Use of fluoroquinolones and the risk of aortic and mitral regurgitation: A nationwide case-crossover study.

BACKGROUND: Recently, there have been conflicting results reporting an increased risk of AR or MR associated with oral fluoroquinolones (FQs).This study investigated whether the use of FQs increases the risk of mitral regurgitation (MR) or aortic regurgitation (AR). METHODS: A retrospective cohort study was conducted by using the Taiwan National Health Insurance research database. A unidirectional case-crossover design without selecting controls from an external population was adopted in this study. A total of 26,650 adult patients with new onset of AR or MR between January 1, 2000, and December 31, 2012, were identified. The risk of outcomes was compared between the hazard period and one of the randomly selected referent periods of the same individuals. RESULTS: Before exclusion of pneumonia diagnosed within 2 months before the index date, patients who took FQs had a significantly greater risk of AR or MR (adjusted odds ratio [aOR] 1.51, 95% confidence interval [CI] 1.30-1.77), any AR (combined AR and MR) (aOR 1.50, 95% CI 1.10-2.04), and any MR (combined AR and MR) (aOR 1.37, 95% CI 1.16-1.62). After exclusion of pneumonia, FQs exposure remained significantly associated with a greater risk of MR (aOR 1.38, 95% CI 1.17-1.62) and any MR (aOR 1.25, 95% CI 1.05-1.48). CONCLUSIONS: The findings suggested that patients treated with FQs could be warned about the potential risk for MR even after considering the possibility of protopathic bias. Reducing unnecessary FQs prescriptions may be considered to reduce the risk of valvular heart disease.

Clinical Outcomes in Type 2 Diabetes Patients After Acute Myocardial Infarction: A Comparison of Sodium-Glucose Cotransporter 2 Inhibitors vs. Non-Users.

To compare clinical outcomes in patients with type 2 diabetes (T2D) after acute myocardial infarction (AMI) using sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs. non-use of SGLT2i. A national cohort study based on the Taiwan National Health Insurance Research Database enrolled 944 patients with T2D who had experienced AMI and were treated with SGLT2i and 8,941 patients who did not receive SGLT2i, respectively, from May 1, 2016, to December 31, 2019. We used propensity score matching to balance covariates across study groups. The follow-up period was from the index date to the independent occurrence of the study outcomes, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. The SGLT2i group exhibited a significantly lower incidence of cardiovascular death (0.865% per year vs. 2.048% per year; hazard ratio (HR): 0.42; 95% confidence interval (CI): 0.24-0.76; P = 0.0042), heart failure hospitalization (1.987% per year vs. 3.395% per year; HR: 0.59; 95% CI: 0.39-0.89; P = 0.0126), and all-cause mortality (3.406% per year vs. 4.981% per year, HR: 0.69; 95% CI: 0.50-0.95; P = 0.0225) compared with the non-SGLT2i group. There were no significant differences between the two groups in the incidence of AMI, ischemic stroke, coronary revascularization, major adverse cardiovascular events, composite renal outcomes, or lower limb amputation. These findings suggest that the use of SGLT2i may have favorable effects on clinical outcomes in patients with T2D after AMI.

Clinical Benefit of Fixed-Dose Combination of Amlodipine and Potent Atorvastatin in Patients With Concomitant Hypertension and Hypercholesterolemia.

BACKGROUND: Hypertension and hypercholesterolemia are important risk factors for cardiovascular disease, and treatment with fixed-dose combination (FDC) regimens is recommended by current guidelines. However, the clinical outcomes of different FDC dosages remain unknown. This study aimed to examine the clinical outcomes of FDC regimens and the free combination of amlodipine and atorvastatin at different dosages. METHODS AND RESULTS: Patients with concurrent hypertension and hypercholesterolemia treated daily with an FDC of 5 mg amlodipine and 10 mg atorvastatin (5/10 fixed group), and FDC of 5 mg amlodipine and 20 mg atorvastatin (5/20 fixed group), or free combination of 5 mg amlodipine and 20 mg atorvastatin (5/20 free group) were identified from the National Health Insurance Research Database of Taiwan. The primary outcome was the composite cardiovascular outcomes, including cardiovascular death, acute myocardial infarction, stroke, and coronary intervention. A total of 9095 patients were eligible for inclusion. The incidence of primary outcome per 1000 person-years was 16.6 in the 5/10 fixed group, 12.6 in the 5/20 fixed group, and 16.5 in the 5/20 free group (5/20 fixed versus 5/20 free: hazard ratio [HR], 0.76 [95% CI, 0.64-0.91]; 5/20 fixed versus 5/10 fixed: HR, 0.76 [95% CI, 0.63-0.90]). CONCLUSIONS: Among patients with concomitant hypertension and hypercholesterolemia, treatment with an FDC of amlodipine and high-dose atorvastatin led to a lower risk of a composite of cardiovascular outcomes than treatment with the free combination or a similar FDC with a lower dose of atorvastatin.

Early Surgery for Infective Endocarditis Complicated With Neurologic Injury.

OBJECTIVES: To estimate the association between early surgery and the risk of mortality in patients with left-sided infective endocarditis in the context of stroke. DESIGN: Retrospective cohort study. SETTING: This study was a multiinstitution study based on the Chang Gung Research Database, which contains electronic medical records from 7 hospitals in northern and southern Taiwan; these include 2 medical centers, 2 regional hospitals, and 3 district hospitals. PARTICIPANTS: Patients with active left-sided infective endocarditis who underwent valve surgery between September 2002 and December 2018. INTERVENTIONS: The authors divided patients into 2 groups, with versus without preoperative neurologic complications, had undergone early (within 7 d) or later surgery, and with brain ischemia or hemorrhage. MEASUREMENTS AND MAIN RESULTS: Three hundred ninety-two patients with a median time from diagnosis to surgery of 6 days were included. No significant differences in postoperative stroke, in-hospital mortality, or follow-up outcomes were observed between the patients with and without neurologic complications. Among the patients with preoperative neurologic complications, patients who underwent early surgery had a lower 30-day postoperative mortality rate (13.1% v 25.8%; hazard ratio, 0.21; 95% CI 0.07-0.67). In the subgroup analysis of the comparison between brain ischemia and hemorrhage groups, there was no significant between-group difference in the in-hospital outcomes or outcomes after discharge. CONCLUSIONS: Early cardiac surgery may be associated with more favorable clinical outcomes in patients with preoperative neurologic complications. Thus, preoperative neurologic complications should not delay surgical interventions.

Outcomes of Endovascular Treatment for Infective Aortic Aneurysms　- A Multicenter Retrospective Study.

BACKGROUND: In Taiwan, infective native aortic aneurysms (INAAs) are relatively common, so the aim of present study was to demonstrate the comparative outcomes of endovascular repair for thoracic and abdominal INAAs.Methods and Results: Patients with naïve thoracic or abdominal INAAs managed with endovascular repair between 2001 and 2018 were included in this multicenter retrospective cohort. The confounding factors were adjusted with propensity score (PS). Of the 39 thoracic and 43 abdominal INAA cases, 41 (50%) presented with aneurysmal rupture, most of which were at the infrarenal abdominal (n=35, 42.7%) or descending thoracic aorta (n=25, 30.5%). Salmonella spp. was the most frequently isolated pathogen. The overall in-hospital mortality rate was 18.3%. The risks of in-hospital death and death due to rupture were significantly lower with thoracic INAAs (12.8% vs. 23.3%; PS-adjusted odds ratio (OR) 0.24, 95% confidence interval (CI) 0.06-0.96; 0.1% vs. 9.3%; PS-adjusted OR 0.11, 95% CI 0.01-0.90). During a mean follow-up of 2.5 years, the risk of all-cause death was significantly higher with thoracic INAAs (35.3% vs. 15.2%; PS-adjusted HR 6.90, 95% CI 1.69-28.19). Chronic kidney disease (CKD) was associated with death. CONCLUSIONS: Compared with thoracic INAAs, endovascular repair of abdominal INAAs was associated with a significantly higher in-hospital mortality rate. However, long-term outcomes were worse for thoracic INAAs, with CKD and infections being the most important predictor and cause of death, respectively.

Long-Term Survival of Patients with Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Single-Center Cohort.

Pulmonary arterial hypertension (PAH) is a rare but severe complication of connective tissue disease (CTD). CTD-associated PAH (CTD-PAH) is the most common subgroup of PAH in East Asia. We prospectively collected 41 patients with CTD-PAH and followed them for a mean period of 43 ± 36 months. The long-term survival rates of the CTD-PAH patients at 1, 2, 3 and 5 years were 90%, 80%, 77%, and 60%, respectively. The non-survivors had more dilated main pulmonary arteries, higher pulmonary artery pressure and pulmonary vascular resistance (PVR). PAH-specific therapy resulted in improvements in functional class, 6-minute walk distance, serum uric acid, right ventricular function and PVR. Increased C-reactive protein during follow-up, indicating inflammatory processes, was also crucial for the management of CTD-PAH. Therefore targeting both PAH and inflammation is important in this specific subgroup of PAH. The results of this study may help develop treatment strategies for CTD-PAH patients.

Visit to Visit Hemoglobin A1c Variation and Long-term Risk of Major Adverse Limb Events in Patients With Type 2 Diabetes.

CONTEXT: Glycemic variation had been demonstrated to be associated with several complications of diabetes. OBJECTIVE: Investigation of the association between visit to visit hemoglobin A1c (HbA1c) variation and the long-term risk of major adverse limb events (MALEs). METHODS: Retrospective database study. Average real variability was used to represent glycemic variations with all the HbA1c measurements during the 4 following years after the initial diagnosis of type 2 diabetes. Participants were followed from the beginning of the fifth year until death or the end of the follow-up. The association between HbA1c variations and MALEs was evaluated after adjusting for mean HbA1c and baseline characteristics. Included were 56 872 patients at the referral center with a first diagnosis of type 2 diabetes, no lower extremity arterial disease, and at least 1 HbA1c measurement in each of the 4 following years were identified from a multicenter database. The main outcome measure was incidence of a MALE, which was defined as the composite of revascularization, foot ulcers, and lower limb amputations. RESULTS: The average number of HbA1c measurements was 12.6. The mean follow-up time was 6.1 years. The cumulative incidence of MALEs was 9.25 per 1000 person-years. Visit to visit HbA1c variations were significantly associated with MALEs and lower limb amputation after multivariate adjustment. People in the highest quartile of variations had increased risks for MALEs (HR 1.25, 95% CI 1.10-1.41) and lower limb amputation (HR 3.05, 95% CI 1.97-4.74). CONCLUSION: HbA1c variation was independently associated with a long-term risk of MALEs and lower limb amputations in patients with type 2 diabetes.

Learning curve for open surgical repair of acute type A aortic dissection.

There is scarce evidence about the surgeon learning curve of acute type A aortic dissection surgery and whether the optimal procedure number exists when training a cardiovascular surgeon. A total of 704 patients with acute type A aortic dissection surgery performed by 17 junior surgeons who can identify their first career surgery from January 1, 2005, to December 31, 2018, are included. The surgeon experience volume is defined as the cumulative number of acute type A aortic dissection surgery of the surgeon since January 1, 2005. The primary outcome was in-hospital mortality. The possibility of non-linearity and cutoffs for surgeon experience volume level was explored using a restricted cubic spline model. The results revealed that more surgeon experience volume is significantly correlated to a lower in-hospital mortality rate (r = - 0.58, P = 0.010). The RCS model shows for an operator who reaches 25 cumulative volumes of acute type A aortic dissection surgery, the average in-hospital mortality rate of the patients can be below 10%. Furthermore, the longer duration from the 1st to 25th operations of the surgeon is significantly correlated to a higher average in-hospital mortality rate of the patients (r = 0.61, p = 0.045). Acute type A aortic dissection surgery has a prominent learning curve in terms of improving clinical outcomes. The findings suggest fostering high-volume surgeons at high-volume hospitals can achieve optimal clinical outcomes.

Fluoroquinolones and Risk of Aortic Aneurysm or Dissection in Patients With Congenital Aortic Disease and Marfan Syndrome.

BACKGROUND: Fluoroquinolone use can be associated with an increased risk of aortic aneurysm (AA) or aortic dissection (AD). The US Food and Drug Administration recently warned against fluoroquinolone use for high-risk patients, such as those with Marfan syndrome. However, the association between fluoroquinolone use and AA/AD risk was unknown in these high-risk patients and therefore it was studied in this work.Methods and Results: Data were collected from a national database between 2000 and 2017 for 550 patients with AA/AD and any congenital aortic disease (mean age 41.5 years; 415 with Marfan syndrome). A case cross-over study was conducted to compare the risk of aortic events (AA/AD) associated with fluoroquinolone and amoxicillin use between the hazard period (from -60 days to -1 day) and a randomly selected reference period (-180 to -121 days; -240 to -181 days; and -300 to -241 days). Compared to the reference period without fluoroquinolone use, fluoroquinolone use during the hazard period was not associated with a greater risk of AA/AD (1.09% vs. 1.09%; odds ratio [OR] 1.000; 95% confidence interval [CI] 0.32-3.10), AA (OR 0.67; 95% CI 0.11-3.99), or AD (OR 1.33; 95% CI 0.30-5.96) in patients with congenital aortic disease or Marfan syndrome. This lack of association was maintained in subgroup analysis, including Marfan syndrome or not, age (≤50 vs. >50 years) and sex. CONCLUSIONS: Fluoroquinolone use was not associated with an increased risk of AA/AD in patients with congenital aortic disease, including Marfan syndrome. More evidence is required for a fluoroquinolone pharmacovigilance plan in these patients.

Outcomes of Percutaneous Coronary Interventions for Long Diffuse Coronary Artery Disease with Extremely Small Diameter.

BACKGROUND: The optimal percutaneous coronary intervention (PCI) strategy and clinical outcomes of long lesions with an extremely small residual lumen remain unclear. This study aimed to assess the efficacy of a modified stenting strategy for diffuse coronary artery disease (CAD) with an extremely small distal residual lumen. METHODS: 736 Patients who received PCI using second-generation drug-eluting stents (DES) ≥38 mm long were retrospectively included and categorized into an extremely small distal vessel (ESDV) group (≤2.0 mm) and a non-ESDV group (>2.0 mm) according to the maximal luminal diameter of the distal vessel (dsDMax). A modified stenting technique was applied by landing an oversized DES in the distal segment with the largest luminal diameter and maintaining the distal stent edge partially expanded. RESULTS: The mean dsDMax and stent lengths were 1.7 ± 0.3 mm and 62.6 ± 18.1 mm in the ESDV group and 2.7 ± 0.5 mm and 59.1 ± 16.0 mm in non-ESDV groups, respectively. The acute procedural success rate was high in both the ESDV and non-ESDV groups (95.8% and 96.5%, p = 0.70) with rare distal dissection (0.3% and 0.5%, p = 1.00). The target vessel failure (TVF) rate was 16.3% in the ESDV group and 12.1% in the non-ESDV group at a median follow-up of 65 months without significant differences after propensity score matching. CONCLUSIONS: PCI using contemporary DES with this modified stenting technique is effective and safe for diffuse CAD with extremely small distal vessels.

Cardiovascular, renal, and lower limb outcomes in patients with type 2 diabetes after percutaneous coronary intervention and treated with sodium-glucose cotransporter 2 inhibitors vs. dipeptidyl peptidase-4 inhibitors.

AIMS: Patients with type 2 diabetes (T2D) who undergo percutaneous coronary intervention (PCI) are at higher risk of adverse cardiovascular and renal events than non-diabetic patients. However, limited evidence is available regarding the cardiovascular, renal, and limb outcomes of patients with T2D after PCI and who were treated with sodium-glucose cotransporter-2 inhibitors (SGLT2i). We compare the specified outcomes in patients with T2D after PCI who were treated with SGLT2i vs. dipeptidyl peptidase-4 inhibitors (DPP4i). METHODS AND RESULTS: In this nationwide retrospective cohort study, we identified 4248 and 37 037 consecutive patients with T2D who underwent PCI with SGLT2i and DPP4i, respectively, for 1 May 2016-31 December 2019. We used propensity score matching (PSM) to balance the covariates between study groups. After PSM, SGLT2i, and DPP4i were associated with comparable risks of ischaemic stroke, acute myocardial infarction, and lower limb amputation. However, SGLT2i was associated with significantly lower risks of heart failure hospitalization [HFH; 1.35% per year vs. 2.28% per year; hazard ratio (HR): 0.60; P = 0.0001], coronary revascularization (2.33% per year vs. 3.36% per year; HR: 0.69; P = 0.0003), composite renal outcomes (0.10% per year vs. 1.05% per year; HR: 0.17; P < 0.0001), and all-cause mortality (2.27% per year vs. 3.80% per year, HR: 0.60; P < 0.0001) than were DPP4i. CONCLUSION: Our data indicated that SGLT2i, compared with DPP4i, were associated with lower risks of HFH, coronary revascularization, composite renal outcomes, and all-cause mortality for patients with T2D after PCI. Further randomized or prospective studies can investigate the effects of SGLT2i in patients with T2D after PCI.

High Triglyceride Variability Increases the Risk of First Attack of Acute Pancreatitis.

INTRODUCTION: Hypertriglyceridemia is the third most common etiology of acute pancreatitis. Whether triglyceride variability, independent of absolute triglyceride levels, is a predictor of acute pancreatitis is unknown. METHODS: We identified 98,819 patients who were diagnosed with hyperlipidemia between January 1, 2007, and December 31, 2013, and had at least 1 triglyceride measurement annually for 4 consecutive years from the Chang Gung Research Database in Taiwan. Triglyceride variability, defined as variability independent of the mean, was calculated in the 4-year run-in period. The patients were stratified according to the quartiles of triglyceride variability and were followed until December 31, 2019, for first attack of acute pancreatitis. RESULTS: During a mean follow-up of 5.9 years, 825 (0.83%) patients were newly diagnosed with acute pancreatitis (14.1 events per 10,000 person-years; 95% confidence interval 13.2-15.1). Triglyceride variability was significantly associated with an increased risk of acute pancreatitis, independent of baseline triglyceride and mean triglyceride levels (hazard ratio, 1.28 [95% confidence interval 1.05-1.57] for the highest vs the lowest quartiles of triglyceride variability; P for trend = 0.006 over the quartiles of triglyceride variability). Subgroup analysis showed that this association was more pronounced among the patients with a higher neutrophil-to-lymphocyte ratio ( P for trend = 0.022). DISCUSSION: In this multi-institutional cohort study, high triglyceride variability was associated with an increased risk of first attack of acute pancreatitis, independent of baseline and mean triglyceride levels. The association between triglyceride variability and acute pancreatitis may be partly mediated by subclinical inflammation.

Revascularization in Patients With Non-ST Elevation Myocardial Infarction and Advanced Chronic Kidney Disease.

OBJECTIVE: To investigate the impact of revascularization on long-term survival and renal outcome in non-ST-elevation myocardial infarction (NSTEMI) patients with severe chronic kidney disease (CKD). PATIENTS AND METHODS: This study includes NSTEMI patients with an estimated glomerular filtration rate <30 mL/min per 1.73 m2, including those on chronic hemodialysis who were identified from the multicenter Chang Gung Research Database from January 1, 2007, to December 31, 2017. Inverse probability of treatment weighting was used to generate comparable groups. The survival and the risk of progression to chronic hemodialysis between those receiving revascularization, either percutaneous coronary intervention or coronary artery bypass graft, and those receiving medical therapy during index hospitalization were compared. RESULTS: A total of 2821 NSTEMI patients with severe CKD, including 1141 patients on chronic hemodialysis, were identified. Of these, 1149 patients received revascularization and 1672 received medical therapies. The differences in demographics, comorbidities, and presentations between groups were balanced after inverse probability of treatment weighting. After a mean follow-up of 1.82 years, revascularization was associated with a lower risk of all-cause mortality (adjusted HR, 0.61; 95% CI, 0.54-0.70). For non-dialysis-dependent patients who had survival to discharge, revascularization had a higher risk of progression to chronic hemodialysis (adjusted HR, 1.83; 95% CI, 1.49-2.26) after a mean follow-up of 2.3 years. CONCLUSION: Revascularization was associated with a lower risk of all-cause mortality in NSTEMI patients with severe CKD. For non-dialysis-dependent patients who survived to discharge, revascularization was associated with a higher risk of progression to chronic hemodialysis.

Beneficial Effects of Fixed-Dose Combination of Amlodipine and Atorvastatin in Patients with Concomitant Hypertension and Hypercholesterolemia: A Multi-Institutional Cohort Study.

Background: Blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) are important risk factors for cardiovascular (CV) diseases. Although treating these factors simultaneously is recommended by current guidelines, only short-term clinical results are available. Objectives: To examine the longer-term efficacy and safety of fixed-dose combination (FDC) versus free combination of amlodipine and atorvastatin in patients with concomitant hypertension and hypercholesterolemia. Methods: Patients with hypertension and hypercholesterolemia were stratified into three groups [FDC of amlodipine 5 mg/atorvastatin 10 mg (Fixed 5/10), FDC of amlodipine 5 mg/atorvastatin 20 mg (Fixed 5/20), and free combination of amlodipine 5 mg/atorvastatin 10 mg (Free 5/10)]. After inverse probability of treatment weighting, the composite CV outcome, liver function, BP, LDL-C and glycated hemoglobin (HbA1c) changes were compared. Results: A total of 1,788 patients were eligible for analysis, and the mean follow-up period was 1.7 year. There was no significant difference in the composite CV outcome among the three groups (Fixed 5/10 6.1%, Fixed 5/20 6.3% and Free 5/10 6.0%). The LDL-C level was significantly reduced in the Fixed 5/20 group (-35.7 mg/dL) compared to the Fixed 5/10 (-23.6 mg/dL) and Free 5/10 (-10.3 mg/dL) groups (p = 0.001 and < 0.001, respectively). The changes in HbA1c were similar among the three groups. Conclusions: FDC of amlodipine and atorvastatin, especially the regimen with a higher dosage of statins, significantly reduced the mid-term LDL-C level compared to a free combination in patients with concomitant hypertension and hypercholesterolemia. Blood sugar level was not significantly changed by this aggressive treatment strategy.

Upregulation of Myocardial Neutrophil Gelatinase-Associated Lipocalin during Development of Heart Failure Caused by Volume-Overload and the Effect in Regulating Activity of Matrix Metalloproteinase-9.

Background: In patients with heart failure (HF), circulating neutrophil gelatinase-associated lipocalin (NGAL) level is increased, which is considered to be a predictor of mortality or renal outcomes. The expression of NGAL in the heart and kidney and its role in HF remain unclear. Methods: Aortocaval fistula was created in rats as a model of volume overload (VO)-induced HF. Results: During the development of HF, NGAL expression was upregulated in the heart but not in the kidney at both transcriptional and translational levels in the compensatory and HF phases, with a similar level in both phases. Cardiomyocytes were identified as the cell type responsible for NGAL expression. Consistent with the myocardial NGAL expression pattern, the plasma NGAL level was increased in both phases, and the level was not significantly different between both phases. We demonstrated the presence of a matrix metalloproteinase (MMP)-9/NGAL complex in cultured medium of cardiomyocytes isolated from volume-overloaded hearts by gelatin zymography. Formation of MMP-9/NGAL complex was shown to enhance the enzymatic activity of MMP-9. We found that early growth response (Egr)-1 was upregulated in the heart in both compensatory and HF phases. In neonatal cardiomyocytes, Egr-1 overexpression induced the gene expression of NGAL, which was dose-dependently suppressed by an interleukin-1 receptor antagonist. Conclusions: During the development of HF due to VO, NGAL was upregulated in the heart but not in the kidney in both compensatory and HF phases, with a similar expression level. Myocardial NGAL upregulation enhanced MMP-9 activity through formation of the MMP-9/NGAL complex. The expression of myocardial NGAL was regulated by Egr-1.

Benzodiazepines in Patients with Heart Failure and Reduced Ejection Fraction.

Background: In patients with heart failure (HF), anxiety or insomnia is prevalent and associated with poor clinical outcomes. Benzodiazepines (BZDs) are one of the most commonly prescribed medications for anxiety or insomnia in Taiwan. Evidence regarding the effects of BZDs on patients with heart failure and reduced ejection fraction (HFrEF) is inconclusive. Objectives: To evaluate whether BZDs can mitigate the adverse effects of anxiety or insomnia on the prognosis of patients with HFrEF. Methods: Patients with HFrEF were identified from the Chang Gung Research Database between January 1, 2007 and December 31, 2018. Those who received BZD prescriptions were defined as the BZD group; patients in the BZD group were then paired with those who had never been prescribed BZDs after matching for age, sex, and baseline left ventricular ejection fraction, defined as the no-BZD group. Propensity score matching was used to balance baseline characteristics. Cox proportional hazards model and the Fine-Gray subdistribution hazard model were used to examine the association between BZD prescription and the risks of adverse cardiovascular outcomes. Results: After propensity score matching, there were 1,941 patients in both BZD and no-BZD groups. The composite of cardiovascular (CV) death or HF hospitalization (HFH) occurred in 64.4% and 54.4% of the patients in the BZD and no-BZD groups, respectively [hazard ratio (HR): 1.44; 95% confidence interval (CI): 1.32-1.56], which was mainly driven by HFH (HR: 1.52; 95% CI: 1.39-1.67). Conclusions: In the patients with HFrEF, those who received BZD were at a higher overall risk of CV death and HFH.

Dual versus Single Antiplatelet Therapy in Medically Treated Acute Myocardial Infarction Patients with Baseline Thrombocytopenia - Insights from a Multi-Institute Cohort Study.

Background: The safety and efficacy of dual antiplatelet therapy (DAPT) in medically treated acute myocardial infarction (AMI) patients with baseline thrombocytopenia (platelet count < 150 × 103/uL) are unclear. Methods: In this multi-institute retrospective cohort study, we included 468 patients with medically treated AMI with baseline thrombocytopenia and separated them into single antiplatelet therapy (SAPT) and DAPT groups according to the discharge anti-thrombotic strategy. The primary outcome was net clinical adverse events (NACEs), defined as a composite of death, ischemic events (myocardial infarction, ischemic stroke, and transient ischemic attack), and major bleeding within 30 days. Results: There were 168 patients in the SAPT group (100 taking aspirin and 68 taking clopidogrel) and 300 in the DAPT group. A primary outcome occurred in 35 (24.11 per 100 patient-months) patients in the SAPT group and 39 (14.26 per 100 patient-months) patients in the DAPT group [adjusted hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.40-1.10; p = 0.1145]. Kaplan-Meier curves showed favorable results in the DAPT group (log-rank p = 0.0243). Bleeding events occurred in 18 (10.71 per 100 patient-months) patients in the SAPT group and 18 (6.40 per 100 patient-months) patients in the DAPT group (adjusted HR: 0.66; 95% CI: 0.32-1.36; p = 0.2573). Conclusions: DAPT versus SAPT as discharge anti-thrombotic strategy in thrombocytopenic patients with medically treated AMI did not significantly improve NACEs at 30 days. However, there was a trend towards favorable outcomes in the DAPT group. These results should be interpreted carefully with respect to the relatively limited trial population and study design.

New-Onset Atrial Fibrillation in Patients With Type 2 Diabetes Treated With Novel Glucose-Lowering Therapies.

CONTEXT: Whether sodium-glucose cotransporter 2 inhibitors (SGLT2is) are associated with lower risk of new-onset atrial fibrillation (AF) compared with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with type 2 diabetes was unknown. OBJECTIVE: We aimed to determine the comparative risk of new-onset AF with SGLT2is vs GLP-1RAs in Asian patients with type 2 diabetes in a real-world setting. METHODS: We used medical data from a multicenter health care provider in Taiwan and enrolled 16 566 and 2746 patients treated with an SGLT2i and a GLP-1RA, respectively, from January 1, 2016, to December 31, 2018. Propensity score weighting was used to balance the baseline covariates. The patients were followed from the drug index date until the occurrence of new-onset AF or the end of the follow-up period. RESULTS: In this study, 54%, 45%, and 1% of the SGLT2i group patients were treated with empagliflozin, dapagliflozin, and canagliflozin, respectively, and 65% and 35% of the GLP-1RA group patients were treated with liraglutide and dulaglutide, respectively. SGLT2is were associated with lower risk of new-onset AF compared with GLP-1RAs after inverse probability of treatment weighting (subdistribution hazard ratio: 0.72; 95% CI, 0.54-0.97; P = 0.028). Subgroup analysis revealed that this finding was consistent among the following high-risk subgroups: older patients, female patients, and patients with cardiovascular disease or chronic kidney disease. CONCLUSION: SGLT2is were associated with lower risk of new-onset AF compared with GLP-1RAs among patients with type 2 diabetes mellitus in a real-world practice.

Angiotensin Receptor-Neprilysin Inhibitors in Patients With Heart Failure With Reduced Ejection Fraction and Advanced Chronic Kidney Disease: A Retrospective Multi-Institutional Study.

Background: Data regarding using angiotensin receptor-neprilysin inhibitor (ARNI) in patients with both heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (CKD) are limited. Methods and Results: Between January 2016 and December 2018, patients with HFrEF and advanced CKD (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min/1.73 m2) were identified from a multi-institutional database in Taiwan. Patients who had never been prescribed with an ARNI, angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB) were excluded. We used inverse probability of treatment weighting (IPTW) to balance baseline covariates, and compared outcomes between ARNI and ACEI/ARB users. There were 206 patients in the ARNI group and 833 patients in the ACEI/ARB group. After IPTW adjustment, the mean ages (65.1 vs. 66.6 years), male patients (68.3 vs. 67.9%), left ventricular ejection fraction (30.5 vs.31.2%), eGFR (20.9 vs. 20.3 mL/min/1.73 m2) were comparable in the ARNI and ACEI/ARB groups. Over 85% of the patients had beta-blockers prescriptions in both groups (86.2 vs. 85.5%). After IPTW adjustment, the mean follow-up durations were 7.3 months and 6.6 months in the ARNI and ACEI/ARB groups, respectively. ARNI and ACEI/ARB users had a comparable risk of the composite clinical event (all-cause mortality or heart failure hospitalization) (hazard ratio [HR], 1.31; 95% confidence interval (CI) 0.91-1.88) and progression to dialysis (HR 1.04; 95% CI 0.54-2.03). In subgroup analysis, dialysis patients who used ARNIs were associated with higher incidence of heart failure hospitalization (subdistribution HR, 1.97; 95% CI 1.36-2.85). Conclusions: Compared with ACEIs or ARBs, ARNIs were associated with comparable clinical and renal outcomes in patients with HFrEF and advanced CKD (eGFR ≤ 30 mL/min/1.73 m2). In short-term, HF hospitalization may occur more frequently among ARNI users, especially in patients on dialysis.

Comparative effectiveness of generic nifedipine versus Adalat long-acting nifedipine for hypertension treatment: A multi-institutional cohort study.

This retrospective multi-institutional database analysis aimed to evaluate the blood-pressure-lowering efficacy and clinical outcomes of a generic versus brand-name nifedipine for hypertension management. A total of 12 693 patients who were prescribed a generic or brand-name nifedipine between January 1, 2011, and December 31, 2018, were identified from the Chang Gung Research Database of Chang Gung Memorial Hospitals, Taiwan. Among them, 2112 (21.4%) were prescribed generic nifedipine. After propensity score matching, both the generic and brand-name groups consisted of 2102 patients. At a mean follow-up of 3 years, the changes in office systolic (p for interaction = .791) and diastolic blood pressure (p for interaction = .689) did not differ significantly between the patients who received the generic and the brand-name nifedipine. There was no significant difference between the two study groups regarding the composite of all-cause mortality, acute myocardial infarction, stroke, coronary revascularization, or hospitalization for heart failure (hazard ratio 0.98, 95% confidence interval 0.85-1.13; p = .774). In conclusion, the generic nifedipine was comparable to its brand-name counterpart regarding office blood pressure reduction and the composite cardiovascular outcome for the treatment of patients with hypertension.