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The recently published randomized trials (RCTs) evaluating the effect of Sodium-glucose cotransporter-2 inhibitors (SGLT2i) in heart failure with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF) led researchers to perform a plethora of systematic reviews (SRs), often providing contradictory conclusions. This overview of reviews was aimed at summarizing the evidence of these SRs, quantifying the overlap, re-analyzing the evidence in case new studies that were identified, and mapping knowledge gaps. Literature search was conducted through Medline, Scopus, and Cochrane until March 22, 2023. Overall, 36 SRs synthesizing results from 18 RCTs were identified. A substantial overlap was identified among the SRs synthesizing large heart failure or cardiovascular outcome trials (CVOTs). Regarding the composite outcome of cardiovascular (CV) mortality or hospitalization for heart failure (HHF), all authors reported a significant favorable effect. A beneficial effect was also noted for CV and all-cause mortality, albeit not significant. Our meta-analysis demonstrated a significant improvement in health-related quality-of-life (HRQoL) as assessed by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS, MD = 1.97, p < 0.001), Total Symptom Score (KCCQ-TSS, MD = 2.29, p < 0.001), Clinical Summary Score (KCCQ-CSS, MD = 1.59, p < 0.001), and the 6-min walking distance (MD = 10.78 m, p = 0.032). Regarding safety, SGLT2i were associated with a significantly lower risk of serious adverse events compared to placebo (RR = 0.94, p = 0.002). The use of SGLT2i in HFpEF is both efficient and safe. Further research is required to clarify the impact of SGTL2i on different subphenotypes of HFpEF and the cardiorespiratory capacity of these patients.
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Insuficiência Cardíaca , Humanos , Volume Sistólico , Revisões Sistemáticas como Assunto , Insuficiência Cardíaca/tratamento farmacológico , Glucose , Sódio/uso terapêuticoRESUMO
AIM: To summarize the evidence of recently published randomized controlled trials (RCTs) studying efficacy, in terms of glycaemic control, and safety of the newly developed once-weekly basal insulin analogues. METHODS: A systematic literature search was conducted through Medline (via PubMed), Cochrane Library and Google Scholar until June 30, 2023. Double-independent study selection, data extraction and quality assessment were performed. Results were summarized with random-effects meta-analysis. RESULTS: A total of 3962 patients with type 2 diabetes mellitus (T2DM) among nine RCTs were analysed. All RCTs had low risk of bias according to the Cochrane Collaboration risk-of-bias tool (RoB2). Once-weekly insulins demonstrated better efficacy in glycated haemoglobin (HbA1c) reduction (mean difference [MD] -0.13%, 95% confidence interval [CI] -0.23, -0.03; P = 0.08) and a significantly greater time in range compared with once-daily insulin analogues (MD 3.54%, 95% CI 1.56, 5.53; P = 0.005). Based on subgroup analyses, the reduction in HbA1c and the odds of achieving an end-of-treatment HbA1c <6.5% were significantly greater for icodec compared to the once-daily insulin (MD -0.18%, 95% CI -0.27, -0.09 [P < 0.001] and odds ratio [OR] 1.75, 95% CI 1.34, 2.29 [P < 0.001], respectively). Once-weekly insulins were associated with higher odds of level 1 hypoglycaemia during the 24-hour period (OR 1.3, 95% CI 1.04, 1.64; P = 0.02) but were safer in terms of level 2 or 3 nocturnal hypoglycaemic events (OR 0.74, 95% CI 0.56, 0.97; P = 0.03). No difference was observed regarding serious adverse events between the two groups. CONCLUSION: The once-weekly basal insulin analogues seem to be at least equally efficient in glycaemic management and safe compared to once-daily injections in people with T2DM. Phase 4 RCTs are expected to shed further light on the effectiveness and safety of once-weekly insulin therapy over the long term.
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Diabetes Mellitus Tipo 2 , Hipoglicemia , Humanos , Insulina/efeitos adversos , Hemoglobinas Glicadas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Hipoglicemia/induzido quimicamente , Insulina Regular HumanaRESUMO
PURPOSE: To investigate microcirculation characteristics of the inner retinal layers at the macula and the peripapillary area using Optical Coherence Tomography Angiography (OCT-A) of patients in early stages of Parkinson's disease (PD). METHODS: 32 PD patients and 46 age- and gender-matched healthy controls were included in this cross sectional study. OCT-A imaging was performed to analyze microcirculation characteristics at each separate macular region (fovea, parafovea, and perifovea) and the peripapillary area of the inner retinal layers. RESULTS: Individuals with PD had significantly lower parafoveal, perifoveal and total vessel density (VD) in the superficial capillary plexus (SCP) than controls (all p < 0.001), while foveal VD was higher in PD eyes than that of controls, though not statistically significant. Similarly, individuals with PD had significantly lower parafoveal, perifoveal and total perfusion in the SCP than control eyes (all p < 0.001), while foveal perfusion was significantly higher in PD eyes than that of controls (p = 0.008). PD eyes had significantly smaller FAZ area and perimeter accompanied by decreased circularity at the SCP as compared to controls (all p < 0.001). Concerning the peripapillary area, individuals with PD had significantly lower radial peripapillary capillary perfusion density and flux index at the SCP than controls (all p < 0.001). All p values remained statistically significant even after using the Bonferroni correction for multiple comparisons, except for that of foveal perfusion. CONCLUSIONS: Our study indicates alterations of the inner retinal layers at the macula and the peripapillary area at the preliminary stages of PD. OCT-A parameters could potentially comprise imaging biomarkers for PD screening and improve the diagnostic algorithms.
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Doença de Parkinson , Vasos Retinianos , Humanos , Estudos Transversais , Angiofluoresceinografia/métodos , Vasos Retinianos/diagnóstico por imagem , Doença de Parkinson/diagnóstico , Microvasos , Tomografia de Coerência Óptica/métodosRESUMO
This study aimed to assess the methods and outcomes of The Measurement Tool to Assess systematic Reviews (AMSTAR) 2 appraisals in overviews of reviews (overviews) of interventions in the cardiovascular field and identify factors that are associated with these outcomes. MEDLINE, Scopus, and the Cochrane Database of Systematic Reviews were searched until November 2022. Eligible were overviews of cardiovascular interventions, analyzing systematic reviews (SRs) of randomized controlled trials (RCTs). Extracted data included characteristics of overviews and SRs and AMSTAR 2 appraisal methods and outcomes. Data were synthesized using descriptive statistics and logistic regression to explore potential associations between the characteristics of SRs and extracted AMSTAR 2 overall ratings ("High-Moderate" vs. "Low-Critically low"). The original results on individual AMSTAR 2 items were entered into the official AMSTAR 2 online tool and the recalculated overall confidence ratings were compared to those provided in overviews. All 34 overviews identified were published between 2019 and 2022. Rating of overall confidence following the algorithm suggested by AMSTAR 2 developers was noted in 74% of overviews. The 679 unique included SRs were mainly of "Critically low" (53%) or "Low" (18.7%) confidence and underperformed in items 2 (Protocol, no = 65.2%) and 7 (List of excluded studies, no = 84%). The following characteristics of SRs were significantly associated with higher overall ratings: Cochrane origin, pharmacological interventions, including exclusively RCTs, citation of methodological and reporting guidelines, protocol, absence of funding and publication after AMSTAR 2 release. Generally, overviews' authors tended to deviate from the original rating scheme and ascribe higher ratings to SRs compared to the official AMSTAR 2 online tool. Most SRs included in overviews of cardiovascular interventions have critically low or low confidence in their results. Overviews' authors should be more transparent about the methods used to derive the overall confidence in SRs.
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Medicina Baseada em Evidências , Projetos de Pesquisa , Revisões Sistemáticas como AssuntoRESUMO
Systematic reviews (SRs) have an important role in the healthcare decision-making practice. Assessing the overall confidence in the results of SRs using quality assessment tools, such as "A MeaSurement Tool to Assess Systematic Reviews 2" (AMSTAR 2), is crucial since not all SRs are conducted using the most rigorous methods. In this article, we introduce a free, open-source R package called "amstar2Vis" (https://github.com/bougioukas/amstar2Vis) that provides easy-to-use functions for presenting the critical appraisal of SRs, based on the items of AMSTAR 2 checklist. An illustrative example is outlined, describing the steps involved in creating a detailed table with the item ratings and the overall confidence ratings, generating a stacked bar plot that shows the distribution of ratings as percentages of SRs for each AMSTAR 2 item, and creating a "ggplot2" graph that shows the distribution of overall confidence ratings ("Critically Low," "Low," "Moderate," or "High"). We expect "amstar2Vis" to be useful for overview authors and methodologists who assess the quality of SRs with AMSTAR 2 checklist and facilitate the production of pertinent publication-ready tables and figures. Future research and applications could further investigate the functionality or potential improvements of our package.
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Lista de Checagem , Software , Revisões Sistemáticas como Assunto , Humanos , Reprodutibilidade dos Testes , Projetos de Pesquisa , Medicina Baseada em Evidências , Algoritmos , Metanálise como AssuntoRESUMO
OBJECTIVE: Multiple systematic reviews (SR) have been performed on the effects of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), often providing conflicting findings. This overview and network meta-analysis (NMA) aimed to summarize SR findings on the efficacy and safety of PCSK9i and provide an updated NMA. MATERIALS AND METHODS: MEDLINE (Pubmed), Scopus, Cochrane, Epistemonikos and Google Scholar were searched from inception to September 21, 2023 for SRs of randomized controlled trials (RCTs) and from January 1, 2020 to September 21, 2023 for additional RCTs. Double-independent study selection, data extraction and quality assessment were performed. Qualitative analysis was performed for SRs and a frequentist random-effects model NMA was performed for RCTs. RESULTS: Totally, 86 SRs and 76 RCTs were included. Alirocumab (77/86 [90%]) and evolocumab (73/86 [85%]) were mostly analyzed. Associations from SRs (35/42 [83%]) and the updated NMA indicated PCSK9i benefit on major adverse cardiovascular events (MACEs). Reductions were also noted for cerebrovascular events (47/66 [71%]), coronary revascularization (29/33 [88%]) and myocardial infarction (41/63 [65%]). Alirocumab was associated with reductions on all-cause mortality (RR=0.82, 95%CI [0.72,0.94]). Data on any CV event reduction were conflicting (7/16 [44%]). Inclisiran appeared effective only on MACEs (RR=0.76, 95%CI [0.61,0.94]). No reductions in heart failure were observed (0/16). No increases were identified between PCSK9i and any (0/35) or serious adverse events (0/52). However, PCSK9i were associated with injection-site reactions (20/28 [71%]). CONCLUSION: PCSK9i appeared to be effective in CV outcomes and their clinical application was generally safe.
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Anticolesterolemiantes , Doenças Cardiovasculares , Dislipidemias , Humanos , Inibidores de PCSK9 , Anticolesterolemiantes/efeitos adversos , Metanálise em Rede , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/induzido quimicamente , LDL-Colesterol , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Pró-Proteína Convertase 9RESUMO
BACKGROUND: Currently, the guidelines for prevention and management of atherosclerosis in patients with Sjogren's syndrome (SS) do not differentiate from those concerning the general population. OBJECTIVES: The present systematic review aimed to summarize evidence from primary studies assessing the risk of subclinical atherosclerosis in patients with primary SS (pSS). METHODS AND RESULTS: Literature was searched until June 2023. Eligible records were randomized controlled trials and observational studies comparing subclinical atherosclerosis markers between pSS patients and healthy controls. DerSimonian-Laird random effects models were used to calculate overall effect estimates. Totally, 19 observational studies comprising 1625 participants were included. Compared to healthy controls, pSS patients had significantly higher values of carotid-femoral intima-media thickness (cfIMT) (MD= 0.07 mm; 95 % CI= [0.04, 0.11]; p <0.001) and were more frequently diagnosed with atherosclerotic plaques (OR= 1.9; 95 % CI= [1.32, 2.74]; p <0.001). Moreover, pSS patients showed a decreased flow and nitrate-mediated dilation (MD = -2.48 %; 95 % CI= [-4.57, -0.39]; p = 0.02, MD= -2.11 %; 95 % CI= [-3.22, -1.01]; p <0.001, respectively). Similar results were observed for the pulse-wave velocity (MD= 0.7 m/s; 95 % CI= [0.36, 1.05]; p <0.001) and the ankle-brachial index (OR= 5.78; 95 % CI= [2.23, 14.99]; p = 0.003). Based on meta-regression analyses, only the disease duration and erythrocyte sedimentation rate were positively and significantly associated with higher cfIMT values. CONCLUSION: Patients with pSS have an increased risk of subclinical atherosclerosis compared to healthy population and thus possibly require early and disease-specific intervention. Further research is warranted for more accurate cardiovascular risk management in SS.
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Aterosclerose , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/epidemiologia , Espessura Intima-Media Carotídea , Aterosclerose/epidemiologia , Aterosclerose/complicações , Fatores de Risco , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Background: Real-world data show limited utilization of direct oral anticoagulants (DOACs) in obese patients (body mass index [BMI] ≥ 30 kg/m2) due to concerns regarding their efficacy and safety in this demographic. Aim: This review aimed to consolidate current evidence on the efficacy and safety of DOACs versus warfarin in obese patients with non-valvular atrial fibrillation (AF) or venous thromboembolism (VTE). The primary efficacy outcome assessed a composite of all-cause mortality, stroke, systemic embolism (SE), and myocardial infarction (MI). Methods: A systematic search was conducted in MEDLINE, SCOPUS, and Cochrane databases from inception to December 28, 2023. Data were synthesized using random-effects meta-analysis. Results: A total of 35 studies involving 434,320 participants were analyzed. DOAC use was associated with a significant reduction in the risk of the composite outcome (RR = 0.80, 95% CI [0.65, 0.98], I2 = 95%), hemorrhagic stroke (RR = 0.58, 95% CI [0.38, 0.88], I2 = 92%), major bleeding (RR = 0.76, 95% CI [0.63, 0.92], I2 = 94%), gastrointestinal bleeding (RR = 0.59, 95% CI [0.49, 0.72], I2 = 88%), and intracranial bleeding (RR = 0.45, 95% CI [0.34, 0.60], I2 = 44%) compared to warfarin. A non-significant benefit of DOACs was observed for all-cause mortality, MI, the composite of stroke or SE, ischemic stroke, SE, VTE, and minor bleeding compared to warfarin. Subgroup analysis indicated no significant effect modification based on the indication for anticoagulation or study design. Conclusions: DOACs demonstrated a favorable efficacy and safety profile in obese individuals compared to warfarin.
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Testing for myocardial ischemia in patients presenting with sustained monomorphic Ventricular Tachycardia(VT) even without evidence of acute myocardial infarction is a tempting strategy that is frequently utilized in clinical practice. Monomorphic VT is mainly caused by re-entry around chronic myocardial scar and active ischemia has no role in its pathogenesis, thus making testing for ischemia futile, at least in theory. This systematic literature review sought to address the usefulness of ischemia testing (mainly coronary angiography) in patients presenting with monomorphic VT through 8 selected studies after evaluating a total of 130 published manuscripts. Particularly, we sought to unveil whether coronary angiography and possibly concomitant revascularization leads to lesser tachycardia recurrence. Our conclusion can be summarized as follows: this approach whether combined with revascularization or not, does not seem to reduce VT recurrence nor does it affect mortality in such patients. Even though most of the published literature points at this direction, validation from randomized controlled trials is imperative.
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Angiografia Coronária , Isquemia Miocárdica , Revascularização Miocárdica , Taquicardia Ventricular , Humanos , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/cirurgia , Revascularização Miocárdica/métodos , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatologia , Angiografia Coronária/métodosRESUMO
Background Clinical and translational research suggests that mineralocorticoid receptor antagonists (MRAs) may prevent atrial fibrosis and electrical remodeling associated with atrial fibrillation (AF). This study aimed to consolidate existing evidence from randomized controlled trials (RCTs) evaluating the effect of MRAs on incident or recurrent AF. Methods Medline, Cochrane Library and Scopus were searched until February 12, 2024. Triple-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using both pairwise and Bayesian and frequentist network meta-analyses. Results Twenty-three RCTs (13,358 participants) were identified. Based on the pairwise random effects meta-analysis, MRAs were associated with a significant reduction in AF events compared to placebo or usual care (risk ratio {RR}= 0.75; 95% confidence interval {CI}= [0.66, 0.87]; P< 0.001; I2= 3%). This protective effect was robust both for new-onset and recurrent AF episodes (subgroup p-value= 0.69), while the baseline HF status was not a significant effect modifier (subgroup p-value= 0.58). MRAs demonstrated a significantly higher reduction in AF events for patients with chronic renal disease compared to placebo (RR= 0.78; 95% CI= [0.62, 0.98]; P= 0.03; I2= 0%). The network meta-analyses revealed that only spironolactone was associated with a significant reduction in AF events (Bayesian RR= 0.76; 95% CI= [0.65, 0.89]; P< 0.001; level of evidence moderate; SUCRA 0.731), while eplerenone and finerenone showed a neutral effect. Conclusion MRAs confer a significant benefit in terms of reducing incident or recurrent AF episodes, irrespective of HF status. In this context, spironolactone may be preferable compared to eplerenone or finerenone.
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Fibrilação Atrial , Teorema de Bayes , Antagonistas de Receptores de Mineralocorticoides , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Humanos , Fibrilação Atrial/tratamento farmacológico , Recidiva , Resultado do TratamentoRESUMO
INTRODUCTION: Several randomized controlled trials (RCTs) have examined mineralocorticoid receptor antagonists (MRAs) in heart failure (HF) with reduced ejection fraction (HFrEF). This systematic review and network meta-analysis (NMA) evaluated the comparative efficacy and safety of MRAs in HFrEF. MATERIALS AND METHODS: MEDLINE(Pubmed), Scopus, Cochrane and ClinicalTrials.gov were searched until April 8, 2024 for RCTs examining the efficacy and/or safety of MRAs in HFrEF. Double-independent study selection, extraction and quality assessment were performed. Random-effects frequentist NMA models were used. Evidence certainty was assessed via Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Totally, 32 RCTs (15685 patients) were analyzed. Eplerenone ranked above spironolactone in all-cause mortality (hazard ratio {HR}=0.78, 95% confidence interval {CI} [0.66,0.91], GRADE:"Moderate"), cardiovascular death (HR=0.74, 95%CI [0.53, 1.04], GRADE:"Low") and in all safety outcomes. Spironolactone was superior to eplerenone in the composite of cardiovascular death or hospitalization (HR=0.67, 95%CI [0.50,0.89], GRADE:"Moderate"), HF hospitalization (HR=0.61, 95%CI [0.43,0.86], GRADE:"Moderate"), all-cause hospitalization (HR=0.51, 95%CI [0.26,0.98], GRADE:"Moderate") and cardiovascular hospitalization (HR=0.56, 95%CI [0.37,0.84], GRADE:"Moderate"). Canrenone ranked first in all-cause mortality, the composite outcome and HF hospitalization. Finerenone ranked first in hyperkalemia (risk ratio [RR]=1.56, 95%CI [0.89,2.74], GRADE:"Moderate"), renal injury (RR=0.56, 95%CI [0.24,1.29]), any adverse event (RR=0.84, 95%CI [0.75,0.94], GRADE:"Moderate"), treatment discontinuation (RR=0.89, 95%CI [0.64,1.23]) and hypotension (RR=1.06, 95%CI [0.12,9.41]). CONCLUSIONS: MRAs are effective in HFrEF with certain safety disparities. Spironolactone and eplerenone exhibited similar efficacy, however, eplerenone demonstrated superior safety. Finerenone was the safest MRA, while canrenone exhibited considerable efficacy, nonetheless, evidence for these MRAs were scarce.
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Insuficiência Cardíaca , Antagonistas de Receptores de Mineralocorticoides , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Volume Sistólico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Volume Sistólico/fisiologia , Volume Sistólico/efeitos dos fármacos , Espironolactona/uso terapêutico , Espironolactona/análogos & derivados , Espironolactona/efeitos adversos , Eplerenona/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: To provide a descriptive insight into the different types of research questions/objectives and associated methodologies of overviews of reviews, supplemented by representative examples from the health care literature. STUDY DESIGN AND SETTING: We searched in methodological articles for information on types and methodologies used in overviews and we explored the typology of reviews to identify similar types in literature of overviews. We categorized the types of overviews based on the research question/objective and the methodological approach used. Indicative examples for each category were selected from a sample of 2,121 overviews that were retrieved between 2000 and 2022 from MEDLINE, Scopus, and Cochrane Database of Systematic Reviews. RESULTS: Based on type of research question, overviews were classified as overviews of reviews of interventions, associations, prediction, diagnostic accuracy, prevalence/incidence, experiences/views, economic evaluation, and measurement properties. Based on the methodological approach, we identified a variety of methods (systematic, living, rapid, scoping, evidence mapping, framework, and methodological) used in overviews. CONCLUSION: The proposed classification and examples provide an essential starting point for future theory-building research on typologies and study designs of overviews of reviews. It is important for methodologists to make vigorous effort to create consensus-based methodological and reporting guidelines to cover these diverse types and key methodological challenges.
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Publicações , Projetos de Pesquisa , Humanos , Revisões Sistemáticas como Assunto , Atenção à SaúdeRESUMO
Currently, the guidelines for the prevention of atherosclerosis in patients with antiphospholipid syndrome (APS) do not differ substantially from those in the general population. We aimed to assess the risk of subclinical atherosclerosis in patients with APS and subjects with antiphospholipid antibody (aPL) positivity. Systematic literature search was conducted through Medline and Scopus until January 2023. Random effects meta-analyses were performed to examine the differences in markers of subclinical atherosclerosis between APS patients, subjects positive for aPLs and healthy controls. Patients with APS had significantly higher values of common carotid artery (CCA) intima-media thickness (IMT) (MDâ¯=â¯0.07 mm; P < 0.0001), internal carotid artery IMT (MDâ¯=â¯0.06 mm; P < 0.01), carotid bifurcation IMT (MDâ¯=â¯0.14 mm; P < 0.01) and were more frequently diagnosed with atherosclerotic plaques compared to controls (ORâ¯=â¯3.73; P < 0.01). Similarly, APS patients showed a decreased flow and nitrate-mediated dilation (MDâ¯=â¯-4.52 %; <0.01, MDâ¯=â¯-1.25 %; P < 0.05, respectively). Interestingly, comparable were the results for subjects with aPL positivity, who had higher CCA-IMT (MDâ¯=â¯0.06 mm; P < 0.01) and higher prevalence of atherosclerotic plaques (ORâ¯=â¯2.59; Pâ¯=â¯0.08) compared to controls. Sensitivity analysis conducted on primary APS patients revealed that the risk of atherosclerosis is associated with APS per se and is not exclusively driven by other underlying conditions. Patients with APS and subjects with aPLs have an increased risk of subclinical atherosclerosis and require early and disease-specific prevention of atherosclerosis.
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Síndrome Antifosfolipídica , Aterosclerose , Placa Aterosclerótica , Humanos , Síndrome Antifosfolipídica/complicações , Espessura Intima-Media Carotídea , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Anticorpos Antifosfolipídeos , Fatores de RiscoRESUMO
OBJECTIVES: This study aimed to evaluate the epidemiology, reporting characteristics, and adherence to the Preferred Reporting Items for Overviews of Reviews (PRIOR) statement of overviews of reviews (overviews) of interventions in the cardiovascular field. STUDY DESIGN AND SETTING: MEDLINE, Scopus, and the Cochrane Database of Systematic Reviews were searched from January 1, 2000, to October 15, 2020. An updated search was performed in MEDLINE, Epistemonikos, and Google Scholar up to August 25, 2022. Overviews of interventions published in English and primarily considering populations, interventions, and outcomes pertinent to the cardiovascular field were eligible. Study selection, data extraction, and PRIOR adherence assessment were performed by two authors independently. RESULTS: We analyzed 96 overviews. Almost half (43/96 [45%]) were published between 2020 and 2022 and contained a median of 15 systematic reviews (SRs) (interquartile range, 9-28). The commonest title terminology was "overview of (systematic) reviews" (38/96 [40%]). Methods for handling SR overlap were reported in 24/96 (25%), methods for assessing primary study overlap in 18/96 (19%), handling of discrepant data in 11/96 (11%), and methods for methodological quality or risk of bias assessment of the primary studies within SRs in 23/96 (24%). Authors included data sharing statements in 28/96 (29%), complete funding disclosure in 43/96 (45%), protocol registration in 43/96 (45%), and conflict of interest statement in 82/96 (85%) overviews. CONCLUSION: Insufficient reporting was identified in methodological characteristics unique in overviews' conduct and most transparency markers. Adoption of PRIOR from the research community could ameliorate overviews' reporting.
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Publicações , Humanos , Revisões Sistemáticas como Assunto , ViésRESUMO
AIMS: The present systematic review aimed to synthesize available data from recently published randomized trials (RCTs) investigating the efficacy and safety of the novel, orally administered, small-molecule glucagon-like peptide 1 receptor agonists (GLP-1RAs) orforglipron and danuglipron for the treatment of type 2 diabetes mellitus (T2DM), obesity or both. METHODS: Literature search was performed through Medline (via PubMed), Cochrane Library and Scopus until August 16, 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with random effects meta-analysis. RESULTS: Totally, 1037 patients among seven RCTs were analyzed. All RCTs had low risk of bias according to the Cochrane Collaboration tool (RoB2). Novel GLP-1RAs led to significant reduction in HbA1c in patients with T2DM compared to controls (MD = -1.03 %; 95 % CI = [-1.29, -0.77]; P < 0.001). A significantly greater weight reduction was also noted both in patients with T2DM or obesity compared to controls (MD = -3.26 kg; 95 % CI = [-4.79, -1.72]; P < 0.001 and MD = -7.52 kg; 95 % CI = [-14.63, -0.41]; P = 0.038, respectively; P for subgroup differences = 0.25). Regarding safety, novel GLP-1RAs showed a neutral effect on the odds of severe hypoglycemia or serious adverse events (OR = 0.34; 95 % CI = [0.09, 1.31]; P = 0.11 and OR = 0.95; 95 % CI = [0.39, 2.34]; P = 0.91, respectively) and significantly higher odds of gastrointestinal, treatment-emergent adverse events (OR = 2.57; 95 % CI = [1.49, 4.42]; P < 0.001) and adverse events leading to discontinuation (OR = 2.89; 95 % CI = [1.22, 6.87]; P = 0.016). CONCLUSION: Preliminary evidence supports that orforglipron and danuglipron are efficient in glycemic control and weight reduction in T2DM, obesity or both. More longitudinal research is warranted in order to provide deeper insights into their efficacy, safety and tolerability before their potential incorporation in the pharmacological arsenal against T2DM or obesity.
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Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Hipoglicemiantes/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Obesidade/tratamento farmacológico , Redução de PesoRESUMO
The present systematic review and meta-analysis aimed to investigate the prognostic value of stress hyperglycemia ratio (SHR) in patients with acute myocardial infarction (AMI). A total of 26 cohort studies, involving 87,974 patients, were analyzed. The frequentist meta-analysis showed that AMI patients with SHR in the upper quantile had a significantly higher hazard of major adverse cardiovascular and cerebrovascular events (MACCE, HR = 1.7; 95 % CI= [1.42, 2.03]; P < 0.001; I2 = 71 %; P <0.01), long-term (HR = 1.64; 95 % CI= [1.49, 1.8]; P < 0.001; I2 = 16 %; P = 0.29) and in-hospital all-cause mortality (OR = 3.87; 95 % CI= [2.98, 5.03]; P < 0.001; I2 = 54 %; P = 0.03) compared to those with lower SHR. Prespecified subgroup analyses revealed that these results were consistent irrespective of diabetes status (P = 0.32 and 0.73 for subgroup differences) and that SHR was a significant predictor of MACCE both in AMI with obstructive coronary arteries (HR = 1.57; 95 % CI= [1.34, 1.83]; P < 0.001; I2 = 66 %; P < 0.01) and MINOCA (HR = 2.57; 95 % CI= [1.86, 3.56]; P < 0.001; I2 = 0 %; P = 0.84). The Bayesian analyses with weakly prior assumptions yielded comparable results with the frequentist approach and provided strong evidence that higher SHR values were associated with significantly greater hazard of MACCE, short-term and long-term mortality. Further, prospective research is warranted to provide deeper insights into this newer index of stress hyperglycemia before its potential incorporation in clinical prediction scores.
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Objective Multiple systematic reviews (SR) have been performed on the effects of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), often providing conflicting findings. This overview and network meta-analysis (NMA) aimed to summarize SR findings on the efficacy and safety of PCSK9i and provide an updated NMA. Materials and methods MEDLINE (Pubmed), Scopus, Cochrane, Epistemonikos and Google Scholar were searched from inception to September 21, 2023 for SRs of randomized controlled trials (RCTs) and from January 1, 2020 to September 21, 2023 for additional RCTs. Double-independent study selection, data extraction and quality assessment were performed. Qualitative analysis was performed for SRs and a frequentist random-effects model NMA was performed for RCTs. Results Totally, 86 SRs and 76 RCTs were included. Alirocumab (77/86 [90%]) and evolocumab (73/86 [85%]) were mostly analyzed. Associations from SRs (35/42 [83%]) and the updated NMA indicated PCSK9i benefit on major adverse cardiovascular events (MACEs). Reductions were also noted for cerebrovascular events (47/66 [71%]), coronary revascularization (29/33 [88%]) and myocardial infarction (41/63 [65%]). Alirocumab was associated with reductions on all-cause mortality (RR=0.82, 95%CI [0.72,0.94]). Data on any CV event reduction were conflicting (7/16 [44%]). Inclisiran appeared effective only on MACEs (RR=0.76, 95%CI [0.61,0.94]). No reductions in heart failure were observed (0/16). No increases were identified between PCSK9i and any (0/35) or serious adverse events (0/52). However, PCSK9i were associated with injection-site reactions (20/28 [71%]). Conclusion PCSK9i appeared to be effective in CV outcomes and their clinical application was generally safe. (AU)
Objetivo Las revisiones sistemáticas (RS) sobre los efectos de los inhibidores de la proproteína convertasa subtilisina/kexina tipo 9 (PCSK9i), presentan resultados contradictorios. Esta revisión general y metaanálisis en red (MER) tiene como objetivo resumir los hallazgos sobre la eficacia y seguridad de los PCSK9i. Materiales y métodos Se realizaron búsquedas en MEDLINE (PubMed), Scopus, Cochrane, Epistemonikos y Google Scholar desde sus inicios hasta el 21 de septiembre de 2023 para las RS de ensayos controlados aleatorios (ECA) y desde el 1 de enero de 2020 hasta 21 de septiembre de 2023 para los ECA adicionales. La selección de estudios, extracción de datos y evaluación de calidad se llevaron a cabo de manera doble e independiente. Se realizó un análisis cualitativo de las SR y un modelo de efectos aleatorios frecuentistas MER para los ECA. Resultados En total, se incluyeron 86 SR y 76 RCT. Alirocumab (77/86 [90%]) y evolocumab (73/86 [85%]) fueron los más analizados. Se reconocieron beneficios de los PCSK9i en eventos cardiovasculares adversos mayores (ECVAM), reducción de eventos cerebrovasculares (47/66 [71%]), revascularización coronaria (29/33 [88%]) e infartos de miocardio (41/63 [65%]). Alirocumab redujo la mortalidad por todas las causas (RR: 0,82; IC del 95%: 0,72-0,94). Los resultados sobre la reducción de cualquier evento cardiovascular (CV) fueron contradictorios (7/16 [44%]). Inclisiran pareció ser efectivo solo en la reducción de ECVAM (RR: 0,76; IC del 95%: 0,61-0,94). No se observaron reducciones en insuficiencia cardíaca (0/16) o relación con eventos adversos serios (0/52). Sin embargo, se asociaron con reacciones en el lugar de la inyección (20/28 [71%]). (AU)