Cardiovascular Outcomes of Sodium-Glucose Cotransporter-2 Inhibitors Therapy in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Systematic Review and Updated Meta-Analysis.

BACKGROUND AND OBJECTIVES: The efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) may depend on renal function, and this raises theoretical concern over its effects on cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). METHODS: This systematic review and updated meta-analysis of randomized controlled trials (RCTs) compared cardiovascular outcomes of patients with T2DM and CKD treated with SGLT2i to placebo. PubMed, Embase, and Cochrane were systematically searched. Prespecified subgroup analyses were performed in strata of estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m² and 45 to 59 mL/min/1.73 m². RESULTS: Nine RCTs comprising 29,146 patients were selected. Average follow-up ranged from 0.75 to 4.2 years. SGLT2i were shown to reduce the risk of all-cause mortality (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79-0.97; p=0.01), the composite of cardiovascular mortality or hospitalizations for heart failure (HHF: HR, 0.71; 95% CI, 0.65-0.78; p<0.001), cardiovascular mortality (HR, 0.86; 95% CI, 0.76-0.98; p=0.02), HHF (HR, 0.62; 95% CI, 0.55-0.71; p<0.001), major adverse cardiovascular events (HR, 0.85; 95% CI, 0.77-0.94; p=0.002), stroke (HR, 0.76; 95% CI, 0.59-0.97; p=0.03), and myocardial infarction (HR, 0.78; 95% CI, 0.67-0.91; p=0.001). These findings were consistent over strata of eGFR, albeit with a lower incidence of stroke in patients treated with SGLT2i with eGFR <45 mL/min/1.73 m² (p-value for interaction=0.04). CONCLUSIONS: Compared with a placebo, patients with T2DM and CKD treated with SGLT2i experience a reduction in all-cause mortality, cardiovascular mortality, and HHF. TRIAL REGISTRATION: PROSPERO Identifier: CRD42023401081.

Once-weekly insulin icodec versus once-daily long-acting insulins for type 2 diabetes mellitus: Systematic review and meta-analysis.

Background: Insulin icodec is a novel, long-acting, once-weekly basal insulin analog. Its comparative efficacy and safety with basal once-daily insulins in type 2 diabetes mellittus is uncertain. Objective: Evaluate potential efficacy, benefits and risks associated with icodec compared to once-daily basal insulin analogs (degludec or glargine). Methods: We systematically searched PubMed, Cochrane, and Embase for randomized controlled trials (RCTs) published until June 2023 comparing icodec versus long-acting insulin analogs (degludec and glargine) in type 2 diabetes mellitus (T2DM) with at least 12 weeks of follow-up. Binary endpoints were assessed with risk ratios (RRs) and continuous endpoints were compared using mean differences (MDs), with 95% confidence intervals (CIs). The protocol was registered in PROSPERO (CRD42023452468). Results: A total of seven RCTs and 3286 patients with T2DM were included, of whom 1509 (60.6%) received icodec treatment. The follow-up period ranged from 16 to 78 weeks. Compared with once-daily basal insulin analogs, icodec led to a greater improvement in HbA1c (MD -0.15%; 95% CI -0.21, -0.10; p < 0.0001; I2 = 0%) and time in range (TIR) (MD 2.83%; 95%CI 0.94; 4.71; p = 0.003; I2 = 22%). Body weight was increased with icodec treatment (MD 0.78 Kg; 95%CI 0.42, 1.15; p < 0.01; I2 = 86%). There was also a higher rate of injection site reactions (RR 1.89; 95%CI 1.12, 3.18; p = 0.016; I2 = 0%) and nasopharyngitis (RR 1.94; 95%CI 1.11, 3.38; p = 0.020; I2 = 0%) in the icodec group, compared with once-daily regimens. There was no significant difference between groups in fasting plasma glucose. Conclusions: In this meta-analysis of RCTs, insulin icodec led to better control of HbA1c and TIR as compared with once-daily insulin regimens, albeit with increased weight gain and a higher rate of injection site reaction in the Icodec group.

Impact of periprocedural myocardial injury after transcatheter aortic valve implantation on long-term mortality: a meta-analysis of Kaplan-Meier derived individual patient data.

Background: Periprocedural myocardial injury (PPMI) frequently occurs after transcatheter aortic valve implantation (TAVI), although its impact on long-term mortality is uncertain. Methods: We performed a pooled analysis of Kaplan-Meier-derived individual patient data to compare survival in patients with and without PPMI after TAVI. Flexible parametric models with B-splines and landmark analyses were used to determine PPMI prognostic value. Subgroup analyses for VARC-2, troponin, and creatine kinase-MB (CK-MB)-defined PPMI were also performed. Results: Eighteen observational studies comprising 10,094 subjects were included. PPMI was associated with lower overall survival (OS) after two years (HR = 1.46, 95% CI 1.30-1.65, p < 0.01). This was also observed when restricting the analysis to overall VARC-2-defined PPMI (HR = 1.23, 95% CI 1.07-1.40, p < 0.01). For VARC-2 PPMI criteria and VARC-2 troponin-only, higher mortality was restricted to the first 2 months after TAVI (HR = 1.64, 95% CI 1.31-2.07, p < 0.01; and HR = 1.32, 95% CI 1.05-1.67, p = 0.02, respectively), while for VARC-2 defined CK-MB-only the increase in mortality was confined to the first 30 days (HR = 7.44, 95% CI 4.76-11.66, p < 0.01). Conclusion: PPMI following TAVI was associated with lower overall survival compared with patients without PPMI. PPMI prognostic impact is restricted to the initial months after the procedure. The analyses were consistent for VARC-2 criteria and for both biomarkers, yet CK-MB was a stronger prognostic marker of mortality than troponin.

Coronary Computed Tomography Angiography Versus Invasive Coronary Angiography in Stable Chest Pain: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The efficacy of coronary computed tomography angiography (CCTA) versus invasive coronary angiography (ICA) among patients with stable chest pain has been studied in several trials with conflicting results. METHODS: We performed a systematic review and meta-analysis comparing CCTA first versus direct ICA among patients with stable chest pain, who were initially referred to ICA. PubMed, EMBASE, and Cochrane Central were searched for randomized controlled trials comparing the 2 strategies. Risk ratios (RRs) and mean differences with 95% CIs were computed for binary and continuous outcomes, respectively. RESULTS: Five randomized controlled trials with a total of 5727 patients were included, of whom 51.1% were referred to CCTA and 22.5% of patients had evidence of ischemia on a prior functional test. In the follow-up ranging from 1 to 3.5 years, 660 of the 2928 patients randomized to CCTA first underwent ICA (23%). Patients who underwent CCTA had lower rates of coronary revascularization (RR, 0.74 [95% CI, 0.66-0.84]; P<0.001) and stroke (RR, 0.50 [95% CI, 0.26-0.98]; P=0.043). Cardiovascular mortality (RR, 0.55 [95% CI, 0.24-1.23]; P=0.146), major adverse cardiovascular events (RR, 0.84 [95% CI, 0.64-1.10]; P=0.198), nonfatal myocardial infarction (RR, 1.09 [95% CI, 0.63-1.88]; P=0.768), and cardiovascular hospitalizations (RR, 0.91 [95% CI, 0.59-1.39]; P=0.669) did not differ significantly between groups. CONCLUSIONS: In patients with stable chest pain referred for ICA, CCTA avoided the need for ICA in 77% of patients otherwise referred for ICA. CCTA was associated with a reduction in the rates of coronary revascularization and stroke compared with direct ICA. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42023383143.

Angiotensin Receptor-Neprilysin Inhibitor Effects on Atherosclerotic Cardiovascular Disease Events: A Meta-Analysis of Randomized Controlled Trials.

Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) associated with a decreased risk of death and hospitalization for selected patients with heart failure (HF). However, its association with improved atherosclerotic cardiovascular disease (ASCVD) events remains unclear. We performed a meta-analysis to evaluate the association of ARNI with ASCVD events in patients with HF. We systematically searched PubMed, Embase, Cochrane, and ClinicalTrials.gov for studies comparing ARNIs with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in terms of myocardial infarction, stroke, angina pectoris, peripheral artery disease, and the composite end point in patients with HF. A total of 8 randomized controlled trials were included, with 17,541 patients assigned to either the ARNI (8,764 patients) or ACEi/ARB (8,777 patients) groups. The incidence of composite end point (risk ratio [RR] 1.03, 95% confidence interval [CI] 0.93 to 1.13, p = 0.63), myocardial infarction (RR 1.02, 95% CI 0.81 to 1.30, p = 0.85), angina pectoris (RR 0.96, 95% CI 0.80 to 1.17, p = 0.70), and stroke (RR 0.99, 95% CI 0.85 to 1.16, p = 0.93) were not statistically different between the ARNI and ACEi/ARB groups. However, ARNI was associated with a higher incidence of peripheral artery disease (RR 1.63, 95% CI 1.05 to 2.52, p = 0.03). In conclusion, this meta-analysis found no association between ARNI therapy and improved ASCVD events in patients with HF.

Once-Weekly Insulin Icodec vs. Once-Daily Insulin Glargine U100 for type 2 diabetes: a systematic review and meta-analysis of phase 2 randomized controlled trials.

Objective: Insulin Icodec is a novel basal insulin analogue designed for once-weekly administration, therefore might propitiate reduction in the frequency of injections and facilitate treatment adherence. This study aimed to determine the glycemic control and safety profile of Insulin Icodec, compared with Glargine U100 in patients with diabetes mellitus type 2. Materials and methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCT) data comparing OnceWeekly Insulin Icodec and Once-Daily Insulin Glargine U100 in patients with type 2 diabetes mellitus. PubMed, Embase, and Cochrane databases were searched for trials published up to May 14, 2022. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Results: Three studies were included comprising 453 patients, 230 (50.77%) using Once-Weekly Insulin Icodec and 223 (49.22%) using Once-Daily Insulin Glargine U100. In the pooled data, Glycated Hemoglobin (MD -0.20% CI -0.33 to -0.07%; P=0.002) change from baseline demonstrated a significantly higher reduction in the Icodec group. Time with Glucose in Range (MD 6.60% CI 3.63 to 9.57%; P < 0.0001) and Insulin Dose Difference (MD 0.97UI CI 0.76 to 1.18UI; P < 0.0001) were higher in the Icodec group. There was no significant difference in fasting plasma glucose, body weight change, hypoglycemia or any adverse event evaluated. Conclusion: OnceWeekly Insulin Icodec was associated with a small reduction in Glycated Hemoglobin, as well as higher Time with Glucose in Range, with similar hypoglycemic adverse events, when compared with Once-Daily Insulin Glargine U100.

Desafios na Atividade Laboral de Pacientes em Hemodiálise e sua Associação com a Qualidade de Vida / Work Activity Challenges among Hemodialysis Patients and Their Impact on Quality of Life

Grande parte dos pacientes em hemodiálise estão em idade laboral, acarretando um desafio na manutenção do seu trabalho. Realizou-se um estudo transversal em centros de hemodiálise no norte de Santa Catarina, entre dezembro de 2020 a fevereiro de 2021. Incluiu-se pacientes entre 18 e 55 anos em hemodiálise há mais de 3 meses. Avaliou-se aspectos relacionados ao trabalho, sua manutenção após início da hemodiálise e a qualidade de vida através do instrumento SF-36. A condição laboral foi avaliada com relação a qualidade de vida através de regressão logística. Dos 108 pacientes, a média de idade foi 43,34 ±8,88 anos, com mediana do tempo em diálise de 19 meses. Dos participantes, 78,9% estavam trabalhando seis meses antes do início da hemodiálise e 39,8% após 6 meses. Não houve diferença em relação ao sexo, idade e estado civil com relação ao trabalho antes ou após 6 meses do início da hemodiálise. Trabalhar foi associado a uma maior qualidade de vida, mesmo após ajuste para outras variáveis (OR=5,30; 95% IC 1,43-19,61, p=0,013). Conclui-se que existe importante queda da manutenção do emprego após início da hemodiálise. O estímulo a manutenção do trabalho pode favorecer uma melhor qualidade de vida nestes pacientes.

Most patients undergoing hemodialysis are of working age, and this poses a challenge in maintaining their jobs. A crosssectional study was carried out in hemodialysis centers in the north of Santa Catarina, between December 2020 and February 2021. Patients aged between 18 and 55 years old on hemodialysis for more than 3 months were included. Aspects related to work, remaining at their job after starting hemodialysis, and quality of life were evaluated using the SF-36 instrument. Their working situation was evaluated in relation to quality of life through logistic regression. Of the 108 patients, the mean age was 43.34 ± 8.88 years old, with a median time on dialysis of 19 months. Of the participants, 78.9% were working six months before starting hemodialysis and 39.8% were working 6 months after. There was no difference in terms of sex, age, and marital status with regards to work before or after 6 months of starting hemodialysis. Working was associated with a better quality of life, even after adjusting for other variables (OR=5.30; 95% CI 1.43-19.61, p=0.013). It is concluded that there is a significant drop in employment after starting hemodialysis. The stimulus to keep working can favor a better quality of life in these patients.

Once-Weekly Insulin Icodec vs. Once-Daily Insulin Glargine U100 for type 2 diabetes: a systematic review and meta-analysis of phase 2 randomized controlled trials

ABSTRACT Objective: Insulin Icodec is a novel basal insulin analogue designed for once-weekly administration, therefore might propitiate reduction in the frequency of injections and facilitate treatment adherence. This study aimed to determine the glycemic control and safety profile of Insulin Icodec, compared with Glargine U100 in patients with diabetes mellitus type 2. Materials and methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCT) data comparing Once-Weekly Insulin Icodec and Once-Daily Insulin Glargine U100 in patients with type 2 diabetes mellitus. PubMed, Embase, and Cochrane databases were searched for trials published up to May 14, 2022. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Results: Three studies were included comprising 453 patients, 230 (50.77%) using Once-Weekly Insulin Icodec and 223 (49.22%) using Once-Daily Insulin Glargine U100. In the pooled data, Glycated Hemoglobin (MD -0.20% CI -0.33 to -0.07%; P=0.002) change from baseline demonstrated a significantly higher reduction in the Icodec group. Time with Glucose in Range (MD 6.60% CI 3.63 to 9.57%; P < 0.0001) and Insulin Dose Difference (MD 0.97UI CI 0.76 to 1.18UI; P < 0.0001) were higher in the Icodec group. There was no significant difference in fasting plasma glucose, body weight change, hypoglycemia or any adverse event evaluated. Conclusions: Once-Weekly Insulin Icodec was associated with a small reduction in Glycated Hemoglobin, as well as higher Time with Glucose in Range, with similar hypoglycemic adverse events, when compared with Once-Daily Insulin Glargine U100.