Buflomedil for intermittent claudication

Background : Intermittent claudication (IC) is pain caused by chronic occlusive arterial disease, that develops in a limb during exercise and is relieved with rest. Buflomedil is a vasoactive agent used to treat peripheral vascular disease. However, its clinical efficacy for IC has not yet been critically examined. This is an update of a Cochrane review first published in 2000, and previously updated in 2007 and 2008. Objectives : To evaluate the available evidence on the efficacy of buflomedil for IC. Search methods : For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12). Selection criteria : Double-blinded, randomized controlled trials (RCTs) in patients with IC (Fontaine stage II) receiving oral buflomedil compared with placebo. Pain-free walking distance (PFWD) and maximum walking distance (MWD) were analysed by standardized exercise test. Data collection and analysis : Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. Main results : We included two RCTs with 127 participants. Both RCTs showed moderate improvements in PFWD for patients on buflomedil. This improvement was statistically significant for both trials (WMD 75.1 m, 95% confidence interval (CI) 20.6 to 129.6; WMD 80.6 m, 95% CI 3.0 to 158.2), the latter being a wholly diabetic population. For both RCTs, MWD gains were statistically significant with wide confidence intervals (WMD 80.7 m, 95% CI 9.4 to 152; WMD 171.4 m, 95% CI 51.3 to 291.5), respectively. Authors' conclusions : There is little evidence available to evaluate the efficacy of buflomedil for IC. Most trials were excluded due to poor quality. The two included trials showed moderately positive results; these are undermined by publication bias since we know of at least another four unpublished, irretrievable, and inconclusive studies. Buflomedil's benefit is small in relation to safety issues and its narrow therapeutic range

Silence of the limbs: pharmacological symptomatic treatment of intermittent claudication

Several oral "vasoactive" drugs claim to increase walking capacity in patients with intermittent claudication (IC). Naftidrofuryl, cilostazol, buflomedil, and pentoxifylline are the most studied molecules. Although spanning several decades, several studies underlying these claims were not properly designed, underpowered or showed clinically doubtful outcomes. The evidence for these "vasoactive" drugs has always been received with scepticism, creating the need for systematic reviews and meta-analyses. This brief review discusses the benefit-risk assessment of vasoactive drugs, by applying a systematic review to evaluate randomized, placebo-controlled trials. Oral naftidrofuryl and cilostazol have an acceptable safety profile as well as sustained evidence (documented by Cochrane analyses) of increased walking capacity. Subsequently, these drugs entered recommendations for peripheral arterial disease (PAD). In contrast, buflomedil and pentoxifylline have limited and/or doubtful evidence to increase walking capacity. Moreover, there were safety concerns about the narrow therapeutic range of buflomedil. Most other "vasoactive" drugs were either inappropriately or insufficiently tested or showed no significant if not negative effects on IC. "Vasoactive" drugs are no substitutes for lifestyle or exercise therapy but are adjuvant treatment to the well-appreciated triad of cardiovascular prevention (antiplatelet agents, statins and ACE-inhibitors), of which statins in their own right have documented claims to significantly increase walking capacity. "Vasoactive" drugs may have a place in the pharmacological management of symptomatic PAD in addition to the basic cardiovascular pharmacotherapy, when revascularization is not indicated, when exercise therapy is not feasible or when there is still insufficient benefit

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Insights into functional mitral regurgitation using the average pixel intensity method

Previously we introduced and validated the average pixel intensity (API) method for grading mitral regurgitation (MR) in a heterogeneous MR population. We now investigated the feasibility and added value of the API method more specifically in patients with functional MR (FMR). We consecutively enrolled 283 patients with pure FMR. Transthoracic echocardiography was performed and MR was assessed using the API method and guideline-recommended parameters, including color Doppler, vena contracta width (VCW) and proximal isovelocity surface area (PISA)-based methods. The API method had an applicability of 98% in this FMR cohort, which was significantly higher than VCW (84%) and PISA-based methods (75%). Overall, the API method had significant correlations with direct parameters of FMR severity, ejection fraction, atrial and ventricular dimensions, pulmonary pressures and New York Heart Association class. Analysis of the API dynamics during MR revealed a typical pattern with early and late systolic peaks in API and a midsystolic nadir, which matched the temporal changes of the effective regurgitant orifice (ERO) during FMR. Based on ROC curves of established FMR severity cut-offs, an API value of 125 au was considered the optimal cut-off to determine severe MR. Interestingly, this API severity cut-off is similar to the API severity cut-off for MR in degenerative MR (DMR), despite different EROA/RV cut-offs in current ESC guidelines for FMR and DMR. The API method is an easy, fast and feasible parameter for grading FMR and may complement the multiparametric assessment of FMR in daily clinical practice

Effectiveness and safety of oral anticoagulants in older patients with atrial fibrillation : a systematic review and meta-analysis

Background and Objective: Atrial fibrillation (AF), the most common cardiac arrhythmia, typically increases with age. Oral anticoagulants (OACs) are the cornerstone of treatment to reduce the associated risk for systemic thromboembolism. Four large randomized controlled trials (RCTs) have shown that non-vitamin K antagonist oral anticoagulants (NOACs) are non-inferior to vitamin K antagonists (VKAs) in preventing stroke and systemic embolism, as well as regarding their risk for major bleeding. However, as vulnerable geriatric patients with AF were largely underrepresented in these trials, physicians are faced with the challenge of choosing the right anticoagulant for geriatric patients in real-life clinical practice. In this vulnerable patient group, NOACs tend to be underused or underdosed due to concerns of excessive fall-related intracranial bleeding, cognitive impairment, multiple drug-drug interactions, low body weight or impaired renal function. As life expectancy continues to rise worldwide, the number of geriatric patients substantially increases. Therefore, there is an urgent need for a critical appraisal of the added value of NOACs in geriatric patients with AF at high thromboembolic and bleeding risk. Methods and Results: This systematic review provides an overview of the literature on the impact of increased age (≥75 years), multimorbidity, polypharmacy, increased falling risk, frailty and dementia on the effectiveness and safety of NOACs as compared to VKAs, after searching the Medline database. Moreover, a meta-analysis on the impact of increased age ≥75 years old was performed after pooling results from 6 post hoc analyses of RCTs and 6 longitudinal observational cohort studies, highlighting the superior effectiveness (hazard ratio (HR) 0.83, 95% confidence interval (CI) [0.74–0.94] for stroke/SE; HR 0.77, 95%CI [0.65–0.92] for mortality) and non-inferior safety (HR 0.93, 95%CI [0.86–1.01] for major bleeding; HR 0.58, 95%CI [0.50–0.67] for intracranial bleeding; HR 1.17, 95%CI [0.99–1.38] for gastrointestinal bleeding) of NOACs versus VKAs in older AF patients. Conclusion: Across geriatric subgroups, apixaban was consistently associated with the most favourable benefit-risk profile and should therefore be preferred in geriatric patients with AF. However, research gaps on the impact of increased falling risk, frailty and baseline dementia were identified, requiring careful consideration while awaiting more results

Septal flash is a prevalent and early dyssynchrony marker in transcatheter aortic valve replacement-induced left bundle branch block

New-onset left bundle branch block (LBBB) is a frequent complication after transcatheter aortic valve replacement (TAVR) and provides an opportunity to study dyssynchrony immediately following acute LBBB. This study aims to (1) assess echocardiographic dyssynchrony in acute TAVR-induced LBBB (TAVR-LBBB), and (2) compare dyssynchrony parameters among different patient groups with LBBB. The study enrolled all TAVR-LBBB patients at Ghent University Hospital between 2013 and 2019. First, acute TAVR-LBBB dyssynchrony was assessed by: (1) septal flash (SF); (2) interventricular mechanical delay (IVMD; cut-off >= 40 ms) and (3) presence of 'classical dyssynchronous strain pattern' assessed with speckle tracking. Secondly, acute TAVR-LBBB patients with SF (LBBBTAVR+SF) were compared to randomly selected LBBB-SF patients with preserved (LBBBSF+PEF) and reduced ejection fraction (LBBBSF+REF). In TAVR-LBBB patients (n = 25), SF was detected in 72% of patients, whereas only 5% of TAVR-LBBB patients showed a classical dyssynchronous strain pattern. IVMD in these TAVR-LBBB patients was 39 ms. In 90% of LBBBTAVR+SF patients, SF was observed within 24 h after LBBB onset. Among LBBB-SF patients, a classical strain pattern was more prevalent in LBBBSF+REF patients compared to LBBBTAVR+SF patients (80% vs. 7%; p < 0.001). IVMD was significantly longer in LBBBSF+PEF patients (52 ms; p = 0.002) and LBBBSF+REF patients (57 ms; p = 0.009) compared to LBBBTAVR+SF patients (37 ms). SF is an early and prevalent marker of LV dyssynchrony in acute TAVR-LBBB, whereas strain-based measures and IVMD do not appear to capture dyssynchrony at this early stage. Our findings from the comparative analysis generate the hypothesis that progressive LBBB-induced LV remodeling may be required for a 'classical dyssynchrony strain pattern' or significant IVMD to occur in TAVR-LBBB patients