Cysteine cathepsins and autoimmune diseases: A bidirectional Mendelian randomization.

Cysteine cathepsins are proteolytic enzymes crucial in various physiological and pathological processes, primarily operating within lysosomes. Their functions include protein degradation, immune system regulation, and involvement in various diseases. While some cysteine cathepsins play important roles in the immune system, their connection to autoimmune diseases remains unclear. This study proposes using Mendelian randomization to explore the causal relationship between cysteine cathepsins and autoimmune diseases. Single nucleotide polymorphisms (SNPs) for cysteine cathepsins were obtained from a publicly available genome-wide association study (GWAS) dataset, while outcome SNP data were sourced from 10 separate GWAS datasets. Mendelian randomization (MR) analysis employed the Wald ratio (WR) and inverse variance weighted (IVW) approach as primary methods, supplemented by the weighted median and MR-Egger methods. Heterogeneity was assessed using Cochran Q test, and sensitivity analysis was conducted using the MR-PRESSO method. The association strength between exposure and outcome was evaluated using odds ratios (OR) with 95% confidence intervals (CI). The study identified a potential positive correlation between elevated cathepsin B and psoriasis (Wald ratio OR = 1.449, 95% CI: 1.053-1.993, P = .0227). Elevated cathepsin F was potentially linked to ulcerative colitis (WR OR = 1.073, 95% CI: 1.021-1.127, P = .0056), ankylosing spondylitis (WR OR = 1.258, 95% CI: 1.082-1.463, P = .0029), and primary biliary cholangitis(PBC) (WR OR = 1.958, 95% CI: 1.326-2.889, P = .0007). Conversely, cathepsin H appeared protective against celiac disease (WR OR = 0.881, 95% CI: 0.838-0.926, P = 6.5e-7), though elevated levels may increase the risk of type 1 diabetes (IVW OR = 1.121, 95% CI: 1.053-1.194, P = .0003) and PBC (WR OR = 1.792, 95% CI: 1.062-3.024, P = .0288). Cathepsin Z was also associated with an increased risk of type 1 diabetes (IVW OR = 1.090, 95% CI: 1.006-1.181, P = .0349). The MR analysis suggests potential risks of cathepsin B with psoriasis, cathepsin F with ulcerative colitis, ankylosing spondylitis, and PBC, and cathepsin Z with type 1 diabetes. Conversely, cathepsin H may protect against celiac disease but could increase the risk of type 1 diabetes and PBC.

Relationship between cathepsins and cardiovascular diseases: a Mendelian randomized study.

Background: Cardiovascular diseases (CVDs) are the leading age-related disorders worldwide, with their prevalence increasing annually. Cathepsins are protein-degrading enzymes essential for processes such as intracellular protein breakdown, apoptosis, and immune responses. Recent studies suggest a potential link between cathepsins and CVDs, yet the exact causal relationship remains to be elucidated. To address this, we propose using Mendelian randomization (MR) to explore the causal relationships between cathepsins and CVDs. Methods: We obtained single nucleotide polymorphism (SNP) data for cathepsins from the INTERVAL study, a publicly accessible genome-wide association study (GWAS) dataset. Outcome SNP data were sourced from seven distinct GWAS datasets, ensuring a comprehensive analysis across multiple cardiovascular outcomes. For MR analysis, we primarily employed the inverse variance weighted (IVW) method, known for its efficiency when all SNPs are valid instruments. This was supplemented by the weighted median and MR-Egger methods to provide robustness against potential violations of MR assumptions, such as pleiotropy. The IVW method offers precision and efficiency, the weighted median method adds robustness against invalid instruments, and the MR-Egger method helps identify and correct for pleiotropic biases. Cochran's Q test was utilized to assess heterogeneity, and sensitivity analyses were conducted using MR-PRESSO and the leave-one-out approach. Results: The strength of the associations between exposure and outcome was measured using odds ratios (ORs), and results were presented with 95% confidence intervals (CIs). The cathepsin E increases the risk of myocardial infarction (MI) (OR = 1.053%, 95% CI: 1.007-1.101, p = 0.024) and ischemic stroke (IS) (OR = 1.06%, 95% CI: 1.019-1.103, p = 0.004). Conversely, cathepsin L2 decreases the risk of chronic heart failure (CHF) (OR = 0.922%, 95% CI: 0.859-0.99, p = 0.025) and atrial fibrillation (AF) (OR = 0.956%, 95% CI: 0.918-0.996, p = 0.033). Cathepsin O was associated with an increased risk of IS (OR = 1.054%, 95% CI: 1.008-1.102, p = 0.021) and AF (OR = 1.058%, 95% CI: 1.02-1.098, p = 0.002). Conclusion: Our MR analysis reveals that cathepsin E is a risk factor for MI and IS, cathepsin L2 offers protective effects against CHF and AF, and cathepsin O increases the risk for IS and AF.

Cost-effectiveness of tirofiban for acute ischemic stroke without large or medium-sized vessel occlusion: A Markov modelling analysis from the Chinese and United States perspectives.

BACKGROUND: The RESCUE BT2 trial recently showcased the efficacy of tirofiban in treating acute ischemic stroke (AIS) without large or medium-sized vessel occlusion. To further assess the value of tirofiban from the perspectives of Chinese and US healthcare system, a study was conducted to evaluate its cost-effectiveness. METHODS: A hybrid model, integrating a short-term decision tree with a long-term Markov model, was developed to assess cost-effectiveness between tirofiban and aspirin for stroke patients without large or medium-sized vessel occlusion. Efficacy data for tirofiban was sourced from the RESCUE BT2 trial, while cost information was derived from published papers. Outcomes measured included respective cost, effectiveness, and incremental cost-effectiveness ratio (ICER). We conducted a one-way sensitivity analysis to assess the robustness of the results. Additionally, we performed probabilistic sensitivity analysis (PSA) through 10,000 Monte Carlo simulations to evaluate the uncertainties associated with the results. RESULTS: The study revealed that tirofiban treatment in AIS patients without large or medium-sized vessel occlusion led to a considerable reduction of 2141 Chinese Yuan (CNY) in total cost, along with a lifetime gain of 0.14 quality-adjusted life years (QALYs). In the US settings, tirofiban also exhibited a lower cost ($197,055 versus $201,984) and higher effectiveness (4.15 QALYs versus 4.06 QALYs) compared to aspirin. One-way sensitivity analysis revealed that post-stroke care costs and stroke utility had the greatest impact on ICER fluctuation in both Chinese and US settings. However, these variations did not exceed the willingness-to-pay threshold. PSA demonstrated tirofiban's superior acceptability over aspirin in over 95% of potential scenarios. CONCLUSION: Tirofiban treatment for AIS without large or medium-sized vessel occlusion appeared dominant compared to aspirin in both China and the US.

Endovascular treatment for basilar artery occlusion: a cost-effectiveness analysis based on a meta-analysis.

Objective: This study aimed to investigate the efficacy and economic effect of endovascular treatment (EVT) combined with standard medical treatment (SMT) vs. SMT alone in Chinese patients with basilar artery occlusion (BAO) from the perspective of the Chinese healthcare system. Methods: We conducted a cost-effectiveness analysis using the results from a meta-analysis comparing EVT and SMT efficacy in Chinese patients with BAO-induced stroke using direct medical costs from the China National Stroke Registry. The meta-analysis's primary outcome was excellent functional outcome (mRS scores of 0-2), with secondary outcomes being poor functional outcome (mRS scores of 3-5) and death (mRS score of 6). To compare EVT plus SMT's cost-effectiveness with that of SMT alone, we constructed a combined decision tree and Markov model with a lifetime duration and a 3-month cycle length. The primary cost-effectiveness outcome was the incremental cost-effectiveness ratio (ICER), representing the incremental cost per incremental quality-adjusted life year (QALY). EVT was considered cost-effective if the ICER was lower than the willingness-to-pay (WTP) threshold of three times the per capita gross domestic product (GDP) in 2021 in China; otherwise, it would not be cost-effective. Results: The meta-analysis results indicated that EVT could increase the incidence of excellent functional outcomes, with a risk ratio (RR) of 2.23 (95% confidence interval, CI, 1.18-4.21), p = 0.01. Simultaneously, EVT reduced the risk of poor functional outcome and mortality in the EVT group, with RRs of 0.83 (95% CI, 0.67-1.03), p = 0.09, and 0.71 (95% CI, 0.59-0.85), p = 0.0002, respectively. The study also found that EVT plus SMT resulted in a lifetime effectiveness of 2.15 QALY (3.88 life years) for 32,213 international dollars (Intl.$) per patient with BAO. In contrast, SMT alone achieved an effectiveness of 1.46 QALY (3.03 life years) with a total cost of Intl.$ 13,592 per patient. The ICER was Intl.$ 27,265 per QALY (Intl.$ 22,098 per life-year), which fell below the WTP threshold. Conclusion: Compared to SMT, EVT improves the prognosis of BAO-induced stroke. Considering the Chinese healthcare system, adding EVT to SMT proves to be cost-effective for patients with BAO compared to SMT alone.

Tislelizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Esophageal Squamous Cell Carcinoma: A Cost-Effectiveness Analysis.

BACKGROUND AND OBJECTIVES: Advanced esophageal squamous cell carcinoma (ESCC) is a prevalent and highly malignant tumor with a poor prognosis. Recently, the RATIONALE-306 trial demonstrated that tislelizumab combined with chemotherapy provided overall survival benefits for these patients. This study aimed to assess the cost-effectiveness of this treatment approach in Chinese patients with advanced ESCC from the perspective of healthcare system. METHODS: A Markov model was constructed to assess the economic and health benefits associated with tislelizumab plus chemotherapy over a 10-year lifetime horizon, utilizing data from the RATIONALE-306 trial. The analysis encompassed the calculation of several key parameters, including the incremental cost-effectiveness ratio (ICER), total cost, incremental cost, total effectiveness, and incremental effectiveness. Tislelizumab was considered cost-effective if the ICER obtained was below the willingness-to-pay (WTP) threshold of US$38,223 per quality-adjusted life-year (QALY); otherwise, it would be deemed not cost-effective. To ensure the robustness of the findings, the results were subjected to one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). RESULTS: In the base-case analysis, the incremental effectiveness and cost associated with tislelizumab plus chemotherapy, compared to chemotherapy alone, were determined to be 0.40 QALY and US$7604, respectively. This resulted in an ICER of US$18,846 per QALY, which is below the WTP threshold of US$38,223 per QALY. Furthermore, the results from the one-way sensitivity analysis and PSA indicated robustness of the findings. CONCLUSION: Our lifetime simulation study demonstrated that, in the case of advanced ESCC, the combination of tislelizumab and chemotherapy offers increased effectiveness compared to chemotherapy alone, albeit at a higher cost. Moreover, considering the current WTP threshold in China, the addition of tislelizumab to chemotherapy is considered a cost-effective approach.

Residual inflammatory risk predicts long-term outcomes following stenting for symptomatic intracranial atherosclerotic stenosis.

BACKGROUND AND PURPOSE: Residual inflammatory risk (RIR) can predict the unfavourable outcomes in patients with minor ischaemic stroke. However, the impact of preprocedural RIR on long-term outcomes in patients with symptomatic intracranial atherosclerotic stenosis (sICAS) who underwent stenting remains understudied. METHODS: This retrospective, single-centre cohort study evaluated consecutive patients with severe sICAS who underwent intracranial stenting. Patients were categorised into four groups based on preprocedural high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L) and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). The long-term clinical outcomes included recurrent ischaemic stroke and death. The long-term imaging outcomes consisted of in-stent restenosis (ISR) and symptomatic ISR (sISR) after stenting. RESULTS: In this study, 952 patients were included, with 751 (78.9%) being male. Forty-six cases were categorised into the RCIR group, 211 into the RIR group, 107 into the RCR group and 588 into the NRR group. Patients with RCIR (adjusted HR 6.163; 95% CI 2.603 to 14.589; p<0.001) and RIR (adjusted HR 2.205; 95% CI 1.294 to 3.757; p=0.004) had higher risks of recurrent ischaemic stroke than those with NRR during the 54 months of median follow-up time. Patients with RCIR (adjusted HR 3.604; 95% CI 1.431 to 9.072; p=0.007) were more likely to occur ISR, and patients in the RIR group showed a significant increase in the risk of sISR (adjusted HR 2.402; 95% CI 1.078 to 5.351; p=0.032) compared with those in the NRR group with a median follow-up time of 11.9 months. CONCLUSIONS: In patients with sICAS, preprocedural RIR may predict long-term recurrent ischaemic stroke, ISR and sISR following intracranial stenting.

Sacubitril-valsartan versus enalapril for the treatment of acute decompensated heart failure in Chinese settings: A cost-effectiveness analysis.

Background: The episode of acute decompensated heart failure (ADHF) is the main cause of hospitalization for heart failure (HF). Sacubitril-valsartan has been proven to be effective in reducing the risks of hospitalization for HF in ADHF. When to initiate sacubitril-valsartan in ADHF to make it the most cost-effective in China remains unclear. Methods: A lifetime Markov model with a 1-month cycle length was developed to evaluate the cost-effectiveness of early or late initiation of sacubitril-valsartan versus enalapril in ADHF. Early initiation of sacubitril-valsartan meant that it was initiated after stabilization from ADHF, and late initiation of sacubitril-valsartan meant that it was initiated after stabilization from HF, which includes no hospitalization for at least three consecutive months. The primary outcome was the incremental cost-effectiveness ratio (ICER), expressed as the ratio of incremental cost to incremental effectiveness. The secondary outcomes were total costs and total effectiveness. Three times of per capita GDP of China in 2021 was set as the willingness-to-pay threshold. One-way sensitivity analysis and probabilistic sensitivity analysis were employed to test the robustness of the results. Results: The early initiation of sacubitril-valsartan treatment resulted in an ICER of 3,662.4 USD per quality-adjusted life year, lower than the willingness-to-pay threshold, and the late initiation of sacubitril-valsartan treatment gained an ICER of 4,444.4 USD/QALY, still lower than the willingness-to-pay threshold. One-way sensitivity analysis showed that our results were robust, and probabilistic sensitivity analysis suggested that early initiation of sacubitril-valsartan in ADHF was cost-effective under a 97.4% circumstance. Conclusion: Early initiation of sacubitril-valsartan after stabilization of ADHF is highly cost-effective compared with the use of enalapril; late initiation of sacubitril-valsartan after stabilization of HF is still cost-effective but not as cost-effective as early initiation of sacubitril-valsartan in ADHF. For Chinese ADHF patients, the time to initiate sacubitril-valsartan should be when the patient is stabilized from ADHF rather than when stabilized from HF, from the perspective of economic evaluation.

Sacubitril/Valsartan for Heart Failure with Preserved Ejection Fraction: A Cost-Effectiveness Analysis from the Perspective of the Chinese Healthcare System.

BACKGROUND AND OBJECTIVES: Sacubitril/valsartan has shown effectiveness in reducing hospitalization compared with valsartan in HFpEF patients with heart failure with preserved ejection fraction (HFpEF). We aimed to investigate the cost effectiveness of sacubitril/valsartan as an alternative to valsartan in Chinese patients with heart failure with HFpEF. METHODS: A Markov model was built to investigate the cost effectiveness of sacubitril/valsartan as an alternative to valsartan in Chinese patients with HFpEF, from the healthcare system perspective. The time horizon was a lifetime, with a cycle length of 1 month. Costs were obtained from local information or published papers, discounted at a rate of 0.05 for future costs. The transition probability and utility were based on other studies. The primary outcome of the study was the incremental cost-effectiveness ratio (ICER). Sacubitril/valsartan was considered cost effective if the ICER obtained was lower than the willingness-to-pay threshold of US dollars (US$) 12,551.5 per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses, as well as scenario analysis, were performed to test robustness. RESULTS: Over a lifetime simulation, a 73-year-old Chinese patient with HFpEF could gain 6.44 QALYs (9.15 life-years) if sacubitril/valsartan plus standard treatment was administered, and 6.37 QALYs (9.07 life-years) if valsartan plus standard treatment was prescribed. The corresponding costs in both groups were US$12,471 and US$8663, respectively. The ICER was US$49,019/QALY (US$46,610/life-year), higher than the willingness-to-pay threshold. Sensitivity analyses and scenario analysis showed that our results were robust. CONCLUSION: Adding sacubitril/valsartan to standard treatment as an alternative to valsartan for the treatment of HFpEF resulted in more effectiveness but higher costs. Sacubitril/valsartan was likely to not be cost effective in Chinese patients with HFpEF. The cost of sacubitril/valsartan needs to reduce to 34% of its current price to be cost effective in this population. Studies based on real-world data are needed to confirm our conclusions.

Endovascular treatment versus standard medical treatment for basilar artery occlusion: a meta-analysis of randomized controlled trials.

OBJECTIVE: Acute ischemic stroke caused by basilar artery occlusion (BAO) is devastating, but the optimal treatment for patients with BAO remains controversial. In this study, the authors aimed to investigate the safety and efficacy of endovascular treatment (ET) versus standard medical treatment (SMT) in patients with BAO. METHODS: The PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs). The primary outcome was good functional outcome, defined as a modified Rankin Scale (mRS) score of 0-3 at 90 days. The secondary efficacy outcome was excellent functional outcome defined as an mRS score of 0-2 at 90 days. The safety outcomes included mortality at 90 days and symptomatic intracranial hemorrhage (sICH). Subgroup analyses were carried out based on race (Asian or non-Asian). RESULTS: Four RCTs of 988 patients (556 in the ET group and 432 in the SMT group) were included in this meta-analysis. The proportion of good functional outcome in the ET group was significantly higher than that in the SMT group (45.1% vs 29.6%; number needed to treat 6.45; RR 1.54, 95% CI 1.16-2.06; p = 0.003, I2 = 60%). The subgroup analysis based on race showed a significant difference between Asian and non-Asian race in the primary outcome (p = 0.03, I2 = 78.5%). Patients in the ET group had a higher rate of excellent functional outcome at 90 days than those in the SMT group (34.9% vs 20.6%; RR 1.83, 95% CI 1.07-3.12; p = 0.03, I2 = 80%). Patients in the ET group had a lower mortality at 90 days (35.6% vs 45.4%; RR 0.77, 95% CI 0.66-0.89; p = 0.0007, I2 = 0%) but a higher rate of sICH (5.4% vs 0.5%; RR 8.29, 95% CI 2.49-27.66; p = 0.0006, I2 = 0%) than those in the SMT group. CONCLUSIONS: ET may improve the functional outcome and reduce mortality at 90 days but increase the risk of sICH compared with SMT in patients with BAO. This conclusion needs to be confirmed in non-Asian populations in future studies. Systematic review registration no.: CRD42022357718 (https://www.crd.york.ac.uk/prospero/).

Cost-Effectiveness of Adding Empagliflozin to Standard Treatment for Heart Failure with Preserved Ejection Fraction Patients in China.

OBJECTIVES: Heart failure is a worldwide health problem and is the leading cause of hospitalization in older patients. Heart failure with preserved ejection fraction (HFpEF) accounts for about 38% of heart failure cases. The latest EMPEROR-Preserved study shows that empagliflozin can reduce the risk of hospitalization in HFpEF, but whether empagliflozin is cost-effective in HFpEF in a Chinese setting remained uninvestigated. METHODS: A simulation of lifetime horizon for a 72-year-old HFpEF patient was conducted using a Markov model. The primary outcome was incremental cost-effectiveness ratio (ICER), expressed as incremental costs per quality-adjusted life-year (QALY). Three times the per capita GDP of China was set as the willingness-to-pay (WTP) threshold. Empagliflozin was considered cost-effective if the ICER was below the WTP threshold, otherwise it would be regarded as not cost-effective. One-way sensitivity and probabilistic sensitivity analysis (PSA) were used to assess uncertainty. RESULTS: After a simulation of lifetime horizon, a 72-year-old HFpEF patient is expected to have an expected QALY of 4.80 in the empagliflozin group, and 4.67 QALY with standard treatment. The costs of empagliflozin and standard treatment are 34,987 (US$5423) and 27,027 (US$4189) Chinese Yuan (CNY), respectively, with an ICER of 63,746 (US$9881)/QALY, lower than the WTP threshold. One-way sensitivity and PSA show that our results are robust. CONCLUSION: In Chinese HFpEF patients, adding empagliflozin to standard treatment is cost-effective, but studies based on real-world data are needed.

Risk of Atrial Fibrillation Following Left Bundle Branch Area Pacing versus Right Ventricular Pacing and Biventricular Pacing: A Systematic Review and Meta-Analysis.

Background: Left bundle branch pacing (LBBP) is a relatively novel physiological pacing strategy with better electrocardiogram characteristics and pacing parameters than other pacing strategies. At present, no meta-analysis or systematic review has examined the risk of atrial fibrillation (AF) after LBBP compared to other pacing strategies. Methods: We searched the PubMed, Embase, and Cochrane Library databases from inception through September 18, 2022 to identify relevant studies reporting AF incidence rates after LBBP. The incidence of AF following LBBP and that associated with other pacing strategies were extracted and summarized for the meta-analysis. We used odds ratios (ORs) and 95% confidence intervals (CIs) as summary estimates. Results: Five studies with 1144 participants were included. The pooled rate of AF was 3.7% (95% CI, 0.8%-8.0%) in the LBBP group and 15.5% (95% CI: 9.6%-22.4%) in the other pacing strategies (right ventricular pacing [RVP] and biventricular pacing [BVP]). Compared with other pacing strategies, LBBP was associated with a lower AF risk (OR, 0.33; 95% CI: 0.22-0.51, I 2 = 0.0%; p = 0.485). Similar results were observed for LBBP when compared with RVP (OR: 0.33, 95% CI: 0.22-0.51, I 2 = 0.0%, p = 0.641) and BVP (OR: 0.47, 95% CI: 0.01-15.22, I 2 = 60.4%, p = 0.112). Conclusions: Compared with BVP and RVP, LBBP was associated with a significantly lower risk of AF. However, further large-sample randomized controlled trials are needed to confirm that LBBP is superior to other pacing strategies in reducing AF risk.

MitraClip for the treatment of heart failure with mitral regurgitation: A cost-effectiveness analysis in a Chinese setting.

Background: Heart failure (HF) with mitral regurgitation is associated with decreased survival. Guideline-directed medical therapy and transcatheter edge-to-edge repair (TEER) are the main options for HF patients with severe mitral regurgitation who are considered high-risk or prohibitive. To date, there have been no studies investigating the cost-effectiveness of MitraClip vs. optimal medical therapy (OMT) in a Chinese setting. Methods: A combined decision tree and Markov model were developed to compare the cost-effectiveness MitraClip vs. OMT with a lifetime simulation. The primary outcome was the incremental cost-effectiveness ratio (ICER), which represented incremental costs per quality-adjusted life-year (QALY). The willingness-to-pay (WTP) threshold was set three times of per capita gross domestic product (GDP) in China in 2021, which was 242,928 CNY. MitraClip would be considered cost-effective if the ICER obtained was lower than the WTP threshold. Otherwise, it would be not considered cost-effective. One-way sensitivity and probabilistic sensitivity analyses were performed to validate the robustness of the results. Results: After a simulation of the lifetime, the overall cost for a patient in the MitraClip cohort was 423,817 CNY, and the lifetime cost in the OMT was 28,369 CNY. The corresponding effectiveness in both cohorts was 2.32 QALY and 1.80 QALY per person, respectively. The incremental cost and increment effectiveness were 395,448 CNY and 0.52 QALY, respectively, and the ICER was 754,410 CNY/QALY. The ICER obtained was higher than the WTP threshold. Sensitivity analysis validated our finding. Conclusion: MitraClip provided effectiveness but with more costs compared with OMT, and the incremental cost-effectiveness ratio obtained was higher than the WTP threshold. MitraClip was considered not cost-effective in Chinese HF patients with secondary mitral regurgitation.

Sacubitril-valsartan for the treatment of hypertension in China: A cost-utility analysis based on meta-analysis of randomized controlled trials.

Background: Sacubitril-valsartan was recommended for heart failure (HF) and proven cost-effective in HF. Recently, sacubitril-valsartan has been recommended to treat hypertension by the Chinese expert consensus. The cost utility of sacubitril-valsartan for hypertension remains uninvestigated. Methods: A meta-analysis of randomized controlled trials (RCTs) was performed to investigate the real efficacy of sacubitril-valsartan on blood pressure, compared with angiotensin receptor blockers or placebo. A lifetime Markov model was developed to compare the cost utility of sacubitril-valsartan vs. valsartan. The primary outcome was the incremental cost-utility ratio (ICUR), representing the ratio of incremental costs to the incremental utility. The willingness-to-pay (WTP) threshold was three times of per capita gross domestic product (GDP) in China in 2021. Sacubitril-valsartan was considered cost-effective if the ICUR obtained was lower than the WTP threshold, otherwise, sacubitril-valsartanis was not cost-effective. Results: A total of 10 RCTs of 5,781 patients were included in the meta-analysis. For comparison of sacubitril-valsartan 400 mg/day vs. valsartan 320 mg/day, a reduction in blood pressure (BP) of -5.97 (-6.38, -5.56) (p < 0.01) was observed. Cost-utility analysis showed that for a 60-year-old patient with hypertension, if sacubitril-valsartan was prescribed as the antihypertensive agent, he had a life expectancy of 11.91 quality-adjusted life-years (QALYs) with costs of 65,066 CNY, and if valsartan was prescribed as the antihypertensive agent, the life expectancy would be 11.82 QALY with costs of 54,769 CNY; thus, an ICUR of 108,622 CNY/QALY was obtained, lower than the WTP threshold. Conclusion: Compared with valsartan, sacubitril-valsartan is more effective in reducing blood pressure and may result in more quality-adjusted life-year, although with higher costs. Sacubitril-valsartan is cost-effective for hypertension in the current China setting under the willingness-to-pay threshold of 3 times of per capita GDP.

Economic Evaluation of Transcatheter Aortic Valve Replacement Compared to Surgical Aortic Valve Replacement in Chinese Intermediate-Risk Patients.

Background: Aortic stenosis (AS) is a severe disease that causes heart failure and sudden death. Transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) are both recommended for patients with intermediate surgical risk, but the cost-effectiveness of TAVR compared to SAVR in China has not been investigated. Methods: A combined decision tree and Markov model were conducted to compare the cost-effectiveness of TAVR versus SAVR with a 5-year simulation. The primary outcome was the incremental cost-effectiveness ratio (ICER), a ratio of incremental costs to incremental quality-adjusted life-year (QALY). One-way sensitive analysis and probabilistic sensitivity analysis (PSA) were conducted to test the robustness of the model. Results: After a simulation of 5 years, the costs of TAVR and SAVR were 54,573 and 35,002 USD, respectively, and the corresponding effectiveness was 2.826 versus 2.712 QALY, respectively. The ICER for the TAVR versus SAVR comparison was 170,056 USD/QALY, which was three times higher than the per capita gross domestic product (GDP) in China. One-way sensitive analysis showed that the cost of the TAVR device impacted the ICER. The TAVR could be cost-effective only in the case where its cost is lowered to 29,766 USD. Conclusion: TAVR is currently not cost-effective in China, but it could be cost-effective with a reduction of costs to 29,766 USD, which is approximately 65% of the current price.

Multiple predictors of in-stent restenosis after stent implantation in symptomatic intracranial atherosclerotic stenosis.

OBJECTIVE: This study aimed to identify predictors of intracranial in-stent restenosis (ISR) after stent placement in symptomatic intracranial atherosclerotic stenosis (ICAS). METHODS: The authors retrospectively collected data from consecutive patients who suffered from symptomatic ICAS and underwent successful stent placement in Beijing Tiantan hospital. Eligible patients were classified into "ISR," "indeterminate ISR," or "no-ISR" groups by follow-up digital subtraction angiography or CT angiography. A multivariate logistic regression model was used to explore the predictors of intracranial ISR after adjustments for age and sex. In addition, ISR and no-ISR patients were divided into two groups based on the strongest predictor, and the incidence of ISR, recurrent stroke, and symptomatic ISR was compared between the two groups. RESULTS: A total of 511 eligible patients were included in the study: 80 ISR, 232 indeterminate ISR, and 199 no-ISR patients. Elevated high-sensitivity C-reactive protein (hs-CRP; odds ratio [OR] 4.747, 95% confidence interval [CI] 2.253-10.01, p < 0.001), Mori type B and C (Mori type B vs Mori type A, OR 3.119, 95% CI 1.093-8.896, p = 0.033; Mori type C vs Mori type A, OR 4.780, 95% CI 1.244-18.37, p = 0.023), coronary artery disease (CAD; OR 2.721, 95% CI 1.192-6.212, p = 0.017), neutrophil/lymphocyte ratio (NLR; OR 1.474 95% CI 1.064-2.042, p = 0.020), residual stenosis (OR 1.050, 95% CI 1.022-1.080, p = 0.001) and concurrent intracranial tandem stenosis (OR 2.276, 95% CI 1.039-4.986, p = 0.040) synergistically contributed to the occurrence of intracranial ISR. Elevated hs-CRP (hs-CRP ≥ 3 mg/L) was the strongest predictor for ISR, and the incidence of ISR in the elevated hs-CRP group and normal hs-CRP group (hs-CRP < 3 mg/L) was 57.14% versus 21.52%, respectively, with recurrent stroke 44.64% versus 16.59%, and symptomatic ISR 41.07% versus 8.52%. CONCLUSIONS: Elevated hs-CRP level, NLR, residual stenosis, Mori type B and C, CAD, and concurrent intracranial tandem stenosis are the main predictors of intracranial ISR, and elevated hs-CRP is crucially associated with recurrent stroke in patients with symptomatic ICAS after intracranial stent implantation.

The Effects of Continuous Positive Airway Pressure Therapy for Secondary Cardiovascular Prevention in Patients with Obstructive Sleep Apnoea: A Systematic Review and Meta-Analysis.

Background: Obstructive sleep apnoea (OSA) is highly prevalent and significantly associated with major adverse cardiovascular events (MACEs). Continuous positive airway pressure (CPAP) treatment has a protective effect on cardiovascular events in OSA patients. However, whether CPAP therapy significant reduces the risk of recurrent cardiovascular (CV) events in OSA patients with established cardiovascular or cerebrovascular diseases remains disputed. We aim to evaluate the effect of CPAP on recurrent cardiovascular outcomes in moderate to severe OSA patients with previous cardiovascular or cerebrovascular diseases. Methods: We searched the electronic databases (PubMed, EMBASE, and Cochrane library) from their inception to August, 2021. Only randomized controlled trials (RCTs) that described the association of CPAP treatment in patients with cardiovascular or cerebrovascular disease and OSA were included in our analysis. The primary outcome of interest was major adverse cardiac or cerebral events (MACCEs), a composite endpoint of myocardial infraction (MI), non-fatal stroke, CV mortality; secondary outcomes included all-caused death, cardiac mortality, myocardial infraction, atrial fibrillation, heart failure, repeat revascularization, angina, stroke, and transient ischemic attack. In addition, subgroup analyses based on CPAP adherence were performed. Result: Six RCTs of 4493 participants were included in the analysis. Compared with usual care, CPAP therapy did not significantly reduce the risk of recurrent MACCEs odds ratio (OR) 0.94, 95% confidence interval (CI) 0.79-1.12, p = 0.5, CV mortality (OR 0.83, 95% CI [0.54-1.26], p = 0.37), myocardial infarction (OR 1.09, 95% CI [0.8-1.47], p = 0.6), heart failure (OR 0.94, 95% CI [0.66-1.33], p = 0.71), stroke (OR 0.9, 95% CI [0.67-1.23], p = 0.52), or all-cause death (OR 0.86, 95% CI [0.63-1.16], p = 0.32). However, the subgroup analyses revealed that CPAP can decrease the risk of CV mortality (OR 0.25, 95% CI [0.08-0.77], p = 0.02) and stoke (OR 0.39, 95% CI [0.15-0.97], p = 0.04) in patients who used it more than 4 hours. Conclusions: CPAP therapy was not associated with reduce the risk of MACCEs in OSA patients with a history of chronic cardiovascular disease who utilize CPAP < 4 hours/night, although CPAP appeared to have a positive effect on CV mortality and stroke among those who used CPAP > 4 hours. The correlation between CPAP and the prognosis of OSA patients warrants further study.

Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure with a Preserved Ejection Fraction: A Meta-Analysis of Randomized Controlled Trials.

Background: Heart failure is prevalent worldwide. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are effective in heart failure patients with reduced ejection fraction, whether SGLT2i are effective in heart failure with preserved ejection fraction (HFpEF) remains to be determined. Methods: All relevant citations in the PubMed, Embase and Cochrane databases were identified from inception to September, 2022. The primary outcome was a composite endpoint of cardiovascular death and hospitalization for heart failure (HHF). A subgroup analysis was performed according to diabetes mellitus status and the ejection fraction. Secondary endpoints were cardiovascular death, hospitalization for heart failure and all cause death. Results: Seven studies involving 11,604 patients were included in the meta-analysis. Compared with placebo, sodium-glucose cotransporter 2 inhibitors reduced the incidence of the primary outcome by 24%, with an odds ratio (OR) and 95% confidence interval (CI) 0.76 [0.69, 0.84]. For secondary outcomes, sodium-glucose cotransporter 2 inhibitors were associated with a lower incidence of hospitalization for heart failure, but not cardiovascular or all-cause death; the OR and 95% CI were 0.73 [0.66, 0.82], 0.92 [0.81, 1.04], 0.96 [0.88, 1.05], respectively. Conclusions: This study proves the clinical efficacy of SGLT2i for treatment of HFpEF patients with or without diabetes, which was mainly driven by prevention of HHF rather than cardiovascular or all-cause death.

Effectiveness of Suprascapular Nerve Block in the Treatment of Hemiplegic Shoulder Pain: A Systematic Review and Meta-Analysis.

Purpose: We aimed to investigate the effectiveness of suprascapular nerve block (SSNB) in patients with hemiplegic shoulder pain (HSP). Background: SSNB is widely used in various shoulder pains, but whether it is effective in HSP remains unknown. Methods: PubMed, Cochrane Library, and Embase databases were searched to identify potential citations. Randomized controlled trials meeting the eligible criteria were included in our analysis. The primary endpoint was Visual Analog Scale (VAS) with a maximum value of 100 and a minimum value of 0. Secondary endpoints were passive range of motion (PROM) that pain starts, and the PROM mainly included abduction, flexion, and external rotation. In addition, the upper extremity Fugl-Meyer assessment (FMA) was also included in our secondary endpoints. Results: Eight studies with 281 patients were included in our analysis. For VAS, there was no obvious difference between SSNB group and control group regardless of the follow-up period (<4 weeks or ≥4 weeks), which were -6.62 (-15.76, 2.53; p = 0.16) and 1.78 (-16.18, 19.74; p = 0.85). For shoulder function, the PROM of abduction, flexion, and external rotation was similar between groups. However, motor function indicator FMA is lower in SSNB control than that in control group, with a mean difference (and 95% CI) of -2.59 (-4.52, -0.66; p = 0.008). Conclusion: SSNB is an effective way for HSP patients. Systematic Review Registration: Registration ID: CRD42021252429.

The relationship between residual cholesterol risk and plaque characteristics in patients with acute coronary syndrome: Insights from an optical coherence tomography study.

BACKGROUND AND AIMS: The impact of residual cholesterol risk (RCR) on plaque characteristics is not fully understood. The study aims to explore the relationship between RCR and plaque features in patients presenting with acute coronary syndrome (ACS). METHODS: All ACS patients undergoing pre-intervention optical coherence tomography (OCT) with high-sensitivity C-reactive protein (hs-CRP) <2 mg/L on admission were retrospectively enrolled from January to December 2017, at Beijing Anzhen Hospital, Capital Medical University. RCR was defined as low density lipoprotein cholesterol (LDL-C) ≥1.8 mmol/L. Patients were divided into the RCR and non-RCR groups according to baseline LDL-C. RESULTS: A total of 90 patients (94 vessels) were included, with 50 in the RCR group and 40 in the non-RCR group, respectively. Compared with the non-RCR group, patients in the RCR group were younger (54.0 ± 11.04 vs. 58.4 ± 9.59, p = 0.049) and had a higher incidence of multivessel disease (6.0% vs. 2.5%, p = 0.028). With regard to plaque characteristics, fibrous plaque (0.0% vs 12.5%, p = 0.003) was less and fibroatheroma (79.6% vs. 50.0%, p = 0.028) was more frequently seen in the RCR group. Patients in the RCR group were more prone to present with plaque rupture (24.1% vs 5.0%, p = 0.008). Cholesterol crystal (22.2% vs 12.5%, p = 0.226) and thin-cap fibroatheroma (25.9% vs. 12.5%, p = 0.109) were more common in the RCR group, though without statistical difference. Multivariate logistic regression showed that RCR (odds ratio [OR]: 7.95, p = 0.011) and smoking (OR: 4.08, p = 0.026) were independent risk factors of plaque rupture in our patients. CONCLUSIONS: ACS patients with RCR are more likely to have atherosclerotic plaque and plaque rupture, indicating a more vulnerable plaque phenotype.

Efficacy and Safety of Transcatheter vs. Surgical Aortic Valve Replacement in Low-to-Intermediate-Risk Patients: A Meta-Analysis.

Background: The efficacy and safety of transcatheter aortic-valve replacement (TAVR) vs. surgical aortic valve replacement (SAVR) for low- to intermediate-surgical risk patients remains uninvestigated. Objectives: We aimed to investigate the efficacy and safety of transcatheter aortic-valve replacement (TAVR) vs. surgical aortic valve replacement (SAVR) for low-intermediate surgical risk patients. Methods: PubMed, Cochrane Library, and Embase databases were searched to identify potential references. Only randomized controlled trials (RCTs) or observational studies using propensity score matching were eligible for screening. The primary endpoint was all-cause death. The secondary outcomes were bleeding, stroke, myocardial infarction (MI), and other complications of aortic-valve replacement. In addition, we performed subgroup analysis based on surgical risk and study type. Results: Eight RCTs and 13 observational studies covering 12,467 patients were included in the current meta-analysis. For patients with low-surgical risk, compared with SAVR, TAVR was found to be associated with a lower mortality at a follow-up period of 1 year (odds ratio, OR: 0.66, 95% CI: [0.46, 0.96], P = 0.03). This benefit disappeared when the follow-up was extended to 2 years (OR: 0.89, 95% CI: [0.61, 1.30], P = 0.56). For patients with intermediate-surgical risk, TAVR showed to have similar mortality with SAVR regardless of follow-up period (30-day, 1-year, or 2-year). TAVR could reduce the incidence of bleeding, AF, and AKI. For complications, such as MI and stroke, TAVR exhibited to have similar safety with SAVR. However, TAVR was found to be associated with a higher incidence of reintervention, major vascular complication, paravalvular leak, and PPI. Conclusion: For patients with a low-to-intermediate surgical risk, TAVR has at least an equivalent clinical effect to SAVR for 2 years after the procedure.