The efficacy and safety of difelikefalin for pruritus in hemodialysis patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-ap) is a common complication that negatively affects the quality of life. Difelikefalin has emerged as a novel FDA-approved drug to manage CKD-ap. This systematic review and meta-analysis will assess the efficacy and safety of Difelikefalin versus placebo to manage CKD-ap. METHODS: PubMed, Scopus, WOS, Central, and Embase were systematically searched until November 2023. RevMan was used to perform meta-analysis. Quality assessment was conducted using the Cochrane RoB 2.0 tool. Results were reported as risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: (CRD42023485979). RESULTS: Five RCTs with a total of 896 participants were included. Difelikefalin significantly decreased the weekly mean WI-NRS score (MD: -0.99 [-1.22, -0.75], p ˂ .00001), 5-D itch scale total score (MD: -1.51 [-2.26, -0.76], p > .0001), and Skindex-10 total score (MD: -7.39 [-12.51, -2.28], p = .005), but showed significantly higher adverse events (RR: 1.26 [1.03, 1.55], p = .03), versus placebo. However, there was no significant difference between both groups in serious adverse events (RR: 1.42 [0.78, 2.57], p = .25) or death (RR: 0.81 [0.19, 3.34], p = .77). CONCLUSION: Difelikefalin appears to be a promising agent for the management of CKD-induced pruritus in patients with end-stage renal disease. However, evidence is still underpowered due to the paucity of the current data; therefore, more robust RCTs are required to confirm the benefit of Difelikefalin.

Comparison of Drug-Coated Balloons With Drug-Eluting Stents in Patients With In-Stent Restenosis: A Systematic Review and Meta-Analysis.

In-stent restenosis (ISR) is the gradual narrowing of the stented coronary segment, presenting as angina or leading to an acute myocardial infarction. Although its incidence has decreased with the use of newer drug-eluting stents (DES), it still carries significant mortality and morbidity risks. We compared the 2 most common interventions for managing DES-related ISR: drug-coated balloons (DCBs) and DES. Electronic databases were searched to identify all randomized controlled trials comparing DCB with DES in patients with DES-ISR. The Mantel-Haenszel method with a random-effects model was used to calculate pooled risk ratios. Five trials comprising 1,100 patients (577 in DCB and 523 in DES group) were included in the final study. The mean follow-up was 42 months. DCB was found to have a higher risk for target lesion revascularization (risk ratio 1.41, p = 0.02) compared with DES. No difference was observed in all-cause mortality, target vessel revascularization, myocardial infarction, or stroke between the 2 intervention arms. In conclusion, management of DES-ISR with DCB has a higher risk of target lesion revascularization compared with re-stenting with DES. The 2 therapeutic interventions are comparable in terms of efficacy and safety profile.

Meta-Analysis Comparing Drug-Coated Balloon Versus Plain Old Balloon Angioplasty for In-stent Restenosis of Coronaries.

BACKGROUND: Despite the advent of newer stents, in-stent restenosis has been a persistent and formidable challenge. Trials have demonstrated the superiority of drug-coated balloons (DCB) over plain-old balloon angioplasty (POBA). A recent AGENT IDE trial highlighted the need for a more comprehensive understanding hence we conducted a meta-analysis aimed at elucidating their respective clinical outcomes. METHODS: A literature search was conducted by 2 investigators (SS and MH) using MEDLINE (EMBASE and PubMed) using a systematic search strategy by PRISMA till November 01, 2023. CRAN-R software was used for statistical analysis. The quality assessment was performed using the Cochrane Risk of Bias tool (Supplemental Table 5). RESULTS: We included 6 studies with a total of 1171 patients. Our analysis showed decreased odds of multiple outcomes with statistically significant results including TVR (OR 0.33, CI 0.19-0.57), TVF (OR 0.30, CI 0.09-0.99), TLR (OR 0.22, CI 0.10-0.46), restenosis (OR 0.1343, CI 0.06-0.27), and MACE (OR 0.2 CI 0.12-0.37). Although MI and all-cause mortality showed decreased odds with all-cause mortality at 0.8 (95% CI: 0.363-2.09), and MI at 0.6 (95% CI: 0.0349-1.07), the reductions did not reach statistical significance. CONCLUSION: Our analysis by scrutinizing six RCTs favored DCB over POBA. However, extensive research for deeper understanding cannot be overemphasized.

Drug-eluting stent vs. Balloon angioplasty in patients with in-stent restenosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: In-stent restenosis (ISR) is seen in up to 20% of cases and is the primary cause of percutaneous coronary intervention (PCI) failure. With the use of re-stenting with a drug-eluting stent (DES), plain old balloon angioplasty (BA) use is decreasing. We aim to compare the efficacy and safety profile of DES over BA in the management of ISR. METHODS: Electronic databases were searched to identify all randomized controlled trials (RCTs) comparing DES to BA for coronary ISR. The mantel-Haenszel method with a random effects model was used to calculate pooled risk ratios (RR). RESULTS: Four trials comprising 912 patients (543 in DES and 369 in the BA group) were included in the final study. The mean follow-up was 45 months. DES was found to be superior with a lower requirement of target vessel revascularization (TVR) (RR: 0.45, 95% CI: 0.31-0.64, p-value <0.0001), and target lesion revascularization (TLR) (RR: 0.59, 95%CI: 0.44-0.78, p-value 0.0002) compared to BA. However, all-cause mortality, cardiovascular mortality, incidence of myocardial infarction (MI), and target lesion thrombosis were not different between the two intervention arms. CONCLUSION: DES was found to be superior to BA for the management of coronary ISR with a reduction in the risk of TLR and TVR. No difference in mortality, risk of MI, or target lesion thrombosis was observed between the two interventions.

Cardiac MRI-Enriched Phenomapping Classification and Differential Treatment Outcomes in Patients With Ischemic Cardiomyopathy.

BACKGROUND: Significant controversy continues to confound patient selection and referral for revascularization and mitral valve intervention in patients with ischemic cardiomyopathy (ICM). Cardiac magnetic resonance (CMR) enables comprehensive phenotyping with gold-standard tissue characterization and volumetric/functional measures. Therefore, we sought to determine the impact of CMR-enriched phenomapping patients with ICM to identify differential outcomes following surgical revascularization and surgical mitral valve intervention (sMVi). METHODS: Consecutive patients with ICM referred for CMR between 2002 and 2017 were evaluated. Latent class analysis was performed to identify phenotypes enriched by comprehensive CMR assessment. The primary end point was death, heart transplant, or left ventricular assist device implantation. A multivariable Cox survival model was developed to determine the association of phenogroups with overall survival. Subgroup analysis was performed to assess the presence of differential response to post-magnetic resonance imaging procedural interventions. RESULTS: A total of 787 patients were evaluated (63.0±11.2 years, 24.8% women), with 464 primary events. Subsequent surgical revascularization and sMVi occurred in 380 (48.3%) and 157 (19.9%) patients, respectively. Latent class analysis identified 3 distinct clusters of patients, which demonstrated significant differences in overall outcome (P<0.001). Latent class analysis identified differential survival benefit of revascularization in patients as well as patients who underwent revascularization with sMVi, based on phenogroup classification, with phenogroup 3 deriving the most survival benefit from revascularization and revascularization with sMVi (hazard ratio, 0.61 [0.43-0.88]; P=0.0081). CONCLUSIONS: CMR-enriched unsupervised phenomapping identified distinct phenogroups, which were associated with significant differential survival benefit following surgical revascularization and sMVi in patients with ICM. Phenomapping provides a novel approach for patient selection, which may enable personalized therapeutic decision-making for patients with ICM.

Impact of Cardiac Magnetic Resonance Left Atrial Ejection Fraction in Advanced Ischemic Cardiomyopathy.

BACKGROUND: The prognostic significance of cardiac magnetic resonance (CMR)-based left atrial ejection fraction (LAEF) is not well defined in the ischemic cardiomyopathy (ICM) cohort. OBJECTIVES: The authors sought to assess the prognostic impact of LAEF, when adjusted for left ventricular remodeling, myocardial infarct size (MIS), left atrial volume index, and functional mitral regurgitation (FMR), on outcomes in patients with advanced ICM. METHODS: ICM patients who underwent CMR were retrospectively evaluated (April 2001-December 2019). LAEF, left atrial volume index, MIS, left ventricular remodeling, and FMR were derived from CMR. The primary clinical endpoint was a composite of all-cause mortality and cardiac transplant. A baseline multivariable Cox proportional hazards regression model was constructed to assess prognostic power of LAEF. RESULTS: There were 718 patients (416 primary events) evaluated, with a median duration of follow-up of 1,763 days (4.8 years) and a mean LAEF of 36% ± 15%. On multivariable analysis, higher LAEF was independently associated with reduced risk (HR: 0.24, 95% CI: 0.12-0.48, P < 0.001), even after adjusting for FMR and MIS. The highest adjusted risk was observed in patients with an LAEF <20% and an MIS of >30% (HR: 3.20, 95% CI: 1.73-5.93). The lowest risk was in patients within the comparator group with an LAEF of >50% and a MIS of <15% (HR: 1.07, 95% CI: 0.81-1.42). CONCLUSIONS: Reduced LAEF is independently associated with increased mortality in ICM. Risk associated with declining LAEF is continuous and incremental to other risk factors for adverse outcomes in patients with ICM even after adjusting for MIS and FMR severity.

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).