To evaluate the efficacy and safety of sitokiren (SPH3127) tablet in patients with mild-to-moderate essential hypertension in comparison to valsartan capsule. This multicentre, randomised, double-blind, parallel Phase III trial was designed in 2 stages. In the 1st stage, eligible patients were randomised to receive 50 mg, 100 mg or 200 mg of SPH3127 tablet or 80 mg of valsartan capsule once daily (QD) for 12 consecutive weeks. In the 2nd stage, eligible patients were randomised to receive assigned dose of SPH3127 tablet based on the results from the 1st stage or valsartan 80 mg QD for 12 consecutive weeks. Primary outcome was the change from baseline in mean sitting diastolic blood pressure (msDBP) at Week 12. Safety outcome measures included any adverse events. Exploratory outcomes included plasma concentration of SPH3127, as well as the assessment of the correlation between SPH3127 exposure with the level of renin inhibition, clinical efficacy and occurrence of adverse events. The 1st stage enrolled 189 patients, of which 129 eligible patients were randomised. High plasma renin activity (PRA) inhibitory effect (83

Background: Human epidermal growth factor receptor 2 (HER2) overexpression is a key therapeutic target for novel antibody-drug conjugates (ADCs) like disitamab vedotin (RC48) in bladder urothelial carcinoma (BLCA), but immunohistochemistry-based assessment is limited by intratumoral heterogeneity and sampling bias. A noninvasive and reliable imaging-based approach is therefore urgently needed. Therefore, this study aimed to construct a noninvasive, imaging-based multimodal model for predicting HER2 expression status in BLCA using tri-phasic CT. Methods: A total of 411 patients from three institutions (2021-2024) who underwent tri-phasic contrastenhanced computed tomography (CT) and HER2 immunohistochemistry (IHC) were included. Patients were classified as HER2-positive (IHC 2+/3+) or negative (IHC 0/1+) based on therapeutic criteria for ADCs. Patients were divided into training, internal validation, and external validation cohorts. Radiomics models, 2.5D and 3D ResNet50 deep learning models, a clinical model, and a multimodal fusion model were developed. Model performance was evaluated using receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis. Results: Tumor architecture (sessile pattern), hydronephrosis, pelvic pain, and radiological lymph node status were identified as independent predictors of HER2 positivity. The 2.5D ResNet50 model achieved an external area under the curve (AUC) of 0.827, significantly outperforming the 3D model (AUC =0.608). The multimodal fusion model showed the best performance, with AUCs of 0.960, 0.908, and 0.873 in the training, internal validation, and external validation cohorts, respectively. In the external cohort, accuracy, sensitivity, and specificity were 0.819, 0.857, and 0.784. The multimodal model significantly outperformed all single-modality models. Conclusions: A tri-phasic CT-based multimodal model enables noninvasive assessment of HER2 expression status in BLCA, providing a promising tool for selection of patients likely to benefit from ADC therapy.

The CH-VAD is a fully magnetically levitated left ventricular assist device (LVAD) designed for optimized hemocompatibility. This study evaluates the clinical outcomes of 77 patients implanted with the CH-VAD across seven centers in China from June 2022 to June 2024. Patients had a mean age of 57.5 years, primarily classified as INTERMACS 2 or 3, with dilated and ischemic cardiomyopathy as the main causes of heart failure (HF). The study reported a 91.6% survival rate at both 6-month and 1-year follow-ups, aligning with international LVAD outcomes. Key adverse events were infrequent, including low rates of right HF, reoperation for bleeding, and driveline infection. Importantly, no pump thrombosis or device failures were noted. The results suggest that the CH-VAD is a reliable and effective long-term mechanical circulatory support option for end-stage HF patients in China, warranting further studies for long-term efficacy evaluation.

Background:Clevidipine emulsion injection is an ultra-short-acting, intravenous calcium-channel blocker that produces a rapid and transient antihypertensive effect. Methods:This is a multicenter, randomized, single-blind, parallel, positive-controlled, noninferiority phase III clinical trial comparing the efficacy and safety of clevidipine and nicardipine in hypertensive emergencies. Participants were randomly assigned in a 1 : 1 ratio to the experimental group (clevidipine emulsion injection) or the positive-control group (nicardipine), and standard safety data were collected. Results:In the per-protocol set (PPS), the primary endpoint showed that 100.0% of patients in the clevidipine group achieved a 15-25% reduction in systolic blood pressure from baseline within 30 min after dosing, compared with 95.9% in the nicardipine group. The absolute difference between the two proportions was 4.1% [95% confidence interval (CI): 0.58, 7.62], with the lower bound exceeding the noninferiority margin of -10%. Secondary endpoints revealed that the median time to reach the target systolic blood pressure (defined as a 15-25% reduction from baseline) was 9.0 (9.0, 12.0) minutes for clevidipine versus 12.0 (12.0, 15.0) minutes for nicardipine, and the between-group difference was statistically significant (P < 0.0001). The proportions of patients who successfully transitioned to oral antihypertensive therapy within 6 h after study drug discontinuation were 96.83% for clevidipine and 95.90% for nicardipine, with no statistically significant difference (P = 0.7459). In the safety set (SS), the safety endpoint showed that the proportion of patients whose systolic blood pressure fell by >25% from baseline within 3 min after dosing was 0.00% for clevidipine and 0.79% for nicardipine, with no statistically significant difference (P = 0.4980). The overall incidence of adverse events was similar between clevidipine and nicardipine. Conclusions:Clevidipine has similar therapeutic effects and safety compared with the nicardipine.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04670809.

FOXN family genes (FOXNs) have a significant role in the progression of various malignancies; nevertheless, the relationship between their genetic variations and the risk of bladder cancer is yet insufficiently comprehended. This study included 580 bladder cancer patients and 1,101 healthy controls, evaluated for 8,695 single nucleotide polymorphisms (SNPs) in FOXNs. The rs10484024 T > C variant in FOXN3 was identified as a significant risk factor for bladder cancer (OR = 1.18, 95

AIMS:Heart failure with preserved ejection fraction (HFpEF) is often underdiagnosed. This study evaluates the HFpEF-ABA score's ability to identify high-risk, undiagnosed HFpEF subgroups with elevated cardiovascular event rates and assesses the impact of intensive blood pressure control in these populations. METHODS:A post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) was performed. The HFpEF-ABA score identified high-risk individuals with undiagnosed HFpEF. Cox proportional hazards regression was used to examine interactions between HFpEF-ABA score groups and intensive blood pressure control on major cardiovascular outcomes. The primary outcome was a composite of myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure and cardiovascular disease death. RESULTS:Among 9265 patients (mean age, 67.9 ± 9.4 years; 35.5% females), 559 primary outcomes occurred during a median follow-up of 3.2 years. An HFpEF-ABA score ≥ 90% was associated with a higher risk of the primary outcome [adjusted hazard ratio (aHR), 1.96 (1.57-2.44); P < 0.001]. When treated as a continuous variable, higher HFpEF-ABA scores were independently associated with an increased risk of the primary composite outcome (P = 0.001), with a modest non-linear relationship observed (P for non-linearity = 0.040). In the intensive treatment group, the absolute reduction in primary outcomes was 5.0 per 1000 patient-years for scores < 90% and 11.2 per 1000 patient-years for ≥ 90%. Intensive blood pressure control reduced primary outcomes in both groups [<90%: aHR, 0.75 (0.62-0.90); ≥90%: aHR, 0.76 (0.51-1.13)] with no significant heterogeneity (P for interaction = 0.944). Serious adverse events did not increase in either group [<90%: aHR, 1.04 (0.96-1.11); ≥90%: aHR, 1.06 (0.88-1.28); P for interaction = 0.801]. CONCLUSIONS:The HFpEF-ABA score identifies high-risk patients with undiagnosed HFpEF who have elevated cardiovascular event rates and benefit from intensive blood pressure control without an increased risk of serious adverse events.

Background: The significance of circular RNA in tumour biology is increasingly recognized. This study aims to explore the value of circFAM64A(3) in the proliferation and immune evasion of bladder cancer. Methods: Bioinformatics were used to identify the differentially expressed circular RNAs in bladder cancer. Proliferation assay, co-culture assay and flow cytometry assay confirmed the oncogenic and immune-evading characteristics of circFAM64A(3) in bladder cancer in vitro and in vivo. Further, mRNA sequencing, RNA pulldown, and RNA immunoprecipitation were used to confirm the downstream targets and pathways regulated by circFAM64A(3). CUT&TAG assay confirmed HIF-1 alpha promoted the expression of circFAM64A(3) under hypoxic. Results: CircFAM64A(3) was significantly high expression in bladder cancer tissues and related with poor prognosis of bladder cancer patients. CircFAM64A(3) promoted bladder cancer cells proliferation and immune evasion in vitro and in vivo. Mechanistically, circFAM64A(3) acted as a sponge to miR-149-5p and reduced the binding of miR-149-5p to IL-6 3 '-UTR. Then, IL-6 activated the JAK/STAT pathway and caused an increase of PDL1. Under hypoxic environment, HIF-1 alpha bound to the promoter of FAM64A and promoted circFAM64A(3) transcription. Conclusion: HIF-1 alpha/circFAM64A(3)/miR-149-5p/IL-6 axis was an important regulatory pathway in bladder cancer proliferation and immune evasion. CircFAM64A(3) may serve as a novel and potentially valuable biological target.

Background: Ischemic left ventricular (LV) aneurysm is associated with LV thrombus and subsequent embolic events. However, there is currently no evidence-based recommendation for anticoagulation in these patients. Objective: To determine the characteristics of LV aneurysms associated with a high risk of thrombus formation. Methods: This retrospective study included all hospitalized patients with ischemic LV aneurysm who underwent cardiac magnetic resonance (CMR) from September 2015 to June 2023. Baseline characteristics and CMR parameters were compared between patients with and without LV thrombus. Factors associated with LV thrombus were identified using univariable and multivariable logistic regression analyses. Results: Among the 317 patients included in this study, 88 (27.8%) had LV thrombus. Patients with LV thrombus demonstrated a higher prevalence of heart failure, lower left ventricular ejection fraction, and greater volume, mass, and global extent of late gadolinium enhancement (LGE). They also exhibited distinct LV aneurysm characteristics, such as a larger maximum transverse dimension (maximum width), a wider aneurysm neck, and a higher aneurysm shape index (ratio of maximum length to neck width). Multivariable logistic regression analyses identified aneurysm neck width (OR 1.33 per 5 mm, 95% CI 1.00–1.77, P = 0.047), shape index (OR 1.63 per 20%, 95% CI 1.23–2.16, P = 0.001), and LGE global extent > 50% (OR 6.58, 95% CI 3.04–14.27, P < 0.001) as significant predictors of LV thrombus. Conclusions: A wider aneurysm neck, a higher aneurysm shape index, and LGE global extent > 50% are associated with LV thrombus in patients with ischemic LV aneurysm.

BACKGROUND:Although preliminary studies have elucidated the clinical relevance of left anterior fascicular block (LAFB) in the general population, its specific impact on disease progression, cardiac functional deterioration, and adverse outcomes in heart failure patients remains underexplored. This study evaluated the short-term prognostic value of LAFB in hospitalized heart failure patients and its influence on cardiac functional improvement. METHODS:This prospective cohort study enrolled 291 hospitalized heart failure patients from Beijing Anzhen Hospital. Patients were categorized into LAFB (n = 78) and no-LAFB (n = 213) groups based on electrocardiographic findings using the Minnesota Code classification. The primary composite endpoint was all-cause mortality and heart failure readmission at 6 months. Secondary endpoints included changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Kaplan-Meier survival analysis and multivariate Cox regression were performed to assess prognostic associations. RESULTS:Patients with LAFB were older (70.46 ± 12.88 vs. 64.98 ± 13.42 years, p = 0.002) and had worse baseline cardiac function, with lower LVEF (30.86 ± 11.10% vs. 33.80 ± 8.49%, p = 0.036) and higher NT-proBNP levels (2397.31 ± 634.24 vs. 2161.23 ± 612.14 pg/mL, p = 0.004). Kaplan-Meier analysis showed worse event-free survival in the LAFB group (log-rank p = 0.012). Multivariate Cox regression indicated that the absence of LAFB was associated with a reduced risk of the primary composite endpoint (hazard ratio [HR] 0.48, 95% confidence interval [95% CI]: 0.23-0.99, p = 0.048). At 6 months, the no-LAFB group exhibited greater LVEF improvement (between-group difference 2.94%, 95% CI: 0.55-5.33) and more pronounced reverse remodeling. CONCLUSION:LAFB is an independent predictor of adverse outcomes in hospitalized heart failure patients and is associated with reduced cardiac functional recovery, highlighting its potential for risk stratification and individualized therapeutic strategies.

BACKGROUND: To evaluate whether cancer modifies the effect of intensive blood pressure control on major cardiovascular outcomes. METHODS: Using data of the SPRINT (Systolic Blood Pressure Intervention Trial), we compared the risk of the composite outcomes of myocardial infarction, other acute coronary syndromes, stroke, heart failure, and cardiovascular death in patients with and without a history of cancer. Using Cox proportional hazards regression, we tested interactions between history of cancer and intensive blood pressure control on major cardiovascular outcomes. RESULTS: The study included a total of 9336 patients, with a mean age of 67.9±9.4 years, among whom 2066 (22.2%) were cancer survivors. Over a median follow-up of 3.2 years, 561 primary cardiovascular outcomes were observed. Cancer survivors had a similar risk of experiencing the primary outcome compared with patients without cancer after multivariable adjustment (adjusted hazard ratio, 0.94 [95% CI, 0.77–1.15]). Intensive blood pressure control reduced risk of the primary cardiovascular outcome similarly for cancer survivors (hazard ratio, 0.70 [95% CI, 0.51–0.97]) and patients without cancer (HR, 0.76 [95% CI, 0.63–0.93]; P for interaction 0.74). CONCLUSIONS: In SPRINT study, intensive blood pressure treatment reduced the risk of major cardiovascular events in cancer survivors to a similar extent to that of patients without cancer. Cancer history not requiring active treatment in last 2 years should not be an obstacle to intensive treatment of hypertension. This post hoc analysis should be considered as hypothesis-generating and merit further clinical trial. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01206062.

Around 70% of patients diagnosed with hypertension exhibit increased levels of renin. SPH3127, an inventive renin inhibitor, has shown favorable tolerability and sustained pharmacodynamic inhibitory impact on plasma renin activity (PRA) during previous phase I trials. This phase II study was conducted to investigate the efficacy and safety of SPH3127 in patients with essential hypertension. This study was conducted in patients with mild to moderate essential hypertension, utilizing a randomized, double-blind, placebo-controlled design. The patients were administered either tablet of SPH3127 at doses of 50 mg, 100 mg, or 200 mg, or a placebo. A total of 122 patients were included in the study, with 121 patients included in the full analysis set. Among these patients, there were 30 individuals in each subgroup receiving different dosage regimens of SPH3127, and 31 patients in the placebo group. The reductions in mean sitting diastolic blood pressure (msDBP) after 8 weeks compared to baseline were 5.7 ± 9.5, 8.6 ± 8.8, and 3.8 ± 10.6 mmHg in the SPH3127 50-, 100-, and 200 mg groups, respectively. In the placebo group, the reduction was 3.1 ± 8.4 mmHg. The corresponding reductions in mean sitting systolic blood pressure (msSBP) were 11.8 ± 13.0, 13.8 ± 11.2, 11.1 ± 13.1, and 7.7 ± 9.7 mmHg in each respective group. SPH3127 is a promising drug for the treatment of patients with essential hypertension. The recommended dosage is 100 mg daily. Clinical trial registration: This study was registered in ClinicalTrials.gov (NCT03756103).

Objectives: To describe a bladder cuff excision method modified with ureteral catheterization to better visualize the ureteral orifice during robot-assisted nephroureterectomy (RANU). Methods: We retrospectively analyzed 66 patients with upper urinary tract urothelial carcinoma of the renal pelvis and/or upper-mid ureter treated between January 2020 and January 2023. Among them, 32 patients (group A) underwent RANU supported by ureteral catheterization, and the remaining patients (group B) received routine transperitoneal RANU. Postoperative cystoscopy was performed routinely to compare the rates of residual ureteral orifice between the two groups. Results: Surgeries were completed uneventfully in all 66 patients, without blood transfusion or conversion to open procedures. The operative time, estimated blood loss, and postoperative length of hospital stay were similar between both groups. However, the mean time required for BCE in group A was shorter than that in group B (9.5 min vs. 16.0 min, p = 0.006). Cystoscopy at postoperative three months showed no ipsilateral ureteral orifice in group A, but residual ureteral orifice was found in 23.5% of patients in group B. During a short follow-up period of 16 months, no patients in group A experienced bladder tumor recurrence. However, two patients (5.9%) in group B developed bladder tumor recurrence, with one experiencing local tumor recurrence at the level of the ureteral stump. Conclusions: Our novel technique enables complete ureteral retrieval, accurate and rapid bladder cuff excision, which makes the procedure less invasive and safely reproducible during robot-assisted nephroureterectomy.

Photodynamic therapy (PDT) is often applied in a clinical setting to treat bladder cancer. However, current photosensitizers report drawbacks such as low efficacy, low selectivity, and numerous side effects, which have limited the clinical values of PDT for bladder cancer. Previously, we developed the first bladder cancer-specific aptamer that can selectively bind to and be internalized by bladder tumor cells versus normal uroepithelium cells. Here, we use an aptamer-based drug delivery system to deliver photosensitizer chlorine e6 (Ce6) into bladder tumor cells. In addition to Ce6, we also incorporate catalase into the drug complex to increase local oxygen levels in the tumor tissue. Compared with free Ce6, an aptamer-guided DNA nanotrain (NT) loaded with Ce6 and catalase (NT-Catalase-Ce6) can specifically recognize bladder cancer cells, produce oxygen locally, induce ROS in tumor cells, and cause mitochondrial apoptosis. In an orthotopic mouse model of bladder cancer, the intravesical instillation of NT-Catalase-Ce6 exhibits faster drug internalization and a longer drug retention time in tumor tissue compared with that in normal urothelium. Moreover, our modified PDT significantly inhibits tumor growth with fewer side effects such as cystitis than free Ce6. This aptamer-based photosensitizer delivery system can therefore improve the selectivity and efficacy and reduce the side effects of PDT treatment in mouse models of bladder cancer, bearing a great translational value for bladder cancer intravesical therapy.

623 Background: According to European Association of Urology (EAU) guidelines, repeated transurethral resection of bladder tumor (re-TURBT) is recommended in a large percentage of non–muscle-invasive bladder cancers (NMIBC) due to possibility of incomplete initial TURBT. However, no reliable predictors have been developed to help select patient candidates who could avoid Re-TURBT in NMIBC. Methods: This was a blinded, observational, prospective multicenter study (NCT05112523). A total of 162 patients who underwent initial TURBT and were scheduled for Re-TURBT were enrolled in this study between June 2021 and August 2023 from four centers. Urine sample of each patient was collected prior to Re-TURBT. High-throughput sequencing of 17 genes and methylation analysis for ONECUT2 CpG sites were combined as a liquid biopsy test panel named OncoUrine. The OncoUrine test results were compared to pathological results at Re-TURBT to assess the performance in predicting residual tumor and predictive value of risk stratification. Patients who received intravesical infusion chemotherapy or BCG were followed up for recurrence analysis. Results: 151 patients were finally included for performance analysis. At Re-TURBT, 48 (31.8%) samples had residual tumor and 103 (68.2%) had no residual tumor. 1 Ta and 2 T1 patients were up staged to T2 at Re-TURBT. Overall, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of OncoUrine test were 77.1%, 77.7%, 61.7%, and 87.9%. Compared to OncoUrine, Cytology prior to Re-TURBT yielded a high specificity of 95.8% but lower sensitivity of 20% and combined with OncoUrine improved the sensitivity to 75.6%. In the overall OncoUrine test results, variants from 12 genes showed positive mutations. TERT, TP53, ERBB2, FGFR3, and PIK3CA were on the top 5 of the lists with other mutations from ERBB3, ERCC2, U2AF1, HRAS, KDM6A, KRAS, and ROHA. 132 were followed up with a median of 362 days (range 21 to 953). 19 patients were found recurred. The pathological results at Re-TURBT, OncoUrine, methylation and TERT results were risk stratification approaches for the recurrence analysis (positive vs. negative, p＜0.05). Conclusions: OncoUrine test after initial TURBT for NMIBC showed promise as to guide patient selection for Re-TURBT and risk stratification in the management of NMIBC. Clinical trial information: NCT05112523 .

Aims: Pemafibrate substantially lowers serum triglyceride (TG) levels and increases high-density lipoprotein cholesterol (HDL-C) levels primarily in Japan, but it has not been evaluated in China. We aimed to confirm the efficacy and safety of pemafibrate in Chinese patients with hypertriglyceridemia and low HDL-C levels by comparing placebo and fenofibrate. Methods: A multicenter, double-masked trial was conducted in China involving 344 patients with high TG and low HDL-C levels randomly assigned to one of four groups: pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, or placebo for 12 weeks. The primary endpoint was the percentage change in fasting TG levels. Results: The percentage change in TG levels from baseline was-34.1%,-44.0%,-30.5%, and 6.5% in the pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, and placebo groups, respectively. Pemafibrate 0.4 mg/d significantly reduced TG levels compared with that in both placebo ( p 0.0001) and fenofibrate groups ( p 0.0083). Significant improvements in HDL-C, remnant cholesterol, and apolipoprotein A1 levels were also observed with both doses of pemafibrate than with the placebo. Pemafibrate showed significantly smaller changes in alanine aminotransferase, aspartate aminotransferase, and serum creatinine levels than those with fenofibrate. Conclusions: In Chinese patients, pemafibrate exhibited superior efficacy in improving TG levels and enhanced hepatic and renal safety compared to fenofibrate. Thus, pemafibrate may represent a promising therapeutic option for dyslipidemia in Chinese patients.

Tobacco carcinogens metabolism-related genes (TCMGs) could generate reactive metabolites of tobacco carcinogens, which subsequently contributed to multiple diseases. However, the association between genetic variants in TCMGs and bladder cancer susceptibility remains unclear. In this study, we derived TCMGs from metabolic pathways of polycyclic aromatic hydrocarbons and tobacco-specific nitrosamines, and then explored genetic associations between TCMGs and bladder cancer risk in two populations: a Chinese population of 580 cases and 1101 controls, and a European population of 5930 cases and 5468 controls, along with interaction and joint analyses. Expression patterns of TCMGs were sourced from Nanjing Bladder Cancer (NJBC) study and publicly available datasets. Among 43 TCMGs, we observed that rs7087341 T > A in AKR1C2 was associated with a reduced risk of bladder cancer in the Chinese population [odds ratio (OR) = 0.84, 95

N6-methyladenosine (m6A) is important in the physiological processes of many species.Methyltransferase-like 16 (METTL16) is a novel discovered m6A methylase, regulating various tumors in an m6A-dependent manner.However, its function in bladder cancer (BLCA) remains largely unclear.In the present study, we found that low expression of METTL16 predicted poor survival in BLCA patients.METTL16 inhibited the proliferation and cisplatin-resistance function of bladder cancer cells in vitro and in vivo.In addition, METTL16 reduced the mRNA stability of prostate transmembrane protein androgen induced-1 (PMEPA1) via binding to its m6A site in the 3'-UTR, thereby inhibited the proliferation of bladder cancer cells and increased the sensitivity of cisplatin through PMEPA1-mediated autophagy pathway.Finally, we found that hypoxia-inducible factor 2α (HIF-2α) exerted its tumor-promoting effect by binding the METTL16 promoter region to repress its transcription.Taken together, High expression of METTL16 predicted better survival in BLCA.METTL16 significantly inhibited bladder cancer cell proliferation and sensitized bladder cancer cells to cisplatin via HIF-2α-METTL16-PMEPA1-autophagy axis in a m6A manner.These findings might provide fresh insights into BLCA therapy.

BACKGROUND:Co-morbid hypertension is strong predictor of adverse cardiovascular (CV) outcomes in patients with atrial fibrillation (AF) but the optimal target for blood pressure (BP) control in this patient population has not been clearly defined. METHODS:The Cardiovascular Risk reduction in patients with Atrial Fibrillation Trial (CRAFT) is an investigator-initiated and conducted, international, multicenter, open-label, parallel-group, blinded outcome assessed, randomized controlled trial of intensive BP control in patients with AF. The aim is to determine whether intensive BP control (target home systolic blood pressure [SBP] <120 mmHg) is superior to standard BP control (home SBP <135 mmHg) on the hierarchical composite outcome of time to CV death, number of stroke events, time to the first stroke, number of myocardial infarction (MI) events, time to the first MI, number of heart failure hospitalization (HFH) events, and time to the first HFH. A sample size of 1,675 patients is estimated to provide 80% power to detect a win-ratio of 1.50 for intensive versus standard BP control on the primary composite outcome. Study visits are conducted at 1, 2, 3, and 6 months postrandomization, and every 6 months thereafter during the study. CONCLUSIONS:This clinical trial aims to provide reliable evidence of the effects of intensive BP control in patients with AF. TRIAL REGISTRATION:The trial is registered at ClinicalTrials.gov (NCT04347330).