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JACC. Heart Failure Feb 2022This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction.
BACKGROUND
The estimated treatment effects of various combinations of contemporary HF medical therapies are not well characterized.
METHODS
We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between January 1987 and January 2020. We included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers (BB), mineralocorticoid receptor antagonists (MRAs), digoxin, hydralazine-isosorbide dinitrate, ivabradine, angiotensin receptor-neprilysin inhibitors (ARNi), sodium glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv-mecarbil. The primary outcome was all-cause death. We estimated the life-years gained in 2 HF populations (BIOSTAT-CHF [BIOlogy Study to TAilored Treatment in Chronic Heart Failure] and ASIAN-HF [Asian Sudden Cardiac Death in Heart Failure Registry]).
RESULTS
We identified 75 relevant trials representing 95,444 participants. A combination of ARNi, BB, MRA, and SGLT2i was most effective in reducing all-cause death (HR: 0.39; 95% CI: 0.31-0.49); followed by ARNi, BB, MRA, and vericiguat (HR: 0.41; 95% CI: 0.32-0.53); and ARNi, BB, and MRA (HR: 0.44; 95% CI: 0.36-0.54). Results were similar for the composite outcome of cardiovascular death or first hospitalization for HF (HR: 0.36; 95% CI: 0.29-0.46 for ARNi, BB, MRA, and SGLT2i; HR: 0.44; 95% CI: 0.35-0.56 for ARNi, BB, MRA, and omecamtiv-mecarbil; and HR: 0.43; 95% CI: 0.34-0.55 for ARNi, BB, MRA, and vericiguat). The estimated additional number of life-years gained for a 70-year-old patient on ARNi, BB, MRA, and SGLT2i was 5.0 years (2.5-7.5 years) compared with no treatment in secondary analyses.
CONCLUSIONS
In patients with HF with reduced ejection fraction, the estimated aggregate benefit is greatest for a combination of ARNi, BB, MRA, and SGLT2i.
Topics: Aged; Angiotensin Receptor Antagonists; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Network Meta-Analysis; Stroke Volume
PubMed: 34895860
DOI: 10.1016/j.jchf.2021.09.004 -
Journal of the American College of... Feb 2022Hypertrophic cardiomyopathy (HCM), a relatively common, globally distributed, and often inherited primary cardiac disease, has now transformed into a contemporary highly...
Hypertrophic cardiomyopathy (HCM), a relatively common, globally distributed, and often inherited primary cardiac disease, has now transformed into a contemporary highly treatable condition with effective options that alter natural history along specific personalized adverse pathways at all ages. HCM patients with disease-related complications benefit from: matured risk stratification in which major markers reliably select patients for prophylactic defibrillators and prevention of arrhythmic sudden death; low risk to high benefit surgical myectomy (with percutaneous alcohol ablation a selective alternative) that reverses progressive heart failure caused by outflow obstruction; anticoagulation prophylaxis that prevents atrial fibrillation-related embolic stroke and ablation techniques that decrease the frequency of paroxysmal episodes; and occasionally, heart transplant for end-stage nonobstructive patients. Those innovations have substantially improved outcomes by significantly reducing morbidity and HCM-related mortality to 0.5%/y. Palliative pharmacological strategies with currently available negative inotropic drugs can control symptoms over the short-term in some patients, but generally do not alter long-term clinical course. Notably, a substantial proportion of HCM patients (largely those identified without outflow obstruction) experience a stable/benign course without major interventions. The expert panel has critically appraised all available data and presented management insights and recommendations with concise principles for clinical decision-making.
Topics: Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Humans
PubMed: 35086661
DOI: 10.1016/j.jacc.2021.11.021 -
BMC Cardiovascular Disorders Apr 2023Myocardial infarction (MI) is one of the life-threatening coronary-associated pathologies characterized by sudden cardiac death. The provision of complete insight into... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Myocardial infarction (MI) is one of the life-threatening coronary-associated pathologies characterized by sudden cardiac death. The provision of complete insight into MI complications along with designing a preventive program against MI seems necessary.
METHODS
Various databases (PubMed, Web of Science, ScienceDirect, Scopus, Embase, and Google scholar search engine) were hired for comprehensive searching. The keywords of "Prevalence", "Outbreak", "Burden", "Myocardial Infarction", "Myocardial Infarct", and "Heart Attack" were hired with no time/language restrictions. Collected data were imported into the information management software (EndNote v.8x). Also, citations of all relevant articles were screened manually. The search was updated on 2022.9.13 prior to the publication.
RESULTS
Twenty-two eligible studies with a sample size of 2,982,6717 individuals (< 60 years) were included for data analysis. The global prevalence of MI in individuals < 60 years was found 3.8%. Also, following the assessment of 20 eligible investigations with a sample size of 5,071,185 individuals (> 60 years), this value was detected at 9.5%.
CONCLUSION
Due to the accelerated rate of MI prevalence in older ages, precise attention by patients regarding the complications of MI seems critical. Thus, determination of preventive planning along with the application of safe treatment methods is critical.
Topics: Humans; Myocardial Infarction
PubMed: 37087452
DOI: 10.1186/s12872-023-03231-w -
Acta Clinica Croatica Dec 2021Congenital long QT syndrome (LQTS) is a disorder of myocardial repolarization defined by a prolonged QT interval on electrocardiogram (ECG) that can cause ventricular... (Review)
Review
Congenital long QT syndrome (LQTS) is a disorder of myocardial repolarization defined by a prolonged QT interval on electrocardiogram (ECG) that can cause ventricular arrhythmias and lead to sudden cardiac death. LQTS was first described in 1957 and since then its genetic etiology has been researched in many studies, but it is still not fully understood. Depending on the type of monogenic mutation, LQTS is currently divided into 17 subtypes, with LQT1, LQT2, and LQT3 being the most common forms. Based on the results of a prospective study, it is suggested that the real prevalence of congenital LQTS is around 1:2000. Clinical manifestations of congenital LQTS include LQTS-attributable syncope, aborted cardiac arrest, and sudden cardiac death. Many patients with congenital LQTS will remain asymptomatic for life. The initial diagnostic evaluation of congenital LQTS includes obtaining detailed personal and multi-generation family history, physical examination, series of 12-lead ECG recordings, and calculation of the LQTS diagnostic score, called Schwartz score. Patients are also advised to undertake 24-hour ambulatory monitoring, treadmill/cycle stress testing, and LQTS genetic testing for definitive confirmation of the diagnosis. Currently available treatment options include lifestyle modifications, medication therapy with emphasis on beta-blockers, device therapy and surgical therapy, with beta-blockers being the first-line treatment option, both in symptomatic and asymptomatic patients.
Topics: Arrhythmias, Cardiac; Death, Sudden, Cardiac; Electrocardiography; Genotype; Humans; Long QT Syndrome; Prospective Studies
PubMed: 35734489
DOI: 10.20471/acc.2021.60.04.22 -
The Cochrane Database of Systematic... May 2023Patients and their relatives often expect to be actively involved in decisions of treatment. Even during resuscitation and acute medical care, patients may want to have... (Review)
Review
BACKGROUND
Patients and their relatives often expect to be actively involved in decisions of treatment. Even during resuscitation and acute medical care, patients may want to have their relatives nearby, and relatives may want to be present if offered the possibility. The principle of family presence during resuscitation (FPDR) is a triangular relationship where the intervention of family presence affects the healthcare professionals, the relatives present, and the care of the patient involved. All needs and well-being must be balanced in the context of FPDR as the actions involving all three groups can impact the others.
OBJECTIVES
The primary aim of this review was to investigate how offering relatives the option to be present during resuscitation of patients affects the occurrence of post-traumatic stress disorder (PTSD)-related symptoms in the relatives. The secondary aim was to investigate how offering relatives the option to be present during resuscitation of patients affects the occurrence of other psychological outcomes in the relatives and what effect family presence compared to no family presence during resuscitation of patients has on patient morbidity and mortality. We also wanted to investigate the effect of FPDR on medical treatment and care during resuscitation. Furthermore, we wanted to investigate and report the personal stress seen in healthcare professionals and if possible describe their attitudes toward the FPDR initiative.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL from inception to 22 March 2022 without any language limits. We also checked references and citations of eligible studies using Scopus, and searched for relevant systematic reviews using Epistomonikos. Furthermore, we searched ClinicalTrials.gov, WHO ICTRP, and ISRCTN registry for ongoing trials; OpenGrey for grey literature; and Google Scholar for additional trials (all on 22 March 2022).
SELECTION CRITERIA
We included randomized controlled trials of adults who have witnessed a resuscitation attempt of a patient (who was their relative) at the emergency department or in the pre-hospital emergency medical service. The participants of this review included relatives, patients, and healthcare professionals during resuscitation. We included relatives aged 18 years or older who have witnessed a resuscitation attempt of a patient (who is their relative) in the emergency department or pre-hospital. We defined relatives as siblings, parents, spouses, children, or close friends of the patient, or any other descriptions used by the study authors. There were no limitations on adult age or gender. We defined patient as a patient with cardiac arrest in need of cardiopulmonary resuscitation (CPR), a patient with a critical medical or traumatic life-threatening condition, an unconscious patient, or a patient in any other way at risk of sudden death. We included all types of healthcare professionals as described in the included studies. There were no limitations on age or gender.
DATA COLLECTION AND ANALYSIS
We checked titles and abstracts of studies identified by the search, and obtained the full reports of those studies deemed potentially relevant. Two review authors independently extracted data. As it was not possible to conduct meta-analyses, we synthesized data narratively.
MAIN RESULTS
The electronic searches yielded a total of 7292 records after deduplication. We included 2 trials (3 papers) involving a total of 595 participants: a cluster-randomized trial from 2013 involving pre-hospital emergency medical services units in France, comparing systematic offer for a relative to witness CPR with the traditional practice, and its 1-year assessment; and a small pilot study from 1998 of FPDR in an emergency department in the UK. Participants were 19 to 78 years old, and between 56% and 64% were women. PTSD was measured with the Impact of Event Scale, and the median score ranged from 0 to 21 (range 0 to 75; higher scores correspond to more severe disease). In the trial that accounted for most of the included participants (570/595), the frequency of PTSD-related symptoms was significantly higher in the control group after 3 and 12 months, and in the per-protocol analyses a significant statistical difference was found in favor of FPDR when looking at PTSD, anxiety and depression, and complicated grief after 1 year. One of the included studies also measured duration of patient resuscitation and personal stress in healthcare professionals during FPDR and found no difference between groups. Both studies had high risk of bias, and the evidence for all outcomes except one was assessed as very low certainty.
AUTHORS' CONCLUSIONS
There was insufficient evidence to draw any firm conclusions on the effects of FPDR on relatives' psychological outcomes. Sufficiently powered and well-designed randomized controlled trials may change the conclusions of the review in future.
Topics: Adult; Aged; Child; Female; Humans; Male; Middle Aged; Young Adult; Anxiety; Anxiety Disorders; Critical Care; Pilot Projects; Randomized Controlled Trials as Topic; Resuscitation
PubMed: 37159193
DOI: 10.1002/14651858.CD013619.pub2 -
Trends in Cardiovascular Medicine Jul 2022The etiology of sudden cardiac death (SCD) in young people continues to attract much attention. This meta-analysis aimed to identify the most frequent causes of SCD in... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The etiology of sudden cardiac death (SCD) in young people continues to attract much attention. This meta-analysis aimed to identify the most frequent causes of SCD in individuals aged ≤35 years, the differences between athletes and non-athletes and geographic areas.
METHODS
Studies published between 01/01/1990 and 01/31/2020 and evaluating post-mortem the aetiology of SCD in young individuals (≤35 years) were included. Individuals were divided into athletes and non-athletes. Studies that did not report separate data between athletes and non-athletes were excluded.
RESULTS
Thirty-four studies met the inclusion criteria, and a total population of 5,060 victims of SCD were analyzed (2,890 athletes, 2,170 non-athletes). Comparing the causes of SCD between athletes and non-athletes, non-ischemic left ventricular scar (NILVS) (5.1% vs. 1.1%, p=0.01) was more frequent in the former, while coronary artery disease (CAD) (19.6% vs. 9.1%, p=0.009), arrhythmogenic cardiomyopathy (ACM) (11.5% vs. 4.7%, p=0.03) and channelopathies (8.4% vs. 1.9%, p=0.02) were more frequent in the latter. In studies published in the last decade, hypertrophic cardiomyopathy (HCM) (p=0.002), dilated cardiomyopathy (p=0.047), and anomalous origin of coronary arteries (AOCA) (p=0.009) were more frequently the causes of SCD in athletes while aortic dissection (0.022) was the cause in non-athletes. HCM (p=0.01) and AOCA (p=0.004) were more frequently the causes of SCD in the US while ACM (p=0.001), structurally normal heart (p=0.02), and channelopathies (p=0.02) were more frequent in Europe.
CONCLUSIONS
Among the causes of SCD, NILVS was the more frequent cause in athletes, while CAD, ACM and channelopathies were more frequent causes in non-athletes. The causes of SCD differ between the US and Europe.
Topics: Adolescent; Athletes; Cardiomyopathy, Hypertrophic; Channelopathies; Coronary Artery Disease; Death, Sudden, Cardiac; Heart Ventricles; Humans
PubMed: 34166791
DOI: 10.1016/j.tcm.2021.06.001 -
Heart Rhythm Jul 2021Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce hospitalizations and death from heart failure (HF), but their effect on arrhythmia expression has been poorly... (Meta-Analysis)
Meta-Analysis
Association of SGLT2 inhibitors with arrhythmias and sudden cardiac death in patients with type 2 diabetes or heart failure: A meta-analysis of 34 randomized controlled trials.
BACKGROUND
Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce hospitalizations and death from heart failure (HF), but their effect on arrhythmia expression has been poorly investigated.
OBJECTIVE
The purpose of this study was to evaluate the association of SGLT2is with arrhythmias in patients with type 2 diabetes mellitus (T2DM) or HF.
METHODS
We searched PubMed and ClinicalTrials.gov. Two independent investigators identified randomized double-blind trials that compared SGLT2is with placebo or active control for adults with T2DM or HF. Primary outcomes were incident atrial arrhythmias, ventricular arrhythmias (VAs), and sudden cardiac death (SCD).
RESULTS
We included 34 randomized (25 placebo-controlled and 9 active-controlled) trials with 63,166 patients (35,883 SGLT2is vs 27,273 control: mean age 53-67 years; 63% male). Medications included canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin. Except for 1 study of HF, all patients had T2DM. Follow-up ranged from 24 weeks to 5.7 years. The cumulative incidence of events was low: 3.6, 1.4, and 2.5 per 1000 patient-years for atrial arrhythmias, VAs and SCD, respectively. SGLT2i therapy was associated with a significant reduction in the risk of incident atrial arrhythmias (odds ratio 0.81; 95% confidence interval 0.69-0.95; P = .008) and the "SCD" component of the SCD outcome (odds ratio 0.72; 95% confidence interval 0.54-0.97; P = .03) compared with control. There was no significant difference in incident VA or the "cardiac arrest" SCD component between groups.
CONCLUSION
SGLT2is are associated with significantly reduced risks of incident atrial arrhythmias and SCD in patients with T2DM. Prospective trials are warranted to confirm the antiarrhythmic effect of SGLT2is and whether this is a class or drug-specific effect.
Topics: Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Global Health; Heart Failure; Humans; Incidence; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33757845
DOI: 10.1016/j.hrthm.2021.03.028 -
Cureus Aug 2023Sudden cardiac death (SCD) is a condition that accounts for a high percentage of cardiovascular fatalities, with ventricular tachyarrhythmias being the most common... (Review)
Review
Sudden cardiac death (SCD) is a condition that accounts for a high percentage of cardiovascular fatalities, with ventricular tachyarrhythmias being the most common cause. There are signs and symptoms of SCD that occur spontaneously without any warning and are deadly. Despite preventative efforts focusing on the use of subcutaneous implanted cardioverter defibrillators (S-ICD) in the highest-risk population categories, a high number of SCDs occur in the normal population and in people who do not have a documented cardiac condition. Therefore, primary prevention for SCD should be a more viable strategy for the general population, considering measures in the form of preventive medicine such as knowing more about any genetic predisposition, family history of any fatal arrhythmia, continuous surveillance after any syncope with unknown causes, etc. However, little data about SCD risk factors are known in comparison with other well-known diseases like ischemic heart disease and stroke. In search of medical databases for relevant medical literature, we looked at PubMed/Medline, the Cochrane Library, and Google Scholar. Thirteen publications were discovered after the papers were located, assessed, and qualifying criteria were applied. The finished articles were done to give an overview of SCD. Some others have shown that the major predisposition for SCD is related to the male gender, which increases the incidence if they have a family history of SCD. We described the importance of obstructive sleep apnea (OSA) as a comorbid condition. Patients with S-ICD and young athletes with a history of ventricular arrhythmia showed us that the predisposition for SCD can be higher than in the normal population. Based on the above, we concluded that more study is required to establish the most important approach for each of the risk factors mentioned in this systematic review in order to apply them in daily practice and have more knowledge about how to apply preventive and therapeutic medicine to the population at risk and the ones that already develop the disease.
PubMed: 37664320
DOI: 10.7759/cureus.42859 -
The Cochrane Database of Systematic... Jun 2020Hyperkalaemia is a common electrolyte abnormality caused by reduced renal potassium excretion in patients with chronic kidney diseases (CKD). Potassium binders, such as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hyperkalaemia is a common electrolyte abnormality caused by reduced renal potassium excretion in patients with chronic kidney diseases (CKD). Potassium binders, such as sodium polystyrene sulfonate and calcium polystyrene sulfonate, are widely used but may lead to constipation and other adverse gastrointestinal (GI) symptoms, reducing their tolerability. Patiromer and sodium zirconium cyclosilicate are newer ion exchange resins for treatment of hyperkalaemia which may cause fewer GI side-effects. Although more recent studies are focusing on clinically-relevant endpoints such as cardiac complications or death, the evidence on safety is still limited. Given the recent expansion in the available treatment options, it is appropriate to review the evidence of effectiveness and tolerability of all potassium exchange resins among people with CKD, with the aim to provide guidance to consumers, practitioners, and policy-makers.
OBJECTIVES
To assess the benefits and harms of potassium binders for treating chronic hyperkalaemia among adults and children with CKD.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 10 March 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-randomised controlled studies (quasi-RCTs) evaluating potassium binders for chronic hyperkalaemia administered in adults and children with CKD.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed risks of bias and extracted data. Treatment estimates were summarised by random effects meta-analysis and expressed as relative risk (RR) or mean difference (MD), with 95% confidence interval (CI). Evidence certainty was assessed using GRADE processes.
MAIN RESULTS
Fifteen studies, randomising 1849 adult participants were eligible for inclusion. Twelve studies involved participants with CKD (stages 1 to 5) not requiring dialysis and three studies were among participants treated with haemodialysis. Potassium binders included calcium polystyrene sulfonate, sodium polystyrene sulfonate, patiromer, and sodium zirconium cyclosilicate. A range of routes, doses, and timing of drug administration were used. Study duration varied from 12 hours to 52 weeks (median 4 weeks). Three were cross-over studies. The mean study age ranged from 53.1 years to 73 years. No studies evaluated treatment in children. Some studies had methodological domains that were at high or unclear risks of bias, leading to low certainty in the results. Studies were not designed to measure treatment effects on cardiac arrhythmias or major GI symptoms. Ten studies (1367 randomised participants) compared a potassium binder to placebo. The certainty of the evidence was low for all outcomes. We categorised treatments in newer agents (patiromer or sodium zirconium cyclosilicate) and older agents (calcium polystyrene sulfonate and sodium polystyrene sulfonate). Patiromer or sodium zirconium cyclosilicate may make little or no difference to death (any cause) (4 studies, 688 participants: RR 0.69, 95% CI 0.11, 4.32; I = 0%; low certainty evidence) in CKD. The treatment effect of older potassium binders on death (any cause) was unknown. One cardiovascular death was reported with potassium binder in one study, showing that there was no difference between patiromer or sodium zirconium cyclosilicate and placebo for cardiovascular death in CKD and HD. There was no evidence of a difference between patiromer or sodium zirconium cyclosilicate and placebo for health-related quality of life (HRQoL) at the end of treatment (one study) in CKD or HD. Potassium binders had uncertain effects on nausea (3 studies, 229 participants: RR 2.10, 95% CI 0.65, 6.78; I = 0%; low certainty evidence), diarrhoea (5 studies, 720 participants: RR 0.84, 95% CI 0.47, 1.48; I = 0%; low certainty evidence), and vomiting (2 studies, 122 participants: RR 1.72, 95% CI 0.35 to 8.51; I = 0%; low certainty evidence) in CKD. Potassium binders may lower serum potassium levels (at the end of treatment) (3 studies, 277 participants: MD -0.62 mEq/L, 95% CI -0.97, -0.27; I = 92%; low certainty evidence) in CKD and HD. Potassium binders had uncertain effects on constipation (4 studies, 425 participants: RR 1.58, 95% CI 0.71, 3.52; I = 0%; low certainty evidence) in CKD. Potassium binders may decrease systolic blood pressure (BP) (2 studies, 369 participants: MD -3.73 mmHg, 95%CI -6.64 to -0.83; I = 79%; low certainty evidence) and diastolic BP (one study) at the end of the treatment. No study reported outcome data for cardiac arrhythmias or major GI events. Calcium polystyrene sulfonate may make little or no difference to serum potassium levels at end of treatment, compared to sodium polystyrene sulfonate (2 studies, 117 participants: MD 0.38 mEq/L, 95% CI -0.03 to 0.79; I = 42%, low certainty evidence). There was no evidence of a difference in systolic BP (one study), diastolic BP (one study), or constipation (one study) between calcium polystyrene sulfonate and sodium polystyrene sulfonate. There was no difference between high-dose and low-dose patiromer for death (sudden death) (one study), stroke (one study), myocardial infarction (one study), or constipation (one study). The comparative effects whether potassium binders were administered with or without food, laxatives, or sorbitol, were very uncertain with insufficient data to perform meta-analysis.
AUTHORS' CONCLUSIONS
Evidence supporting clinical decision-making for different potassium binders to treat chronic hyperkalaemia in adults with CKD is of low certainty; no studies were identified in children. Available studies have not been designed to measure treatment effects on clinical outcomes such as cardiac arrhythmias or major GI symptoms. This review suggests the need for a large, adequately powered study of potassium binders versus placebo that assesses clinical outcomes of relevance to patients, clinicians and policy-makers. This data could be used to assess cost-effectiveness, given the lack of definitive studies and the clinical importance of potassium binders for chronic hyperkalaemia in people with CKD.
Topics: Aged; Cause of Death; Chelating Agents; Chelation Therapy; Chronic Disease; Humans; Hyperkalemia; Middle Aged; Polymers; Polystyrenes; Potassium; Quality of Life; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Silicates
PubMed: 32588430
DOI: 10.1002/14651858.CD013165.pub2 -
Neurology Apr 2022A recent Food and Drug Administration warning concerning an arrhythmogenic potential of lamotrigine created concern in the neurologic community. This warning was based... (Review)
Review
BACKGROUND AND OBJECTIVES
A recent Food and Drug Administration warning concerning an arrhythmogenic potential of lamotrigine created concern in the neurologic community. This warning was based on in vitro studies, but no clinically relevant risk was considered. This rapid systematic review aims to elucidate the risk of lamotrigine on sudden death or ECG abnormalities.
METHODS
We conducted a systematic search of Ovid Medline and Ovid Embase, including randomized controlled trials and observational studies and studies of people with or without epilepsy, with the outcome measures sudden unexpected death in epilepsy (SUDEP) or sudden cardiac death as well as the development or worsening of ECG abnormalities. We evaluated the sudden death definitions used in all included studies, as some could have used unclear or overlapping definitions. We used the American Academy of Neurology risk of bias tool to evaluate the class of evidence and the GRADE approach to evaluate our confidence in the evidence.
RESULTS
We included 26 studies with 24,962 participants, of whom 2,326 used lamotrigine. Twelve studies showed no significant risk of SUDEP for lamotrigine users. One study reporting on sudden cardiac death and 3 studies with unclear sudden death definitions did not report an elevated risk of death in lamotrigine users compared to controls. In 10 studies reporting on ECG measures, there was no statistically significant increased risk among lamotrigine users except in 2 studies. These 2 studies reported either "slight increases" in PR interval or an increased PQ interval that the primary study authors believed to be related to structural cardiac differences rather than an effect of lamotrigine. One study was rated Class II; all others were Class III or IV. We had very low confidence in the evidence following the GRADE assessment. None of the studies examined the risk of lamotrigine in people with preexisting cardiac conditions.
DISCUSSION
There is insufficient evidence to support or refute that lamotrigine is associated with sudden death or ECG changes in people with or without epilepsy as compared to antiseizure medication or placebo, due to the high risk of bias in most studies and low precision and inconsistency in the reported results.
Topics: Anticonvulsants; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Epilepsy; Humans; Lamotrigine; Risk Factors
PubMed: 35260442
DOI: 10.1212/WNL.0000000000200164