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Diabetes, Obesity & Metabolism Feb 2024The results from the SUSTAIN-6 trial generated some uncertainty regarding the association between incretin-based drugs [dipeptidyl peptidase-4 (DPP-4) inhibitors and... (Meta-Analysis)
Meta-Analysis
AIM
The results from the SUSTAIN-6 trial generated some uncertainty regarding the association between incretin-based drugs [dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)] and the risk of diabetic retinopathy. Our objective was to synthesize the available evidence from observational studies regarding the use of incretin-based drugs and the risk of diabetic retinopathy among individuals with type 2 diabetes.
MATERIALS AND METHODS
We systemically searched Cochrane Library, Embase and Medline to identify observational studies of interest. Risk of bias was assessed using the ROBINS-I tool. Data from included studies were pooled using the DerSimonian and Laird random-effect model with the Hartung-Knapp extension.
RESULTS
We included 14 studies in the systematic review, with 10 examining DPP-4 inhibitors and seven examining GLP-1 RAs. Nine studies investigated incident diabetic retinopathy, six investigated diabetic retinopathy progression and two investigated both outcomes. Seven studies were at moderate risk of bias, four at serious risk of bias and three at critical risk of bias. Data pooled across studies showed no association between the use of DPP-4 inhibitors (risk ratio: 0.98, 95% confidence interval: 0.83, 1.17) or GLP-1 RAs (risk ratio: 0.87, 95% confidence interval: 0.56, 1.34) and the risk of diabetic retinopathy.
CONCLUSION
This study suggests that the use of incretin-based drugs is not associated with the risk of diabetic retinopathy among individuals with type 2 diabetes. However, these findings should be interpreted with caution considering the limited quality of some of the available evidence.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Hypoglycemic Agents; Incretins; Observational Studies as Topic
PubMed: 38031234
DOI: 10.1111/dom.15367 -
Cureus Oct 2023With the advent of modern antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been modified into a chronic manageable condition, prolonging... (Review)
Review
With the advent of modern antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been modified into a chronic manageable condition, prolonging the lifespan of people living with HIV (PLHIV). This has resulted in an increased non-AIDS-related morbidity in the HIV-infected population. Our aim is to study the role of contemporary ART in tackling the risk of atherosclerosis and cardiovascular disease (CVD) in PLHIV. We searched through the databases of PubMed, PubMed Central, and Cochrane Library for pertinent articles using the medical subject headings (MeSH) "HIV infection", "Atherosclerosis", and "Antiretroviral agents". The articles published in the past five years were retrieved, screened for relevance, and assessed for quality before being included in the review. This review was performed following the PRISMA 2020 guidelines. The results indicate that the incidence of dyslipidemia with integrase strand transfer inhibitors (INSTIs) is greater than with non-nucleoside reverse transcriptase inhibitors (NNRTIs) and lesser than with protease inhibitors (PIs). INSTIs are indispensably associated with weight gain and obesity. High triglyceride (TG) and oxidized low-density lipoproteins to low-density lipoproteins (oxLDL/LDL) ratio levels and low high-density lipoprotein (HDL) levels are seen in patients taking PIs. A higher incidence of hypertension and metabolic syndrome (MetS) was noticed with INSTIs compared to NNRTIs. PI intake for >5 years increases the risk of subclinical atherosclerosis. Increased risk of myocardial infarction with INSTIs was observed in a study, while another study reported decreased risk. HIV infection independently increases the risk for atherosclerosis and CVD. Although contemporary ART decreases this enhanced risk, it inherently increases the risk for abnormal lipid profile, MetS, weight gain, and obesity. Further research into the risk of atherosclerosis and CVD with newer ART drugs is essential for decoding the underlying mechanisms and preventing adverse cardiac outcomes in PLHIV.
PubMed: 38021858
DOI: 10.7759/cureus.47730 -
ESC Heart Failure Feb 2024Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors,... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of new potassium binders on renin-angiotensin-aldosterone system inhibitor optimization in heart failure patients: a systematic review and meta-analysis.
Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors, which can hinder the excretion of potassium, resulting in hyperkalaemia. New potassium binders (NPBs) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through 26 April 2023. The risk of bias assessment was conducted, following Cochrane's updated Risk of Bias 2 assessment tool. We used the fixed-effects model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023426113). We included six RCTs with a total of 1432 patients. NPB was significantly associated with successful mineralocorticoid receptor antagonist (MRA) optimization [RR: 1.13 with 95% CI (1.02-1.25), P = 0.02], decreased patients with MRA at less than the target dose [RR: 0.72 with 95% CI (0.57-0.90), P = 0.004], and decreased hyperkalaemic episodes [RR: 0.42 with 95% CI (0.24-0.72), P = 0.002]. However, there was no difference between NPB and placebo regarding angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor/neprilysin inhibitor (ANRi) optimization [RR: 1.02 with 95% CI (0.89-1.17), P = 0.76] and serum potassium change [MD: -0.31 with 95% CI (-0.61 to 0.00), P = 0.05], with an acceptable safety profile except for the increased incidence of hypokalaemia with NPB [RR: 1.57 with 95% CI (1.12-2.21), P = 0.009]. NPB has been shown to improve GDMT outcomes by enhancing MRA optimization and reducing hyperkalaemic episodes. However, there are limited data on the effects of NPB on ACEi/ARB/ANRi optimization. Future RCTs should investigate ACEi/ARB/ANRi optimization and conduct head-to-head comparisons of NPB (patiromer and sodium zirconium cyclosilicate).
Topics: Humans; Aldosterone; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Heart Failure; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Potassium; Renin-Angiotensin System
PubMed: 38012095
DOI: 10.1002/ehf2.14588 -
Expert Opinion on Drug Metabolism &... Dec 2023Vildagliptin, a dipeptidyl peptidase-4 inhibitor, is indicated to cure type 2 diabetes mellitus (T2DM). This systematic literature search aims to assess the current... (Review)
Review
INTRODUCTION
Vildagliptin, a dipeptidyl peptidase-4 inhibitor, is indicated to cure type 2 diabetes mellitus (T2DM). This systematic literature search aims to assess the current knowledge about the clinical pharmacokinetics (PK) of vildagliptin to provide recommendations for clinical use to prevent the harmful effects of this drug.
METHODS
The PubMed, Science Direct, EBSCO, Cochrane Central Register of Controlled Trials, and Google Scholar databases were screened for articles related to the clinical PK of vildagliptin using systematic search strategies.
RESULTS
The literature search identified 2118 records, among which 28 were subsumed in this systematic review that fulfilled the inclusion standards.
CONCLUSIONS
This systematic review can help dose optimization among critically ill patients (e.g. renal impairment) without exposing them to the drug's toxic effects.
Topics: Humans; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Vildagliptin
PubMed: 38008954
DOI: 10.1080/17425255.2023.2288252 -
Journal of the Formosan Medical... May 2024The introduction of non-vitamin K antagonist oral anticoagulants (NOACs), with a non-inferior or superior clinical efficacy profile compared to vitamin K antagonists... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
The introduction of non-vitamin K antagonist oral anticoagulants (NOACs), with a non-inferior or superior clinical efficacy profile compared to vitamin K antagonists (VKAs), has significantly improved the safety profile and treatment adherence of patients with non-valvular atrial fibrillation (AF). However, few studies have compared the effectiveness and safety of NOACs. Therefore, we conducted this systematic review and network meta-analysis to compare the safety and clinical effectiveness of NOACs and VKAs in patients with non-valvular AF.
METHODS
An online bibliographic search was conducted to retrieve real-world evidence studies published between January 2019 and June 2022.
RESULTS
Dabigatran was associated with lower risks of major bleeding, ischemic stroke, and intracranial hemorrhage than warfarin. Among the NOACs, only dabigatran had a lower risk of all-cause mortality than warfarin. Dabigatran was also associated with lower risks of major bleeding and intracranial hemorrhage than rivaroxaban.
CONCLUSION
Our meta-analysis confirms that dabigatran's real-world safety and clinical effectiveness align with the results of pivotal clinical trials.
Topics: Humans; Atrial Fibrillation; Warfarin; Anticoagulants; Network Meta-Analysis; Dabigatran; Administration, Oral; Hemorrhage; Stroke; Rivaroxaban; Vitamin K
PubMed: 37996330
DOI: 10.1016/j.jfma.2023.10.014 -
Cardiology Journal 2024Bivalirudin is associated with fewer major bleeding events than heparin in patients undergoing percutaneous coronary intervention (PCI), but confounding effects of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bivalirudin is associated with fewer major bleeding events than heparin in patients undergoing percutaneous coronary intervention (PCI), but confounding effects of concomitant glycoprotein IIb/IIIa inhibitors, routine femoral artery access, and less potent effects of clopidogrel limits meaningful comparisons. The present study is a systematic review and meta-analysis to compare bivalirudin to heparin in contemporary practice.
METHODS
The Cochrane Library, PubMed, EMBASE, and Ovid MEDLINE databases were searched for relevant studies, including comparisons between bivalirudin and heparin in the current medical era from inception to December 23, 2021. Studies reporting incidences of major adverse cardiac events (MACE) and net adverse clinical events (NACE) in patients undergoing PCI and meeting the inclusion criteria were retained. Data extraction was performed by three independent reviewers.
RESULTS
The meta-analysis included 8 studies. Compared to heparin, bivalirudin during PCI was associated with a lower NACE risk, lower all-cause death, and similar MACE risk, with a pooled risk ratio of 0.82 (95% confidence interval [CI] 0.69-0.97, p = 0.02), 0.83 (95% CI 0.74-0.94, p = 0.002), and 0.93 (95% CI 0.78-1.10, p = 0.38), respectively. Moreover, the reduction in NACE was mainly attributed to reduced bleeding (22% reduction in the risk of major bleeding, 95% CI 0.63-0.97, p = 0.03).
CONCLUSIONS
These findings suggest that bivalirudin use during PCI reduced the risk of NACE and all-cause death but did not reduce the risk of MACE compared with heparin use in PCI. More studies specifically designed for anticoagulation strategies and a personalized anticoagulation regimen to comprehensively balance bleeding and ischemia risks are required.
Topics: Humans; Hirudins; Heparin; Percutaneous Coronary Intervention; Peptide Fragments; Acute Coronary Syndrome; Recombinant Proteins; Anticoagulants; Antithrombins; Hemorrhage; Treatment Outcome
PubMed: 37964648
DOI: 10.5603/cj.90956 -
Circulation Mar 2024Device-detected atrial fibrillation (also known as subclinical atrial fibrillation or atrial high-rate episodes) is a common finding in patients with an implanted... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Device-detected atrial fibrillation (also known as subclinical atrial fibrillation or atrial high-rate episodes) is a common finding in patients with an implanted cardiac rhythm device and is associated with an increased risk of ischemic stroke. Whether oral anticoagulation is effective and safe in this patient population is unclear.
METHODS
We performed a systematic review of MEDLINE and Embase for randomized trials comparing oral anticoagulation with antiplatelet or no antithrombotic therapy in adults with device-detected atrial fibrillation recorded by a pacemaker, implantable cardioverter defibrillator, cardiac resynchronization therapy device, or implanted cardiac monitor. We used random-effects models for meta-analysis and rated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE). The review was preregistered (PROSPERO CRD42023463212).
RESULTS
From 785 citations, we identified 2 randomized trials with relevant clinical outcome data: NOAH-AFNET 6 (Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes; 2536 participants) evaluated edoxaban, and ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; 4012 participants) evaluated apixaban. Meta-analysis demonstrated that oral anticoagulation with these agents reduced ischemic stroke (relative risk [RR], 0.68 [95% CI, 0.50-0.92]; high-quality evidence). The results from the 2 trials were consistent (I statistic for heterogeneity=0%). Oral anticoagulation also reduced a composite of cardiovascular death, all-cause stroke, peripheral arterial embolism, myocardial infarction, or pulmonary embolism (RR, 0.85 [95% CI, 0.73-0.99]; I=0%; moderate-quality evidence). There was no reduction in cardiovascular death (RR, 0.95 [95% CI, 0.76-1.17]; I=0%; moderate-quality evidence) or all-cause mortality (RR, 1.08 [95% CI, 0.96-1.21]; I=0%; moderate-quality evidence). Oral anticoagulation increased major bleeding (RR, 1.62 [95% CI, 1.05-2.50]; I²=61%; high-quality evidence).
CONCLUSIONS
The results of the NOAH-AFNET 6 and ARTESiA trials are consistent with each other. Meta-analysis of these 2 large randomized trials provides high-quality evidence that oral anticoagulation with edoxaban or apixaban reduces the risk of stroke in patients with device-detected atrial fibrillation and increases the risk of major bleeding.
Topics: Humans; Administration, Oral; Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Ischemic Stroke; Pyridines; Stroke; Thiazoles; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37952187
DOI: 10.1161/CIRCULATIONAHA.123.067512 -
Genetics Research 2023Pharmacogenetics is a potential approach that can be applied to decline the burden of rivaroxaban's ADRs. The current systematic review and meta-analysis aim to identify... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Pharmacogenetics is a potential approach that can be applied to decline the burden of rivaroxaban's ADRs. The current systematic review and meta-analysis aim to identify genetic variants correlated with rivaroxaban exposure and evaluate their importance.
METHODS
We systematically searched PubMed, Web of Science, and Scopus databases for all observational and interventional studies. The fixed effect method was used to pool the data when the Q-test's value was higher than 0.1. We used random models when the value was less than 0.1.
RESULTS
Data from ten studies (4721 participants) were analyzed in the current review. Qualitative synthesis from included studies found that two variants of ABCB1 (rs1045642 and rs2032582) and one variant of APOB (rs13306198) are potential contributors to rivaroxaban concentrations. Both wild homozygotes (AA) and heterozygotes (AC) of rs1045642 have significantly lower rivaroxaban concentrations compared to mutated homozygotes (CC) (SMD = 0.516, 95% CI: 0.115 to 0.917; SMD = 0.772, 95% CI: 0.088 to 1.455, respectively). Nevertheless, pooling unadjusted odds ratios did not yield a statistically significant correlation between rivaroxaban ADRs and genetic mutations.
CONCLUSION
This study revealed that being an AC or CC for rs1045642 is attributed to a considerably higher rivaroxaban level in participants using rivaroxaban. That is to say, rs1045642 is a remarkable predictor of rivaroxaban metabolism. We concluded that identifying rs1045642 before drug administration might decrease ADRs although further studies adjusted for potential confounders are strongly suggested.
Topics: Humans; Rivaroxaban; Pharmacogenetics; Homozygote; Heterozygote; Drug-Related Side Effects and Adverse Reactions
PubMed: 37942082
DOI: 10.1155/2023/6105320 -
Alternative Therapies in Health and... Apr 2024Heart failure with preserved ejection fraction (HFpEF) is a prevalent and clinically significant condition characterized by limited treatment options. In this context,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Heart failure with preserved ejection fraction (HFpEF) is a prevalent and clinically significant condition characterized by limited treatment options. In this context, the objective of this meta-analysis is to evaluate the effectiveness of sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in managing HFpEF.
METHODS
A systematic search of relevant studies was conducted in PubMed, Embase, Web of Science, and Cochrane Library. Randomized controlled trials comparing sacubitril/valsartan to ACEIs or ARBs in HFpEF patients were included. Inclusion criteria: LVEF>45%, NYHA II-IV, Sac/Val vs ACEI/ARB, RCTs, treatment duration >3 months, sample size ≥25 per group. Exclusion criteria: Animal studies, unclear/missing data, poor quality, case studies/expert opinions.Hospitalization for heart failure and cardiovascular mortality were the primary outcomes, while the additional results included mortality from all causes, improvement of NYHA class, modifications in NT-proBNP, and with LVEF.
RESULTS
Sacubitril/valsartan substantially reduced heart failure hospitalization rates compared to ACEIs and ARBs, according to a total of six studies involving 5,201 participants (Relative Risk, 0.78; 95% CI, 0.65 to 0.85; P = .001). Nonetheless, there were no significant improvements in mortality due to cardiovascular disease (Relative Risk, 0.94; 95% CI, 0.79-1.12; P = .563). Sacubitril/valsartan did not affect total mortality from all causes significantly (Relative Risk, 0.95; 95% CI, 0.84-1.09; P = .453), but it did enhance NYHA classification (Relative Risk, 1.25; 95% CI, 1.10-1.43; P = .001). NT-proBNP levels decreased substantially (Weighted Mean Difference, -266.67; 95% CI, -525.86 to -7.47), whereas there had been little major shift in LVEF (Weighted Mean Difference, 1.49; 95% CI, -1.33 to 4.21; P = .342).
CONCLUSIONS
Sacubitril/valsartan may provide superior benefits in reducing heart failure hospitalization rates, NT-proBNP levels, and improving NYHA classification in patients with HFpEF compared to ACEIs and ARBs. Sacubitril/valsartan might be considered as a preferred treatment option for HFpEF patients due to its benefits in reducing heart failure hospitalization rates and improving symptom severity.
Topics: Humans; Valsartan; Heart Failure; Biphenyl Compounds; Aminobutyrates; Drug Combinations; Stroke Volume; Angiotensin Receptor Antagonists; Tetrazoles; Aged; Angiotensin-Converting Enzyme Inhibitors
PubMed: 37917889
DOI: No ID Found -
PloS One 2023Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of this analysis is to compare drug treatments of DKD by means of a systemic review and a network meta-analysis.
METHODS
We searched Medline, CENTRAL and clinicaltrials.gov for randomized, controlled studies including adults with DKD treated with the following drugs of interest: single angiotensin-converting-enzyme-inhibitor or angiotensin-receptor-blocker (single ACEi/ARB), angiotensin-converting-enzyme-inhibitor and angiotensin-receptor-blocker combination (ACEi+ARB combination), aldosterone antagonists, direct renin inhibitors, non-steroidal mineralocorticoid-receptor-antagonists (nsMRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). As primary endpoints, we defined: overall mortality and end-stage kidney disease, as secondary endpoints: renal composite outcome and albuminuria and as safety endpoints: acute kidney injury, hyperkalemia and hypotension. Under the use of a random effects model, we computed the overall effect estimates using the statistic program R4.1 and the corresponding package "netmeta". Risk of bias was assessed using the RoB 2 tool and the quality of evidence of each pairwise comparison was rated according to GRADE (Grading of Recommendations Assessment, Development and Evaluation).
RESULTS
Of initial 3489 publications, 38 clinical trials were found eligible, in total including 42346 patients. Concerning the primary endpoints overall mortality and end stage kidney disease, SGLT2i on top of single ACEi/ARB compared to single ACEi/ARB was the only intervention significantly reducing the odds of mortality (OR 0.81, 95%CI 0.70-0.95) and end-stage kidney disease (OR 0.69, 95%CI 0.54-0.88). The indirect comparison of nsMRA vs SGLT2i in our composite endpoint suggests a superiority of SGLT2i (OR 0.60, 95%CI 0.47-0.76). Concerning safety endpoints, nsMRA and SGLT2i showed benefits compared to the others.
CONCLUSIONS
As the only drug class, SGLT2i showed in our analysis beneficial effects on top of ACEi/ARB treatment regarding mortality and end stage kidney disease and by that reconfirmed its position as treatment option for diabetic kidney disease. nsMRA reduced the odds for a combined renal endpoint and did not raise any safety concerns, justifying its application.
Topics: Adult; Humans; Angiotensin-Converting Enzyme Inhibitors; Diabetic Nephropathies; Angiotensin Receptor Antagonists; Network Meta-Analysis; Sodium-Glucose Transporter 2 Inhibitors; Kidney Failure, Chronic; Angiotensins; Diabetes Mellitus
PubMed: 37917640
DOI: 10.1371/journal.pone.0293183