Babikir Kheiri

Ticagrelor versus clopidogrel after fibrinolytic therapy in patients with ST-elevation myocardial infarction: a systematic review and meta-analysis of randomized clinical trials

Dual antiplatelet therapy with aspirin and clopidogrel are recommended as adjuncts to fibrinolytic-treated patients with ST-elevation myocardial infarction (STEMI). However, the role of switching to ticagrelor within 24xa0h of fibrinolytics compared with clopidogrel continuation in this setting is uncertain. Hence, we conducted a comprehensive search of electronic databases for all randomized clinical trials (RCTs) that evaluated the safety and efficacy of ticagrelor versus clopidogrel after fibrinolytic therapy in patients with STEMI. A random-effects model was used to calculate the risk ratios (RRs) and 95% confidence intervals (CIs). A total of 5 RCTs that evaluated the efficacy of ticagrelor post-fibrinolysis were identified. We included 3 RCTs with 3999 total patients for our meta-analysis. The results showed similar short-term clinical outcomes between ticagrelor and clopidogrel with regard to rates of Bleeding Academic Research Consortium (BARC) typeu2009≥u20092 bleeding (RR 0.94; 95% CI 0.56–1.60; Pu2009=u20090.83), major adverse cardiovascular events (RR 0.87; 95% CI 0.49–1.52; Pu2009=u20090.62), mortality (RR 0.92; 95% CI 0.53–1.59; Pu2009=u20090.77), myocardial infarction (RR 0.76; 95% CI 0.43–1.36; Pu2009=u20090.36), and stroke (RR 0.93; 95% CI 0.50–1.73; Pu2009=u20090.82). Our results demonstrate that in STEMI patients treated with fibrinolytic therapy, switching to ticagrelor was associated with similar bleeding and ischemic outcomes compared with clopidogrel continuation.

Vitamin D deficiency and risk of cardiovascular diseases: a narrative review

Vitamin D, a fat-soluble prohormone, has wide-ranging roles in the regulation of many physiological processes through their interactions with the vitamin D receptors (VDR). It plays a major role in bones and calcium metabolism. Vitamin D deficiency is not uncommon and it has been associated with many health-related issues, including skeletal and non-skeletal complications. The association of low vitamin D and cardiovascular diseases and risk factors has been explored in both animal and human studies. However, studies and trials on the effect of vitamin D supplementation on cardiovascular risk factors and hypertension are conflicting with inconsistent results. Therefore, large, well-powered randomized controlled trials are warranted. If successful, supplementation with easy and low-cost vitamin D can impact our health positively. Here, we summarized the evidence for the association of vitamin D, cardiovascular diseases and risk factors, including coronary artery diseases, stroke, and hypertension, and mortality, with special consideration to resistant hypertension.

Meta-Analysis of Genotype-Guided Versus Standard Dosing of Vitamin K Antagonists

Vitamin K antagonist (VKA) is a commonly prescribed anticoagulant with a narrow therapeutic window. Genetic polymorphisms account for high VKA dosage variability. Hence, we performed an updated meta-analysis of all randomized clinical trials (RCTs) comparing genotype-guided VKA versus standard dosing algorithms. We conducted a systematic search of electronic databases from inception to October 2017 for all RCTs. The primary outcome was the percentage of time in therapeutic range (TTR). Secondary outcomes were international normalized ratio >4, major and all bleeding events, thromboembolism, adverse and serious adverse events, and all-cause mortality. We calculated the weighted mean difference for the primary outcome and risk ratio (RR) for secondary outcomes using a random-effect model. We included 20 RCTs and analyzed a total of 5,980 adult patients. Our pooled analysis showed greater improvement in TTR for the genotype-guided group in comparison with the standard group (mean difference 3.41%, 95% confidence interval [CI] 0.71 to 6.10, pu2009=u20090.01). In addition, there were significant reductions in major and all bleeding events ((RR 0.35, 95% CI 0.20 to 0.63, pu2009=u20090.0004) and (RR 0.79, 95% CI 0.66 to 0.95, pu2009=u20090.01), respectively). However, there were no significant differences between the groups for international normalized ratio >4 (RR 0.89, 95% CI 0.80 to 1.00, pu2009=u20090.06), thromboembolism (RR 0.81, 95% CI 0.56 to 1.17, pu2009=u20090.25), serious adverse events (RR 0.79, 95% CI 0.61 to 1.03, pu2009=u20090.08), any adverse events (RR 0.94, 95% CI 0.88 to 1.01, pu2009=u20090.07), or all-cause mortality (RR 0.73, 95% CI 0.32 to 1.66, pu2009=u20090.46). In conclusion, genotype-guided VKA dosing can improve the TTR and reduce the risk for bleeding episodes, in comparison with standard dosing algorithms.

Association between changes in the intrathoracic impedance and ventricular arrhythmias in patients with heart failure

Ventricular arrhythmias (VAs) are independently related to mortality risk in patients with heart failure (HF). The wide availability of implantable cardioverter defibrillators and cardiac resynchronization therapy devices now offers an opportunity to clinically correlate the two disease processes. We hypothesized that there is an association between changes in the intrathoracic impedance and episodes of VA.

Management of atrial fibrillation in older patients: A network meta-analysis of randomized controlled trials

To the Editor, Atrial fibrillation (AF) is common in older patients and ∼35% of the patients with AF are above age 80 years.1 Without underlying heart disease, AF in older patients may occur because of agingdriven changes in cardiac structure and functions, such as increased stiffness.1 Besides this population experiencing minimal or no AF symptoms, AF in older age is associated with a higher stroke risk.1 Yet, the optimal management strategy for this population is lacking. Therefore, we conducted a network meta-analysis to evaluate the effects of different treatment strategies in this population. We registered our protocol with PROSPERO (CRD42018089053). Electronic databases were searched independently by BK, AA, and MO; data were extracted independently by TH, MB, and SC; and disagreements were resolved by BK. We conducted a random-effects model to calculate odds ratios (ORs) and 95% credible intervals (CIs) usingBayesian frameworkwithMarkovChainMonteCarlo simulation. Inconsistency was assessed by comparing the deviance residuals and deviance information criteria statistics in fitted consistency and inconsistency models. We used NetMetaXL v1.6.1 (Cornerstone Research Group, Burlington, Canada) and WinBUGS v1.4.3 (MRC Biostatistics Unit, Cambridge, UK) for the analysis. We included only four2–5 of 15 eligible randomized controlled trials because of substantial missing/unreported data. There were 6016 total patients and a median follow-up of 40.5 months. The results (Figure 1) showed that catheter ablation (OR: 0.27; 95%CI: 0.11-0.65) and rate control (OR: 0.51; 95% CI: 0.33-0.79) were associated with a lower composite of all-cause mortality and cardiovascular hospitalization than antiarrhythmic medications. In a subset of patients with heart failure (HF), there was no significant difference in mortality and HF hospitalization between ablation and rate-control strategies (OR: 0.46; 95%CI: 0.19–1.09). In a post hoc analysis of the SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure) trial, patients> 70 with AF and HF (n = 738) assigned to nebivolol had nonsignificant lower incidence of all-cause mortality or cardiovascular hospitalization than the placebo group (37.1% vs. 39.8%; hazard ratio (HR): 0.92; 95% CI:0.73-1.17).4 In contrast, the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) sub-study for septuagenarians with AF (n = 1874) showed that rate control, in comparison with rhythm control, was associated with significantly lower all-cause mortality (18% vs. 23%; HR: 0.77; 95%CI: 0.63-0.94).3 In the PALLAS (Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of Standard Therapy) trial (N = 3236), patients≥65who received dronedarone had significantly worse coprimary outcomes (stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes) than the placebo group (2.7% vs. 1.2%; HR: 2.29; 95% CI: 1.34-3.94) and the trial was stopped prematurely for safety reasons.5 In contrast, subgroup analysis of the CASTLE-AF (CatheterAblation versus StandardConventional Therapy in Patients with Left Ventricular Dysfunction and Atrial Fibrillation) trial for patients ≥65 with AF and HF (n = 168) showed no difference in the composite of death or hospitalization between ablation and medical therapy (39.8% vs. 56.5%; HR: 0.79; 95% CI: 0.50−1.23).2 We should note that the patients in these studies may be healthier than the real-world population. Our results demonstrated the superiority of ablation and rate control over antiarrhythmic medications in older patients with AF for the composite of all-cause mortality and cardiovascular hospitalization. These findings are suggestive of the more pronounced harmful proarrhythmic effects of antiarrhythmic medications in older patients, mainly due to their diminished medications clearance.1,3 Although rate-control strategy is often preferred in this population, care should be taken to avoid the increased risks of bradyarrhythmias and orthostatic hypotension and, thus, more lenient rate control is advisable.1,4 Nevertheless, data fromprospective studies have showed the superiority of ablation in older patients with AF in terms of significant reduction of AF burden, better survival rate, lower stroke rate in patients who maintained normal sinus rhythm, and the safety of oral anticoagulation discontinuation after successful AF suppression by ablation without increased risk of stroke.6 However, careful assessment of the procedural-related complications in this frail population should be always discussed in relation to the patient-physician decision-making process. To close knowledge gaps forAFmanagement in older patients, studies are needed to better understand the aging-driven mechanisms of AF development. Furthermore, adequately powered trials to evaluate the differences between rhythm and rate strategies on the structural modeling, functional capacity, and quality of life relevant to this underrepresented population are warranted.

From a burn scar to malignancy! Marjolin’s ulcer, a disease of wound neglect

Abstract Marjolins ulcer is a rare and aggressive type of Squamous Cell Carcinoma (SCC) originating from previously chronic non-healing inflamed skin or trauma, and often after burns in up to 2% of cases. We are presenting a case of SCC secondary to a 30-year history of burn scar. Wound care and traumatic wound closure to prevent malignant degeneration is advisable and should be considered by medical providers.

Tenecteplase versus alteplase for management of acute ischemic stroke: a pairwise and network meta-analysis of randomized clinical trials

Tenecteplase is a genetically mutated variant of alteplase with superior pharmacodynamic and pharmacokinetic properties. However, its efficacy and safety in acute ischemic strokes are limited. Hence, we conducted a study to evaluate the efficacy and safety of tenecteplase compared with alteplase in acute ischemic stroke. Electronic databases were searched for randomized clinical trials (RCTs) comparing tenecteplase with alteplase in acute ischemic stroke patients eligible for thrombolysis. We evaluated various efficacy and safety outcomes using random-effects models for both pairwise and Bayesian network meta-analyses along with meta-regression analyses. We included 5 RCTs with a total of 1585 patients. Compared with alteplase, tenecteplase treatment was associated with significantly greater complete recanalization (odd ratio [OR] 2.01; 95% confidence interval [CI] 1.04–3.87; pu2009=u20090.04) and early neurological improvement (OR 1.43; 95% CI 1.01–2.03; pu2009=u20090.05). There were no differences between the two thrombolytics in terms of excellent recovery (modified Rankin Scale [mRS] 0–1; OR 1.17; 95% CI 0.95–1.44; pu2009=u20090.13), functional independence (mRS 0–2; OR 1.24; 95% CI 0.78–1.98), poor recovery (mRS 4–6; OR 0.78; 95% CI 0.49–1.25; pu2009=u20090.31), complete/partial recanalization (OR 1.51; 95% CI 0.70–3.26; pu2009=u20090.30), any intracerebral hemorrhage (OR 0.81; 95% CI 0.56–1.17; pu2009=u20090.26), symptomatic intracerebral hemorrhage (OR 0.98; 95% CI 0.52–1.83; pu2009=u20090.94), or mortality (OR 0.83; 95% CI 0.54–1.26; pu2009=u20090.38). In network meta-analysis, there were better efficacy and imaging-based outcomes with tenecteplase 0.25xa0mg/kg without increased risk of safety outcomes. Our results demonstrate that in acute ischemic stroke, thrombolysis with tenecteplase is at least as effective and safe as alteplase.

Non-vitamin K antagonist oral anticoagulants in cardioversion of atrial fibrillation: a network meta-analysis

Atrial fibrillation (AF) is the most common cardiac arrhythmia and it is associated with increased risk of stroke and systemic embolism [1]. Restoration of sinus rhythm is an important strategy to improve symptoms, functional status, and quality of life in AF patients [2]. In the case of cardioversion (electrical or pharmacological), therapeutic anticoagulation needs to be established for at least 3 weeks prior to cardioversion in patients with AF ≥ 48 h and continued for at least 4 weeks afterwards to mitigate the risk of peri-cardioversion thromboembolism [3–5]. Traditionally, vitamin K antagonists (VKAs) have been used to reduce this risk. However, a direct thrombin inhibitor (dabigatran) and factor Xa inhibitors (apixaban, rivaroxaban, edoxaban, betrixaban) are increasingly used in this clinical setting [6]. In a recent published pairwise meta-analysis of patients undergoing both electrical and pharmacological cardioversion for non-valvular AF (n = 8564), which included 7 trials (RE-LY, ROCKET-AF, ARISTOTLE, ENGAGE AF-TIMI 48, X-VeRT, ENSUREAF, and EMANATE), patients receiving non-vitamin K antagonist oral anticoagulants (NOACs) had a nonsignificantly lower risk of stroke and systemic embolism (RR 0.70, 95% CI 0.33–1.55; P = 0.34) as well as of major bleeding (RR 0.86; 95% CI 0.47–1.58; P = 0.62) than those receiving VKAs [7]. The authors concluded that NOACs are as effective and safe as VKAs for peri-cardioversion thromboembolism prevention. Nevertheless, individual comparisons between direct thrombin inhibitors, factor Xa inhibitors, and VKA are lacking. Therefore, we conducted a network meta-analysis (NMA) to evaluate the efficacy and safety of each anticoagulant in patients with non-valvular AF undergoing cardioversion. While NMA (or mixed-treatment comparison) allows for the comparison of multiple treatments, it fully preserves randomization and accounts for potential differences between investigated treatments. In the present study, we used a Bayesian random-effects model and data were analyzed using Markov–Chain Monte–Carlo (MCM) methods. We assumed a vague prior distribution to derive the posterior distribution of the treatment effects and we calculated odd ratios (ORs) and Bayesian 95% credible intervals (CIs). Inconsistency was assessed with deviance residuals and deviance information criteria statistics in fitted consistency and inconsistency models. All analyses were conducted using NetMetaXL v1.6.1 and WinBUGS v1.4.3. We included seven studies [8–14] similar to the recently published pairwise meta-analysis [7]. Figure 1 shows the evidence network diagram. Our results showed no significant difference in the incidence of stroke and systemic embolism

Dupilumab safety and efficacy in uncontrolled asthma: a systematic review and meta-analysis of randomized clinical trials

Abstract Objective: We aimed to perform a meta-analysis evaluating the efficacy and safety of dupilumab in patients with uncontrolled asthma. Data source: A search of electronic databases was performed using PubMed, Cochrane library and Embase. Study selection: The literature search was conducted independently by two reviewers. Only randomized controlled trials (RCTs) that compared between placebo and dupilumab in patients with uncontrolled asthma were included in this analysis. Pooled risk ratios (RRs) and mean differences (MDs) with their corresponding 95% confidence intervals (CIs) were calculated for dichotomous and continuous data, respectively. Results: A total of four RCTs representing 2,992 patients were included. Pooled analysis showed significant reductions of the annualized rate of severe asthma exacerbation in the dupilumab group compared with placebo (RR 0.44; 95% CI 0.35–0.055; Pu2009<u20090.01; I2u2009=u200942%). In addition, the absolute forced expiratory volume at 1u2009s (FEV1) changes were significantly increased for the dupilumab group (MD 0.14; 95% CI: 0.12–0.17; Pu2009<u20090.01; I2u2009=u20090%). Finally, there were no significant differences between both groups in the development of any adverse event, serious adverse events, adverse events leading to death, discontinuation of medication due to adverse event or the occurrence of upper respiratory tract, influenza or bronchitis infections. However, dupilumab was associated with an increased risk of injection site reactions compared with placebo (RR 1.91; 95% CI 1.41, 2.59; Pu2009<u20090.01; I2u2009=u200924%). Conclusion: Among patients with uncontrolled asthma, the addition of dupilumab was associated with a reduced risk of severe asthma exacerbations and improvement in FEV1 without an increased risk of adverse events apart from injection site reactions with dupilumab.

Percutaneous Closure of Patent Foramen Ovale in Migraine: A Meta-Analysis of Randomized Clinical Trials

Previous studies have reported the association of patent foramen ovale (PFO) with migraine. Up to 50% of patients with migraine with aura have demonstrated evidence of a right-to-left shunt (RLS) by transcranial Doppler [(1)][1]. The mechanism underpinning this association has been postulated to be