Mean Difference Research Articles

Empagliflozin: unlocking new potentials in heart failure decongestion

Abstract Background Managing acute heart failure (AHF) remains a formidable challenge in cardiology, primarily due to the limitations of conventional decongestive therapies. This study explores the efficacy of Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, in decongestion management for AHF. Methods Conducted in a tertiary care setting, this prospective cohort study involved 450 patients, divided equally into an Empagliflozin group and a control group receiving standard care. The study assessed changes in body weight, clinical congestion scores, hematocrit levels, and NT-proBNP levels as primary outcomes over a period of 90 days. Safety and adverse events related to Empagliflozin were also monitored. Results Empagliflozin led to a significant reduction in body weight (mean difference at Day 15: −1.95 kg, P<0.0001), and clinical congestion scores (mean difference at Day 15: −0.35, P=0.0050). Hematocrit levels increased significantly (mean increase at Day 15: 1.65%, P<0.0001), and NT-proBNP levels showed a more substantial decrease in the Empagliflozin group compared to the placebo. Safety profiles were consistent with previous studies, showing no significant increase in adverse events. Conclusion Empagliflozin demonstrates a substantial improvement in decongestion management in AHF patients, offering a promising alternative to traditional therapies. The findings indicate potential broader applications in heart failure management and support the need for updated clinical guidelines incorporating Empagliflozin as a therapeutic option in AHF.

The effects of a dyadic empowerment-based heart failure management (De-HF) programme on self-care and HRQL : a randomized controlled trial

Abstract Background The ever-growing epidemiology of heart failure (HF) and its detrimental impacts on patients’ quality of life and healthcare cost urge for effective interventions to ameliorate the modifiable prognostic factors. As substantial evidence suggests ineffective self-care as an important candidate especially for the post-discharge outcomes, various care approaches are developed to optimize this behavioral outcome. However, even family carers are heavily involved in the self-care process, dyadic approach to improve the health outcomes of both interactive partners are least applied in the HF transitional care model. Purpose To evaluate the effects of a dyadic empowerment-based heart failure management program (De-HF) on dyadic health and hospital service utilization outcomes. Methods This double-blind RCT randomized 88 HF patient-carer dyads to receive the De-HF program or a dialectic education program, after hospital discharge. Based on the Theory of Dyadic Illness Management, the 16-week De-HF Program, comprising i) a dyadic assessment, ii) five online empowerment modules and iii) follow-up telecare, integrated explicit strategies (scenario-based training, teach-back and goal-setting) to actively engage the care dyads in collaborative disease management. Figure 1 is the graphical presentation of the De-HF Program. The primary outcome is health-related quality of life (HRQL) of the care dyads. Secondary outcomes include patients’ self-care as well as shared care and perceived control of the dyad. Results The mean age of the HF patients was 76.8 (9.4). The patients were in moderate disease severity [NYHA II/II: 56/44%; mean LVEF = 42.5%]. Figure 2 shows the consort flow diagram. After adjusting the socio-demographic characteristic, two-way analysis of covariance showed that patients in the De-HF program showed significantly greater improvement in patients’ self-care domains [Mean difference in change of score (95% CI): Self-care maintenance = 7.15 (1.82-12.46),Cohen’s d = 0.26, p=0.009; Self-care management = 10.04(3.29-16.79), Cohen’s d=0.65, p=0.004; symptom perception = 15.59 (8.20-22.98), Cohen’s d=0.928, p<0.001] and Minnesota Living with Heart Failure score [Mean different in the change of score (95% CI) = -11.45 (-18.24 - -4.66). Cohen’s d = -0.742, p=0.001]. The patient-carer dyads also have significantly greater improvement in perceived control (p=0.001) and collaborative disease management in terms of joint decision-making (p=0.001) and sense of reciprocity (p=0.026). Conclusion Dyadic science has evolved in self-care research for HF. This trial provides the first evidence to inform the positive effects of a theory-based dyadic transitional care program in improving the collaborative self-care management in a family context and patient health outcome. Longer-term evaluation on the effects of De-HF program on health service utilization outcomes and cost-effectiveness will be followed.The De-HF Managment ProgramThe Consort Flow Diagram

The upfront lipid-lowering combination therapy of statins and ezetimibe vs statin monotherapy in the reduction of cardiovascular outcomes. A meta-analysis.

Abstract Background Despite some data in last few years, there is still some inconsistency concerning the effectiveness and safety of the upfront intensive lipid lowering combination therapy (LLT; of moderate to high intensity statin therapy and ezetimibe) in comparison to high intensity statin therapy and recommended by some guidelines stepwise therapy approach. Purpose We sought to evaluate the efficacy of combination LLT compared with statin monotherapy for cardiovascular outcomes, LDL-C reduction, and associated adverse events. Methods A systematic literature search was conducted using PubMed, Embase, and ClinicalTrial.gov to identify relevant articles published from inception until 29th December 2023. The outcomes were assessed using pooled odds ratio (OR) for categorical data and mean difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CI). Results A total of 11 studies (8 randomized controlled trials and 3 cohort studies) with 106,358 were involved in the analysis. The mean age of the patients in the combination LLT and statin monotherapy group was 65.3 and 65.7 years, respectively. Pooled analysis shows that combination LLT significantly reduces the LDL-C level from the baseline (MD, -12.13 mg/dl [0.31 mmol/l] (95%CI: -18.26 to -5.99 mg/dl), p<0.001), all-cause mortality (ACM) (OR, 0.75, 95%CI: 0.62 to 0.92, p=0.01), cardiovascular mortality (CVM) (OR 0.75, 95%CI: 0.66 to 0.84, p<0.001), major adverse cardiovascular events (MACE) (OR, 0.72 95%CI: 0.63 to 0.82, p<0.001), non-significant reduction in the incidence of stroke (OR 0.82, 95%CI: 0.66 to 1.01, p=0.06) when compared with statin monotherapy alone. Similarly, the therapy discontinuation rate was comparable between combination LLT and statin monotherapy groups (OR, 0.87 (95%CI: 0.53 to 1.40), p=0.56). The risk of adverse events related to the gastrointestinal tract (OR, 1.12 (95%CI: 0.93 to 1.36), p=0.23) and musculoskeletal system (OR, 0.88 (95%CI: 0.52 to 1.50), p=0.65) was comparable between both the groups of patients. Conclusion Combination LLT was associated with an overall greater reduction in LDL-C, a lower risk of ACM, MACE, and CVM compared to statin monotherapy alone.Forest Plot of desired outcomes.Central illustration with key findings.

Posterior wall isolation for persistent atrial fibrillation catheter ablation: an updated systematic review and meta-analysis

Abstract Background The ability of catheter ablation (CA) to prevent arrhythmic recurrences in patients with persistent atrial fibrillation (PeAF) remains suboptimal. In this context, the results of studies conducted with both thermal and non-thermal technologies, that evaluated the effect of adding electrical isolation of the posterior wall of the left atrium (PWI) to isolation of the pulmonary veins alone (PVI) have provided conflicting data. Purpose To compare the efficacy and safety of an ablative strategy with the addition of PWI to PVI versus PVI alone in patients with PeAF undergoing a first ablation procedure. Methods We searched electronic databases for observational studies and randomized controlled trials (RCTs) comparing PVI+PWI versus PVI alone as first CA procedure for PeAF, regardless of the technologies used. The efficacy outcomes were recurrence of any atrial tachyarrhythmias lasting more than 30 seconds, recurrence of atrial fibrillation (AF) and atrial flutter/atrial tachycardia (AFlu/AT). The safety outcome was relevant procedural complications defined as a composite of vascular complications, pericardial effusion or tamponade, phrenic nerve palsy, stroke, atrio-esophageal fistula, and death. The procedural time was compared between the ablation strategies studied. The software RevMan 5.4 was used to estimate the risk ratio (RR) and mean difference (MD) with the relative confidence intervals (CI), using a random-effect model. Results Thirteen studies (8 RCTs and 5 observational studies) counting a total of 2994 PeAF patients (1304 treated with PVI+PWI and 1690 with PVI alone; 1847 RF, 600 cryo and 547 PFA) were included in the analysis. Mean age was 65.2±4.1 years, and 26% were female. Mean follow-up period was 14.5±4.8 years. There were no significant differences in the risk of recurrence of any atrial tachyarrhythmias (RR 0.88; 95% CI 0.68-1.14) between the ablation strategies studied. Patients treated with PWI+PVI experienced a reduced risk of recurrence of AF (RR 0.67; 95% CI 0.48-0.94; p = 0.02) balanced by a trend towards increased risk of AFlu/AT (RR 1.74; 95% CI 0.99-3.06; p = 0.06) as compared with PVI alone strategy. No statistically significant differences in the risk of relevant procedural complication were identified between the studied groups (RR 0.94; 95% CI 0.50-1.78 – Fig. 2A). Procedural time was longer in the PWI+PVI group as compared with PVI alone (MD 30.63 min; 95% CI 8.60-52.65 min; p=0.006 – Fig. 2B). Conclusions Our metanalysis shows that, in patients with PeAF treated for the first time with CA, PWI+PVI versus PVI alone was not associated with a reduction of atrial tachyarrhythmias recurrence and required longer procedural times. Nonetheless, a reduction in the risk of AF recurrence and a trend towards an increased risk of AFlu/AT were identified. No differences in the risk of relevant procedural complications were found between the ablation strategies studied.Figure 2

Intermittent levosimendan infusions for advanced heart failure: a systematic review and meta-analysis of randomized controlled trials

Abstract Background Intermittent intravenous infusions of levosimendan have been shown to provide benefits in patients with advanced heart failure (AHF), preventing HF rehospitalization and mortality. Purpose We aim to investigate the efficacy of intermittent intravenous levosimendan infusion in patients with AHF. Methods A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until September 2023. We used the random-effects model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI). Finally, we implemented a trial sequential analysis (TSA) to improve the reliability of our results. Results We included 15 RCTs with 1,181 patients. Intermittent levosimendan was significantly associated with an improved left ventricular ejection fraction (LVEF) compared to placebo (MD: 6,39, 95% CI [3.04, 9.73], P= 0.002; I2=75, P=0.0005), with cumulative Z-score of change after ≤ 1 week passing the monitoring boundaries favors the levosimendan but did not cross the required information size. Additionally, there was a significant improvement in the all-cause mortality rate favoring levosimendan (RR: 0.60, 95% CI [0.40, 0.90], P= 0.01; I2=9, P=0.36). However, There was no difference between intermittent levosimendan and placebo in all-cause rehospitalization rate (RR: 0.75, 95% CI [0.46, 1.22], P= 0.25; I2=70, P=0.04) or event-free survival rate (RR: 0.97, 95% CI [0.72, 1.30], P= 0.84; I2=63, P=0.03). Conclusion In patients with AHF, intermittent levosimendan significantly improved LVEF and all-cause mortality rate. However, there was no effect on rehospitalization or event-free survival.Figure 1.LVEF and TSAFigure 2.Mortality, Rehospital, Surviva

Cardioprotective role of statins in breast cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis

Abstract Background Statins may have cardioprotective effects in patients undergoing cardiotoxic chemotherapy regimens. Yet, their role in mitigating anthracycline and/or trastuzumab-induced cardiotoxicity in patients with breast cancer remains unclear. Purpose To perform a systematic review and meta-analysis to evaluate the efficacy of statins in mitigating anthracycline and/or trastuzumab-induced cardiotoxicity among patients with breast cancer. Methods We systematically searched PubMed, Embase, and Cochrane databases until January 2024 for studies comparing the efficacy of statin therapy versus no statin therapy in breast cancer patients receiving either anthracyclines, trastuzumab, or both. Cardiotoxicity was defined as per the definition of each individual study. A random-effects model was used to assess pooled risk ratios (RR) and mean differences (MD) with corresponding 95% confidence intervals. Statistical analyses were performed using Review Manager version 5.4.1. Results We included five studies, of which two were randomised trials. The pooled population comprised 1,839 anthracyclines and/or trastuzumab-treated patients with breast cancer, of whom 864 (47%) received statin therapy. In the pooled analyses, cardiotoxicity was significantly lower in the statin therapy group as compared with the no statin therapy group (RR 0.45; 95% CI 0.27 to 0.72; p=0.001; Figure 1A), additionally statin therapy was associated with a significantly lower reduction in left ventricular ejection fraction as compared with no statin therapy (MD 4.11%; 95% CI 2.68 to 5.53; p<0.00001; Figure 1B). Conclusion In this meta-analysis, statin therapy in anthracyclines and/or trastuzumab-treated patients with breast cancer was associated with lower cardiotoxicity and decline in left ventricular ejection fraction.

Provisional stenting : drug-coated versus uncoated balloon for side branch in coronary bifurcation lesions: randomized study

Abstract Introduction The rePOT technique is a novel and easily applied approach for coronary bifurcations. Drug-Coated Balloon (DCB) angioplasty is increasingly being utilized in management of small vessels and coronary bifurcation lesions. Herein, we propose a new approach for treating coronary bifurcation lesions with the application of DCB to treat the side-branch in addition to the rePOT technique: the POT-sideDCB-POT technique. Materiel and Method: We described for the first time the POT-sideDCB-POT method for true bifurcation lesions (including the side-branch ostium), which is in line with the recommended management algorithm of the European Bifurcation Club8 consisting of a sequential approach to bifurcation stenting using the provisional strategy. The POT-sideDCB-POT is easy to perform and respects the geometry of all the three bifurcation segments. Results Overall, 100 patients with CBLs treated with provisional stenting using DES were included from our studie,50 with DCB side branche and 50 with UCB With a follow-up duration of 12 months, SB protection with DCB was associated with a lower degree of postoperative diameter stenosis (mean difference (MD): −10.35%, 95% confidence interval (CI): −13.17 to−8.53, p < 0.001; I2 = 0%) and less late lumen loss (MD: −0.18 mm, 95% CI:−0.28 to−0.10, p < 0.001; I2 = 69%) of SB compared to those with UCB. Moreover, SB protection with DCB was associated with reduced risks of target lesion revascularization (risk ratio [RR]: 0.45, 95% CI: 0.27 to 0.88, p = 0.02; I2 = 0%) and major adverse cardiovascular events (RR: 0.42, 95% CI: 0.27 to 0.66, p < 0.01; I2 = 0%). Subgroup analysis according to the study design showed similar results. Conclusions For patients with CBL treated with provisional stenting using DES, SB protection with DCB was associated with better angiographic and clinical outcomes than those with UCB.

Recent cardiac rehabilitation and its impact on cardiopulmonary exercise test variables in Brazilian cardiac transplant recipients

Abstract Introduction Heart transplantation (HTx) is an option for restoring the functional capacity of individuals with end-stage heart failure (HF). Cardiac rehabilitation (CR) plays an important role in improving variables related to cardiopulmonary exercise testing (CPET) in post-HTx patients. Purpose To evaluate whether CR is effective in improving CPET variables in Brazilian patients post-recent HTx compared to a Control Group (CG). Methods Retrospective comparative study composed of two groups: CR group (CRG) and CG. These recent HTx patients (aged 14 to 73 years) initiated CR within 150 days and were recruited from an HTx outpatient clinic at a south Brazilian public university hospital between 2014 and 2023. CPET was performed at three different times: pre-HTx (Time 01), post-recent HTx (Time 02), and post-CR or post-follow-up for CG (Time 03). This study was approved by the Institutional Review Board (protocol No. 20180651). Statistical analysis used Generalized Estimating Equations with alpha ≤ 0.05, and the mean difference (MD) data were presented along with 95% confidence interval (CI). Results CRG (n=18) had a mean age of 47.3±15.6 years and CG (n=11) 48.6±12.5 years (P=0.81). The mean time to start CRG was 62.2±9.6 days (minimum: 21; maximum: 147). There was an interaction for the Group*Time factor for the following CPET variables: VO2peak (P=0.039); VEmax (P=0.009); VO2 on second ventilatory threshold (P<0.001); HR on VT2 (P=0.030) and T½ (P=0.002). The main results are summarized in Table 1. We highlight that there was a difference in the comparison between groups at Time 03 for the variable VO2peak: MD: 5.16 ± 1.95 (95% CI: 1.3 to 9.0; P = 0.008), favorable to CRG. Conclusion Early CR after very recent HTx significantly increase peak VO2peak, VEmax, T½ and VO2 and HR at the VT2 compared to the control group (CG).

Advanced nursing practise as a preventive approach for adults with intellectual disabilities

Abstract Background Various barriers impede access to preventive health services for people with intellectual disabilities in Germany. As a result, they are more likely to suffer from certain chronic diseases. Internationally, Advanced Nursing Practice (ANP) has proven to be a suitable approach to care for this group. In Germany, ANP is not yet widespread. The aim of this study is to improve healthcare for people with intellectual disabilities through ANP-led case management. Methods A randomized controlled trial was conducted in an urban community setting. Inclusion criteria were: ICD-10 diagnosis F70-F79, age ≥18 and care level ≤3. The intervention group (IG) received four outreach home visits focused on prevention and health promotion. The control group (CG) received usual care. Allocation was done using computer-assisted, permuted block randomization. Researchers were blinded during data collection and analysis. The primary outcome was health status after 12 months (t2) (WHODAS). Secondary outcomes were health status after 6 months (t1), health-related quality of life (HQOL) after 6 and 12 months (EQ5D-VAS), and resilience after 6 and 12 months (RS-11). Analysis was performed via ANCOVA with Bonferroni correction at a significance level of 0.025. Results 214 participants were randomized. At t2, 176 participants remained (IG: n = 85, CG: n = 91). Health status at t2 showed a mean difference (MD) of -4.58 points in favor of the IG (p = 0.01). For resilience, a MD of + 1.95 (t2) points in favor of the IG was obtained (p = 0.05). We measured a MD for HQOL of -1.19 (p = 0.72) in favor of the CG. Conclusions A clinically relevant effect of ANP-led case management was achieved on the health status, but not on resilience and HQOL. ANP for people with intellectual disabilities can contribute to health promotion and thereby improve the community health. Therefore, ANP can be used as an innovative approach in the course of reorganization of healthcare for vulnerable populations in Germany. Key messages • ANP-led case management can have a clinically relevant effect on the heal status of people with intellectual disabilities over the course of one year. • ANP-led case management can be seen as a new approach to health promotion and disease prevention in Germany.

Sex-specific clinical outcomes and healthcare resource utilization in the 5 years following hospitalization for heart failure

Abstract Background Heart failure (HF) a leading cause of hospitalization, and sex differences in care have been described. Purpose We assessed sex-specific clinical outcomes and healthcare resource utilization following hospitalization for HF. Methods This was an exploratory analysis of patients hospitalized for HF across 10 Canadian hospitals enrolled in the Patient-Centred Care Transitions in HF pragmatic cluster-randomized trial. Primary outcome was all-cause mortality. Secondary outcomes included all-cause readmissions, HF readmissions, emergency department (ED) visits, and healthcare resource utilization. Outcomes were obtained via linkages with administrative datasets. Results The 4441 patients (50.7% female) had high event rates. At 5 years of follow-up, 63.6% male and 65.5% of male and female patients, respectively, had died (p=0.19); 85.4% and 84.4% of male and female patients, respectively, were readmitted with no sex differences in mean [SD] all-cause readmissions (males, 2.8 [7.8] and females, 3.0 [8.4], p=0.54) or HF readmissions (males, 0.9 [3.6] and females, 0.9 [4.5], p=0.80) per person. The mean (SD) annual total healthcare costs per patient was $80334 (116762) for males and $81010 (112625) for females, with no sex difference (p=0.90); however, there were sex differences in cost breakdown: males incurred greater costs from specialist, hemodialysis, and day surgical care, and females incurred greater costs from home visits and long-term care. Conclusions Males and females were at similarly high risk of mortality and readmissions, and had similar total healthcare costs following hospitalized for HF. Notwithstanding similar risks, males received relatively more specialist and invasive care, and females received relatively more supportive care.

Left atrial longitudinal strain behavior in patients with cryptogenic stroke - a case control study

Abstract Background A significant percentage of ischemic strokes classified as cryptogenic stroke (CS) where the definition is varied according to the type of classification used. Left atrial (LA) function has a role in determining the possible cardio-embolic source of stroke. Using speckle tracking transthoracic echocardiography (TTE) we can detect the early changes in left atrial function by measuring left atrial longitudinal strain (LALS). Aim To evaluate the left atrial stain in patients with a cryptogenic stroke as compared to a healthy papulation. Method and results We recruited 50 cryptogenic ischemic stroke patients with mean age of 44.7 years and 50 % were male who treated consecutively as for first CS, and 50 age-and sex-matched healthy stroke-free controls. Using Speckle tracking TTE analysis we measured the global , passive and active longitudinal LA strain corresponding to the reservoir (LASRES), conduit(LASCD), and contractile function(LASCT),respectively in addition to standard other LA parameters and filling pressure parameters of Left ventricle(LV) in both group. Data were compared using t-test and Mann-Whitney test. Cryptogenic stroke patients as compared with controls had significantly reduced value of all components of LALS [Mean value of LASRES, LASCD and LASCT in CS group versus control group were 25.15±6.79 versus 43.95±4.62 (P-value <0.01), 14.41±3.53 versus 25.68±3.30 (P- value <0.01), 10.73±3.35 versus 18.28±1.60 (P-value <0.01) respectively] (Figure 1 and Figure 2). There were no significant differences in means of LA area and LA volume index in both groups (P value >0.05). Between parameters of LV filling pressures, it was noticed that early diastolic transmitral flow velocity (E) and early diastolic velocity at annulus (E’) were statistically lower in CS patients as compared to control group (P-value <0.01). In addition, the Cluster and Discriminant analysis used confirmed that LASRES, LASCD and LASCT were significantly lower in value in cryptogenic stroke patients in comparison to Control group which can be used to detect early LA dysfunction. Conclusion LA longitudinal strain in all components were significantly impaired in patients with CS. Measuring LALS parameters can be useful in determining early LA dysfunction in cryptogenic stroke patients.Figure 1-left atrial strain components.Figure 2 -left atrial strain component.

Sheathless versus standard guiding catheters for transradial percutaneous coronary interventions: a systematic review and meta-analysis

Abstract Introduction The sheathless trans-radial (TR) technique is a novel approach that may offer potential benefits over the conventional TR approach. We aim to comprehensively compare and analyze the safety and effectiveness of these two catheter types in trans-radial percutaneous coronary interventions (PCI). Methods We conducted comprehensive searches across PubMed, CENTRAL, WOS, Scopus, and EMBASE until July 2023. Pooled data were reported using risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, along with a 95% confidence interval (CI). Results We included 12 studies with 16,988 patients. Notably, the radial artery spasm (RAS) (RR: 0.26, 95% CI: [0.09, 0.77], p = 0.02) and cross-over to the femoral site (RR: 0.22 [0.08, 0.60], p = 0.003) were significantly lower in the sheathless group. However, post-procedural radial artery occlusion (RAO) was significantly higher in the sheathless group (RR: 2.30, 95% CI: [1.52, 3.49], p = 0.0001). Also, we did not find a significant difference between both groups in success rate (RR: 1.03, 95% CI: [0.95, 1.06], p = 0.10) and all-cause mortality (RR: 0.41, 95% CI: [0.16, 1.04], p = 0.06). Conclusion The sheathless TR approach showed lower rates of RAS and femoral conversion. However, it also increased RAO. Thus, more trials are needed to confirm this technique's long-term outcomes and complications.Figure 1

Pharmacist care for hypertension management among patients with diabetes: a systematic review

Abstract Background Improving blood pressure (BP) control is of major importance among patients with diabetes, due to their high risk of micro- and macrovascular complications. Community-based models of care with the involvement of pharmacists and other nonphysician healthcare providers can help manage hypertension. We aimed to estimate the effectiveness of pharmacist interventions, alone or in collaboration, on BP among outpatients with diabetes and hypertension. Methods We conducted systematic searches of randomized controlled trials assessing the effect of pharmacist interventions on BP among outpatients with hypertension and diabetes compared to usual care. The outcome was the systolic and diastolic BP change or BP control. We performed a meta-analysis with random effects models and results are presented by mean difference along with relative 95% CI.We will perform subgroup analyses for the types and intensity (duration, frequeny) of pharmacist interventions, patients’ characteristics, and healthcare settings. The protocol was registered in PROSPERO (CRD42021279751) and published in an open-access peer-reviewed journal. Results Out of 2048 study records identified by electronic database searching, we included 9 studies, with 5067 participants, published between 2008 and 2022. These studies were conducted mainly in North America (n = 5; other regions: n = 4). The intervention was led by the pharmacist in 78% of the studies and in collaboration with other healthcare providers in 22%. Pharmacist intervention included patient education in 67%, healthcare providers education in 11% of studies and feedback to healthcare providers in 44% of the studies. Systolic and diastolic BP were reduced after pharmacist intervention by -5.6 mmHg (95% CI: -10.6 to -0.6) and -4.1 mmHg (95% CI: -7.1 to -1.2) respectively. Additional analyses will be presented at the congress. Conclusions Pharmacist interventions improve blood pressure control in hypertensive diabetic outpatients. Key messages • Recent hypertension guidelines recommend pharmacist involvement in hypertension care management. • This systematic review provide updated evidence on the effect of pharmacist interventions on hypertension management of patients with diabetes.

Intensive blood pressure lowering after endovascular thrombectomy in acute ischaemic stroke: an updated systematic review and meta-analysis of randomized controlled trials

Abstract Background Endovascular thrombectomy is an effective treatment in those with acute ischemic stroke. However, following successful reperfusion there are still many uncertainties as to the factors which influence patient outcome. Effective blood pressure management in this cohort has been elicited as one of these factors, with worse outcomes seen at both the high and low extremes. Purpose Pinpointing an optimal systolic blood pressure target after this procedure is still uncertain. We aimed to perform an updated meta-analysis of randomised controlled trials (RCTs) to evaluate the safety and efficacy of intensive blood pressure management as compared to conventional blood pressure management in this patient population. Methods We searched various electronic databases, including Embase, MEDLINE (via PubMed), and CENTRAL, to retrieve relevant RCTs evaluating a strategy of intensive blood pressure management after endovascular thrombectomy compared to conventional management. We pooled risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous outcomes, using RevMan 5.4. Results The meta-analysis included 4 RCTs with a total of 1560 patients. According to the analysis, intensive blood pressure management was associated with a statistically significant decrease in the number of patients showing functional independence (modified Rankin scale mRS score=0-2) at 90 days (RR 0.81; CI = 0.72-0.91; I2 = 12%). Regarding 90-day mortality, the pooled results from three RCTs showed no statistically significant difference between the intensive blood pressure management group and the conventional blood pressure management group (RR 1.17; CI = 0.90-1.52; I2 = 0%). There was no statistically significant difference between the two groups regarding the incidence of intracerebral haemorrhage (ICH) (RR 1.05; CI = 0.90-1.23; I2 = 0%) and the incidence of symptomatic intracerebral haemorrhage (sICH) (RR 1.10; CI = 0.76-1.60; I2 = 0%). Conclusion The meta-analysis showed no benefit of intensive lowering of blood pressure in terms of functional independence at 90 days, mortality rates, and incidence of ICH. Future large-scale trials should focus on other interventions to improve prognosis in these patients.Figure 1Figure 2

The effects of Tai Chi and Baduanjin on breast cancer patients: systematic review and meta-analysis of randomized controlled trials

BackgroundTai Chi and Baduanjin are nonpharmacological interventions that are widely applied among cancer patients.ObjectiveThis meta-analysis aimed to assess the effect of Tai Chi and Baduanjin on breast cancer patients by summarizing and pooling the results of previous studies.MethodsThe PubMed, Embase, Web of Science, Scopus and Cochrane Library and several databases were searched up to December 1, 2023, to identify high-quality RCTs. Relevant terms such as Tai Chi and Baduanjin were used as keywords. Stata 15.0 software and Review Manager (version 5.3; Cochrane Training) were used to screen the studies, extract the data, code the data, and perform the meta-analysis. The mean differences (MDs) and standardized mean differences (SMDs) with 95% CIs were used to calculate continuous variables. The Cochrane risk of bias assessment tool was used to evaluate the risk of bias. The PICOS framework was used to develop the following eligibility criteria: (i) population - breast cancer patients; (ii) intervention - Tai Chi and Baduanjin intervention; (iii) comparison - Tai Chi and Baduanjin group and different intervention (e.g., regular intervention, routine rehabilitation training, waiting list, sham Qigong, usual care, no intervention); (iv) outcomes - cognitive ability, shoulder joint function, anxiety, depression, fatigue, sleep quality, quality of life; and (v) study design - randomized controlled trial.ResultsFrom January 2013 to December 2023, we included a total of 16 RCTs involving 1247 patients. A total of 647 patients were in the experimental group and were treated with Tai Chi and Baduanjin, while 600 patients were in the control group and were treated with traditional methods. The results of our meta-analysis indicate that Tai Chi and Baduanjin yield outcomes that are comparable to those of traditional treatment methods. Specifically, Tai Chi and Baduanjin significantly increased cognitive function, increased shoulder joint function, improved sleep quality indicators and improved quality of life indicators. Furthermore, Tai Chi and Baduanjin significantly reduced anxiety symptoms, depression symptoms, and fatigue symptoms among breast cancer patients. Sensitivity analysis was performed, a funnel plot was constructed. No publication bias was indicated by Egger’s or Begg’s test.ConclusionOverall, Tai Chi and Baduanjin are viable and effective nonpharmacological approaches for treating breast cancer patients, as they yield better results than traditional treatment methods. However, these findings should be interpreted with caution due to the limited number of controlled trials, small sample sizes, and low quality of the evidence.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023469301.

The efficacy of IV iron in anemic heart failure patients: a systemic review and meta-analysis of randomised controlled trials

Abstract Introduction Iron deficiency in the context of heart failure is a multifaceted concern, where the intricate interplay between diminished iron stores, impaired absorption mechanisms, and reduced recycled iron in the reticuloendothelial system adds a layer of complexity to patient management. Initial attempts to address this issue with oral iron treatments have been questioned due to its poor absorption. Intravenous iron therapy is now preferred, as it has been shown to reduce heart failure hospitalisations and cardiovascular mortality. However, there is a lack of randomised studies specifically focused on heart failure patients, highlighting the need for more targeted investigations. Purpose The aim of this review is to provide reliable evidence from published randomised controlled trials (RCTs) regarding the beneficial effect of IV iron in heart failure patients. Methods We systematically searched PubMed, Web of Science, Scopus, and Cochrane Central, and EMBASE from inception until December 2023. We included randomised controlled trials (RCTs) comparing the effect of IV iron in heart failure patients versus placebo. The primary outcomes were 6MWT mean change, ferritin concentration mean change, transferrin saturation mean change and worsening heart failure. All data were pooled as either Mean difference in the random effect model with the corresponding SD or pooled as RR and 95% CI for dichotomous data. Results Twelve RCTs involving 6800 patients were included in the analysis. The overall effect on the measured primary outcomes was in favour of IV iron in terms of 6MWT mean change (MD= 34.45, 95% CI [ 29.58 to 39.31], P=<0.0001), ferritin concentration mean change (MD= 219.18, 95% CI [ 208.7 to 229.66], P=<0.0001), transferrin saturation mean change (MD= 9.77, 95% CI [ 8.14 to 1.39], P=<0.0001) and worsening heart failure (RR= 0.46, 95% CI [ 0.31 to 0.69], P=0.002). Conclusion The introduction of the IV iron therapy to heart failure patients showed a beneficial effect in terms of the measured haematological and cardiovascular metrics, which include 6MW test mean change, ferritin concentration mean change, and worsening heart failure.6MWT mean changeFerritin mean change

A review on efficacy of polygenic risk score information on behavioral change and clinical outcomes

Abstract Background Polygenic Risk Score (PRS) represents a promising advancement in personalized medicine, enabling the inherited risk assessment for disease outcomes based on the effect of various common genetic variants. The utilization of PRS information to promote the adoption of healthier behaviors has witnessed an increase interest in recent years, but its full potential still needs to be fully addressed. Methods This systematic review aims to assess the efficacy of disclosing PRS information on individuals’ engagement in risk-reducing interventions. CENTRAL database has been searched up to December 2023 to identify randomized controlled trials (RCTs) comparing the disclosure of PRS results, with scenarios where other or no information is provided. We performed a preliminary meta-analysis on the mean difference of clinical and psychological outcomes between the two arms. Results Out of 4419 results, we included 12 studies. Trials focused on primary (83%), secondary (8%) and tertiary (8%) preventive interventions. As for the possible diseases predicted by the PRS, cardiovascular diseases (33%) were the most common (n = 4), along with cancers (33%), diabetes (25%) and metabolic disease (8%). PRS result disclosure was compared to standard care (n = 7), no information provided (n = 4), and family risk (n = 1). By pooling data from four comparable studies, we report a reduction in the mean difference for LDL cholesterol in the intervention group of -6.39mg/dL (95%CI -10.09, -2.70, I²=0%, p < 0.001). No significant changes were observed for systolic and diastolic blood pressure, and weight, in 3 studies and 4 analyzed studies, respectively. An increase in anxiety levels was observed towards the PRS group in 4 studies (SMD 0.24, 95%CI 0.02, 0.46, I² = 66%, p = 0.03). Conclusions Preliminary analysis show small or no effects of PRS disclosure on intermediate health or psychological outcomes. Larger trials assessing the potentiality of PRS disclosure are still needed. Key messages • From the analysis of twelve preventive trials on the efficacy of PRS on behavior change, we report a positive effect on LDL cholesterol reduction. • Larger well conducted trials are needed to integrate PRS-based information into future preventive strategies.

Early In-Bed Cycle Ergometry With Critically Ill, Mechanically Ventilated Patients: Statistical Analysis Plan for CYCLE (Critical Care Cycling to Improve Lower Extremity Strength), an International, Multicenter, Randomized Clinical Trial.

Survivors of critical illness are at risk of developing physical dysfunction following intensive care unit (ICU) discharge. ICU-based rehabilitation interventions, such as early in-bed cycle ergometry, may improve patients' short-term physical function. Before unblinding and trial database lock, we describe a prespecified statistical analysis plan (SAP) for the CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) randomized controlled trial (RCT). CYCLE is a 360-patient, international, multicenter, open-label, parallel-group RCT (1:1 ratio) with blinded primary outcome assessment at 3 days post-ICU discharge. The principal investigator and statisticians of CYCLE prepared this SAP with approval from the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes (including adverse events) and describes the planned primary, secondary, and subgroup analyses. The primary outcome of the CYCLE trial is the Physical Function Intensive Care Unit Test-scored (PFIT-s) at 3 days post-ICU discharge. The PFIT-s is a reliable and valid performance-based measure. We plan to use a frequentist statistical framework for all analyses. We will conduct a linear regression to evaluate the primary outcome, incorporating randomization as an independent variable and adjusting for age (≥65 years versus <65 years) and center. The regression results will be reported as mean differences in PFIT-s scores with corresponding 95% CIs and P values. We consider a 1-point difference in PFIT-s score to be clinically important. Additionally, we plan to conduct 3 subgroup analyses: age (≥65 years versus <65 years), frailty (Baseline Clinical Frailty Scale ≥5 versus <5), and sex (male versus female). CYCLE was funded in 2017, and enrollment was completed in May 2023. Data analyses are complete, and the first results were submitted for publication in 2024. We developed and present an SAP for the CYCLE RCT and will adhere to it for all analyses. This study will add to the growing body of evidence evaluating the efficacy and safety of ICU-based rehabilitation interventions. ClinicalTrials.gov NCT03471247; https://clinicaltrials.gov/ct2/show/NCT03471247 and NCT02377830; https://clinicaltrials.gov/ct2/show/NCT02377830. RR1-10.2196/54451.

Effects of lipid-lowering therapies on lipoprotein(a) levels in patients with dyslipidemia: a systematic review and network meta-analysis of 64 randomised controlled trials

Abstract Background Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular disease. However, there has yet to be a drug approved specifically for lowering Lp(a). There is paucity of studies evaluating the use of current lipid-lowering agents, and their effects, if any, on Lp(a). Purpose We aimed to identify and compare the effects of lipid-lowering therapies on Lp(a) levels, cardiovascular and safety outcomes, in patients with dyslipidemia. Methods A systematic search was performed across four databases (PubMed, Embase, Scopus, Cochrane) for randomised controlled trials (RCTs) published from inception to 3 January 2023. The percentage change of serum Lp(a) levels, cardiovascular and safety outcomes were compared among statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin), fibrates, ezetimibe, niacin, PCSK9 inhibitors (alirocumab, evolocumab, bococizumab) and inclisiran, in patients with primary dyslipidemia. Frequentist network meta-analysis was performed to compare the treatment effects among different drug classes, stratified by use of background statin therapy. Results A total of 64 RCTs were included, comprising 55,256 patients. In patients on background statin therapy, PCSK9 inhibitors significantly lowered Lp(a) levels, compared with placebo (mean difference [MD] -26.8, 95% confidence intervals [95%CI] -30.8 to -22.7), ezetimibe (MD -21.6, 95%CI -31.4 to -11.8), fibrates (MD -19.4, 95%CI -37.4 to -1.5), and niacin (MD -13.8, 95%CI -25.6 to -2.1). PCSK9 inhibitors were associated with lower risk of major adverse cardiovascular events and similar risk of treatment-related adverse events than placebo. Comparing the PCSK9 inhibitors, evolocumab achieved greater Lp(a)-lowering than alirocumab in patients on background statin therapy (MD -11.4, 95%CI -18.6 to -4.1), including those with heterozygous familial hypercholesterolemia. Niacin also achieved 12.9% (95%CI 1.8 to 24.0) reduction in Lp(a) compared with placebo, but had a higher risk of treatment-related adverse effects than fibrates. Statin monotherapy did not affect Lp(a) levels, regardless of type or intensity of statin therapy. Ezetimibe and fibrate had no effect on Lp(a) levels. Conclusions PCSK9 inhibitors produced the greatest effect on Lp(a) levels, compared with other lipid-lowering therapies. Further studies into PCSK9 inhibitors are necessary to characterise their efficacy and safety specifically for Lp(a)-lowering, and elucidate the impact of Lp(a) reduction on cardiovascular risk.% change in Lp(a) levels

Temporal changes in FFR in initially deferred vessels in symptomatic patients

Abstract Background A sizeable proportion of deferred patients based on non ischemic FFR, continue to experience symptoms. Evaluation of serial temporal changes in FFR may help guide follow up and management in such patients. Methods Consecutive patients undergoing FFR evaluation in whom PCI was deferred were followed. Patients who had repeat angiographic evaluation for recurrent symptoms and who had FFR re-measured in the same artery were analyzed. In patients who had progression to ischemic FFR, we performed multivariate analysis to identify the factors most associated with accelerated progression. Results 796 non-ischemic lesions in 559 patients, by FFR were deferred for medical management. Among them 48 patients with 56 lesions underwent repeat FFR evaluation at a mean follow up of 686 ± 418 days (range 30 to 1649) for persistent or recurrent symptoms. FFR value significantly changed from initial mean of 0.85 ± 0.04 to 0.82 ± 0.07 with a mean difference of 0.032 ± 0.01 (P = 0.003) (Figure 1a). 51 lesions were initially non ischemic with FFR &amp;gt; 0.80. Among these 22 (41%) lesions progressed to develop ischemia (FFR &amp;lt; 0.80) from an initial mean FFR of 0.85 ± 0.037 to 0.75 ± 0.051 with a mean difference of 0.1 ± 0.054 ( P &amp;lt;0.001) (Figure 1 b). Among the remaining 30 patients there was no significant change in FFR (0.87 ± 0.048 vs 0.87 ± 0.041; mean difference 0.006 ± 0.05; P = 0.54). Differences in baseline characteristics were as follows (lesion progression vs. none): Age (61±5 vs 63±5;p=0.12), stenosis (58±12 vs 52±10;p=0.07) FFR (0.84±0.04 vs 0.86±0.05;p=0.2); DM (29% ± 58%; p=0.07) smoking 43 ± 48%) prior MI/revascularization (90% vs. 79%; p=0.34) CKD 5% vs. 15%; p=0.24) ACS (38% vs. 38%) and LAD (38% vs. 36%). Conclusion Among lesions, initially deferred PCI based on non ischemic FFR, recurrence of symptoms should prompt re-evaluation of ischemia as a large proportion (~40%) of these lesions may demonstrate progression to ischemia (FFR&amp;lt;0.80).Factors associated with progressive decline in FFR warrant further study.Repeat FFR value changesRepeat FFR with ischemia development