[Statins and influenza mortality: systematic review and meta-analysis]. / Estatinas y mortalidad por influenza: revisión sistemática y meta-análisis.

BACKGROUND: Due to their anti-inflammatory properties, it has been suggested that the use of statins could influence the evolution of influenza virus infection. AIM: To evaluate the effect of statin therapy on mortality from influenza. METHODS: A meta-analysis that included studies evaluating the use of statins in patients with influenza and reporting data on mortality, after searching the PubMed/MEDLINE, Embase, and Cochrane Controlled Trials databases, was performed. A random effects model was applied. The risk of bias was analyzed and a sensitivity analysis was performed. RESULTS: Eight studies (10 independent cohorts), which included a total of 2,390,730 patients, were identified and eligible for analysis. A total of 1,146,995 subjects analyzed received statins, while 1,243,735 subjects were part of the control group. Statin therapy was associated with lower mortality (OR: 0.66; 95% CI: 0.51-0.85). The sensitivity analysis showed that the results were robust. CONCLUSION: Our data suggest that, in a population with influenza, the use of statins was associated with a significant reduction in mortality. These results must be confirmed in future clinical trials.

Estatinas y mortalidad por influenza: revisión sistemática y meta-análisis / Statins and influenza mortality: systematic review and meta-analysis

INTRODUCCIÓN: Debido a sus propiedades antiinflamatorias, se ha planteado que el uso de las estatinas podría influir en la evolución de la infección por el virus de influenza. OBJETIVO: Evaluar el efecto de la terapia con estatinas sobre la mortalidad por influenza. MATERIAL y MÉTODOS: Se realizó un meta-análisis que incluyó estudios que evaluaron el uso de estatinas en pacientes con influenza e informaron los datos sobre mortalidad, después de buscar en las bases de datos PubMed/MEDLINE, Embase y Cochrane Controlled Trials. Se aplicó un modelo de efectos aleatorios. Se analizó el riesgo de sesgos y se desarrolló un análisis de sensibilidad. RESULTADOS: Se identificaron y se consideraron elegibles para el análisis ocho estudios (diez cohortes independientes), que incluyeron un total de 2.390.730 de pacientes. Un total de 1.146.995 de sujetos analizados recibieron estatinas mientras que 1.243.735 de sujetos formaron parte del grupo control. La terapia con estatinas se asoció con una menor mortalidad (OR: 0,66; IC 95%: 0,51-0,85). El análisis de sensibilidad mostró que los resultados fueron robustos. CONCLUSIONES: Nuestros datos sugieren que, en una población con influenza, el uso de estatinas se asoció con una reducción significativa de la mortalidad. Estos resultados deben confirmarse en futuros ensayos clínicos.

BACKGROUND: Due to their anti-inflammatory properties, it has been suggested that the use of statins could influence the evolution of influenza virus infection. AIM: To evaluate the effect of statin therapy on mortality from influenza. METHODS: A meta-analysis that included studies evaluating the use of statins in patients with influenza and reporting data on mortality, after searching the PubMed/MEDLINE, Embase, and Cochrane Controlled Trials databases, was performed. A random effects model was applied. The risk of bias was analyzed and a sensitivity analysis was performed. RESULTS: Eight studies (10 independent cohorts), which included a total of 2,390,730 patients, were identified and eligible for analysis. A total of 1,146,995 subjects analyzed received statins, while 1,243,735 subjects were part of the control group. Statin therapy was associated with lower mortality (OR: 0.66; 95% CI: 0.51-0.85). The sensitivity analysis showed that the results were robust. CONCLUSION: Our data suggest that, in a population with influenza, the use of statins was associated with a significant reduction in mortality. These results must be confirmed in future clinical trials.

Effectiveness of Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy on Lipid Levels in Type 2 Diabetes: a Meta-analysis.

INTRODUCTION: Obesity and its co-morbidities, including type 2 diabetes (T2DM) and dyslipidemia, are accompanied by excess cardiovascular morbi-mortality. Aside from excess low density lipoprotein-cholesterol (LDL-C), atherogenic dyslipidemia (AD), mainly characterized by elevated triglycerides and decreased high density lipoprotein-cholesterol (HDL-C) levels, is often present in T2DM obese patients. Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), has become a reference treatment in that population. However, the respective effects of RYGB vs SG on lipid metabolism in T2DM patients have been rarely studied. METHODS: A meta-analysis of randomized controlled trials, comparing the effects of RGYBG vs SG on lipid metabolism 12 months after surgery in T2DM patients, was performed. RESULTS: Four studies including a total of 298 patients (151 patients in the RYGB and 147 patients in the SG group) were examined. Despite a greater decrease in body mass index and greater improvement in glycemic control in RYGB compared to SG. RYGB vs SG was more effective in reducing total cholesterol, LDL-C, and non-HDL-C levels (mean difference [MD] -26.10 mg/dL, 95 % CI -38.88 to -13.50, p<0.00001; [MD] -20.10 mg/dL, 95 % CI -27.90 to -12.20, p<0.00001 and MD 31.90 mg/dl, 95 % CI -46.90 to -16.80, p<0.00001, respectively). CONCLUSIONS: The superiority of RYGB vs SG in reducing LDL-C, with an effect comparable to a moderate-intensity statin, suggests RYBG should be favored in hypercholesterolemic T2DM patients in order to further reduce cardiovascular risk.

Elevated lipoprotein (a) levels and risk of peripheral artery disease outcomes: A systematic review.

BACKGROUND: Despite strong association of elevated lipoprotein (a) (Lp(a)) levels with incident coronary and cerebrovascular disease, data for incident peripheral artery disease (PAD) are less robust. The main objective of the present systematic review was to analyze the association between elevated Lp(a) levels and PAD outcomes. METHODS: This systematic review was performed according to PRISMA guidelines. A literature search was performed to detect randomized clinical trials or observational studies with a cohort design that evaluated the association between Lp(a) levels and PAD outcomes. RESULTS: Fifteen studies including 493,650 subjects were identified and considered eligible for this systematic review. This systematic review showed that the vast majority of the studies reported a significant association between elevated Lp(a) levels and the risk of PAD outcomes. The elevated Lp(a) levels were associated with a higher risk of incident claudication (RR: 1.20), PAD progression (HR: 1.41), restenosis (HR: 6.10), death and hospitalization related to PAD (HR: 1.37), limb amputation (HR: 22.75), and lower limb revascularization (HR: 1.29 and 2.90). In addition, the presence of elevated Lp(a) values were associated with a higher risk of combined PAD outcomes, with HRs in a range between 1.14 and 2.80, despite adjusting for traditional risk factors. Heterogeneity of results can be explained by different patient populations studied and varying Lp(a) cut-off points of Lp(a) analyzed. CONCLUSION: This systematic review suggests that evidence is available to support an independent positive association between Lp(a) levels and the risk of future PAD outcomes. PROSPERO Registration No.: 289253.

Prognostic role of cardiopulmonary exercise testing in pulmonary hypertension: a systematic review and meta-analysis.

INTRODUCTION: Several studies have evaluated the relation between variables of cardiopulmonary exercise testing (CPET) and major clinical events in pulmonary hypertension (PH) patients, although the results were conflicting. The main objective of this study was to investigate the prognostic value of the CPET derived parameters on all-cause mortality or urgent transplantation in PH patients. MATERIAL AND METHODS: A meta-analysis of time-to-event outcomes were performed from observational studies that evaluated the predictive value of CEPT-related variables [peak oxygen uptake (VO2) and the ventilation to CO2 production slope (VE/VCO2)] in PH patients, reporting data from mortality or urgent transplantation, after searching the PubMed/MEDLINE, Embase, Science Direct, Scopus, Google Scholar, and Cochrane databases. A random-effects meta-analysis model was then applied. RESULTS: Nine eligible studies, including 986 patients, were identified and considered eligible for the quantitative analyses. This meta-analysis showed that high peak VO2 was associated with a lower mortality or transplant occurrence (HR: 0.81; 95% CI: 0.78-0.85, I2 = 29%). In addition, high VE/VCO2 slope was associated with a higher incidence of the primary endpoint (HR: 1.04; 95% CI: 1.02-1.06, I2 = 78%). The sensitivity analysis showed that the results were robust. CONCLUSIONS: Our data suggest that in a population with PH the CPET-related variables have predictive capacity regarding mortality and the risk of transplantation. Future studies should establish the best cut-off points for these CPET-related variables.

Effects of lipid-lowering therapy on major adverse limb events in patients with peripheral arterial disease: A meta-analysis of randomized clinical trials.

OBJECTIVE: Patients with peripheral artery disease (PAD) are at increased risk of major adverse limb events (MALE). Furthermore, MALE have several clinical implications and a poor prognosis, so prevention is a fundamental issue. The main objective of the present meta-analysis of randomized clinical trials is to evaluate the effect of different lipid-lowering therapies on MALE incidence in patients with PAD. METHODS: A meta-analysis of randomized studies that evaluated the use of lipid-lowering therapy in patients with PAD and reported MALE was performed, after searching the PubMed/MEDLINE, Embase, ScieLO, Google Scholar, and Cochrane Controlled Trials databases. A fixed- or random-effects model was used. RESULTS: Five randomized clinical trials including 11,603 patients were identified and considered eligible for the analyses (5903 subjects were allocated to receive lipid-lowering therapy, while 5700 subjects were allocated to the respective placebo/control arms). The present meta-analysis revealed that lipid-lowering therapy was associated with a lower incidence of MALE (OR: 0.76, 95% confidence interval: 0.66-0.87; I2: 28%) compared to placebo/control groups. The sensitivity analysis shows that the results are robust. CONCLUSION: This study demonstrated that the use of lipid-lowering therapy compared with the placebo/control arms was associated with a marked reduction in the risk of MALE. Physicians involved in the monitoring and treatment of patients with PAD must work hard to ensure adequate lipid-lowering medication in these patients.

Prognostic value of statin therapy in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA): a meta-analysis.

BACKGROUND: Given the complex aetiology and a limited amount of evidence, the medical treatment (including statin use) of myocardial infarction with non-obstructive coronary artery disease (MINOCA) remains uncertain. The objective of the present study was to evaluate the effect of statin therapy on major cardiovascular events (MACE) and mortality in MINOCA patients. METHODS: A systematic review and meta-analysis of time-to-event outcomes were performed of studies of statin therapy on MINOCA patients, reporting data from MACE or mortality, after searching the PubMed/MEDLINE, Embase, Science Direct, Scopus, Google Scholar, and Cochrane databases. A fixed-effects meta-analysis model was then applied. RESULTS: Six observational studies of statin therapy on MINOCA, involving a total of 11,171 patients, were identified and considered eligible for analysis (9129 subjects received statin therapy while 2042 patients were part of the respective control arms). Quantitative analysis (5 studies were included) showed that statin use was associated with lower mortality (HR: 0.65; 95% CI: 0.56-0.75, I2: 0%). Also, the meta-analysis showed that statin therapy was associated with a lower incidence of MACE (HR: 0.78; 95% CI: 0.69-0.88, I2:27%). CONCLUSION: Our data suggest that in a population with MINOCA, the use of statin therapy results in significant reduction on MACE and mortality. These results must be confirmed in future clinical trials.

Glucagon-like Peptide-1 Receptor Agonists and Cardioprotective Benefit in Patients with Type 2 Diabetes Without Baseline Metformin: A Systematic Review and Update Meta-analysis.

INTRODUCTION: Sodium Glucose Co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) were associated with a reduction in cardiovascular disease events in cardiovascular outcomes trials (CVOTs) in type 2 diabetes. Most of the patients included in these trials received metformin as background therapy. AIM: To evaluate the effect of glucagon-like peptide 1 receptor agonists on major cardiovascular events (MACE) and mortality in metformin-naïve patients with type 2 diabetes. METHODS: A systematic review and meta-analysis of randomized controlled clinical trials of GLP-1RAs on type 2 diabetes population was performed, after searching the PubMed/MEDLINE, Embase, Scielo, Google Scholar and Cochrane Controlled Trials databases. The primary endpoint was MACE. The secondary endpoints were cardiovascular death and all-cause mortality. A meta-analysis of time-to-event outcomes was performed. This meta-analysis was registered in PROSPERO (CRD42021260040) RESULTS: Seven trials, including 11510 patients, were identified and considered eligible for the analyses. GLP-1RAs were associated with a significant reduction in MACE incidence (HR: 0.86, 95% confidence interval: 0.79-0.94; I2: 0%). The secondary endpoints analysis showed a non-significant reduction in all-cause mortality (HR: 0.86, 95% confidence interval: 0.73-1.00 I2: 0%) and cardiovascular mortality (HR: 0.81, 95% confidence interval: 0.63-1.05; I2: 0%). CONCLUSIONS: In this meta-analysis, GLP-1RAs reduced the incidence of MACE in patients with type 2 diabetes without metformin at baseline, without significant reduction in all-cause mortality and cardiovascular mortality. These results support the fact that when a GLP-1RAs is administered, the benefit on cardiovascular outcomes is independent of the use of metformin.

Effect of anti-inflammatory therapy on major cardiovascular events in patients with diabetes: A meta-analysis.

BACKGROUND: In patients with coronary artery disease anti-inflammatory drugs have been shown to be effective in reducing cardiovascular events. The effect of this intervention in the population with type 2 diabetes mellitus (T2DM) is poorly explored. The main objective of this study was to evaluate the effect of anti-inflammatory therapy on the incidence of major cardiovascular events (MACE) in patients with T2DM. METHODS: A meta-analysis of randomized studies that evaluated the use of anti-inflammatory therapy in patients with T2DM and reported MACE was performed, after searching the PubMed/MEDLINE, Embase, Scielo, Google Scholar and Cochrane Controlled Trials databases. A fixed or random effects models were used. RESULTS: Five studies were selected for the analysis (2075 subjects in the anti-inflammatory therapy arm and 2490 patients in the placebo/control arm). All studies included patients with T2DM and history of coronary artery disease. Four studies evaluated the use of colchicine and one of them canakinumab. The use of anti-inflammatory therapy was associated with a lower risk of MACE (HR: 0.80; 95% CI, 0.69-0.93; I2 = 24%). The sensitivity analysis shows that the results are robust. CONCLUSION: This meta-analysis demonstrated that the use of anti-inflammatory therapy in patients with T2DM and atherosclerotic cardiovascular disease was associated with reduced risk of MACE. These results suggest the need to consider the inflammatory pathway as a potential therapeutic target in patients with T2DM.

Effect of Bempedoic Acid on atherogenic lipids and inflammation: A meta-analysis / Efecto del ácido bempedoico en los índices aterogénicos de los lípidos y la inflamación: meta-análisis

Background: Bempedoic acid is a novel non-statin drug that was developed to treat hyperlipidemia in combination with other lipid-lowering drugs in those patients who need additional lipid lowering. Objectives: (1) To investigate the lipid efficacy of bempedoic acid; (2) to analyze the anti-inflammatory effects of bempedoic acid estimated through high sensitivity C-reactive protein (hsCRP). Methods: We performed a meta-analysis including randomized trials of bempedoic acid therapy, reporting low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and hsCRP with a minimum of 4 weeks of follow-up. The primary endpoint was defined as the percentage change in lipids and hsCRP levels measured from baseline to follow-up, comparing groups of subjects on bempedoic acid versus placebo. Results: Seven eligible trials of bempedoic acid (3892 patients) were included. The bempedoic acid therapy was associated with a significant reduction in LDL-C levels [−20.3% (CI 95% −23.5 to −17.1)]; I2=43%]. Similarly, a significant percentage reduction in the apolipoprotein B levels [−14.3% (CI 95% −16.4 to −12.1)]; p<0.05; I2=46%], non-HDL-C levels [−15.5% (CI 95% −18.1 to −13.0)]; p<0.05; I2=53%] and hsCRP [−23.4% (CI 95% −32.6 to −14.2)]; p<0.05; I2=69%] was demonstrated with the bempedoic acid use. The sensitivity analysis showed that the results were robust. Conclusion: Our data suggests that the use of bempedoic acid significantly reduces the levels of all atherogenic lipid markers, including LDL-C, non-HDL-C and apolipoprotein B. Furthermore, considering hsCRP levels, the drug produces an anti-inflammatory effect.(AU)

Antecedentes: El ácido bempedoico es un fármaco nuevo no perteneciente al grupo de las estatinas, que fue desarrollado para tratar la hiperlipidemia, junto con otros fármacos liporreductores, en aquellos pacientes que necesitan una reducción lipídica adicional. Objetivos: (1) Estudiar la eficacia anti-lipídica del ácido bempedoico; (2) analizar los efectos antiinflamatorios del ácido bempedoico, calculados a través de la proteína C reactiva de alta sensibilidad (hsCRP). Métodos: Realizamos un meta-análisis incluyendo ensayos aleatorios de terapia de ácido bempedoico, reportando colesterol de lipoproteína de baja densidad (LDL-C), colesterol de lipoproteína de no alta densidad (no-HDL-C), apolipoproteína B y hsCRP con un mínimo de 4 semanas de seguimiento. El objetivo primario se definió como el cambio porcentual de lípidos y niveles de hsCRP medidos desde el inicio hasta el seguimiento, comparando los sujetos de los grupos ácido bempedoico frente a placebo. Resultados: Se incluyeron siete ensayos elegibles de ácido bempedoico (3.892 pacientes). La terapia de ácido bempedoico se asoció a una reducción significativa de los niveles de LDL-C [−20,3% (IC 95% de −23,5 a −17,1)]; I2 = 43%]. De igual modo, se demostró una reducción porcentual significativa de los niveles de apolipoproteína B [−14,3% (IC 95% de −16,4 a −12,1)]; p < 0,05; I2 = 46%], niveles de no-HDL-C [−15,5% (IC 95% de −18,1 a −13)]; p < 0,05; I2 = 53%] y hsCRP [−23.4% (IC 95% de −32,6 a −14,2)]; p < 0,05; I2 = 69%] con el uso de ácido bempedoico, reflejando el análisis de sensibilidad que los resultados eran sólidos. Conclusión: Nuestros datos sugieren que el uso de ácido bempedoico reduce significativamente los niveles de todos los marcadores lipídicos aterogénicos, incluyendo LDL-C, no-HDL-C y la apolipoproteína B. Además, considerando los niveles de hsCRP, el fármaco produce un efecto antiinflamatorio.(AU)

Statin use in patients with elevated serum hepatic transaminases at baseline: A meta-analysis.

AIMS: Clinical trials showed that statin therapy decreased cardiovascular events without significantly raising the level of transaminases. However, the information in subjects with altered liver test at baseline is more limited. The objectives of this meta-analysis were to analyze the liver safety and cardiovascular benefit when using a statin-based lipid-lowering treatment compared to a less intensive treatment or placebo, in subjects with abnormal liver tests at baseline. DATA SYNTHESIS: We performed a meta-analysis including randomized trials of statin-based lipid-lowering therapy versus less intensive lipid-lowering therapy or placebo, reporting worsening hepatic test (>3 ULN) and cardiovascular events in patients with abnormal liver tests at baseline. The random-effects model was performed. This meta-analysis was performed according to PRISMA guidelines. Five eligible trials, including 2548 patients were identified and considered eligible for the analyses. A more intensive statin-based lipid-lowering therapy were associated with a similar occurrence of serious alteration of liver tests (OR: 0.90, 95% confidence interval: 0.21-3.99; I2: 64%) compared to less intensive or placebo treatments. Likewise, more intensive lipid-lowering strategies were associated with a significant reduction in major cardiovascular events (OR: 0.34, 95% confidence interval: 0.17-0.70; I2: 66%). CONCLUSIONS: In this study, a more intensive statin-based lipid-lowering treatment, compared with less intensive treatment or placebo, showed a similar incidence of worsening transaminases levels in patients with abnormal liver tests at baseline. Also, a reduction in cardiovascular events was observed when a more intensive lipid-lowering therapy was used.

¿La colchicina puede prevenir el infarto agudo de miocardio? Revisión sistemática y metaanálisis / Can colchicine prevent acute myocardial infarction? Systematic review and meta-analysis

RESUMEN Introducción y objetivos: La asociación entre el uso de colchicina y la incidencia de infarto agudo de miocardio (IAM) es heterogénea. El objetivo principal del presente estudio fue evaluar el efecto de la colchicina sobre la incidencia de IAM. La evaluación de la incidencia de accidente cerebrovascular (ACV) y la mortalidad cardiovascular fueron los objetivos secundarios. Material y métodos: Se realizó un metaanálisis de estudios aleatorizados que evaluaron el uso de colchicina en pacientes con enfermedad aterosclerótica y que reportaron los eventos cardiovasculares, luego de una búsqueda en las bases de datos PubMed/MEDLINE, Embase, Scielo y Cochrane Controlled Trials. Se utilizó un modelo de efectos fijos o aleatorios según la heterogeneidad observada. Resultados: Se seleccionaron para el análisis del punto final primario 7 estudios (con un total de 5966 sujetos en la rama colchicina y 5948 pacientes en la rama control). Este metaanálisis demostró que la terapia con colchicina se asoció a un menor riesgo de IAM (OR: 0,76, IC 95%: 0,62-0,92; I2=15%). Asimismo, se observó una reducción significativa en la incidencia de ACV, sin un efecto significativo en la mortalidad cardiovascular, con la intervención farmacológica. Conclusión: El uso de colchicina en pacientes con enfermedad cardiovascular aterosclerótica se asoció a una reducción significativa en la incidencia de IAM. La incorporación de la colchicina dentro del arsenal terapéutico de la enfermedad cardiovascular deberá ser considerada por las futuras guías de práctica clínica.

SUMMARY Introduction and objectives: The association between the use of colchicine and the incidence of acute myocardial infarction (AMI) is inconsistent. The main objective of this study was to evaluate the effect of colchicine on the incidence of AMI. Assessment of the incidence of stroke and cardiovascular mortality were secondary endpoints. Methods: A meta-analysis of randomized studies that evaluated the use of colchicine in patients with atherosclerotic disease and reported cardiovascular events was performed, after searching the PubMed/MEDLINE, Embase, Scielo and Cochrane Controlled Trials databases. A fixed or random effects model were used depending on the heterogeneity observed. Results: Seven studies were selected for the analysis of the primary end point (5966 subjects in the colchicine arm and 5948 patients in the control arm). This meta-analysis demonstrated that colchicine therapy was associated with a lower risk of AMI (OR: 0.76, 95% CI: 0.62-0.92; I2 = 15%). Likewise, a significant reduction in the incidence of stroke was observed without a significant effect on cardiovascular mortality with pharmacological intervention. Conclusion: The use of colchicine in patients with atherosclerotic cardiovascular disease was associated with a significant reduction in the incidence of AMI. The incorporation of colchicine into the therapeutic arsenal of cardiovascular disease should be considered by future clinical practice guidelines.

Novel antidiabetic drugs and risk of cardiovascular events in patients without baseline metformin use: a meta-analysis.

AIMS: To evaluate the effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major cardiovascular events (MACE) in metformin-naïve patients with type 2 diabetes (T2D). METHODS AND RESULTS: A meta-analysis was performed of randomized controlled clinical trials of GLP-1RAs and SGLT-2 inhibitors on T2D populations, after searching the PubMed/MEDLINE, Embase, and Cochrane Controlled Trials databases. The primary endpoint was MACE. The secondary endpoint, explored in the subgroup of SGLT-2 inhibitors studies, was cardiovascular death or hospitalization for heart failure. A random-effects meta-analysis model was applied. Six eligible trials (three studies of SGLT-2 inhibitors and three trials of GLP-1RAs), including 13 049 patients, were identified and considered eligible for the analyses. The new antidiabetic drugs were associated with a significant reduction in MACE [odds ratio (OR): 0.80, 95% confidence interval: 0.70-0.93; I2: 53%]. The subgroup analysis showed the following findings: GLP-1RAs group, OR: 0.77 (95% confidence interval 0.67-0.88); SGLT-2 inhibitors, OR: 0.85 (95% confidence interval 0.63-1.15). SGLT-2 inhibitors were associated with a significant reduction in hospitalization for heart failure or cardiovascular mortality incidence (OR: 0.67, 95% confidence interval: 0.47-0.95; I2: 78%). CONCLUSION: In this meta-analysis, new antidiabetic drugs reduced the incidence of MACE in metformin-naïve T2D patients. The beneficial effect was especially observed in the GLP-1RAs subgroup. The use of SGLT-2 inhibitors was associated with a reduction in cardiovascular death or hospitalization for heart failure. These results support the fact that metformin would not be indispensable to obtain positive cardiovascular effects when new antidiabetic drugs are administered.

LDL-C Levels Below 55 mg/dl and Risk of Hemorrhagic Stroke: A Meta-Analysis.

OBJECTIVE: To evaluate the effect of very low levels of LDL-C (< 55 mg/dl) achieved with lipid-lowering therapy on hemorrhagic stroke incidence. METHODS: We performed a meta-analysis including randomized trials that achieved LDL-C levels under 55 mg/dl in more intensive lipid-lowering arms, regardless of the lipid-lowering drug used. A fixed-effects model was used. This meta-analysis was performed according to PRISMA guidelines. RESULTS: Eight eligible trials including 122.802 patients, were identified and considered eligible for the analyses. A total of 62.526 subjects were allocated to receive more intensive lipid-lowering therapy while 60.276 subjects were allocated to the respective control arms. There were no differences in the incidence of hemorrhagic stroke between the group that received a more intensive lipid-lowering therapy (achieved LDL-C level <55 mg/dl), and the group that received a less intense scheme (OR, 1.05; 95%CI, 0.85-1.31). The statistical heterogeneity was low (I2 = 2%). The sensitivity analysis showed that the results were robust. CONCLUSIONS: The use of more intensive lipid-lowering therapy that achieved an LDL-C level lower than 55 mg/dl in patients with high cardiovascular risk, is not associated with an increased risk of hemorrhagic stroke. Considering the cardiovascular benefit and safety observed with the achievement of very low LDL-C values, the challenging lipid goals recommended by the new guidelines seem consistent.

Effect of Bempedoic Acid on atherogenic lipids and inflammation: A meta-analysis.

BACKGROUND: Bempedoic acid is a novel non-statin drug that was developed to treat hyperlipidemia in combination with other lipid-lowering drugs in those patients who need additional lipid lowering. OBJECTIVES: (1) To investigate the lipid efficacy of bempedoic acid; (2) to analyze the anti-inflammatory effects of bempedoic acid estimated through high sensitivity C-reactive protein (hsCRP). METHODS: We performed a meta-analysis including randomized trials of bempedoic acid therapy, reporting low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and hsCRP with a minimum of 4 weeks of follow-up. The primary endpoint was defined as the percentage change in lipids and hsCRP levels measured from baseline to follow-up, comparing groups of subjects on bempedoic acid versus placebo. RESULTS: Seven eligible trials of bempedoic acid (3892 patients) were included. The bempedoic acid therapy was associated with a significant reduction in LDL-C levels [-20.3% (CI 95% -23.5 to -17.1)]; I2=43%]. Similarly, a significant percentage reduction in the apolipoprotein B levels [-14.3% (CI 95% -16.4 to -12.1)]; p<0.05; I2=46%], non-HDL-C levels [-15.5% (CI 95% -18.1 to -13.0)]; p<0.05; I2=53%] and hsCRP [-23.4% (CI 95% -32.6 to -14.2)]; p<0.05; I2=69%] was demonstrated with the bempedoic acid use. The sensitivity analysis showed that the results were robust. CONCLUSION: Our data suggests that the use of bempedoic acid significantly reduces the levels of all atherogenic lipid markers, including LDL-C, non-HDL-C and apolipoprotein B. Furthermore, considering hsCRP levels, the drug produces an anti-inflammatory effect.

Aspirin in primary prevention. Meta-analysis stratified by baseline cardiovascular risk.

Introducción: La utilidad de la aspirina en la prevención primaria es todavía objeto de controversia. Los avances médicos y la variabilidad del riesgo cardiovascular podrían explicar la heterogeneidad de los estudios publicados, y las poblaciones de alto riesgo tendrían mayor beneficio. Objetivo: Analizar los efectos de la aspirina en pacientes sin antecedentes cardiovasculares y evaluar los resultados de acuerdo con el riesgo cardiovascular de las poblaciones. Métodos: Se incluyeron estudios que evaluaron el uso de la aspirina en comparación con placebo en la prevención primaria. Se analizó la combinación de muerte cardiovascular, infarto agudo de miocardio (IAM) y accidente cerebrovascular (ACV) isquémico. El punto final de seguridad fue la combinación de ACV hemorrágico y sangrado mayor. Se clasificaron los estudios en riesgo bajo y moderado/ alto, de acuerdo con el número de episodios en la rama de placebo. Resultados: Se evaluaron 13 estudios (n = 164,225), ocho de riesgo cardiovascular bajo (n = 118,455) y cinco de moderado/alto (n = 45,770). Se observó una reducción del punto final combinado en el grupo de aspirina (OR 0.90; IC 95%, 0.85-0.94), sin diferencias en mortalidad cardiovascular (OR 0.94; IC 95%, 0.86-1.04). No se identificaron diferencias entre los subgrupos de riesgo. Se reconocieron mayores complicaciones hemorrágicas en el grupo de aspirina (OR 1.45; IC 95%, 1.32-1.60), sin diferencias entre los subgrupos de riesgo. Conclusión: La aspirina se relacionó con una leve disminución de IAM y ACV isquémico en términos absolutos, sin diferencias en la mortalidad cardiovascular. Esto, junto con el aumento de las complicaciones hemorrágicas, se traduce en una ausencia de beneficio clínico neto. El riesgo cardiovascular basal de la población no modificó los resultados. Background: The usefulness of aspirin in primary prevention continues to be the subject of debate. Medical advances and the variability of cardiovascular risk could explain the heterogeneity of the published studies. High risk populations would have greater benefit. Objective: Analyzing the effects of aspirin in patients without cardiovascular disease and evaluating the results according to the cardiovascular risk of the populations. Methods: Studies evaluating aspirin versus placebo in primary prevention were included. The primary endpoint was the combined cardiovascular death, acute myocardial infarction (AMI) and ischemic stroke. The final safety point was the combination of hemorrhagic stroke and major bleeding. The studies were classified into low and moderate/high risk, according to the number of events in the placebo arm. Results: Thirteen studies were evaluated (n = 164,225), eight of low cardiovascular risk (n = 118,455) and five of moderate/high risk (n = 45,770). There was a reduction of the combined endpoint in the aspirin group (odds ratio [OR] 0.90; 95% confidence interval [CI], 0.85-0.94), without differences in cardiovascular mortality (OR 0.94; 95% CI, 0.86-1.04). No differences were observed when comparing the risk subgroups. Greater hemorrhagic complications were observed in the aspirin group (OR 1.45; 95% CI, 1.32-1.60), without differences between the risk subgroups. Conclusion: Aspirin was associated with a slight decrease in AMI and ischemic stroke in absolute terms, with no differences in cardiovascular mortality. This accompanied by the increase in hemorrhagic complications, results in an absence of net clinical benefit. The baseline cardiovascular risk of the population did not affect the results.

Aspirina en la prevención primaria. Metaanálisis estratificado por riesgo cardiovascular basal / Aspirin in primary prevention. Meta-analysis stratified by baseline cardiovascular risk

Resumen Introducción: La utilidad de la aspirina en la prevención primaria es todavía objeto de controversia. Los avances médicos y la variabilidad del riesgo cardiovascular podrían explicar la heterogeneidad de los estudios publicados, y las poblaciones de alto riesgo tendrían mayor beneficio. Objetivo: Analizar los efectos de la aspirina en pacientes sin antecedentes cardiovasculares y evaluar los resultados de acuerdo con el riesgo cardiovascular de las poblaciones. Métodos: Se incluyeron estudios que evaluaron el uso de la aspirina en comparación con placebo en la prevención primaria. Se analizó la combinación de muerte cardiovascular, infarto agudo de miocardio (IAM) y accidente cerebrovascular (ACV) isquémico. El punto final de seguridad fue la combinación de ACV hemorrágico y sangrado mayor. Se clasificaron los estudios en riesgo bajo y moderado/ alto, de acuerdo con el número de episodios en la rama de placebo. Resultados: Se evaluaron 13 estudios (n = 164,225), ocho de riesgo cardiovascular bajo (n = 118,455) y cinco de moderado/alto (n = 45,770). Se observó una reducción del punto final combinado en el grupo de aspirina (OR 0.90; IC 95%, 0.85-0.94), sin diferencias en mortalidad cardiovascular (OR 0.94; IC 95%, 0.86-1.04). No se identificaron diferencias entre los subgrupos de riesgo. Se reconocieron mayores complicaciones hemorrágicas en el grupo de aspirina (OR 1.45; IC 95%, 1.32-1.60), sin diferencias entre los subgrupos de riesgo. Conclusión: La aspirina se relacionó con una leve disminución de IAM y ACV isquémico en términos absolutos, sin diferencias en la mortalidad cardiovascular. Esto, junto con el aumento de las complicaciones hemorrágicas, se traduce en una ausencia de beneficio clínico neto. El riesgo cardiovascular basal de la población no modificó los resultados.

Abstract Background: The usefulness of aspirin in primary prevention continues to be the subject of debate. Medical advances and the variability of cardiovascular risk could explain the heterogeneity of the published studies. High risk populations would have greater benefit. Objective: Analyzing the effects of aspirin in patients without cardiovascular disease and evaluating the results according to the cardiovascular risk of the populations. Methods: Studies evaluating aspirin versus placebo in primary prevention were included. The primary endpoint was the combined cardiovascular death, acute myocardial infarction (AMI) and ischemic stroke. The final safety point was the combination of hemorrhagic stroke and major bleeding. The studies were classified into low and moderate/high risk, according to the number of events in the placebo arm. Results: Thirteen studies were evaluated (n = 164,225), eight of low cardiovascular risk (n = 118,455) and five of moderate/high risk (n = 45,770). There was a reduction of the combined endpoint in the aspirin group (odds ratio [OR] 0.90; 95% confidence interval [CI], 0.85-0.94), without differences in cardiovascular mortality (OR 0.94; 95% CI, 0.86-1.04). No differences were observed when comparing the risk subgroups. Greater hemorrhagic complications were observed in the aspirin group (OR 1.45; 95% CI, 1.32-1.60), without differences between the risk subgroups. Conclusion: Aspirin was associated with a slight decrease in AMI and ischemic stroke in absolute terms, with no differences in cardiovascular mortality. This accompanied by the increase in hemorrhagic complications, results in an absence of net clinical benefit. The baseline cardiovascular risk of the population did not affect the results.

Effect of bempedoic acid on new onset or worsening diabetes: A meta-analysis.

INTRODUCTION: Bempedoic acid is a new agent that reduces low-density lipoprotein cholesterol. Since inhibits cholesterol synthesis through a different mechanism than statins, the adverse effects related to it may also be different. Therefore, the objective of the present meta-analysis was to evaluate the effect of bempedoic acid on new onset or worsening diabetes. METHODS: We performed a meta-analysis including randomized trials of bempedoic acid therapy, reporting new onset or worsening diabetes with a minimum of 4 weeks of follow-up. The fixed-effects model was performed. This meta-analysis was performed according to PRISMA guidelines. RESULTS: Five eligible trials of bempedoic acid, including 3629 patients, were identified and considered eligible for the analyses. A total of 2419 subjects were allocated to receive bempedoic acid while 1210 subjects were allocated to the respective control arms. Bempedoic acid therapy is associated with a significant reduction in new onset or worsening diabetes [Odds Ratio: 0.66, 95% confidence interval: 0.48-0.90; I2: 0%]. CONCLUSION: This data suggests that the use of bempedoic acid significantly reduces the new onset or worsening diabetes risk. This finding should be confirmed with future studies.

Role of non-statin lipid-lowering therapy in coronary atherosclerosis regression: a meta-analysis and meta-regression.

BACKGROUND: Several studies have investigated the association between non-statin lipid-lowering therapy and regression of atherosclerosis. However, these studies were mostly small and their results were not always robust. The objectives were: (1) to define if a dual lipid-lowering therapy (statin + non-statin drugs) is associated with coronary atherosclerosis regression, estimated by intravascular ultrasound (IVUS); (2) to assess the association between dual lipid-lowering-induced changes in low density lipoprotein cholesterol (LDL-C) and non-high-density-lipoprotein cholesterol (non-HDL-C) levels and atherosclerosis regression. METHODS: A meta-analysis including trials of non-statin lipid-lowering therapy, reporting LDL-C, non-HDL-C and total atheroma volume (TAV) with a minimum of 6 months of follow-up was performed. The primary endpoint was defined as the change in TAV measured from baseline to follow-up, comparing groups of subjects on statins alone versus combination of statin and non-statin drugs. The random-effects model and meta-regression were performed. RESULTS: Eight eligible trials of non-statin lipid-lowering drugs (1759 patients) were included. Overall, the dual lipid-lowering therapy was associated with a significant reduction in TAV [- 4.0 mm3 (CI 95% -5.4 to - 2.6)]; I2 = 0%]. The findings were similar in the stratified analysis according to the lipid-lowering drug class (ezetimibe or PCSK9 inhibitors). In the meta-regression, a 10% decrease in LDL-C or non-HDL-C levels, was associated, respectively, with 1.0 mm3 and 1.1 mm3 regressions in TAV. CONCLUSION: These data suggests the addition of ezetimibe or PCSK9 inhibitors to statin therapy results in a significant regression of TAV. Reduction of coronary atherosclerosis observed with non-statin lipid-lowering therapy is associated to the degree of LDL-C and non-HDL-C lowering. Therefore, it seems reasonable to achieve lipid goals according to cardiovascular risk and regardless of the lipid-lowering strategy used (statin monotherapy or dual treatment).

Psoriasis and Cardiovascular Risk: A Comprehensive Review.

Psoriasis is a systemic inflammatory disorder that involves complex pathogenic interactions between the innate and adaptive immune systems. Individuals with psoriasis have an increased risk of developing other chronic health diseases such cardiovascular disorders. The high incidence of cardiovascular events in the population with psoriasis could be explained by several mechanisms. The high prevalence of traditional cardiovascular risk factors and metabolic abnormalities contributes to the high cardiovascular burden in patients with psoriasis. Likewise, the presence of systemic inflammation in combination with metabolic abnormalities may act in a synergistic manner to increase cardiovascular risk in these patients. This review focused on epidemiologic and clinical evidence linking psoriasis to cardiovascular risk factors and cardiovascular disease. We described the possible pathophysiological mechanisms that justify this association and analyzed the best way to stratify the cardiovascular risk in patients with psoriasis. We also described the usefulness of the therapies frequently used in cardiovascular prevention and analyzed the impact of the specific psoriasis medication on cardiovascular risk factors or major atherosclerotic events. Knowledge of the application of different cardiovascular prevention strategies could mean an advantage in performing the difficult task of estimating cardiovascular risk and treating cardiovascular risk factors in this particular group of patients.