Clinical Events Research Articles

FRED-UK: Multicentre UK experience of FRED and FRED Jr flow re-direction endoluminal device for intracranial aneurysms: 6 months and 1 year clinical and anatomical results.

Flow diverting stents (FDS) are an established endovascular treatment for intracranial aneurysms but are reported to have varying rates of adequate occlusion and thromboembolic complications. This study reports clinical safety and efficacy results of the FRED and FRED Jr FDS in clinical practice in the UK at 6 months and 1 year. The FRED-UK study is a single arm, multicentre, prospective, observational study conducted in the UK. Safety was reviewed by evaluating morbidity (modified Rankin Score ≤2) and mortality. Efficacy was assessed as adequate occlusion of the treated aneurysm. A clinical event committee and core laboratory independently assessed clinical and anatomical results. Seven neurointerventional centers treated 61 patients, 57 of which met the full inclusion and exclusion criteria. Of these, 75.4% were treated with FRED and 24.6% with FRED Jr. The aneurysms were located on the cavernous or supraclinoid internal carotid artery (ICA) in 75.4%, on the anterior cerebral artery (ACA) or anterior communicating artery (Acom) in 21.1%, and on the middle cerebral artery (MCA) in 3.5%. 57.9% of aneurysms were small (<10 mm), 40.4% were large (10-24 mm) and 1.8% were giant (≥25 mm). All-cause morbidity and mortality were 0% at 6 and 12 months, and adequate occlusion was 86.7% at 12 months in the per protocol population. The FRED and FRED Jr devices are safe and efficacious in the treatment of intracranial aneurysms.

Efficacy and Safety of Immune Checkpoint Inhibitors on Advanced Cervical Cancer: A Systematic Review and Meta-analysis.

This study aims to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) in patients with histologically proven advanced cervical cancer. MEDLINE (through PubMed), Web of Science, Embase, and the Cochrane Library were comprehensively searched. Eligible studies were clinical trials investigating the efficacy and safety on ICIs in patients with confirmed advanced cervical cancer. Response rates and adverse events rates were pooled using either a random-effects model or a fixed-effects model based on the I2 value. A total of 12 clinical trials with 523 women diagnosed with advanced cervical cancer were included. Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors were identified. The pooled objective response (OR) rate, complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate of PD1 antibodies were 0.24 (95% CIs: 0.11-0.39; I2=90%, P<0.01), 0.03 (95% CIs: 0.02-0.05; I2=0%, P =0.92), 0.20 (95% CIs: 0.08-0.36; I2=91%, P<0.01), 0.31 (95% CIs: 0.23-0.40; I2=79%, P<0.01), respectively. Adverse events (AEs) rate of any grade was 0.81 (95% CIs: 0.72-0.88; I2=83%, P<0.01). This study indicates that PD-1/PD-L1 inhibitors reveal acceptable clinical responses and tolerable adverse events in the treatment of advanced cervical cancer. Well-designed clinical trials investigating the efficacy and safety of immune checkpoint inhibitors (ICIs) are needed.

Efficacy and Safety of Repeat Per-oral Endoscopic Myotomy After Failed POEM for Achalasia: A Systematic Review and meta-analysis.

Per-oral endoscopic myotomy (POEM) is an effective option for treating achalasia. Despite its high efficacy, a fraction of patients remain symptomatic after POEM, and the data on the optimal management of these patients is limited. Few studies have evaluated the effectiveness of repeat POEM after a failed POEM. To evaluate the efficacy and safety of repeat POEM for persistent symptoms after the initial POEM. We searched major databases from inception to April 2024 to identify studies evaluating the efficacy and safety of repeat POEM after failed POEM in patients with achalasia. Our outcomes of interest were clinical success (a reduction in the Eckardt score to ≤3 after the procedure), adverse events, and differences in pre-procedure and post-procedure Eckardt scores. Using the random effects model, we calculated pooled rates with 95% CI for categorical variables and mean difference (MD) with 95% CI for continuous variables. We included 6 observational studies with 123 patients. The mean time between myotomies ranged from 12.2 to 13.5 months. The pooled rate (95% CI) of clinical success was 82.69% (95% CI; 69.65%-93.06%). The pooled rate (95% CI) of adverse events was 17.97% (95% CI: 5.08%-35.15%). The pooled mean±SD post-procedure Eckardt score was 1.63±1.93. The mean post-procedure Eckardt score was significantly lower than the re-procedure Eckardt score, MD (95% CI): 3.68 (2.58, 4.78). Repeated POEM is an effective option for persistent symptoms of achalasia after initial POEM; however, it is associated with nontrivial adverse events.

Cervical Cancer 2010-2019: An Upper Midwest Catchment of 40,000 Square Miles.

American Indian (AI) women have a higher incidence and mortality from cervical cancer than non-Hispanic White (NHW) women in the US. Our purpose is to detail the clinical events in the cervical cancer prevention continuum among the AI and White women with cervical cancer on the US frontier. A cancer center with a nearly 40,000 square-mile catchment area maintained a detailed cancer registry connected to the clinic records of all cervical cancer patients between 2010-2019. This catchment area provided records of both an AI and a White population. Descriptive and inferential statistics and modeling predictions detailed the prevention continuum. Among the 126 with cervical cancer, 20% were AI, and 78% were White. Sixty percent did not participate in cervical cancer screening within the 5 years before their diagnosis, and on average, 9.2 years passed since the last cervical cancer screening. 91% presented with symptoms, and most women presented with 2 or more symptoms. Thirteen percent underwent a colposcopic diagnostic step, significantly delaying the time to diagnosis compared to other diagnostic steps. Sixty-nine percent of the histopathologic diagnoses were squamous cell carcinoma, and 27% were adenocarcinoma. Forty-nine percent presented at stage I regardless of histopathology. Chemotherapy and radiation therapy were most commonly combined. Sixty-three percent of the population survived, and 42% survived at least 3 years from diagnosis. Younger age and earlier stages at diagnosis were the significant adjusted predictors of survival. Our detailed cervical cancer prevention continuum events provide new data questioning the use of colposcopy for women symptomatic at presentation.

Personalized Patient Data and Behavioral Nudges to Improve Adherence to Chronic Cardiovascular Medications

Poor medication adherence is common. Text messaging is increasingly used to change patient behavior but often not rigorously tested. To compare different types of text messaging strategies with usual care to improve medication refill adherence among patients nonadherent to cardiovascular medications. Patient-level randomized pragmatic trial between October 2019 to April 2022 at 3 US health care systems, with last follow-up date of April 11, 2023. Adult (18 to <90 years) patients were eligible based on diagnosis of 1 or more cardiovascular condition(s) and prescribed medication to treat the condition. Patients who did not opt out and had a 7-day refill gap were randomized to 1 of 4 study groups. Generic text message refill reminders (generic reminder); behavioral nudge text refill reminders (behavioral nudge); behavioral nudge text refill reminders plus a fixed-message chatbot (behavioral nudge + chatbot); usual care. Primary outcome was refill adherence based on pharmacy data using proportion of days covered at 12 months. Secondary outcomes were clinical events of emergency department visits, hospitalizations, and mortality. Among 9501 enrolled patients, baseline characteristics across the 4 groups were comparable (mean age, 60 years; 47% female [n = 4351]; 16% Black [n = 1517]; 49% Hispanic [n = 4564]). At 12 months, the mean proportion of days covered was 62.0% for generic reminder, 62.3% for behavioral nudge, 63.0% for behavioral nudge + chatbot, and 60.6% for usual care (P = .06). In adjusted analysis, when compared with usual care, mean proportion of days covered was 2.2 percentage points (95% CI, 0.3-4.2; P = .02) higher for generic reminder, 2.0 percentage points (95% CI, 0.1-3.9; P = .04) higher for behavioral nudge, and 2.3 percentage points (95%, 0.4-4.2; P = .02) higher for behavioral nudge + chatbot, none of which were statistically significant after multiple comparisons correction. There were no differences in clinical events between study groups. Text message reminders targeting patients who delay refilling their cardiovascular medications did not improve medication adherence based on pharmacy refill data or reduce clinical events at 12 months. Poor medication adherence may be due to multiple factors. Future interventions may need to be designed to address the multiple factors influencing adherence. ClinicalTrials.gov Identifier: NCT03973931.

Economic impact of dapagliflozin in the management of chronic kidney disease in Italy: results from a micro-simulation model

Background: Dapagliflozin, approved in the treatment of patients with chronic kidney disease (CKD), has demonstrated attenuation of CKD progression and a reduced risk of cardio-renal outcomes and all-cause mortality (ACM) versus placebo, in addition to standard of care (SoC). The aim of this economic evaluation was to assess the potential medical care cost offsets associated with reduced rates of cardio-renal outcomes in Italy. Methods: A comparative micro-simulation model estimated the outcome-related costs of dapagliflozin plus SoC versus SoC alone over a 3-year horizon based on the DAPA-CKD trial. Incidence rates of end-stage kidney disease (ESKD), hospitalizations for heart failure (hHF), acute kidney injury (AKI) and ACM were estimated for a treated population of 90,564 patients. Associated direct medical costs for non-fatal events (ESKD, hHF and AKI) were calculated using available literature and national tariffs. The analysis was restricted to outcome-associated costs and did not consider the cost of drug treatments and disease management. Results: Patients treated with dapagliflozin plus SoC experienced fewer incident events of ESKD (6,540 vs 9,751), hHF (2,146 vs 4,242), AKI (3,772 vs. 5,271) and ACM (5,780 vs 8,037) per 90,564 treated patients versus those treated with SoC alone. Reductions (–35,6%) in clinical events (ESKD, hHF and AKI) were associated with a 34.4% reduction in total costs (€ 170 million) over 3 years. The clinical effect of dapagliflozin on ESKD management accounted for a € 134.5 million reduction in total costs. Conclusion: Based on the DAPA-CKD trial, dapagliflozin may prevent cardio-renal event incidence with a positive effect upon the Italian National Healthcare Service (NHS). Over three years, we estimated that dapagliflozin can reduce the Italian NHS expenditure associated with the management of ESKD, hHF and AKI events by 34.4% (€ 170 million).

The Relationship of Diuretics and Dietary Sodium in Patients with Heart Failure: An Analysis of the SODIUM-HF Trial

BackgroundSODIUM-HF was a large clinical trial testing dietary sodium restriction compared to usual care in patients with heart failure that showed no reduction in clinical events. It has been suggested that diuretic doses in response to dietary sodium modification may have influenced the trial results. ObjectiveWe assessed the effects of baseline diuretic dose and diuretic dose changes on clinical outcomes in the SODIUM-HF trial. MethodsDiuretics were converted to furosemide-equivalent diuretic total daily doses. Furosemide dose was treated as a continuous variable and also stratified into 0 mg, 1–39 mg, 40 mg, 41–80 mg, and >80 mg daily. The baseline diuretic dose and change in diuretic dose were assessed and correlated with dietary sodium restriction and changes in dietary sodium intake. We then examined the relationship between diuretic dosing and the primary outcomes of SODIUM-HF (cardiovascular-related emergency department visit, cardiovascular-related hospitalization, and all-cause mortality). ResultsOf the 806 patients enrolled in the SODIUM-HF trial, 784 had known diuretic status at baseline: 209 patients (26.7%) with 0 mg, 134 patients (17%) with 1-39 mg, 205 patients (26.1%) with 40 mg, 118 patients (15.1%) with 41-80 mg, and 118 patients (15.1%) with >80 mg. No correlation was found between dietary sodium intake and diuretic dose, either at baseline or change throughout the study (P>0.05). For the primary outcomes, the 2-year risk of primary outcomes was strongly correlated with diuretic dose at baseline across the overall SODIUM-HF population (P<0.001). No significant association was found between the treatment arm and the risk of primary outcomes, within each baseline diuretic dose range or with change in diuretic dose (both P>0.05). ConclusionsAlthough a higher baseline diuretic dose was associated with worse clinical outcomes, no association was found between dietary sodium restriction, baseline or change in diuretic dose and the primary outcomes.

Efficacy and safety of double-dose statin monotherapy versus moderate-intensity statin combined with ezetimibe dual therapy in diabetic patients: a systematic review and meta-analysis of randomized controlled trials.

Cardiovascular disease is a leading cause of mortality, especially in individuals with type 2 diabetes mellitus and dyslipidemia. Despite adequate statin therapy, some patients fail to achieve the target low-density lipoprotein-cholesterol levels. Trials have compared doubling the statin dose with the addition of ezetimibe. A systematic literature search was performed using various databases. Forest plots were constructed for pooled analysis with statistical significance set at P < 0.05. Seven trials were included. Monotherapy showed no significant difference compared with dual therapy for low-density lipoprotein-cholesterol levels [mean difference (MD): -5.03; P = 0.37], high-density lipoprotein-cholesterol levels (MD: 0.01; P = 0.95), total cholesterol (MD: -2.38; P = 0.66), and triglycerides (MD: 5.37; P = 0.67) at follow-up compared to baseline. Monotherapy significantly reduced serious clinical adverse events (risk ratio: 0.21; P = 0.04), with no difference in treatment-related adverse effects, discontinuation due to treatment-related or overall adverse events.

Disruption of serotonin homeostasis in intestinal organoids provides insights into drug-induced gastrointestinal toxicity

Drug-induced gastrointestinal toxicity is a frequent clinical adverse event that needs to be carefully monitored and managed to ensure patient compliance. While preclinical assessment of drug-induced gastrointestinal toxicity mostly relies on animal experimentation, intestinal organoids have gained increasing attention to identify gastrointestinal toxicants in vitro. Nonetheless, current in vitro protocols primarily assess structural alterations induced by drugs, whereas gastrointestinal adverse events can often stem from functional disturbances. Disruption of serotonin signaling in the gastrointestinal tract is associated with impaired motility, as well as nausea and vomiting. We aimed to investigate alterations of serotonin homeostasis in organoids derived from the canine small intestine as a driver of drug-induced gastrointestinal toxicity. Treatment of the organoids with a compound (NVS-1) inducing acute gastrointestinal toxicity in dogs as well as with three tyrosine kinase inhibitors with known preclinical and clinical gastrointestinal adverse effects (afatinib, crizotinib and vandetanib) led to increased supernatant serotonin levels. Mechanistic assays showed that, while NVS-1 and afatinib stimulate serotonin release, crizotinib and vandetanib inhibit serotonin re-uptake via direct inhibition of the serotonin re-uptake transporter. Using a data mining approach, we further suggest that inhibition of serotonin re-uptake could contribute to gastrointestinal toxicity observed with multiple marketed drugs. In conclusion, we present the implementation of a novel in vitro gastrointestinal toxicity endpoint that could complement current methods and serve as a mechanistic and predictive/screening tool for drug-induced gastrointestinal toxicity.

Non-target lesion progression: Unveiling critical predictors and outcomes in patients with in-stent restenosis

BackgroundPercutaneous coronary intervention (PCI) has become the primary treatment for coronary artery disease. However, while PCI effectively addresses severe stenosis or occlusive lesions in target vessels, the progression of non-target vessel plaque remains a critical determinant of long-term patient prognosis. AimsThe purpose of this study was to investigate the impact of non-target vascular plaque progression on prognosis after PCI for ISR. MethodsThis study included 195 patients diagnosed with ISR and multivessel disease who underwent successful PCI with drug-eluting stent (DES) placement, along with intraoperative optical coherence tomography (OCT) assessment of the culprit stent. Subsequent rechecked coronary angiography categorized eligible patients into non-target lesion progression (N-TLP) and no-N-TLP groups. We evaluated the baseline morphological characteristics of N-TLP by OCT and investigated the relationship between N-TLP, non-culprit vessel-related major adverse cardiovascular events (NCV-MACE), and pan-vascular disease-related clinical events (PVD-CE) incidence. ResultsMultivariate logistic regression analysis revealed that diabetes mellitus (OR 3.616, 95% CI: 1.735–7.537; P = 0.001), uric acid level (OR 1.005, 95% CI: 1.001–1.009; P = 0.006), in-stent neoatherosclerosis (ISNA) (OR 1.334, 95% CI: 1.114–1.985; P = 0.047) and heterogeneous neointima morphology (OR 2.48, 95% CI: 1.18–5.43; P = 0.019) were independent predictors for N-TLP. Furthermore, N-TLP was associated with a high incidence of NCV-MACE (19.4% vs 6.9%, P = 0.009) and PVD-CE (83.9% [95% CI: 79.7%–88.3%] vs 93.1% [95% CI: 88.4%–98.0%], P = 0.038) after PCI in ISR patients. ConclusionDiabetes, uric acid levels, ISNA, and heterogeneous neointima are predictive factors for subsequent rapid plaque progression, with N-TLP exacerbating the incidence of NCV-MACE and PVD-CE after PCI.

Reporting on Adverse Clinical Events

Reporting on Adverse Clinical Events

An Analysis of Opioid Consumption and Patient Recovery after Hysterectomy by Surgical Approach.

Background: Minimally invasive hysterectomy is preferred to open hysterectomy due to lower morbidity, but recent data regarding the association of surgical approach with patient recovery and opioid consumption are lacking. Objective: To analyze how postoperative opioid use and return to baseline activity vary by surgical approach for hysterectomy. Study design: This was a retrospective cohort study including hysterectomy patients from the Michigan Surgical Quality Collaborative registry that was linked to the State of Michigan's prescription drug monitoring program. We analyzed two primary outcomes with respect to surgical approach: opioid consumption in the 30 days following surgery, measured in morphine milligram equivalents (MMEs), and return to baseline activity >4 weeks after surgery. Adjusting for demographics, comorbidities, preoperative opioid use, surgical indication, clinical events at 30 days postoperatively, and surgical approach, we used multivariable linear regression and logistic regression models to identify factors associated with our primary outcomes. Results: Lower opioid consumption was reported with minimally invasive hysterectomy, with mean postoperative opioid consumption (95% CI) of 32.70 (27.15-38.26) MMEs for vaginal, 39.91 (37.17-42.65) MMEs for laparoscopic, and 54.97 (48.81-61.13) MMEs for open hysterectomy. Other covariates associated with lower opioid consumption included older age and year of surgery in 2019 versus 2018. Predicted probability of return to baseline activities >4 weeks after surgery was 51% (44-57%), 43% (40-45%), and 64% (60-69%) for vaginal, laparoscopic, and open hysterectomy, respectively. Conclusion: Minimally invasive approaches to hysterectomy are associated with lower postoperative opioid consumption and a more rapid recovery relative to open hysterectomy.

US cost-effectiveness analysis of apixaban compared with warfarin, dabigatran and rivaroxaban for nonvalvular atrial fibrillation, focusing on equal value of life years and health years in total.

Aim: Warfarin and direct-acting oral anticoagulants (DOACs) are widely prescribed to patients with nonvalvular atrial fibrillation (NVAF) to reduce risk of stroke and systemic embolism (SE). This study aimed to assess the cost-effectiveness of apixaban compared with warfarin, dabigatran and rivaroxaban, for patients with NVAF from a US healthcare payer (Medicare) perspective. Methods: A cohort-level Markov model was developed based on a previously published model, for the US setting, factoring in anticipated price decreases due to market entry of generic drugs. Two retrospective cohort studies in US Medicare patients provided inputs to quantify clinical events in the base case setting and in a scenario analysis. For this study, equal value of life-years (evLYs) and health years in total (HYT) were used. Cost-effectiveness was assessed based on a willingness-to-pay threshold of $100,000 per evLY gained (evLYG) or HYT gained (HYTG). Results: Apixaban treatment was associated with gains of 2.23, 1.08 and 1.72 evLYs and 2.26, 1.08 and 1.73 HYTs, compared with warfarin, dabigatran and rivaroxaban, respectively. In the base case analysis from a Medicare perspective, apixaban was cost-effective (i.e., value for money) compared with warfarin, dabigatran and rivaroxaban, with corresponding incremental cost-effectiveness ratio (ICER) per evLYG (and HYTG) of $10,501 ($10,350), $7809 ($7769) and $758 ($768), respectively. When a societal perspective was included, and in a scenario analysis using US Medicare data from the Ray et al. study to quantify treatment effects, apixaban dominated rivaroxaban (i.e., less expensive and more effective) in terms of ICER per evLYG (and HYTG). Conclusion: Using dynamic pricing assumptions, treatment with apixaban compared with warfarin, dabigatran and rivaroxaban was associated with incremental evLYs and HYT and represents a cost-effective treatment option in patients with NVAF, from a US healthcare payer (Medicare) perspective.

The Efficacy and Safety of Tranexamic Acid Combined with Rivaroxaban in Prevention of Clinical Events in Patients after Total Knee/ Hip Arthroplasty: A Meta-analysis

Aims To evaluate the efficacy and safety of tranexamic acid combined with rivaroxaban in prevention of clinical events in patients after TKA/THA through meta-analysis of randomized controlled trials. Materials and Methods Randomized Controlled Trials (RCTs) were retrieved from medical literature databases. Risk ratios (RR) Standard mean difference (SMD) and 95% confidence intervals (CI) were calculated to compare the primary and safety endpoints. Results In total, 21 articles (32 trial comparisons) were retrieved which contained 2909 patients. In general, 1718 patients (59.06%) were randomized to experimental group whereas 1191 patients (40.94%) were randomized to control group. The result showed that TXA combined with rivaroxaban significantly reduce TBL, BTV, BTR and the incidence of MB compared to the control group; there were no significant differences in NMB between experimental group and control group. Conclusion This meta-analysis reveals that TXA combined with rivaroxaban can significantly reduce TBL, BTV, the incidence of blood transfusion and the incidence of MB compared to the control group, which proved that its efficacy and safety are trustworthy.

Integrated Assessment of Coronary Physiology Based on Coronary Angiography in Heart Transplant Patients.

Early detection of cardiac allograft vasculopathy after heart transplant (HTx) with invasive coronary angiography is challenging. The study aimed to determine if computational techniques able to assess epicardial lesions, by means of Murray's law-based quantitative flow ratio (μFR), and microvascular physiology, by means of angiography microvascular resistance (AMR), enhance risk stratification in HTx patients with nonsignificant coronary artery disease. The cohort consisted of 86 consecutive HTx patients (200 epicardial vessels) with stenosis < 50% at baseline. μFR ≤ 0.80 indicated coronary ischemia, while AMR ≥ 2.5 suggested microvascular dysfunction. Clinical events were assessed over a median follow-up of 43 months, focusing on the relationship between μFR and target vessel failure (TVF), and between AMR and heart failure (HF) hospitalizations. At baseline, mean μFR was 0.94 ± 0.08, with eight vessels (4.0%) disclosing flow-limiting lesions, while AMR was 2.4 ± 0.7, with 80 vessels/40 patients (40.0%/46.5%) having microvascular dysfunction. TVF-related segments were associated with lower mean μFR values (0.89 ± 0.14 vs. 0.95 ± 0.05; p < 0.007) compared TVF-free segments. At the receiver operating characteristic curve a μFR ≤ 0.93 demonstrated an area under the curve of 0.632 (95% CI: 0.562-0.699) in predicting TVF occurrence, showing an accuracy of 76.0%, a sensitivity of 46.9%, a specificity of 81.6%, a negative predictive value of 89.0%, and a positive predictive value of 32.6%. μFR ≤ 0.93 showed a significant interaction with TVF occurrence at 43 months (32.6% vs. 11.0%; HR: 2.96; 95% CI: 1.26-6.96; p = 0.013). Microvascular dysfunction showed a significant interaction with HF hospitalizations occurence (AMR: 2.8 ± 4.4 vs. 2.4 ± 4.5; p = 0.001; CMD: 27.5% vs. 4.3%; HR: 7.36; 95% CI: 2.45-22.07; p = 0.002). Angiography-derived epicardial and microvascular physiology computation may improve risk stratification of heart transplanted patients.

Low level of hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in compensated cirrhotic patients

BACKGROUND Whether patients with compensated cirrhosis and low-level viremia (LLV) of hepatitis B should receive antiviral therapy (AVT) is still controversial, and published results are inconsistent. AIM To investigate the link between LLV in compensated cirrhosis and prognosis concerning hepatocellular carcinoma (HCC), decompensation, and liver-related events. METHODS The PubMed, EMBASE, and Cochrane Library databases were searched up to March 5, 2023. Outcomes of interest were assessed by pooled hazard ratios (HRs). The study was registered with PROSPERO (CRD42023405345). RESULTS Six cohort studies representing 3155 patients were included. Compared with patients with undetectable HBV DNA, patients with LLV was associated with increased risk of HCC (HR: 2.06, 95%CI: 1.36-3.13; Q -statistic-P = 0.07, I 2 = 51%) regardless of receiving AVT or not (AVT group: HR: 3.14; 95%CI: 1.73-5.69; Q -statistic-P = 0.60, I 2 = 0%; un-AVT group: HR: 1.73, 95%CI: 1.09-2.76; Q -statistic-P = 0.11, I 2 = 50%). The pooled results showed no statistical association between LLV and decompensation of cirrhosis (HR: 2.06, 95%CI: 0.89-4.76; Q -statistic-P = 0.04, I 2 = 69%), and liver-related events (HR: 1.84, 95%CI: 0.92-3.67; Q -statistic-P = 0.03, I 2 = 72%), respectively. Grading of Recommendations Assessment, Development and Evaluation assessment indicated moderate certainty for HCC, very low certainty for decompensation of cirrhosis and liver-related clinical events. CONCLUSION LLV in compensated cirrhotic patients is associated with increased risk of HCC, higher tendency for hepatic decompensation and liver-related events. Closer screening of HCC should be conducted in this population.

Cost-effectiveness analysis of anticoagulation options for non-valvular atrial fibrillation in Iran

BackgroundAtrial fibrillation (AF) imposes a substantial economic and clinical burden, particularly in developing countries like Iran. This study aimed to evaluate the cost-effectiveness of anticoagulation options for non-valvular atrial fibrillation (NVAF) in Iran.MethodsWe conducted a cost-effectiveness analysis comparing warfarin, apixaban, dabigatran 110 mg, dabigatran 150 mg, and rivaroxaban for NVAF patients from the Iranian payer’s perspective. A Markov model with a lifetime horizon was used to estimate costs and quality-adjusted life years (QALYs). The model incorporated clinical event rates, case-fatality rates, and utility values. Uncertainty was assessed using deterministic sensitivity analysis and probabilistic sensitivity analysis.ResultsAmong the interventions, warfarin had the lowest cost ($1,755) but apixaban resulted in the highest QALYs (7.33). Apixaban was the most cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of $2,026 per QALY gained compared to warfarin. Apixaban dominated other treatments, with lower costs and higher QALYs. Probabilistic sensitivity analysis indicated that at Iran’s willingness-to-pay threshold of $4,387 per QALY gained, apixaban had a high probability of being cost-effective (88.2%).ConclusionOur study provides strong evidence for healthcare decision-makers in Iran, showing that apixaban is a cost-effective treatment for NVAF, potentially enhancing patient outcomes and optimizing healthcare expenditures.

Sling fiber preservation during POEM reduces incidence of postoperative reflux symptoms.

Gastroesophageal reflux disease (GERD) after peroral endoscopic myotomy (POEM) has been a limiting factor with POEM. Sling-fiber preservation during POEM was reported to reduce postoperative GERD in Japan. This study investigates the efficacy of this technique in a western population. This is a retrospective, single-center study of patients undergoing POEM from October 2017 to January 2023. The initial cohort of patients were treated by conventional POEM, after which a second cohort underwent POEM with sling-fiber preservation. The primary outcome was the incidence of postoperative reflux symptoms. The secondary outcomes were clinical success rate (Eckardt score≤3), procedure time, and adverse events rate. Multivariate regression was then performed to identify factors associated with the incidence of postoperative reflux symptoms. One hundred and forty eight POEM cases (52.5 ± 15.6y/o, female: 61[43%]) were included. The mean procedure time (108.6 ± 34.5 vs. 109.1 ± 45.7min, P = 0.93) was similar between the groups. In the sling-fiber preservation group, gastric myotomy length was significantly longer (2.2 ± 0.7 vs. 1.6 ± 0.8cm, P < 0.05), yet the incidence rate of postoperative reflux symptoms at follow-up was significantly lower (22.4% vs. 42.3%, P < 0.05). The clinical success rate was similar between groups (89.5% vs. 83.1%, P = 0.32), and the rate of adverse events requiring intervention (13.5% vs. 12.2%, P = 0.36) was similar. Regression analysis indicated that, after adjusting for other risk factors of postoperative GERD, sling-fiber preservation during POEM had an odds ratio of 0.24 (95% CI: 0.07-0.85, P < 0.05) for the incidence of reflux symptoms. Sling-fiber preservation during POEM reduces the incidence of postoperative reflux symptoms. As such, sling-fiber preservation may be a useful solution to reduce post-POEM GERD in western populations.

Abbreviated or Standard Antiplatelet Therapy After PCI in Diabetic Patients at High Bleeding Risk

BackgroundAbbreviated antiplatelet therapy (APT) reduces bleeding without increasing ischemic events in largely unselected high bleeding risk (HBR) patients undergoing percutaneous coronary intervention (PCI). Diabetes mellitus (DM) is associated with higher ischemic risk, and its impact on the safety and effectiveness of abbreviated APT in HBR PCI patients remains unknown. ObjectivesThis study sought to investigate the comparative effectiveness of abbreviated (1 month) vs standard (≥3 months) APT in HBR patients with and without DM after biodegradable polymer sirolimus-eluting coronary stent implantation. MethodsThis was a prespecified analysis from the MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With a Abbreviated Versus Prolonged DAPT Regimen) trial, which randomized 4,579 HBR patients (1,538 [34%] with DM) to abbreviated (n = 2,295) or standard (n = 2,284) APT. The coprimary outcomes were net adverse clinical events (NACEs; composite of all-cause death, myocardial infarction, stroke, and major bleeding), major adverse cardiac or cerebral events (MACCEs; all-cause death, myocardial infarction, and stroke), and major or clinically relevant nonmajor bleeding at 11 months. ResultsHBR patients with DM had higher risks of MACCEs (HR: 1.28; 95% CI: 1.00-1.63) and similar net adverse or bleeding events compared with nondiabetic subjects. Abbreviated compared with standard APT was associated with similar NACEs and MACCEs (Pinteraction = 0.47 and 0.59, respectively) and reduced major or clinically relevant nonmajor bleeding (Pinteraction = 0.55) irrespective of diabetes status. ConclusionsMACCE and NACE rates were similar, and bleeding rates were lower with abbreviated APT in patients with or without diabetes. Therefore, diabetes status did not modify the treatment effects of abbreviated vs standard APT in HBR patients after biodegradable polymer sirolimus-eluting coronary stent implantation. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With a Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020)

Rationale and Design of Dual Antiplatelet Therapy in Patients with Coronary Multi-Vessel Disease (DAPT-MVD): A Multicenter, Randomized, Controlled Trial.

The optimal duration of dual antiplatelet therapy (DAPT) for patients with coronary multi-vessel disease (MVD) who have received drug-eluting stents (DES) remains unclear. The Dual Antiplatelet Therapy in Patients with Coronary Multi-Vessel Disease (DAPT-MVD) study is a multicenter, open-label, randomized controlled trial designed to assess the efficacy and safety of extended DAPT in MVD patients 12 months following DES implantation. We plan to enroll 8250 patients across approximately 100 sites in China. Participants will be randomized in a 1:1 ratio to receive either extended DAPT (75 mg clopidogrel plus 75-150 mg aspirin daily) or monotherapy (75-150 mg aspirin daily) beyond 12 months post-DES implantation. The follow-up period will last at least 12 months, with all potential endpoints adjudicated by a blinded Clinical Events Committee. The primary endpoint is major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. As of April 2024, a total of 8250 participants have been enrolled in the study. The mean age of the enrolled patients was 60.5 ± 8.8years, with 5753 (69.7%) being men. The DAPT-MVD study is the first large-scale trial to evaluate the efficacy and safety of prolonged DAPT with clopidogrel plus aspirin beyond 12 months after DES implantation in MVD patients. The trial will provide novel insights into the optimal duration of DAPT for MVD patients (ClinicalTrials. gov ID: NCT04624854. Registered on 10/27/2020).