Dual Antithrombotic Therapy versus Anticoagulant Monotherapy for Major Adverse Limb Events in Patients with Concomitant Lower Extremity Arterial Disease and Atrial Fibrillation: A Propensity Score Weighted Analysis.

OBJECTIVE: Patients with symptomatic lower extremity arterial disease (LEAD) are recommended to receive antiplatelet therapy, while direct oral anticoagulants (DOACs) are standard for stroke prevention in patients with atrial fibrillation (AF). For patients with concomitant LEAD and AF, data comparing dual antithrombotic therapy (an antiplatelet agent used in conjunction with a DOAC) vs. DOAC monotherapy are scarce. This retrospective cohort study, based on data from the Taiwan National Health Insurance Research Database, aimed to compare the efficacy and safety of these antithrombotic strategies. METHODS: Patients with AF who underwent revascularisation for LEAD between 2012 - 2020 and received any DOAC within 30 days of discharge were included. Patients were grouped by antiplatelet agent exposure into the dual antithrombotic therapy and DOAC monotherapy groups. Inverse probability of treatment weighting was used to mitigate selection bias. Major adverse limb events (MALEs), ischaemic stroke or systemic embolism, and bleeding outcomes were compared. Patients were followed until the occurrence of any study outcome, death, or up to two years. RESULTS: A total of 1 470 patients were identified, with 736 in the dual antithrombotic therapy group and 734 in the DOAC monotherapy group. Among them, 1 346 patients received endovascular therapy as the index revascularisation procedure and 124 underwent bypass surgery. At two years, dual antithrombotic therapy was associated with a higher risk of MALEs than DOAC monotherapy (subdistribution hazard ratio [SHR] 1.34, 95% confidence interval [CI] 1.15 - 1.56), primarily driven by increased repeat revascularisation. Dual antithrombotic therapy was also associated with a higher risk of major bleeding (SHR 1.43, 95% CI 1.05 - 1.94) and gastrointestinal bleeding (SHR 2.17, 95% CI 1.42 - 3.33) than DOAC monotherapy. CONCLUSION: In patients with concomitant LEAD and AF who underwent peripheral revascularisation, DOAC monotherapy was associated with a lower risk of MALEs and bleeding events than dual antithrombotic therapy.

Major adverse cardiovascular and limb events in people with diabetes treated with GLP-1 receptor agonists vs SGLT2 inhibitors.

AIMS/HYPOTHESIS: This study aimed to assess the real-world outcomes of people with diabetes mellitus treated with glucagon-like peptide-1 receptor agonists (GLP1RAs) compared with those treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) in terms of major adverse cardiovascular and limb events. Peripheral artery disease is a common cause of morbidity in people with diabetes. Previous cardiovascular outcome trials have demonstrated the benefits of GLP1RAs and SGLT2is for reducing various cardiovascular events, but the safety and efficacy of these drugs on limb outcomes remain subject to debate and ambiguity. METHODS: A retrospective cohort study was conducted in which data were collected from the Taiwan National Health Insurance Research Database. In total, 379,256 individuals with diabetes receiving either GLP1RA or SGLT2i with treatment initiated between 1 May 2016 and 31 December 2019 were identified. The primary outcome was major adverse limb events (MALE), defined as the composite of newly diagnosed critical limb ischaemia, percutaneous transluminal angioplasty or peripheral bypass for peripheral artery disease, and non-traumatic amputation. The secondary outcome was major adverse cardiac events, which was a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal ischaemic stroke. Other examined outcomes included death from any cause and hospitalisation for heart failure. Propensity score matching was performed at a 1:4 ratio between the GLP1RA and SGLT2i groups to mitigate possible selection bias. RESULTS: A total of 287,091 patients were eligible for analysis, with 81,152 patients treated with SGLT2i and 20,288 patients treated with GLP1RA after matching. The incidence of MALE was significantly lower in the GLP1RA group than in the SGLT2i group (3.6 vs 4.5 events per 1000 person-years; subdistribution HR 0.80; 95% CI 0.67, 0.96), primarily due to a lower incidence of critical limb ischaemia. The reduced risks of MALE associated with GLP1RA use were particularly noticeable in people with diabetic peripheral neuropathy (subdistribution HR 0.66 vs 1.11; p for interaction 0.006). CONCLUSIONS/INTERPRETATION: In people with diabetes, GLP1RA use was associated with significantly reduced risks of MALE compared with SGLT2i within the first 2 years after initiation, especially among people with diabetic neuropathy.

Mortality risk in patients with underweight or obesity with peripheral artery disease: a meta-analysis including 5,735,578 individuals.

OBJECTIVES: The "obesity paradox" - in which patients with obesity exhibit superior survival than normal-weight counterparts - has been reported for several diseases. However, obesity is a well-known risk factor for cardiovascular disease, and whether the obesity paradox is present in peripheral artery disease (PAD) is unknown. METHODS: A comprehensive search for studies that reported mortality in patients with PAD grouped by BMI identified 12 studies. We compared the survival of underweight patients with those who were not underweight, and patients with obesity against those without. Underweight was defined by a BMI value of <18.5 kg/m2 in most studies and obesity by BMI ≥ 30 kg/m2. Subgroup analyses were performed according to length of follow-up, presentation of PAD, and mode of revascularization. Meta-regression analyses were conducted, with covariates including age, sex, presence of coronary artery disease (CAD) and diabetes mellitus (DM). RESULTS: The mortality risk of underweight patients with PAD was significantly higher compared to those who are not underweight (HR 1.72, 95% CI 1.38-2.14; I2 = 84.2%). In contrast, the mortality risk of patients with obesity with PAD was significantly lower than those without (HR 0.78, 95% CI 0.62-0.97; I2 = 89.8%). These findings remained consistent regardless of the presentation of PAD, revascularization, age, sex, or presence of CAD. The risk of death in the short-term of underweight patients (HR 1.50, 95% CI 0.47-4.72) and patients with obesity (HR 0.86, 95% CI 0.66-1.13) were not significantly different from their counterparts. The meta-regression showed that of the association between obesity and better survival was more pronounced in studies with a greater proportion of patients with concomitant CAD (regression coefficient -0.029, 95% CI -0.054 to -0.004). CONCLUSIONS: In patients with PAD, mortality is higher among underweight patients and lower among patients with obesity. The mechanisms underlying the obesity paradox in patients with PAD remain to be elucidated, and further evidence is required to guide optimal weight control strategies in these patients.

Short- and Long-Term Outcomes of Catheter-Directed Thrombolysis versus Pulmonary Artery Embolectomy in Pulmonary Embolism: A National Population-Based Study.

OBJECTIVES: This study aimed to compare the short-term and long-term follow-up outcomes of catheter-directed thrombolysis (CDT) with those of pulmonary artery embolectomy (PAE) for patients with acute pulmonary embolism (PE) included in a nationwide cohort. BACKGROUND: Data allowing direct comparisons between CDT and PAE are lacking in the literature, and the optimal management of high-risk and intermediate-risk PE is still debated. METHODS: A retrospective cohort study was conducted with data for 2001 through 2013 collected from the Taiwan National Health Insurance Research Database (NHIRD). Patients who were first admitted for PE and treated with either CDT or PAE were included and compared. In-hospital outcomes included in-hospital death and safety (bleeding and cardiac arrhythmias) outcomes. Follow-up outcomes included all-cause mortality and recurrent PE during the 1- and 2-year follow-up periods and through the last follow-up. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to minimize possible selection bias, including indices for multimorbidity such as the Charlson's Comorbidity Index (CCI) and HAS-BLED scores. RESULTS: A total of 389 patients treated between January 1, 2001, and December 31, 2013, were identified; 169 underwent CDT and 220 underwent PAE. After IPTW, there were no significant differences in in-hospital mortality (18.2% vs 21.3%; odds ratio 1.07, 95% confidence interval [CI]: 0.70-1.62) or the incidence of safety outcomes between the CDT and PAE groups. The risks of all-cause mortality (30% vs 29.5%; hazard ratio 1.16, 95% CI: 0.89-1.53), recurrent PE (7.2% vs 8.7%; subdistribution hazard ratio [SHR] 0.68, 95% CI: 0.39-1.21) and new-onset pulmonary hypertension (SHR 0.25, 95% CI: 0.05-1.32) were also not significantly different between the CDT and PAE groups at 2 years of follow-up. Subgroup analysis indicated that PAE may be associated with a more favorable 2-year mortality in patients <65 years old, patients with CCI scores of <3, patients with HAS-BLED scores of 1 to 2, and patients without cardiogenic shock (all P for interaction <.05). CONCLUSIONS: In patients with PE who required reperfusion therapy, CDT and PAE resulted in similar in-hospital and long-term all-cause mortality rates and long-term rates of recurrent PE. Bleeding risks were also comparable in the 2 groups.

The efficacy and safety of novel classes of glucose-lowering drugs for cardiovascular outcomes: a network meta-analysis of randomised clinical trials.

AIMS/HYPOTHESIS: Several cardiovascular outcome trials on sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been released recently, including trials enrolling patients with congestive heart failure (CHF) and chronic kidney disease (CKD). Comparisons of the efficacy and safety of SGLT2i, glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) thus require an update. Assessments in patient subgroups, i.e., as stratified by age or the presence of CHF, CKD or atherosclerotic cardiovascular disease (ASCVD), are also currently lacking. METHODS: We searched the PubMed, Embase and Cochrane databases for relevant studies published up until 5 December 2020. RCTs comparing SGLT2i, GLP-1RA and DPP-4i with placebo (or other controls) or with each other with cardiovascular (CV) or renal outcomes were eligible for inclusion. The primary efficacy endpoint was 3-point major adverse cardiovascular events (3P-MACE), which are defined as CV death, non-fatal myocardial infarction and non-fatal ischaemic stroke. All-cause mortality, hospitalisation for heart failure (HHF) and composite renal outcomes were also analysed. Pre-specified subgroup analyses of 3P-MACE were also performed. RESULTS: A total of 21 trials with 170,930 participants were included in this network meta-analysis. Both GLP-1RA and SGLT2i were associated with lower risks of 3P-MACE than placebo (RR 0.89, 95% CI 0.84, 0.94 and RR 0.88, 95% CI 0.83, 0.94, respectively). GLP-1RA and SGLT2i were also associated with lower risks of 3P-MACE than DPP-4i (RR 0.89, 95% CI 0.82, 0.98 and RR 0.89, 95% CI 0.81, 0.97, respectively). A comparison between SGLT2i and GLP-1RA demonstrated no difference in their risks of 3P-MACE (RR 0.99, 95% CI 0.91, 1.08). Only GLP-1RA was associated with a lower risk of stroke compared with placebo (RR 0.85, 95% CI 0.76, 0.94). SGLT2i is superior to GLP-1RA in reducing HHF (RR 0.76, 95% CI 0.68, 0.84) and renal outcomes (RR 0.78, 95% CI 0.65, 0.93). Subgroup analyses indicated that the benefits of SGLT2i and GLP-1RA were more pronounced in elderly patients, white and Asian patients, those with established ASCVD and those with longer durations of diabetes mellitus and worse glycaemic control. CONCLUSIONS/INTERPRETATION: SGLT2i and GLP-1RA are superior to DPP-4i in terms of CV and renal outcomes. GLP-1RA is the only drug class that reduces the risk of stroke. SGLT2i is superior in reducing HHF and renal outcomes. Therefore, the choice between SGLT2i and GLP-1RA should be individualised according to patient profiles. PROSPERO REGISTRATION NUMBER: CRD42020206600.

Major adverse cardiovascular and limb events in patients with diabetes treated with GLP-1 receptor agonists vs DPP-4 inhibitors.

AIMS/HYPOTHESIS: The safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP1RAs) and dipeptidyl peptidase-4 inhibitors (DPP4is) in major cardiovascular adverse events were previously examined in cardiovascular outcome trials. However, the effects of these drugs on adverse limb outcomes were poorly examined. This study aimed to determine the real-world outcomes of patients with diabetes mellitus receiving GLP1RAs as compared with those receiving DPP4is in terms of major adverse cardiovascular and limb events. METHODS: A retrospective cohort study was conducted with data collected by the Taiwan National Health Insurance database between 1 May 2011 and 31 December 2017. Patients who were treated for type 2 diabetes with a GLP1RA or DDP4i during this period (n = 1,080,993), were identified. The primary outcome was a composite of major adverse limb events, defined as peripheral artery disease (PAD), critical limb ischaemia, percutaneous transluminal angioplasty or peripheral bypass for PAD, and amputation. The secondary cardiovascular outcome was the composite of cardiovascular death, non-fatal myocardial infarction and non-fatal ischaemic stroke. Propensity-score matching (PSM) at a 1:3 ratio between GLP1RA and DPP4i groups was done to minimise possible selection bias. RESULTS: A total of 948,342 individuals treated between 1 May 2011 and 31 December 2017, were identified, with 4460 in the GLP1RA group and 13,380 in the DPP4i group after PSM. The incidence of primary composite outcome events was significantly lower in those treated with GLP1RAs compared with those treated with DPP4is (2.59 vs 4.22 events per 1000 person-years; subdistribution HR [SHR] 0.63 [95% CI 0.41, 0.96]), primarily due to lower rates of amputation (1.29 events per 1000 person-years for GLP1RAs vs 2.4 events per 1000 person-years for DPP4is; SHR 0.55 [95% CI 0.30, 0.99]). Treatment with GLP1RAs was also associated with significantly lower risks of secondary composite outcome events (11.02 vs 17.95 events per 1000 person-years; HR 0.62 [95% CI 0.51, 0.76]). Moreover, the observed beneficial effects of GLP1RAs on reducing composite adverse limb outcomes were particularly noticeable in the non-cardiovascular patients and statin users (p for interaction <0.05). CONCLUSIONS/INTERPRETATION: In individuals with diabetes, the use of GLP1RAs was associated with significantly lower risks of major adverse limb events when compared with the use of DPP4is. The reduction in risk was driven largely by reduced rate of amputations. Moreover, treatment with GLP1RAs was also associated with lower risks of cardiovascular death, non-fatal stroke, non-fatal myocardial infarction and death from any cause. However, some unexplored confounding factors may exist in this observation study and future large-scale randomised controlled trials are needed.

Left Ventricular Segmentation, Warping, and Myocardial Registration for Automated Strain Measurement.

The left ventricular global longitudinal strain (LVGLS) is a crucial prognostic indicator. However, inconsistencies in measurements due to the speckle tracking algorithm and manual adjustments have hindered its standardization and democratization. To solve this issue, we proposed a fully automated strain measurement by artificial intelligence-assisted LV segmentation contours. The LV segmentation model was trained from echocardiograms of 368 adults (11,125 frames). We compared the registration-like effects of dynamic time warping (DTW) with speckle tracking on a synthetic echocardiographic dataset in experiment-1. In experiment-2, we enrolled 80 patients to compare the DTW method with commercially available software. In experiment-3, we combined the segmentation model and DTW method to create the artificial intelligence (AI)-DTW method, which was then tested on 40 patients with general LV morphology, 20 with dilated cardiomyopathy (DCMP), and 20 with transthyretin-associated cardiac amyloidosis (ATTR-CA), 20 with severe aortic stenosis (AS), and 20 with severe mitral regurgitation (MR). Experiments-1 and -2 revealed that the DTW method is consistent with dedicated software. In experiment-3, the AI-DTW strain method showed comparable results for general LV morphology (bias - 0.137 ± 0.398%), DCMP (- 0.397 ± 0.607%), ATTR-CA (0.095 ± 0.581%), AS (0.334 ± 0.358%), and MR (0.237 ± 0.490%). Moreover, the strain curves showed a high correlation in their characteristics, with R-squared values of 0.8879-0.9452 for those LV morphology in experiment-3. Measuring LVGLS through dynamic warping of segmentation contour is a feasible method compared to traditional tracking techniques. This approach has the potential to decrease the need for manual demarcation and make LVGLS measurements more efficient and user-friendly for daily practice.

The effects of mineralocorticoid receptor antagonists on cardiovascular outcomes in patients with end-stage renal disease and heart failure.

AIMS: Mineralocorticoid receptor antagonists (MRAs) have been shown to provide survival benefits in patients with heart failure; however, MRA use in patients with chronic kidney disease has been limited by safety concerns. The effects of MRAs on outcomes in patients with end-stage renal disease (ESRD) and heart failure remain unknown. The aim of this study was to evaluate the effects of MRAs on cardiovascular outcomes in patients with heart failure under maintenance dialysis in a real-world setting. METHODS AND RESULTS: A retrospective cohort study was conducted by collecting data from the Taiwan National Health Insurance Research Database (NHIRD). Patients diagnosed with heart failure and ESRD and who started maintenance dialysis between 1 January 2001 and 31 December 2013 were identified. Patients were grouped according to MRA prescription. The outcomes of interest included cardiovascular (CV) death, hospitalization for heart failure (HHF), all-cause mortality, acute myocardial infarction (AMI), ischaemic stroke, any coronary revascularization procedures, and new-onset hyperkalaemia. Propensity score matching was performed at a 1:3 ratio between MRA users and non-users to minimize selection bias. A total of 50 872 patients who satisfied our inclusion and exclusion criteria were identified. After 1:3 matching, 2176 patients were included in the MRA group, and 6528 patients were included in the non-MRA group. The risk of CV death was significantly lower among patients who received MRAs than those who did not (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.80-0.95), as was the risk of all-cause mortality (HR 0.88, 95% CI 0.83-0.94). Reductions in the risks of CV death and all-cause mortality were more prominent among patients undergoing haemodialysis and those with coronary artery disease. CONCLUSIONS: In patients undergoing regular dialysis who are diagnosed with heart failure, the use of MRAs is associated with lower risks of all-cause mortality and CV death. The benefits of MRA treatment in heart failure may persist in patients with ESRD. Further investigations through randomized controlled trials are needed to assess the efficacy and safety of MRAs in this high-risk population.

Efficacy and Safety of Direct Oral Anticoagulants for Stroke Prevention in Older Patients With Atrial Fibrillation: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Although older patients with atrial fibrillation are at heightened risk of thromboembolic and bleeding events, their optimal treatment choice remains uncertain. METHODS AND RESULTS: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that compared thromboembolic or bleeding outcomes between a direct oral anticoagulant (DOAC) and a vitamin K antagonist (VKA) and reported outcomes for patients aged ≥75 years with atrial fibrillation. The efficacy outcome was the composite of stroke and systemic embolism. Safety outcomes included major bleeding, any clinically relevant bleeding, and intracranial hemorrhage. Each DOAC and VKA was compared pairwise in a network meta-analysis. High- and low-dose regimens and factor IIa and Xa inhibitors were also compared. Seven randomized controlled trials were included in the analysis. Stroke and systemic embolism risks did not differ significantly among DOACs. There were no significant differences in major bleeding between each DOAC and VKA. Intracranial hemorrhage risk was significantly lower with dabigatran, apixaban, and edoxaban than with VKA and rivaroxaban, which had similar risks. High-dose regimens led to lower risks of stroke or systemic embolism compared with VKA and low-dose regimens, with both doses having similar bleeding risks. CONCLUSIONS: In patients aged ≥75 years with atrial fibrillation, DOACs were associated with fewer thromboembolic events compared with VKA, whereas dabigatran, apixaban, and edoxaban were associated with lower risks of intracranial hemorrhage compared with VKA and rivaroxaban. REGISTRATION: URL: www.crd.york.ac.uk/prospero/. Unique identifier: CRD42022329557.

Differential effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular and renal outcomes according to renal function: a dose-response meta-analysis involving 10 randomized clinical trials and 71 553 individuals.

BACKGROUND: The main target of sodium-glucose cotransporter 2 inhibitors (SGLT2i), the sodium-glucose cotransporters 2, is found in the kidneys, and their activity is reduced in patients with chronic kidney disease (CKD). How the efficacy of SGLT2i may vary in patients with different levels of renal impairment has not been fully elucidated. METHODS: We searched the PubMed databases for relevant studies published through May 25, 2022. Randomized control trials comparing SGLT2i with placebo and reporting cardiovascular or renal outcomes were included. The primary outcome was the composite of major adverse cardiovascular events (MACE), which were defined as cardiovascular death (CV death), nonfatal myocardial infarction (MI), and nonfatal ischemic stroke. Secondary outcomes included the components of MACE, all-cause mortality, hospitalization for heart failure (HHF), the composite of CV death and HHF, and composite renal outcomes. Linear meta-regression analysis was used to assess the effects of estimated glomerular filtration rate (eGFR) on the risks associated with SGLT2i treatment vs placebo for all outcomes. Nonlinear meta-regression analysis was also performed for MACE to investigate the combined influence of reduced drug efficacy in CKD but possible greater risk reduction in a population with higher risk at baseline. Further analyses were performed by including additional study-level covariates, including the prevalence of diabetes mellitus (DM), heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD). RESULTS: Risk ratios for MACE, CV death, nonfatal MI, HHF, and composite renal outcomes associated with SGLT2i treatment were not significantly related to baseline eGFR values. A positive association was observed between eGFR values and the risk of stroke with SGLT2i use (regression coefficient ß = .0109, 95% confidence interval [CI] 0.0029-0.0188). A similar positive association was observed between eGFR values and the composite outcome of CV death and HHF (ß = .0025, 95% CI 0.0000-0.0051). The results of the meta-regression analyses, including the additional covariates of DM, HF, and ASCVD, were consistent with the results of the primary analyses for most outcomes. CONCLUSION: The protective effects of SGLT2i for reducing most adverse cardiovascular and renal outcomes persisted in patients with variable degrees of renal impairment. The observed benefits such as preventing CV death, HF worsening, or stroke may be greater for patients with more severe CKD. Considering the cardiovascular and renal benefits associated with SGLT2i treatment, patients with CKD should be treated aggressively to improve outcomes. PROSPERO REGISTRATION NUMBER: CRD42021273500.

Inhalable chitosan-based hydrogel as a mucosal adjuvant for hydroxychloroquine in the treatment for SARS-CoV-2 infection in a hamster model.

BACKGROUND: Effective therapy for COVID-19 remains limited. Hydroxychloroquine (HCQ) has been considered, but safety and efficacy concerns remain. Chitosan exhibits antiviral and immunomodulatory effects, yet how the combination of HCQ and chitosan performs in treating COVID-19 is unknown. METHODS: Male Syrian hamsters were inoculated intranasally with standardized stocks of the SARS-CoV-2 virus. Hamsters were allocated to saline (PBS), chitosan oligosaccharide (COS), HCQ, or COS + HCQ groups and received corresponding drugs. On days 1, 7, and 14 post-infection, two animals from each group were euthanized for sample collection. Viral loads were measured in lung homogenates. Biochemistry markers, cytokines, and immunoglobulins were analyzed from hamster sera. HCQ concentrations were compared between the blood, bronchoalveolar lavage, and lung tissues. All groups underwent histopathology exams of the lungs. Additional hamsters were treated with the same drugs to assess for toxicities to the heart and liver. RESULTS: Among all groups, viral loads in the COS + HCQ group were the lowest by day 8. The COS + HCQ group produced the highest interleukin (IL)-6 levels on day 4, and the highest IL-10, IgA and IgG levels on day 8. HCQ concentrations were higher in the COS + HCQ group's lungs than the HCQ group, despite having received half the dose of HCQ. Histopathology demonstrated earlier inflammation resolution and swifter viral clearance in the COS + HCQ group. There was no evidence of cardiac or hepatic injury in hamsters that received HCQ. CONCLUSION: In hamsters infected with the SARS-CoV-2 virus, the combination of intranasal COS and HCQ was associated with increased HCQ absorption in the lungs, more effective immune responses, without increasing the risk of hepatic or cardiac injuries.

Correction: Mobile Health-Based Thermometer for Monitoring Wound Healing After Endovascular Therapy in Patients With Chronic Foot Ulcer: Prospective Cohort Study.

[This corrects the article DOI: 10.2196/26468.].

Sex differences following percutaneous coronary intervention or coronary artery bypass surgery for acute myocardial infarction.

BACKGROUND: Women have been underrepresented in the literature; the effects of female sex on outcomes in patients with acute myocardial infarction (AMI) remain unclear. OBJECTIVES: This study compares the real-world outcomes of women and men with AMI who have undergone revascularization via percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). METHODS: This is a retrospective cohort study utilizing data from the Taiwan National Health Insurance database. We identified patients who were admitted for AMI and who underwent coronary revascularization during the index admission period between January 1, 2001, and December 31, 2013. Patients were then categorized based on the treatment received into PCI and CABG groups. In-hospital and long-term outcomes were compared between women and men in each group. Interaction tests were then performed to determine whether the differences between sexes were modified by the mode of revascularization. Analyses were repeated after propensity score matching between women and men in each group to minimize possible confounders. We also conducted subgroup analyses, stratifying by the presence of diabetes mellitus, congestive heart failure, and chronic kidney disease. RESULTS: We enrolled 67,534 patients who met the inclusion criteria in the analysis; 60,207 patients had undergone PCI (13,514 female and 46,693 male), while 7327 patients had received CABG (1762 female and 5565 male). Prior to matching, enrolled female patients were older on average, with more comorbidities. In-hospital and long-term outcomes were worse in women, particularly in the PCI group. After matching, the incidence of hospitalization for heart failure (HHF) was higher in women (10.4% vs 8.0%, OR 1.32, 95% CI 1.22-1.43), with fewer repeat revascularizations (28.1% vs 32.4%, OR 0.84, 95% CI 0.81-0.88). Both observations were more pronounced in the PCI group (HHF: P for interaction = 0.0496; repeat revascularization: P for interaction = 0.021). CONCLUSIONS: Women presenting with AMI exhibited worse in-hospital and long-term outcomes than men, especially among women who received PCI as the initial mode of revascularization. Women who underwent PCI were more likely to be admitted for heart failure during follow-up. Possible socioeconomic inequalities or a distinct pathobiology of cardiac ischemia between sexes may underlie these results; thus, further investigation is needed.

Association of Statin Therapy With Major Adverse Cardiovascular and Limb Outcomes in Patients With End-stage Kidney Disease and Peripheral Artery Disease Receiving Maintenance Dialysis.

Importance: Controversy exists regarding whether statin therapy has benefits for patients with kidney failure, and the consequences of statin therapy for patients with kidney failure and concomitant peripheral artery disease (PAD) are particularly uncertain. Objective: To evaluate the association of statin therapy with cardiovascular (CV) and limb outcomes among patients with kidney failure and concomitant PAD and dyslipidemia who are receiving long-term maintenance dialysis. Design, Setting, and Participants: This retrospective cohort study used data from the Taiwan National Health Insurance Research Database. A total of 20 731 patients with kidney failure receiving long-term maintenance dialysis who were diagnosed with PAD and dyslipidemia between January 1, 2001, and December 31, 2013, were identified, and 10 767 patients met study criteria. Data were analyzed from June 8, 2021, to June 2, 2022. Main Outcomes and Measures: Primary outcomes were all-cause death and the composite of endovascular therapy (EVT) and amputation. Other outcomes of interest included CV events (CV death, acute myocardial infarction, ischemic stroke, and hospitalization for heart failure), major adverse limb events (new-onset claudication, new-onset critical limb ischemia, EVT, and nontraumatic amputation), and all-cause readmission. All outcomes were examined at 1 year and 3 years of follow-up. To minimize selection bias, propensity score matching on a 1:1 ratio was performed among patients receiving statin therapy (statin group) and patients not receiving statin therapy (nonstatin group). A defined daily dose (DDD) approach was used to evaluate whether the association of statin therapy with the risk of primary outcomes was dose dependent. Results: Among 20 731 patients with kidney failure and concomitant PAD and dyslipidemia receiving long-term maintenance dialysis, 10 767 patients (5593 women [51.9%]; mean [SD] age, 68.5 [11.5] years; all of Taiwanese ethnicity) met the predetermined study criteria; of those, 3597 patients were receiving statin therapy, and 7170 were not. A total of 6470 patients (mean [SD] age, 66.4 [11.3] years; 3359 women [51.9%]) were included in the 1:1 propensity score-matched cohort, with 3235 patients in each group (statin and nonstatin). The incidence and risk of CV and all-cause death were significantly lower in the statin group vs the nonstatin group at 3 years of follow-up (CV death: 611 patients [18.9%] vs 685 patients [21.2%]; hazard ratio [HR], 0.86 [95% CI, 0.77-0.96]; P = .008; all-cause death: 1078 patients [33.3%] vs 1138 patients [35.2%]; HR, 0.92 [95% CI, 0.84-0.996]; P = .04). Statin use was also associated with a significantly lower incidence and risk of the composite adverse limb outcome of EVT and amputation at 3 years of follow-up (314 patients [9.7%] vs 361 patients [11.2%]; subdistribution HR, 0.85 [95% CI, 0.73-0.99]; P = .04). Results of subgroup analyses were consistent with those of the primary analysis across all subgroup variables. In the adjusted dose-response analysis, the risk reduction associated with statin use increased in a dose-dependent manner for both all-cause death (HR: 0.95 for DDD <0.50, 0.92 for DDD 0.50-0.99, 0.85 for DDD 1.00-1.49, and 0.79 for DDD ≥1.50; P = .002 for trend) and the composite outcome of EVT and amputation (subdistribution HR: 0.79 for DDD <0.50, 0.78 for DDD 0.50-0.99, 0.82 for DDD 1.00-1.49, and 0.58 for DDD ≥1.50; P = .002 for trend) compared with no statin therapy; however, not all findings in the DDD analysis were statistically significant. Conclusions and Relevance: In this cohort study, statin therapy was associated with reductions in the risk of all-cause death, CV death, and the composite adverse limb outcome of EVT and amputation. These findings suggest that statin therapy may have protective CV and limb benefits for patients with kidney failure and concomitant PAD who are receiving long-term maintenance dialysis.

Mobile Health-Based Thermometer for Monitoring Wound Healing After Endovascular Therapy in Patients With Chronic Foot Ulcer: Prospective Cohort Study.

BACKGROUND: Foot temperature may increase after endovascular therapy, but the relationship between foot temperature and wound healing is unclear. OBJECTIVE: This study was performed to evaluate the feasibility of a mobile health (mHealth)-based thermometer for foot temperature monitoring in patients with chronic foot ulcer before and after endovascular therapy and to determine the association between temperature change and wound healing time. METHODS: This was a prospective cohort study. Patients who had a chronic foot ulcer (>3 months) and underwent endovascular therapy between July 2019 and December 2019 were included. The participants received standard medical care and endovascular therapy for revascularization. The mHealth-based thermometer, composed of 4 temperature-sensing chips, was put on the foot before and after endovascular therapy. Data from the chips were transferred to an associated mobile phone app via Bluetooth. Wound healing time was estimated using the Kaplan-Meier method, and the associations between baseline characteristics and clinical outcomes were evaluated using a Cox proportional hazard model. RESULTS: A total of 163 patients with chronic foot ulcer who underwent endovascular therapy were enrolled and followed up until wound healing was complete or for 180 days. The mean foot temperature before endovascular therapy was 30.6 (SD 2.8 °C). Foot temperature increased significantly (mean 32.1 °C, SD 2.8 °C; P=.01) after the procedure. Wound healing time was significantly different in the Kaplan-Meier curves of the patient group with temperature changes ≥2 °C and the group with temperature changes ≤2 °C (log-rank P<.001). A foot temperature increase ≥2 °C after endovascular therapy was associated with increased wound healing in univariate analysis (hazard ratio [HR] 1.78, 95% CI 1.24-2.76, P=.02), and the association remained significant in multivariate analysis (HR 1.69, 95% CI 1.21-2.67, P=.03). CONCLUSIONS: The mHealth-based thermometer was feasible and useful for foot temperature monitoring, which may provide health care professionals with a new endpoint for endovascular therapy. Foot temperature increases ≥2 °C after endovascular therapy were associated with faster wound healing in patients with chronic foot ulcer. Further studies are needed, however, to confirm these findings.

Clinical Adverse Events Associated with Sodium-Glucose Cotransporter 2 Inhibitors: A Meta-Analysis Involving 10 Randomized Clinical Trials and 71 553 Individuals.

CONTEXT: SGLT2is are first-line antidiabetic agents with demonstrated cardiovascular benefits. Prior meta-analyses have examined adverse events (AEs) associated with these drugs in general, but such knowledge needs to be updated with the results of more recent trials. In addition, the occurrence of various AEs with different underlying diseases is unknown. OBJECTIVE: This meta-analysis aimed to investigate the occurrence of various AEs associated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) and to examine the level of risk of AEs in patients with different underlying diseases. METHODS: We conducted a quantitative meta-analysis of randomized controlled trials (RCTs) retrieved from the MEDLINE and EMBASE databases and the Cochrane library on January 31, 2021. Outcomes of interest included 4 overall safety outcomes (AEs) and 12 specified safety outcomes. Further analyses were performed on various subgroups, which were defined based on the status of diabetes mellitus (DM), atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease, and congestive heart failure, and by the dosage of SGLT2i (high dose vs low dose). RESULTS: Our analysis included 10 eligible studies with a total of 71 553 participants. The meta-analysis showed that SGLT2i led to increased risks of genital infection (risk ratio [RR] 3.56, 95% CI 2.84-4.46), urinary tract infection (RR 1.06, 95% CI 1.00-1.12), diabetic ketoacidosis (RR 2.23, 95% CI 1.36-3.63), and volume depletion (RR 1.14, 95% CI 1.06-1.23). However, the use of SGLT2i was associated with reduced risks of any serious AE (RR 0.92, 95% CI 0.90-0.94), acute kidney injury (AKI) (RR 0.84, 95% CI 0.77-0.91), and hyperkalemia (RR 0.84, 95% CI 0.72-0.99). Within the different subgroups, the risk of amputation was higher in patients with ASCVD than in those without (RR 1.44 vs 0.96, P = .066). CONCLUSION: The use of SGLT2is is generally safe. SGLT2is may be associated with increased risks of genital infection but are protective against AKI. Of note, the risk of amputation was higher in patients with ASCVD. The key to the safe use of SGLT2is lies in the identification of high-risk populations and close surveillance of patients after treatment.

Efficacy and safety of ticagrelor versus clopidogrel in patients with non-ST-elevation myocardial infarction in Taiwan.

The clinical efficacy of ticagrelor versus clopidogrel has not been replicated in East Asian populations. The pronounced bleeding risk with ticagrelor was of concern given the increased bleeding tendency in Asian populations. This study evaluated efficacy and safety of ticagrelor versus clopidogrel in patients with non-ST-elevation myocardial infarction (NSTEMI) in the entire Taiwan. We used the Taiwan National Health Insurance Research Database to identify 6203 patients aged ≥ 20 years with NSTEMI hospitalization and prescription of dual antiplatelets at discharge between January 2014 and December 2014. Cohorts of ticagrelor and clopidogrel were matched 1:1 based on propensity score matching to balance baseline covariates. The primary composite efficacy endpoints included death from any cause, non-fatal myocardial infarction, and non-fatal stroke. The secondary efficacy endpoints were the individual components. The primary safety endpoint was major bleeding requiring hospitalization. The incidence of primary efficacy endpoint was 20.3% in the ticagrelor users and 20.7% in the clopidogrel users (adjusted HR 0.94; 95% CI 0.73-1.22), with the median (interquartile range, IQR) follow-up period of 5.2 (2.3-8.5) months. The incidence of primary safety endpoint was 2.3% in the ticagrelor users and 3.2% in the clopidogrel users (adjusted HR 0.67; 95% CI 0.33-1.35). Regarding the secondary efficacy endpoint, patients treated with ticagrelor had significantly lower incidence of stroke (adjusted HR 0.44; 95% CI 0.21-0.94; p = 0.033). In this nationwide Taiwanese cohort of NSTEMI, treatment with ticagrelor after discharge, as compared to clopidogrel, had similar rates of ischemic composite events and major bleeding. Nevertheless, the median follow-up time was only 5.2 months, and the reduced stroke events with ticagrelor compared to clopidogrel needs further verification.

Midterm Prognosis of Patients With Pulmonary Embolism Receiving Catheter-Directed Thrombolysis or Systemic Thrombolysis: A Nationwide Population-Based Study.

Background This study compared the efficacy and safety between catheter-directed thrombolysis (CDT) and systemic thrombolysis for patients with acute pulmonary embolism (PE) with midterm follow-up. Methods and Results We conducted a prospective open cohort study by using data from the Taiwan National Health Insurance Research Database for 2001 to 2013. Patients who were first admitted for PE and were treated by either systemic thrombolysis or CDT were included and compared. Inverse probability of treatment weighting, based on the propensity score, was used to mitigate possible selection bias. A total of 145 CDT-treated and 1158 systemic thrombolysis-treated patients with PE were included. The in-hospital mortality rate was significantly lower in the CDT group (12.7% versus 21.4%; odds ratio, 0.49; 95% CI, 0.36-0.67) after inverse probability of treatment weighting. No significant differences between the groups were observed for the safety (bleeding) outcomes. In patients who survived the index PE admission, the 1-year all-cause mortality rate was significantly lower in the CDT group after inverse probability of treatment weighting (12.2% versus 13.2%; hazard ratio [HR], 0.73; 95% CI, 0.56-0.94). Treatment with CDT was also associated with lower risks of recurrent PE (9.3% versus 17.5%; subdistribution HR, 0.52; 95% CI, 0.41-0.66). The difference remained through the last follow-up. Conclusions Among patients with PE requiring reperfusion therapy, those accepting CDT had lower all-cause mortality and recurrent PE over both short-term and midterm follow-up periods than those receiving systemic thrombolysis. The bleeding risk was similar for both groups. These findings should be cautiously validated in future randomized trials.