospital P2Y12 inhibitor switching in 1794 ACS patients undergoing PCI. Results Switching occurred in 636 (35.5%) patients of which in the form of clopidogrel to a novel agent, novel agent to clopidogrel and between prasugrel and ticagrelor in 574 (90.4%), 34 (5.3%) and 27 (4.3%) patients, respectively. Presentation to non PCI-capable hospital, bivalirudin use, age ≥75 years (inverse predictor), and regional trends emerged as predictive factors of switching to a novel agent. At combined in-hospital and one-month follow-up, propensity matched pairs analysis showed no differences in major adverse cardiovascular (MACE) or bleeding events between switching from clopidogrel to a novel agent vs novel agent constant administration. More Bleeding Academic Research Consortium type 1, type 2 and any type events and fewer MACE were seen when switching from clopidogrel to a novel agent vs only clopidogrel administration (23.7%, 3.8%, 30.6%, 1.2% vs 8.9%, 1.2%, 12.0%, 3.8% with P P = .03, P P = .03 respectively). Conclusions In a real-life experience with contemporary antiplatelet treatment in ACS patients undergoing PCI, in-hospital switching represents common clinical practice. Clinical factors and regional practice differences seem to affect this strategy's choice, while switching to a novel agent may be associated with higher risk of bleeding.