Ahmed Abdalla

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.

Prevalence of occult celiac disease in females with iron deficiency in the United States: an NHANES analysis

ABSTRACT Aim: The prevalence of celiac disease (CD) in patients with iron deficiency (ID) is estimated at 0–6% in European countries. The prevalence of celiac disease in patients with iron deficiency in the USA is unknown. Given the treatable nature of gluten hypersensitivity, estimating the prevalence of CD in patients with ID can help to determine the need to screen these patients for occult CD. Methods: Data were obtained from the NHANES database, a nationally representative health survey conducted from 2009 to 2010. We included 2,105 females aged 6 years or older. Iron deficiency was defined as serum ferritin level <20 ng/ml and considered positive for celiac disease when subjects were tested positive for both immunoglobulin A (IgA) tissue transglutaminase antibody and IgA endomysial antibody. Subjects were divided between two groups (ID and non-ID). The association of CD and ID, which was the primary outcome, was obtained after adjusting for other covariates using logistic regression. Results: Among the sample of 2,105 subjects, 569 had ID and 1536 did not have ID. Five people were identified as having CD among the ID group, as were two people in the non-ID group. After adjusting for selected covariates, the prevalence of CD was higher in female subjects with ID with OR of 12.5 (95% CI 1.74–90). Conclusions: The overall prevalence of celiac disease in the USA’ female population is low, however, the prevalence is higher in subjects with iron deficiency. Further prospective studies are needed to validate our findings.

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.

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

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

Catheter ablation of atrial fibrillation with heart failure: An updated meta-analysis of randomized trials

INTRODUCTIONnAtrial fibrillation (AF) and heart failure (HF) often coexist. We conducted this meta-analysis to assess the efficacy and safety of catheter ablation in this population.nnnMETHODSnElectronic databases were searched for all randomized clinical trials (RCTs) that evaluated catheter ablation in patients with left ventricular systolic dysfunction (LVSD). We calculated the weighted mean differences (MDs) and risk ratios (RRs) using a random-effects model.nnnRESULTSnWe included 7 RCTs with 851 patients (mean follow-up was 18u202fmonths). Catheter ablation in patients with LVSD was associated with significantly lower HF hospitalization rates (RR 0.57; 95% CI: 0.45-0.72; Pu202f<u202f0.01), reduced all-cause mortality (RR 0.52; 95% CI: 0.35-0.76; Pu202f<u202f0.01), improved left ventricular ejection fraction (MD 7.40; 95% CI: 3.37-11.43; Pu202f<u202f0.01), increased 6-minute walk test (MD 26.96; 95% CI: 6.39-47.54; Pu202f=u202f0.01), and improved peak oxygen consumption (VO2) (MD 3.17; 95% CI: 1.05-5.28; Pu202f<u202f0.01), without significant increased risks of serious adverse events (RR 1.05; 95% CI: 0.96-1.16; Pu202f=u202f0.30) compared with medical treatment.nnnCONCLUSIONSnIn this meta-analysis of RCTs, catheter ablation was associated with significant improvements in the clinical, structural, and functional capacity of patients with AF and coexisting HF compared with medical treatment.

Is Peripherally Inserted Central Catheter–Related Thrombosis Associated With ABO Blood Group? A Case–Control Pilot Study

Peripherally inserted central catheter (PICC) use is associated with many complications including line-related thrombosis. Several studies and meta-analyses confirmed the increased risk to develop venous thromboembolism in non-O blood group individuals. Our pilot study aimed to examine whether PICC-related thrombosis is influenced by ABO blood group. We identified patients admitted to Hurley Medical Center between March 2012 and March 2016 who had PICC placed during their admission, had their ABO blood group identified in their medical record, and had upper extremity venous Doppler ultrasound performed on the same side of PICC. We excluded pregnant women, patients on anticoagulation initiated before PICC insertion, and patients with active cancer. Data of 227 patients who met our criteria were analyzed. Of these patients, 140 (61.7%) patients had PICC-related thrombosis (cases) and 86 (37.9%) patients had O blood group. Controls were patients who had PICC and did not develop PICC-related thrombosis. Multivariate logistic regression revealed no association between PICC-related thrombosis and ABO blood group (adjusted odds ratio: 1.1; 95% confidence interval: 0.6-2.0; P = .733). Therefore, our data suggest that non-O blood group does not increase the odds of having PICC-related thrombosis.