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Drug Safety Jun 2021Sphingosine-1-phosphate modulators are approved for the treatment of multiple sclerosis and are under development for other immune-mediated conditions; however, safety... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Sphingosine-1-phosphate modulators are approved for the treatment of multiple sclerosis and are under development for other immune-mediated conditions; however, safety concerns have arisen.
OBJECTIVE
The objective of this systematic review was to investigate the safety profile of S1P modulators in patients with multiple sclerosis, ulcerative colitis, Crohn's disease, psoriasis, and systemic lupus erythematosus.
METHODS
We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from 1 January, 1990 through 1 April, 2020. We also performed a manual review of conference databases from 2017 through 2020. The primary outcome was the occurrence of adverse events and serious adverse events. We also estimated the occurrence of serious infections, herpes zoster infection, malignancy, bradycardia, atrio-ventricular block, and macular edema. We performed a meta-analysis of controlled studies to assess the risks of such events.
RESULTS
We identified 3843 citations; of these, 26 studies were finally included, comprising 9604 patients who were exposed to a sphingosine-1-phosphate modulator. A meta-analysis of randomized controlled trials showed an increased risk in herpes zoster infection [risk ratio, 1.75 (95% confidence interval 1.09-2.80)], bradycardia [2.64 (1.77-3.96)], and atrio-ventricular block [1.73 (1.03-2.91)] among subjects exposed to sphingosine-1-phosphate modulators as compared with a placebo or an active comparator.
CONCLUSIONS
We found an increased risk of herpes zoster infection, and transient cardiovascular events among patients treated with sphingosine-1-phosphate modulators.
CLINICAL TRIAL REGISTRATION
PROSPERO CRD42020172575.
Topics: Bradycardia; Crohn Disease; Herpes Zoster; Humans; Multiple Sclerosis; Psoriasis
PubMed: 33666900
DOI: 10.1007/s40264-021-01057-z -
Frontiers in Pharmacology 2020Ozanimod has been approved for use in the treatment of relapsing forms of multiple sclerosis by the United States FDA. As a novel, orally available sphingosine... (Review)
Review
Ozanimod has been approved for use in the treatment of relapsing forms of multiple sclerosis by the United States FDA. As a novel, orally available sphingosine 1-phosphate receptor modulator, ozanimod selectively binds to S1P1 and S1P5 receptor with high affinity, minimizing safety concerns caused by S1P receptor activation. e systematically searched PUBMED, EMBASE database, and Cochrane Library database to identify randomized controlled trials (RCTs) from inception to June 28, 2020. Trials were considered eligible if they 1) were randomized clinical trials (RCTs); 2) enrolled adult participants diagnosed with Relapsing-remitting MS; 3) compared ozanimod with placebo or any other approved DMDs that evaluated in phase III or phase II clinical trials; 4) enrolled over 100 participants; 5) provided any available information for predefined primary or secondary outcomes. 2917 participants from three high-quality, multi-centered randomized clinical trials were pooled in our analysis. We found that using ozanimod was significantly associated with the reduction of the annualized relapse rate during the treatment period (RR, -0.10 [95% CI, -0.15, -0.06]). Also, the decreased number of gadolinium-enhancing lesions at the end of the trial was relative to the treatment of ozanimod (ozanimod, 0.29; control, 0.65; RR, -0.20 [95% CI, -0.34, -0.06]). Compared with patients in the control group, the number of new or enlarging T2 lesions over the treatment period decreased in patients treated with ozanimod (ozanimod, 1.82; control, 3.55; RR, -1.12 [95% CI, -1.52, -0.71]). As to the safety endpoints, patients in the ozanimod group reported a lower rate of adverse events (ozanimod, 66.03%; control, 77.07%; RR, 0.64 [95% CI, 0.43, 0.95]). Similar incidence of infection-related TEAEs was found across treatment groups (nasopharyngitis: ozanimod, 11.19%; control, 9.83%; RR, 1.10 [95% CI, 0.77-1.57]; urinary-tract infection: ozanimod, 3.81%; control, 2.97%; RR, 1.29 [95% CI, 0.83-2.00]). No case of macular edema was noted as well as second-degree, type 2, or third-degree atrioventricular block. As for the subgroup analysis, compared with 0.5 mg ozanimod, 1 mg ozanimod is related with a significant reduction of the annualized relapse rate during the treatment period (1 mg ozanimod, 0.18; 0.5 mg ozanimod, 0.24; RR, 0.05 [95% CI, 0.01, 0.09])and a decreased number of new or enlarging T2 lesions over the treatment period (1 mg ozanimod,1.58; 0.5 mg ozanimod, 2.05; RR, 0.49 [95% CI, 0.19, 0.79]). No significant difference in causing adverse events between 1 and 0.5 mg was found. Our meta-analysis found that, with favorable safety performance, the use of ozanimod as a treatment of relapsing-remitting multiple sclerosis in adults was associated with a significant reduction of the annualized relapse rate during the treatment period, decreased number of gadolinium-enhancing lesions at the end of the trial, and lowered number of new or enlarging T2 lesions over the treatment period. Ozanimod 1 mg outperformed 0.5 mg dose in efficacy without increasing the risk of adverse events.
PubMed: 33658933
DOI: 10.3389/fphar.2020.589146 -
JTCVS Open Jun 2021Atrioventricular conductions disturbances, requiring permanent pacemaker implantation (PPI), represent a potential complication after transcatheter aortic valve...
OBJECTIVES
Atrioventricular conductions disturbances, requiring permanent pacemaker implantation (PPI), represent a potential complication after transcatheter aortic valve implantation (TAVI), However, little is known about the pacemaker dependency after PPI in this patient setting. This systematic review analyses the incidence of PPI, the short-term (1-year) pacing dependency, and predictors for such a state after TAVI.
METHODS
We performed a systematic search in PUBMED, EMBASE, and MEDLINE to identify potentially relevant literature investigating PPI requirement and dependency after TAVI. Study data, patients, and procedural characteristics were extracted. Odds ratio (OR) with 95% confidence intervals were extracted.
RESULTS
Data from 23 studies were obtained that included 18,610 patients. The crude incidence of PPI after TAVI was 17% (range, 8.8%-32%). PPI occurred at a median time of 3.2 days (range, 0-30 days). Pacing dependency at 1-year was 47.5% (range, 7%-89%). Self-expandable prosthesis (pooled OR was 2.14 [1.15-3.96]) and baseline right bundle branch block (pooled OR was 2.01 [1.06-3.83]) showed 2-fold greater risk to maintain PPI dependency at 1 year after TAVI.
CONCLUSIONS
Although PPI represents a rather frequent event after TAVI, conduction disorders have a temporary nature in almost 50% of the cases with recovery and stabilization after discharge. Preoperative conduction abnormality and type of TAVI are associated with higher PPI dependency at short term.
PubMed: 36003550
DOI: 10.1016/j.xjon.2021.02.002 -
European Heart Journal. Quality of Care... Mar 2021Permanent pacemaker implantation (PPI) may be required after transcatheter aortic valve implantation (TAVI). Evidence on PPI prediction has largely been gathered from... (Meta-Analysis)
Meta-Analysis
Predictors of pacemaker implantation after transcatheter aortic valve implantation according to kind of prosthesis and risk profile: a systematic review and contemporary meta-analysis.
AIMS
Permanent pacemaker implantation (PPI) may be required after transcatheter aortic valve implantation (TAVI). Evidence on PPI prediction has largely been gathered from high-risk patients receiving first-generation valve implants. We undertook a meta-analysis of the existing literature to examine the incidence and predictors of PPI after TAVI according to generation of valve, valve type, and surgical risk.
METHODS AND RESULTS
We made a systematic literature search for studies with ≥100 patients reporting the incidence and adjusted predictors of PPI after TAVI. Subgroup analyses examined these features according to generation of valve, specific valve type, and surgical risk. We obtained data from 43 studies, encompassing 29 113 patients. Permanent pacemaker implantation rates ranged from 6.7% to 39.2% in individual studies with a pooled incidence of 19% (95% CI 16-21). Independent predictors for PPI were age [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01-1.09], left bundle branch block (LBBB) (OR 1.45, 95% CI 1.12-1.77), right bundle branch block (RBBB) (OR 4.15, 95% CI 3.23-4.88), implantation depth (OR 1.18, 95% CI 1.11-1.26), and self-expanding valve prosthesis (OR 2.99, 95% CI 1.39-4.59). Among subgroups analysed according to valve type, valve generation and surgical risk, independent predictors were RBBB, self-expanding valve type, first-degree atrioventricular block, and implantation depth.
CONCLUSIONS
The principle independent predictors for PPI following TAVI are age, RBBB, LBBB, self-expanding valve type, and valve implantation depth. These characteristics should be taken into account in pre-procedural assessment to reduce PPI rates. PROSPERO ID CRD42020164043.
Topics: Aortic Valve Stenosis; Bundle-Branch Block; Heart Valve Prosthesis; Humans; Pacemaker, Artificial; Transcatheter Aortic Valve Replacement
PubMed: 33289527
DOI: 10.1093/ehjqcco/qcaa089 -
World Journal of Cardiology Aug 2020Treatment of congenitally corrected transposition of great arteries (cc-TGA) with anatomic repair strategy has been considered superior due to restoration of the...
BACKGROUND
Treatment of congenitally corrected transposition of great arteries (cc-TGA) with anatomic repair strategy has been considered superior due to restoration of the morphologic left ventricle in the systemic circulation. However, data on long term outcomes are limited to single center reports and include small sample sizes.
AIM
To perform a systematic review and meta-analysis for observational studies reporting outcomes on anatomic repair for cc-TGA.
METHODS
MEDLINE and Scopus databases were queried using predefined criteria for reports published till December 31, 2017. Studies reporting anatomic repair of minimum 5 cc-TGA patients with at least a 2 year follow up were included. Meta-analysis was performed using Comprehensive meta-analysis v3.0 software.
RESULTS
Eight hundred and ninety-five patients underwent anatomic repair with a pooled follow-up of 5457.2 patient-years (PY). Pooled estimate for operative mortality was 8.3% [95% confidence interval (CI): 6.0%-11.4%]. 0.2% (CI: 0.1%-0.4%) patients required mechanical circulatory support postoperatively and 1.7% (CI: 1.1%-2.4%) developed post-operative atrioventricular block requiring a pacemaker. Patients surviving initial surgery had a transplant free survival of 92.5% (CI: 89.5%-95.4%) per 100 PY and a low rate of need for pacemaker (0.3/100 PY; CI: 0.1-0.4). 84.7% patients (CI: 79.6%-89.9%) were found to be in New York Heart Association (NYHA) functional class I or II after 100 PY follow up. Total re-intervention rate was 5.3 per 100 PY (CI: 3.8-6.8).
CONCLUSION
Operative mortality with anatomic repair strategy for cc-TGA is high. Despite that, transplant free survival after anatomic repair for cc-TGA patients is highly favorable. Majority of patients maintain NYHA I/II functional class. However, monitoring for burden of re-interventions specific for operation type is very essential.
PubMed: 32879705
DOI: 10.4330/wjc.v12.i8.427 -
Evidence-based Complementary and... 2020A meta-analysis was conducted on the clinical efficacy and safety of Wenxin granules and propafenone for the therapy of atrial premature beats (APBs).
OBJECTIVE
A meta-analysis was conducted on the clinical efficacy and safety of Wenxin granules and propafenone for the therapy of atrial premature beats (APBs).
METHODS
A randomized controlled trial (RCT) of Wenxin granules and propafenone in the therapy of APB was systematically searched until June 1, 2019. Meta-analysis was conducted with review manager (RevMan) 5.3. For the evaluation of methodological quality for randomized controlled trials, the Cochrane tool was used to assess the risk of bias. For the evaluation of the evidence quality, the online GRADEpro GDT was used.
RESULTS
Eleven RCTs with 1149 participants were included in this study. It has been identified that Wenxin granules combined with propafenone have better clinical efficacy than the use of propafenone alone in the treatment of APB (OR = 3.89, 95% CI (2.03, 7.44), < 0.0001, low-dose propafenone; OR = 4.24, 95% CI (1.32, 13.60), = 0.02, high-dose propafenone). There is no difference in clinical efficacy between the Wenxin granules alone and high-dose propafenone in the treatment of APB (OR = 1.17, 95% CI (0.65, 2.11), = 0.60), and Wenxin granules alone are superior to the low-dose propafenone in the treatment of APB (OR = 2.56, 95% CI (1.34, 4.89), = 0.004). Wenxin granules combined with propafenone can reduce the incidence of sinus bradycardia caused by propafenone (OR = 0.15, 95% CI (0.03, 0.70), = 0.02). There was no significant difference between Wenxin granules combined with propafenone and propafenone alone in causing the atrioventricular block, dizziness, xerostomia, gastrointestinal symptoms, and tongue paresthesia. There was no significant difference between Wenxin granules alone and propafenone alone in causing dizziness, xerostomia, gastrointestinal symptoms, tongue paresthesia, frequent premature ventricular contractions, and prolongation of R-R interval.
CONCLUSION
Very low-quality evidence showed that Wenxin granules may be superior to low-dose propafenone in the treatment of APB. Wenxin granules may reduce the incidence of sinus bradycardia caused by propafenone. Limited by the quality of included RCTs, the conclusions of this study still need further verification.
PubMed: 32774412
DOI: 10.1155/2020/3961091 -
Journal of Interventional Cardiology 2020Transcatheter aortic valve replacement (TAVR) is now the treatment of choice for patients with severe aortic stenosis regardless of their surgical risk. Right bundle... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Transcatheter aortic valve replacement (TAVR) is now the treatment of choice for patients with severe aortic stenosis regardless of their surgical risk. Right bundle branch block (RBBB) can be a predictor for development of significant atrioventricular (AV) block after TAVR, requiring permanent pacemaker implantation (PPI). However, data related to the risk of PPI requirement with preexisting RBBB is scarce. Hence, this systematic review and meta-analysis aims to assess clinical outcomes of patients undergoing TAVR with RBBB on preexisting electrocardiogram.
METHODS
We performed a systematic literature review to identify randomized and nonrandomized clinical studies that reported any clinical impact of patients undergoing TAVR with preexisting RBBB. A total of eight databases including PubMed (Medline), Embase, Cochrane Library, ACP Journal Club, Scopus, DARE, and Ovid containing articles from January 2000 to May 2020 were analyzed.
RESULTS
We identified and screened 224 potential eligible publications through the databases and found 14 relevant clinical trials for a total of 15,319 participants. There was an increased 30-day pacemaker implantation rate of 38.1% in the RBBB group compared to 11.4% in the no RBBB group with a risk ratio of 3.56 (RR 3.56 (95% CI 3.21-3.93, < 0.01)). There was an increased 30-day all-cause mortality in the RBBB group of 9.5% compared with 6.3% in the no RBBB group with an odds ratio of 1.60 (OR 1.60 (95% CI 1.14-2.25, < 0.01)).
CONCLUSION
This study indicates that patients with preexisting RBBB have higher incidence of PPI and all-cause mortality after TAVR compared with patients without RBBB. Further trials are needed to compare the clinical outcomes based on TAVR valve types and assess the benefit of PPI in patients with new-onset RBBB after TAVR.
Topics: Aortic Valve Stenosis; Atrioventricular Block; Bundle-Branch Block; Electrocardiography; Humans; Postoperative Complications; Prognosis; Risk Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 32774182
DOI: 10.1155/2020/1789516 -
Journal of Cardiovascular... Jun 2020Although right ventricular pacing (RVP) may impair ventricular function, it is commonly used for advanced atrioventricular block (AVB) and normal or mildly reduced... (Meta-Analysis)
Meta-Analysis
Network meta-analysis of His bundle, biventricular, or right ventricular pacing as a primary strategy for advanced atrioventricular conduction disease with normal or mildly reduced ejection fraction.
INTRODUCTION
Although right ventricular pacing (RVP) may impair ventricular function, it is commonly used for advanced atrioventricular block (AVB) and normal or mildly reduced ejection fraction (EF). We aimed to compare His bundle pacing (HBP), biventricular pacing (BiVP), and RVP for advanced AVB in patients with normal or mildly reduced EF.
METHODS AND RESULTS
MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov, Scopus, and Web of Science were searched. Outcomes were all-cause death, heart failure hospitalizations (HFH), EF, left ventricular volumes, 6-minute walk test, and QRS duration. HBP or BiVP was compared with RVP. Subsequently, network meta-analysis compared the three pacing options. Our protocol was registered in PROSPERO (CRD42018094132). Six studies compared BiVP and RVP (704 vs 614 patients) and four compared HBP and RVP (463 vs 568 patients). Follow-up was 6 months to 5 years. There was significantly lower mortality and HFH with HBP or BiVP as compared with RVP (odds ratio [OR], 0.66, [0.51-0.85], P = .002; OR, 0.61 [0.45-0.82], P < .001, respectively]. HBP or BiVP also showed significant increase in EF and decrease in QRS duration (mean difference [MD], 5.27 [3.86-6.69], P < .001; MD -42.2 [-51.2 to -33.3], P < .001, respectively). In network meta-analysis, HBP and BiVP were associated with significantly improved survival compared to RVP, with surface under the cumulative ranking curve (SUCRA) probability of 79.4%, 69.4%, and 1.2% for HBP, BiVP, and RVP, respectively. For HFH, SUCRA probability was 91.5%, 57.2%, and 1.3%, respectively.
CONCLUSION
HBP or BiVP were the superior strategies to reduce all-cause death and HFH for advanced AVB with normal or mildly reduced EF, with no significant difference between BiVP and HBP.
Topics: Action Potentials; Atrioventricular Block; Bundle of His; Cardiac Pacing, Artificial; Cardiac Resynchronization Therapy; Heart Rate; Humans; Network Meta-Analysis; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Function, Right
PubMed: 32275339
DOI: 10.1111/jce.14490 -
Clinical Toxicology (Philadelphia, Pa.) Sep 2020Cannabis use results in elevation of heart rate and blood pressure immediately after use, primarily due to sympathetic nervous system stimulation and parasympathetic...
Cannabis use results in elevation of heart rate and blood pressure immediately after use, primarily due to sympathetic nervous system stimulation and parasympathetic nervous system inhibition. These effects may precipitate cardiac dysrhythmia. The objective of our study was to analyze systematically the pertinent medical literature regarding the putative association between cannabis use and cardiac dysrhythmia. We queried PubMed, Google Scholar, and OpenGrey, and reviewed results for relevance. We graded clinical trials, observational and retrospective studies, case series and reports using Oxford Centre for Evidence-Based Medicine guidelines. The relevant publications identified included one Level I systematic review and meta-analysis of six human studies, 16 Level II studies with 6,942 subjects, nine Level III studies with 3,797,096 subjects and two systematic and scoping reviews with 30 cases. Cannabis-induced tachycardia was highlighted in 17 of 28 (61%) Level I-III articles followed by a generalized description of dysrhythmia in eight (29%). Specific dysrhythmias noted in the Level I-III articles included atrial fibrillation, atrial flutter, atrioventricular block, premature ventricular contractions, premature atrial contractions, ventricular tachycardia, and ventricular fibrillation. Other reported findings on electrocardiogram included ST segment elevation, P, and T wave changes. Only one Level III study reported a decreased risk of atrial fibrillation from cannabis use in patients hospitalized for heart failure (Odds ratio = 0.87). There were 39 case series (Level IV) and case reports (Level V) with 42 subjects. Average age was 30 ± 12 years, and only ten (24%) were female. The most common dysrhythmia mentioned in the Level IV and V articles was ventricular fibrillation (21%), followed by atrial fibrillation (19%), ventricular tachycardia (12%), third degree atrioventricular block (12%), and asystole (12%). There were four cases (10%) of symptomatic bradycardia. Notable electrocardiographic changes included ST segment elevation (29%), Brugada pattern in leads V1, V2 (14%), and right bundle branch block (12%). There were eight cases of cardiac arrest, of whom five expired. Cannabis use is associated with increased risk of cardiac dysrhythmia, which is rare but may be life-threatening. Clinicians and nurses should inquire about acute and chronic cannabis use in their patients presenting with tachycardia, bradycardia, dysrhythmia, chest pain, and/or unexplained syncope. Patients who use cannabis should be educated on this deleterious association, especially those with underlying cardiac disease or risk factors.
Topics: Adolescent; Adult; Arrhythmias, Cardiac; Chest Pain; Electrocardiography; Female; Humans; Male; Marijuana Use; Risk Factors; Syncope; Young Adult
PubMed: 32267189
DOI: 10.1080/15563650.2020.1743847 -
Heart Rhythm Aug 2020Failure of drugs and catheter ablation procedures for the treatment of ventricular arrhythmias is still extremely relevant. Recently, stereotactic body radiotherapy has...
Failure of drugs and catheter ablation procedures for the treatment of ventricular arrhythmias is still extremely relevant. Recently, stereotactic body radiotherapy has been introduced to treat therapy refractory patients. In this systematic review (International Prospective Register of Systematic Reviews, CRD42019133212), we aimed to summarize electrophysiological and histopathological effects of radioablation in animals, patients, and extracted and perfused hearts. A systematic search was performed in OVID MEDLINE, OVID Embase, the Cochrane Central Register of Controlled Trials, Web of Science, Google Scholar, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) from inception to September 2019. Identified records were independently screened for eligibility by 2 reviewers. Risk of bias and methodological quality were assessed using the SYRCLE, ROBINS-I, or Murad tool and tailored to the different study designs. We included 13 preclinical and 10 clinical publications. Large heterogeneity in study designs prompted a narrative synthesis approach. Baseline, (pre-)procedural details, outcome, target tissue analyses, and safety data were extracted and summarized. In animal studies evaluating electrophysiological parameters, radioablation induced a reduction in voltage/potential amplitude or bidirectional block in target areas in 93.2% of animals. Atrioventricular block (first to third degree) was induced in 78.3% of animals, and in studies evaluating ventricular arrhythmia inducibility, 75% reduction was achieved. In patients, predominantly ventricular tachycardias were targeted with >85% reduction in arrhythmia episodes during follow-up with an encouraging short-term safety profile. Preclinical and clinical evidence on the efficacy and safety of radioablation is limited in both quantity and quality. The results of radioablation for therapy refractory patients with ventricular tachycardia are promising, but further research is needed.
Topics: Catheter Ablation; Heart Conduction System; Humans; Tachycardia, Ventricular
PubMed: 32205299
DOI: 10.1016/j.hrthm.2020.03.013