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Arquivos de Neuro-psiquiatria Jan 2023Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent...
BACKGROUND
Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent of platelet aggregation and vasoconstriction, and it is used to prevent CVD. Nevertheless, patients may have treatment failure due to genetic variants that modify the metabolism of the drug causing aspirin resistance (AR).
OBJECTIVES
To realize a systematic literature review to determine the impact of genetic variants on AR.
METHODS
Articles published in the MEDLINE/PubMed, Cochrane, Scopus, LILACS, and SCIELO databases were systematically screened. A total of 290 articles were identified and 269 articles were excluded because they did not comply with the previously established inclusion criteria. A total of 20 case-control studies and 1 cohort was included.
RESULTS
The genetic variants rs1126643 (), rs3842787 (), rs20417 (), and rs5918 () were the most studied. As for relevance, of the 64 genetic variants evaluated by the articles, 14 had statistical significance ( < 0.05; 95% confidence interval [CI]) in at least one article. Among them, the following have had unanimous results: rs1371097 (), rs1045642 (), rs1051931 and rs7756935 (), rs2071746 (), rs1131882 and rs4523 (), rs434473 (), rs9315042 (), and rs662 (), while these differ in real interference in AR: rs5918 (), rs2243093 (), rs1330344 (), and rs20417 (). As study limitations, we highlight the nonuniform methodologies of the analyzed articles and population differences.
CONCLUSION
It is noteworthy that pharmacogenetics is an expanding area. Therefore, further studies are needed to better understand the association between genetic variants and AR.
Topics: Humans; Aspirin; Cardiovascular Diseases; Cyclooxygenase 2; Pharmacogenetics; Platelet Aggregation Inhibitors; Drug Resistance
PubMed: 36918009
DOI: 10.1055/s-0042-1758445 -
The Cochrane Database of Systematic... Mar 2023Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be associated with significant complications that uncommonly cause permanent vision loss. Complications include elevated intraocular pressure, corneal blood staining, anterior and posterior synechiae, and optic nerve atrophy. People with sickle cell trait or disease may be particularly susceptible to increases in intraocular pressure and optic atrophy. Rebleeding is associated with an increase in the rate and severity of complications.
OBJECTIVES
To assess the effectiveness of various medical interventions in the management of traumatic hyphema.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 3); MEDLINE Ovid; Embase.com; PubMed (1948 to March 2022); the ISRCTN registry; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The last date of the search was 22 March 2022.
SELECTION CRITERIA
Two review authors independently assessed the titles and abstracts of all reports identified by the electronic and manual searches. We included randomized and quasi-randomized trials that compared various medical (non-surgical) interventions versus other medical interventions or control groups for the treatment of traumatic hyphema following closed-globe trauma. We applied no restrictions on age, gender, severity of the closed-globe trauma, or level of visual acuity at time of enrollment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane and assessed the certainty of evidence using GRADE.
MAIN RESULTS
We included 23 randomized and seven quasi-randomized studies with a total of 2969 participants. Interventions included antifibrinolytic agents (systemic and topical aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), corticosteroids (systemic and topical), cycloplegics, miotics, aspirin, conjugated estrogens, traditional Chinese medicine, monocular versus bilateral patching, elevation of the head, and bed rest. We found no evidence of an effect on visual acuity for any intervention, whether measured within two weeks (short term) or for longer periods. In a meta-analysis of two trials, we found no evidence of an effect of aminocaproic acid on long-term visual acuity (RR 1.03, 95% confidence interval (CI) 0.82 to 1.29) or final visual acuity measured up to three years after the hyphema (RR 1.05, 95% CI 0.93 to 1.18). Oral tranexamic acid appeared to provide little to no benefit on visual acuity in four trials (RR 1.12, 95% CI 1.00 to 1.25). The remaining trials evaluated the effects of various interventions on short-term visual acuity; none of these interventions was measured in more than one trial. No intervention showed a statistically significant effect (RRs ranged from 0.75 to 1.10). Similarly, visual acuity measured for longer periods in four trials evaluating different interventions was also not statistically significant (RRs ranged from 0.82 to 1.02). The evidence supporting these findings was of low or very low certainty. Systemic aminocaproic acid reduced the rate of recurrent hemorrhage (RR 0.28, 95% CI 0.13 to 0.60), as assessed in six trials with 330 participants. A sensitivity analysis omitting two studies not using an intention-to-treat analysis reduced the strength of the evidence (RR 0.43, 95% CI 0.17 to 1.08). We obtained similar results for topical aminocaproic acid (RR 0.48, 95% CI 0.20 to 1.10) in two trials with 131 participants. We assessed the certainty of the evidence as low. Systemic tranexamic acid had a significant effect in reducing the rate of secondary hemorrhage (RR 0.33, 95% CI 0.21 to 0.53) in seven trials with 754 participants, as did aminomethylbenzoic acid (RR 0.10, 95% CI 0.02 to 0.41), as reported in one study. Evidence to support an associated reduction in risk of complications from secondary hemorrhage (i.e. corneal blood staining, peripheral anterior synechiae, elevated intraocular pressure, and development of optic atrophy) by antifibrinolytics was limited by the small number of these events. Use of aminocaproic acid was associated with increased nausea, vomiting, and other adverse events compared with placebo. We found no evidence of an effect on the number of adverse events with the use of systemic versus topical aminocaproic acid or with standard versus lower drug dose. The number of days for the primary hyphema to resolve appeared to be longer with the use of systemic aminocaproic acid compared with no use, but this outcome was not altered by any other intervention. The available evidence on usage of systemic or topical corticosteroids, cycloplegics, or aspirin in traumatic hyphema was limited due to the small numbers of participants and events in the trials. We found no evidence of an effect between a single versus binocular patch on the risk of secondary hemorrhage or time to rebleed. We also found no evidence of an effect on the risk of secondary hemorrhage between ambulation and complete bed rest.
AUTHORS' CONCLUSIONS
We found no evidence of an effect on visual acuity of any of the interventions evaluated in this review. Although the evidence was limited, people with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhage. However, hyphema took longer to clear in people treated with systemic aminocaproic acid. There is no good evidence to support the use of antifibrinolytic agents in the management of traumatic hyphema, other than possibly to reduce the rate of secondary hemorrhage. The potentially long-term deleterious effects of secondary hemorrhage are unknown. Similarly, there is no evidence to support the use of corticosteroids, cycloplegics, or non-drug interventions (such as patching, bed rest, or head elevation) in the management of traumatic hyphema. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.
Topics: Humans; Adrenal Cortex Hormones; Aminocaproic Acid; Antifibrinolytic Agents; Aspirin; Glaucoma; Hyphema; Mydriatics; Tranexamic Acid
PubMed: 36912744
DOI: 10.1002/14651858.CD005431.pub5 -
Brain Sciences Feb 2023Cardiovascular disease (CVD), including heart disease and stroke, continues to be the leading cause of death worldwide. Patients with mental health disorders, including... (Review)
Review
Cardiovascular disease (CVD), including heart disease and stroke, continues to be the leading cause of death worldwide. Patients with mental health disorders, including schizophrenia (SCZ) are known to have an increased risk for CVD. Given the association with metabolic syndrome, patients with SCZ are often prescribed metformin and statins but its impact remains unsatisfactory. The use of aspirin (ASA) to decrease cardiovascular risk in the general population has been thoroughly investigated and clear guidelines are currently in place. Since adjuvant treatment with ASA could possibly decrease CVD risk and mortality in SCZ, we conducted a systematic review of the literature to determine the state of the current literature on this subject. Our systematic review points to gaps in the literature on CVD prevention in SCZ and illustrates an obvious need for further research. Although several studies have shown increased CVD risk in SCZ, to date, no research has been conducted on the utilization of CVD preventative treatment such as ASA for SCZ.
PubMed: 36831911
DOI: 10.3390/brainsci13020368 -
Frontiers in Pharmacology 2022Proton pump inhibitors (PPIs) are usually prescribed to prevent gastrointestinal (GI) complications in patients receiving dual antiplatelet therapy (DAPT). This...
Efficacy and safety of concomitant use of proton pump inhibitors with aspirin-clopidogrel dual antiplatelet therapy in coronary heart disease: A systematic review and meta-analysis.
Proton pump inhibitors (PPIs) are usually prescribed to prevent gastrointestinal (GI) complications in patients receiving dual antiplatelet therapy (DAPT). This systematic review and meta-analysis aimed to explore the efficacy and safety of the concomitant use of PPIs with aspirin-clopidogrel DAPT in patients with Coronary heart disease (CHD). The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to August 2022 for eligible studies. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the clinical outcomes. Subgroup analysis was conducted according to different PPI subtypes, populations, follow-up times and study types. This study was registered on PROSPERO (CRD42022332195). A total of 173,508 patients from 18 studies [2 randomized controlled trials (RCTs), 3 analyses of RCTs, and 13 cohort studies] were included in this study. Pooled data revealed that coadministration of PPIs significantly increased the risk of major adverse cardiovascular events (MACEs) (HR = 1.15, 95% CI = 1.06-1.26, = .001) and reduced the risk of gastrointestinal (GI) complications (HR = 0.44, 95% CI = 0.30-0.64, .0001). Subgroup analysis results showed that the esomeprazole users and patients with coronary stenting in the PPI group were associated with an increased risk of MACEs compared with the non-PPI group. The occurrence of MACEs in PPI users was more common than that in non-PPI users in long-term follow-up (≥12 months) studies and in the observational studies. There was no significant differences in the incidences of net clinical adverse events (NACEs), all-cause mortality, or cardiac death between the two groups. In patients with CHD, the concomitant use of PPIs with aspirin and clopidogrel was associated with a reduced risk of GI complications but could increase the rates of MACEs (particularly in patients receiving esomeprazole or with coronary stenting). There was no clear evidence of an association between PPI use and NACEs, all-cause mortality, or cardiac death. The results could have been affected by the follow-up time and study type. Further large-scale RCTs with long-term follow-up are needed.
PubMed: 36703730
DOI: 10.3389/fphar.2022.1021584 -
The Cochrane Database of Systematic... Jan 2023This is an update of the Cochrane Review last published in 2017. Survivors of stroke due to intracerebral haemorrhage (ICH) are at risk of major adverse cardiovascular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the Cochrane Review last published in 2017. Survivors of stroke due to intracerebral haemorrhage (ICH) are at risk of major adverse cardiovascular events (MACE). Antithrombotic (antiplatelet or anticoagulant) treatments may lower the risk of ischaemic MACE after ICH, but they may increase the risk of bleeding.
OBJECTIVES
To determine the overall effectiveness and safety of antithrombotic drugs on MACE and its components for people with ICH.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (5 October 2021). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL: the Cochrane Library 2021, Issue 10), MEDLINE Ovid (from 1948 to October 2021) and Embase Ovid (from 1980 to October 2021). The online registries of clinical trials searched were the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (5 October 2021). We screened the reference lists of included randomised controlled trials (RCTs) for additional, potentially relevant RCTs.
SELECTION CRITERIA
We selected RCTs in which participants with ICH of any age were allocated to a class of antithrombotic treatment as intervention or comparator.
DATA COLLECTION AND ANALYSIS
In accordance with standard methodological procedures recommended by Cochrane, two review authors assessed each selected RCT for its risk of bias and extracted data independently. The primary outcome was a composite of MACE, and secondary outcomes included death, individual components of the MACE composite, ICH growth, functional status and cognitive status. We estimated effects using the frequency of outcomes that occurred during the entire duration of follow-up and calculated a risk ratio (RR) for each RCT. We grouped RCTs separately for analysis according to 1) the class(es) of antithrombotic treatment used for the intervention and comparator, and 2) the duration of antithrombotic treatment use (short term versus long term). We pooled the intention-to-treat populations of RCTs using a fixed-effect model for meta-analysis, but used a random-effects model if RCTs differed substantially in their design or there was considerable heterogeneity (I ≥ 75%) in their results. We applied GRADE to assess the certainty of the evidence.
MAIN RESULTS
We identified seven new completed RCTs for this update, resulting in the inclusion of a total of nine RCTs based in secondary care, comprising 1491 participants (average age ranged from 61 to 79 years and the proportion of men ranged from 44% to 67%). The proportion of included RCTs at low risk of bias, by category was: random sequence generation (67%), allocation concealment (67%), performance (22%), detection (78%), attrition (89%), and reporting (78%). For starting versus avoiding short-term prophylactic dose anticoagulation after ICH, no RCT reported MACE. The evidence is very uncertain about the effect of starting short-term prophylactic dose anticoagulation on death (RR 1.00, 95% CI 0.59 to 1.70, P = 1.00; 3 RCTs; very low-certainty evidence), venous thromboembolism (RR 0.84, 95% CI 0.51 to 1.37, P = 0.49; 4 RCTs; very low-certainty evidence), ICH (RR 0.24, 95% CI 0.04 to 1.38, P = 0.11; 2 RCTs; very low-certainty evidence), and independent functional status (RR 2.03, 95% CI 0.78 to 5.25, P = 0.15; 1 RCT; very low-certainty evidence) over 90 days. For starting versus avoiding long-term therapeutic dose oral anticoagulation for atrial fibrillation after ICH, starting long-term therapeutic dose oral anticoagulation probably reduces MACE (RR 0.61, 95% CI 0.40 to 0.94, P = 0.02; 3 RCTs; moderate-certainty evidence) and probably reduces all major occlusive vascular events (RR 0.27, 95% CI 0.14 to 0.53, P = 0.0002; 3 RCTs; moderate-certainty evidence), but probably results in little to no difference in death (RR 1.05, 95% CI 0.62 to 1.78, P = 0.86; 3 RCTs; moderate-certainty evidence), probably increases intracranial haemorrhage (RR 2.43, 95% CI 0.88 to 6.73, P = 0.09; 3 RCTs; moderate-certainty evidence), and may result in little to no difference in independent functional status (RR 0.98, 95% CI 0.78 to 1.24, P = 0.87; 2 RCTs; low-certainty evidence) over one to three years. For starting versus avoiding long-term antiplatelet therapy after ICH, the evidence is uncertain about the effects of starting long-term antiplatelet therapy on MACE (RR 0.89, 95% CI 0.64 to 1.22, P = 0.46; 1 RCT; moderate-certainty evidence), death (RR 1.08, 95% CI 0.76 to 1.53, P = 0.66; 1 RCT; moderate-certainty evidence), all major occlusive vascular events (RR 1.03, 95% CI 0.68 to 1.55, P = 0.90; 1 RCT; moderate-certainty evidence), ICH (RR 0.52, 95% CI 0.27 to 1.03, P = 0.06; 1 RCT; moderate-certainty evidence) and independent functional status (RR 0.95, 95% CI 0.77 to 1.18, P = 0.67; 1 RCT; moderate-certainty evidence) over a median follow-up of two years. For adults within 180 days of non-cardioembolic ischaemic stroke or transient ischaemic attack and a clinical history of prior ICH, there was no evidence of an effect of long-term cilostazol compared to aspirin on MACE (RR 1.33, 95% CI 0.74 to 2.40, P = 0.34; subgroup of 1 RCT; low-certainty evidence), death (RR 1.65, 95% CI 0.55 to 4.91, P = 0.37; subgroup of 1 RCT; low-certainty evidence), or ICH (RR 1.29, 95% CI 0.35 to 4.69, P = 0.70; subgroup of 1 RCT; low-certainty evidence) over a median follow-up of 1.8 years; all major occlusive vascular events and functional status were not reported.
AUTHORS' CONCLUSIONS
We did not identify beneficial or hazardous effects of short-term prophylactic dose parenteral anticoagulation and long-term oral antiplatelet therapy after ICH on important outcomes. Although there was a significant reduction in MACE and all major occlusive vascular events after long-term treatment with therapeutic dose oral anticoagulation for atrial fibrillation after ICH, the pooled estimates were imprecise, the certainty of evidence was only moderate, and effects on other important outcomes were uncertain. Large RCTs with a low risk of bias are required to resolve the ongoing dilemmas about antithrombotic treatment after ICH.
Topics: Male; Adult; Humans; Middle Aged; Aged; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Atrial Fibrillation; Cerebral Hemorrhage; Stroke; Anticoagulants
PubMed: 36700520
DOI: 10.1002/14651858.CD012144.pub3 -
Journal of Thrombosis and Haemostasis :... Feb 2023Retinal vein occlusion (RVO) represents a common thrombotic disorder. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Retinal vein occlusion (RVO) represents a common thrombotic disorder.
OBJECTIVES
In this meta-analysis, we evaluated the efficacy and safety of anticoagulant and antiplatelet therapy in RVO.
METHODS
MEDLINE and EMBASE were searched up to December 2021 for observational studies and randomized controlled trials including patients with RVO. Efficacy outcomes were best-corrected visual acuity improvement, recurrent RVO, fluorescein angiography improvement, cardiovascular events, and safety outcomes were major bleeding and intraocular bleeding.
RESULTS
A total of 1422 patients (15 studies) were included. Antiplatelet therapy was administered to 477 patients (13 studies), anticoagulant therapy to 312 patients (12 studies), and 609 (7 studies) patients received no antithrombotic treatment. The treatment duration ranged between 0.5 and 3 months. The median follow-up duration was 12 months. Best-corrected visual acuity improvement was reported in 58% of the patients (95% confidence interval [CI], 45%-69%) overall, 64% (95% CI, 58%-71%) in those on anticoagulant therapy, and 33% (95% CI, 21%-47%) in those on antiplatelet therapy. The rates of recurrent RVO was 11% (95% CI, 7%-17%), 7% (95% CI, 2%-19%), and 15% (95% CI, 8%-28%), respectively. The rate of recurrent RVO in untreated patients was 9% (95% CI, 6%-14%). The rate of major bleeding was 5% (95% CI, 3%-9%) overall, 4% (95% CI, 2%-9%) in those on anticoagulant therapy, and 7% (95% CI, 2%-23%) in those on antiplatelet therapy.
CONCLUSION
Anticoagulant therapy was associated with higher visual acuity improvement and fewer recurrent RVO events than antiplatelet therapy, at the cost of an acceptable proportion of bleeding complications.
Topics: Humans; Platelet Aggregation Inhibitors; Retinal Vein Occlusion; Anticoagulants; Thrombosis; Hemorrhage
PubMed: 36700511
DOI: 10.1016/j.jtha.2022.10.003 -
Frontiers in Cardiovascular Medicine 2022Antithrombotic secondary prevention in stable cardiovascular disease (SCVD) patients at high ischemic risk remains unclear. We compared the efficacy and safety of...
Secondary prevention of antithrombotic therapy in patients with stable cardiovascular disease at high ischemic risk: A network meta-analysis of randomized controlled trials.
AIMS
Antithrombotic secondary prevention in stable cardiovascular disease (SCVD) patients at high ischemic risk remains unclear. We compared the efficacy and safety of aspirin monotherapy, clopidogrel monotherapy, ticagrelor monotherapy, rivaroxaban monotherapy, clopidogrel plus aspirin, ticagrelor plus aspirin, and rivaroxaban plus aspirin in the high-risk ischemic cohorts.
METHODS AND RESULTS
Eleven randomized controlled trials were included ( = 111737). The primary outcomes were major cardiovascular and cerebrovascular events (MACEs) and major bleeding. A random effects model was used for frequentist network meta-analysis. Odds ratio (OR) and 95% credible intervals (CI) were reported as a summary statistic. Compared with aspirin monotherapy, rivaroxaban plus aspirin [OR 0.79 (95% CI, 0.69, 0.89)], ticagrelor plus aspirin [0.88 (0.80, 0.98)], clopidogrel plus aspirin [0.56 (0.41, 0.77)] were associated with a reduced risk of MACEs, but rivaroxaban monotherapy [0.92 (0.79, 1.07)], ticagrelor monotherapy [0.68 (0.45, 1.05)], and clopidogrel monotherapy [0.67 (0.43, 1.05)] showed no statistically significant difference. However, rivaroxaban monotherapy and all dual antithrombotic strategies increased the risk of major bleeding to varying degrees, with ticagrelor plus aspirin associated with the highest risk of major bleeding. The net clinical benefit favored clopidogrel or ticagrelor monotherapy, which have a mild anti-ischemic effect without an increase in bleeding risk.
CONCLUSION
The present network meta-analysis suggests that clopidogrel or ticagrelor monotherapy may be recommended first in this cohort of SCVD at high ischemic risk. But clopidogrel plus aspirin or rivaroxaban plus aspirin can still be considered for use in patients with recurrent MACEs.
PubMed: 36698936
DOI: 10.3389/fcvm.2022.1040473 -
Frontiers in Cardiovascular Medicine 2022Clopidogrel, prasugrel, ticagrelor, and low-dose rivaroxaban are all optional strategies in conjunction with aspirin for long-term treatment of chronic coronary artery...
BACKGROUND
Clopidogrel, prasugrel, ticagrelor, and low-dose rivaroxaban are all optional strategies in conjunction with aspirin for long-term treatment of chronic coronary artery disease. The aim of this research was to assess the efficacy and safety of long-term anti-thrombotic treatment of chronic coronary heart disease.
METHODS
PubMed (MEDLINE), Embase, Clinical Trials Registry ClinicalTrials.gov, and The Cochrane Library were searched through November 2021, to identify randomized controlled trials that compared long term anti-thrombotic therapy for coronary heart disease. Data were extracted to assess eligibility by two independent reviewers. Random-effects meta-analysis was used to pool results.
RESULTS
Eleven randomized controlled trials were included (88,462 patients). In a network meta-analysis, the rivaroxaban compared to the clopidogrel regimen showed lower relative risks (RRs) for death of any cause (0.71; 95% confidence interval [CI], 0.52-0.96), major adverse cardiac events (MACE) (0.73; 95% CI, 0.57-0.93), and cerebrovascular events (0.48; 95% CI, 0.30-0.78). The RR of cerebrovascular events was also lower for the rivaroxaban compared to the ticagrelor 60 mg regimen (0.72; 95% CI, 0.52-0.99). For the prasugrel regimen, the RRs were lower of myocardial infarction incidence versus all extended strategies: clopidogrel plus aspirin (0.76; 95% CI, 0.58-0.99), rivaroxaban (0.60; 95% CI, 0.38-0.93), ticagrelor 60 mg (0.61; 95% CI, 0.42-0.89), and ticagrelor 90 mg (0.63; 95% CI, 0.41-0.97). None of the dual strategies were associated with differences in major bleeding compared to the prasugrel regimen.
CONCLUSIONS AND RELEVANCE
The rivaroxaban regimen appeared to be the preferred long-term anti-thrombotic regimen in preventing all-cause mortality. Our available results tend to support the efficacy of extended anti-thrombotic therapy consisting of prasugrel in lowering MI incidence compared to the other strategies, without increased risk of bleeding. However, additional large-scale direct clinical trials are needed to further determine the adequate long-term anti-thrombotic regimens for treating chronic coronary syndrome.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020186583, identifier CRD42020186583.
PubMed: 36698921
DOI: 10.3389/fcvm.2022.1016390 -
The Cochrane Database of Systematic... Jan 2023Kawasaki disease (KD) is an acute systemic vasculitis (inflammation of the blood vessels) that mainly affects children. Symptoms include fever, chapped lips, strawberry... (Review)
Review
BACKGROUND
Kawasaki disease (KD) is an acute systemic vasculitis (inflammation of the blood vessels) that mainly affects children. Symptoms include fever, chapped lips, strawberry tongue, red eyes (bulbar conjunctival injection), rash, redness, swollen hands and feet or skin peeling; and enlarged cervical lymph nodes. High fevers and systemic inflammation characterise the acute phase. Inflammation of the coronary arteries causes the most serious complication of the disease, coronary artery abnormalities (CAAs). The primary treatment is intravenous immunoglobulin (IVIG) and acetylsalicylic acid (ASA/aspirin), with doses and regimens differing between institutions. It is important to know which regimens are the safest and most effective in preventing complications.
OBJECTIVES
To evaluate the efficacy and safety of IVIG in treating and preventing cardiac consequences of Kawasaki disease.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 26 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) investigating the use of IVIG for the treatment of KD. We included studies involving treatment for initial or refractory KD, or both.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were incidence of CAAs and incidence of any adverse effects after treatment. Our secondary outcomes were acute coronary syndromes, duration of fever, need for additional treatment, length of hospital stay, and mortality. We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We identified 31 RCTs involving a total of 4609 participants with KD. Studies compared IVIG with ASA, another dose or regimen of IVIG, prednisolone, or infliximab. The majority of studies reported on primary treatment, so those results are reported below. A limited number of studies investigated secondary or tertiary treatment in IVIG-resistant patients. Doses and regimens of IVIG infusion varied between studies, and all studies had some concerns related to risk of bias. Primary treatment with IVIG compared to ASA for people with KD Compared to ASA treatment, IVIG probably reduces the incidence of CAAs in people with KD up to 30 days (odds ratio (OR) 0.60, 95% confidence interval (CI) 0.41 to 0.87; 11 studies, 1437 participants; moderate-certainty evidence). The individual studies reported a range of adverse effects, but there was little to no difference in numbers of adverse effects between treatment groups (OR 0.57, 95% CI 0.17 to 1.89; 10 studies, 1376 participants; very low-certainty evidence). There was limited evidence for the incidence of acute coronary syndromes, so we are uncertain of any effects. Duration of fever days from treatment onset was probably shorter in the IVIG group (mean difference (MD) -4.00 days, 95% CI -5.06 to -2.93; 3 studies, 307 participants; moderate-certainty evidence). There was little or no difference between groups in need for additional treatment (OR 0.27, 95% CI 0.05 to 1.57; 3 studies, 272 participants; low-certainty evidence). No study reported length of hospital stay, and no deaths were reported in either group. Primary treatment with IVIG compared to different infusion regimens of IVIG for people with KD Higher-dose regimens of IVIG probably reduce the incidence of CAAs compared to medium- or lower-dose regimens of IVIG up to 30 days (OR 0.60, 95% CI 0.40 to 0.89; 8 studies, 1824 participants; moderate-certainty evidence). There was little to no difference in the number of adverse effects between groups (OR 1.11, 95% CI 0.52 to 2.37; 6 studies, 1659 participants; low-certainty evidence). No study reported on acute coronary syndromes. Higher-dose IVIG may reduce the duration of fever compared to medium- or lower-dose regimens (MD -0.71 days, 95% CI -1.36 to -0.06; 4 studies, 992 participants; low-certainty evidence). Higher-dose regimens may reduce the need for additional treatment (OR 0.29, 95% CI 0.10 to 0.88; 4 studies, 1125 participants; low-certainty evidence). We did not detect a clear difference in length of hospital stay between infusion regimens (MD -0.24, 95% CI -0.78 to 0.30; 3 studies, 752 participants; low-certainty evidence). One study reported mortality, and there was little to no difference detected between regimens (moderate-certainty evidence). Primary treatment with IVIG compared to prednisolone for people with KD The evidence comparing IVIG with prednisolone on incidence of CAA is very uncertain (OR 0.60, 95% CI 0.24 to 1.48; 2 studies, 140 participants; very low-certainty evidence), and there was little to no difference between groups in adverse effects (OR 4.18, 95% CI 0.19 to 89.48; 1 study; 90 participants; low-certainty evidence). We are very uncertain of the impact on duration of fever, as two studies reported this outcome differently and showed conflicting results. One study reported on acute coronary syndromes and mortality, finding little or no difference between groups (low-certainty evidence). No study reported the need for additional treatment or length of hospital stay.
AUTHORS' CONCLUSIONS
The included RCTs investigated a variety of comparisons, and the small number of events observed during the study periods limited detection of effects. The certainty of the evidence ranged from moderate to very low due to concerns related to risk of bias, imprecision, and inconsistency. The available evidence indicated that high-dose IVIG regimens are probably associated with a reduced risk of CAA formation compared to ASA or medium- or low-dose IVIG regimens. There were no clinically significant differences in incidence of adverse effects, which suggests there is little concern about the safety of IVIG. Compared to ASA, high-dose IVIG probably reduced the duration of fever, but there was little or no difference detected in the need for additional treatment. Compared to medium- or low-dose IVIG, there may be reduced duration of fever and reduced need for additional treatment. We were unable to draw any conclusions regarding acute coronary syndromes, mortality, or length of hospital stay, or for the comparison IVIG versus prednisolone. Our findings are in keeping with current guideline recommendations and evidence from long-term epidemiology studies.
Topics: Child; Humans; Mucocutaneous Lymph Node Syndrome; Immunoglobulins, Intravenous; Acute Coronary Syndrome; Prednisolone; Aspirin; Inflammation; Fever
PubMed: 36695415
DOI: 10.1002/14651858.CD014884.pub2 -
Pharmaceuticals (Basel, Switzerland) Dec 2022The effects of acetylsalicylic acid (ASA) on mood disorders (MD) and on inflammatory parameters in preclinical and clinical studies have not yet been comprehensively... (Review)
Review
The effects of acetylsalicylic acid (ASA) on mood disorders (MD) and on inflammatory parameters in preclinical and clinical studies have not yet been comprehensively evaluated. The aim of this study was to systematically summarize the available knowledge on this topic according to PRISMA guidelines. Data from preclinical and clinical studies were analyzed, considering the safety and efficacy of ASA in the treatment of MD and the correlation of inflammatory parameters with the effect of ASA treatment. Twenty-one studies were included. Both preclinical and clinical studies found evidence indicating the safety and efficacy of low-dose ASA in the treatment of all types of affective episodes in MD. Observational studies have indicated a reduced risk of all types of affective episodes in chronic low-dose ASA users (HR 0.92, 95% CI: 0.88, 0.95, p < 0.0001). An association between ASA response and inflammatory parameters was found in preclinical studies, but this was not confirmed in clinical trials. Further long-term clinical trials evaluating the safety and efficacy of ASA in recurrent MD, as well as assessing the linkage of ASA treatment with inflammatory phenotype and cytokines, are required. There is also a need for preclinical studies to understand the exact mechanism of action of ASA in MD.
PubMed: 36678565
DOI: 10.3390/ph16010067