Referral, Diagnosis, and Pharmacological Management of Peripheral Artery Disease: Perspectives from Taiwan.

Peripheral artery disease (PAD) imposes a heavy burden of major adverse cardiovascular events that are associated with considerable mortality and morbidity, and major adverse limb events (e.g., thrombectomy, revascularization, amputation) that can substantially impact patients' daily functioning and quality of life. Global registry data have indicated that PAD is an underdiagnosed disease in Taiwan, and its associated risk factors remain inadequately controlled. This review discusses the burden of PAD in Taiwan, major guidelines on PAD management, and the latest clinical trial outcomes. Practical experience, opinions, and the latest trial data were integrated to derive a series of clinical algorithms - patient referral, PAD diagnosis, and the antithrombotic management of PAD. These algorithms can be adapted not only by physicians in Taiwan involved in the clinical management of patients with PAD but also by general practitioners in local clinics and regional hospital settings, with the ultimate aim of improving the totality of PAD patient care in Taiwan.

The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: a nationwide cohort study.

BACKGROUND: Although a few meta-analyses were conducted to compare the risk of incident atrial fibrillation (AF) between sodium-glucose cotransporter-2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and other anti-hyperglycemic agents using indirect or direct comparison, the above analyses showed conflicting results with each other. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i, GLP-1RA, and dipeptidyl peptidase-4 inhibitor (DPP4i) among a large longitudinal cohort of diabetic patients. METHODS: In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, a total of 344,893, 44,370, and 393,100 consecutive patients with type 2 diabetes without preexisting AF receiving GLP-1RA, SGLT2i, and DPP4i, respectively, were enrolled from May 1, 2016, to December 31, 2019. We used 1:1 propensity score matching (PSM) to balance covariates across paired study groups. Patients were followed from the drug index date until the occurrence of AF, death, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. RESULTS: After PSM, there were 245,442, 43,682, and 39,190 paired cohorts of SGLT2i-DPP4i, SGLT2i-GLP-1RA, and GLP-1RA-DPP4i, respectively. SGLT2i treatment was associated with lower risk of new-onset AF in participants with type 2 diabetes compared with either DPP4i [hazard ratio (HR):0.90; 95% confidential interval (CI) 0.84-0.96; P = 0.0028] or GLP-1RA [HR 0.74; 95% CI 0.63-0.88; P = 0.0007] treatment after PSM. There was no difference in the risk of incident AF between GLP-1RA and DPP4i users [HR 1.01; 95% CI 0.86-1.19; P = 0.8980]. The above findings persisted among several important subgroups. Dapagliflozin was specifically associated with a lower risk of new-onset AF compared with DPP4i (P interaction = 0.02). CONCLUSIONS: Compared with DPP4i, SGLT2i but not GLP-1RA was associated with a lower risk of incident AF in patients with type 2 diabetes.

Postoperative Stroke After Type A Aortic Dissection Repair: Hemorrhage Versus Ischemia.

BACKGROUND: Postoperative stroke is a severe and potentially disabling complication following surgical intervention for acute type A aortic dissection (ATAAD). This retrospective study aims to compare the early and late outcomes between patients who had hemorrhagic and ischemic stroke after undergoing ATAAD repair surgery. METHODS: Between January 2007 and June 2020, a total of 685 consecutive patients underwent ATAAD repair at our institution. Patients who had a preoperative stroke or were unconscious at presentation were excluded from this study. Of the 656 included for analysis, 102 (15.5%) patients had a postoperative stroke confirmed by computed tomography angiography. The strokes were classified into the ischemia group (n = 83, 12.7%) and hemorrhage group (n = 19, 2.9%). Clinical features, surgical information, postoperative complications, modified Rankin Scale (mRS) scores after discharge, and 5-year cumulative survival rates were compared. RESULTS: Demographics, comorbidities, and presentations of ATAAD were similar between the two groups, except a higher rate of preoperative antithrombotic medication was found in the hemorrhage group. The hemorrhage group was associated with a higher complexity of aortic arch replacement, longer cardiopulmonary bypass, and aortic clamping times than the ischemia group. A higher in-hospital mortality rate (42.1% versus 20.5%; p = 0.048) and a higher median mRS score at the 3-month follow-up after discharge (6[3-6] versus 4[2-6]; p = 0.027) were found in the hemorrhage group. The hemorrhage group showed a lower 5-year cumulative survival rate (23.4% versus 57.8%; p = 0.003) compared with the ischemia group. CONCLUSIONS: Postoperative hemorrhagic stroke was associated with poorer neurological outcomes and lower survival rates than those with ischemic stroke. Patients who have complex arch replacement, long cardiopulmonary bypass and aortic clamping times are at risk for postoperative hemorrhagic stroke and should have intensive neurological surveillance for early diagnosis and treatment after ATAAD repair surgery.

A HANC Risk Stratification Score for Antiplatelet Therapy Optimization with Low-Dose Prasugrel in Taiwanese Acute Coronary Syndrome Patients from the Switch Study.

Background: A significant proportion of acute coronary syndrome (ACS) patients experience high on-treatment platelet reactivity (HPR) on clopidogrel-based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). Objectives: This study assessed key independent risk factors associated with significant HPR risk on clopidogrel, but not prasugrel, in the Switch Study cohort of 200 Taiwanese ACS patients who switched from clopidogrel to low-dose prasugrel for maintenance DAPT after PCI. Methods: Univariate analysis and stepwise multivariate logistic regression analysis were conducted to identify key independent risk factors for HPR on clopidogrel, but not prasugrel. Results: A HANC [H: low hemoglobin (< 13 g/dL for men and < 12 g/dL for women); A: age ≥ 65 years; N: non-ST elevation myocardial infarction; C: chronic kidney disease as defined by estimated glomerular filtration rate < 60 mL/min] risk stratification score was developed, and demonstrated optimal sensitivity and specificity at a cutoff score of ≥ 2. The HANC score compared favorably against the recently validated ABCD score in the full Switch Study cohort (n = 200), and the ABCD-GENE score in a genotyped cohort (n = 102). Conclusions: The HANC score may serve to alert clinicians to patients at potentially higher HPR risk on clopidogrel, but not prasugrel. Further research to validate this score and assess its correlation with clinical outcomes is warranted.

Clinical Outcomes in Atrial Fibrillation Patients With a History of Cancer Treated With Non-Vitamin K Antagonist Oral Anticoagulants: A Nationwide Cohort Study.

Background and Purpose: Data on clinical outcomes for nonvitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation and cancer are limited, and patients with active cancer were excluded from randomized trials. We investigated the effectiveness and safety for NOACs versus warfarin among patients with atrial fibrillation with cancer. Methods: In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, we identified a total of 6274 and 1681 consecutive patients with atrial fibrillation with cancer taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. Propensity score stabilized weighting was used to balance covariates across study groups. Results: There were 1031, 1758, 411, and 3074 patients treated with apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. After propensity score stabilized weighting, NOAC was associated with a lower risk of major adverse cardiovascular events (hazard ratio, 0.63 [95% CI, 0.50­0.80]; P=0.0001), major adverse limb events (hazard ratio, 0.41 [95% CI, 0.24­0.70]; P=0.0010), venous thrombosis (hazard ratio, 0.37 [95% CI, 0.23­0.61]; P<0.0001), and major bleeding (hazard ratio, 0.73 [95% CI, 0.56­0.94]; P=0.0171) compared with warfarin. The outcomes were consistent with either direct thrombin inhibitor (dabigatran) or factor Xa inhibitor (apixaban, edoxaban, and rivaroxaban) use, among patients with stroke history, and among patients with different type of cancer and local, regional, or metastatic stage of cancer (P interaction >0.05). When compared with warfarin, NOAC was associated with lower risk of major adverse cardiovascular event, and venous thrombosis in patients aged <75 but not in those aged ≥75 years (P interaction <0.05). Conclusions: Thromboprophylaxis with NOACs rather than warfarin should be considered for the majority of the atrial fibrillation population with cancer.

Effectiveness and Safety of Direct Oral Anticoagulants in an Asian Population with Atrial Fibrillation Undergoing Dialysis: A Population-Based Cohort Study and Meta-Analysis.

PURPOSE: Whether direct oral anticoagulants (DOACs) are more effective and safer than warfarin among Asian patients with non-valvular atrial fibrillation (NVAF) undergoing dialysis remains unclear. METHODS: We first compared the risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding associated with DOACs compared with warfarin, in NVAF Asians undergoing dialysis using the Taiwan National Health Insurance Research Database (NHIRD) (Aim 1). Next, we searched PubMed and Medline from January 1, 2010 until January 31, 2020, to perform a systematic review and meta-analysis of all observational real-world studies comparing DOACs with warfarin specifically focused on NVAF patients with stage 4 or 5 chronic kidney disease undergoing dialysis (Aim 2). Finally, we tested the hypothesis whether AF patients undergoing dialysis treated with OACs (warfarin and DOACs) would be associated with lower risk of adverse clinical outcomes as compared to those without OACs using the Taiwan NHIRD (Aim 3). RESULTS: From June 1, 2012, to December 31, 2017, a total of 3237 and 9263 NVAF patients comorbid with ESRD receiving oral anticoagulant (OACs) (490 on DOAC, 2747 on warfarin) or no OACs, respectively, were enrolled. Propensity score matching was used to balance covariates across the study groups. For the comparison of DOAC vs. warfarin (Aim 1), DOACs had comparable risks of IS/SE and major bleeding to warfarin in our present cohort. From the original 85 results retrieved, nine studies (including our study) with a total of 6490 and 22,494 patients treated with DOACs and warfarin were included in the meta-analysis, respectively. There were 5343 (82%) and 20,337 (90%) patients treated with DOACs and warfarin undergoing dialysis, respectively. The pooled meta-analysis also indicated no difference of the effectiveness (HR:0.90; [95%CI:0.74-1.10]; P = 0.32) and safety outcomes (HR:0.75; [95%CI:0.54-1.05]; P = 0.09) between DOACs and warfarin (Aim 2). For the comparison of OAC (+) vs. OAC (-) (Aim 3), OAC-treatment was associated with a higher risk of IS/SE (hazard ratio (HR):1.54; [95% confidential interval (CI):1.29-1.84];P < 0.0001) and comparable risk of major bleeding compared to those without OAC treatment. CONCLUSIONS: DOACs did not provide benefit over warfarin regarding effectiveness and safety in AF patients undergoing dialysis. The use of OAC was not associated with a lower risk of IS/SE in ESRD AF patients when compared to those without OAC use.

Major adverse cardiovascular and limb events in patients with diabetes and concomitant peripheral artery disease treated with sodium glucose cotransporter 2 inhibitor versus dipeptidyl peptidase-4 inhibitor.

BACKGROUND: Whether sodium glucose co-transporter 2 inhibitors (SGLT2i) are associated with a lower risk of cardiovascular as well as adverse lower limb events in patients with type-2 diabetes mellitus (T2DM) and concomitant peripheral artery disease (PAD) is unclear. We aimed to evaluate the risk of cardiovascular and limb events, and death associated with the use of SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i) among a longitudinal and national cohort of patients with T2DM. METHODS: In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, we identified a total of 11,431 and 93,972 consecutive T2DM patients with PAD taking SGLT2i and DPP4i, respectively, from May 1, 2016, to December 31, 2017. We used 1:1 propensity score matching (PSM) to balance covariates across study groups. Patients were followed from the drug index date until the occurrence of clinical outcomes, death, discontinuation of the index drug, or the end of the study period, whichever occurred first. RESULTS: Overall, 56% and 44% of the patients were treated with dapagliflozin and empagliflozin, respectively. The use of SGLT2i had comparable risks of ischemic stroke and acute myocardial infarction, and was associated with lower risks of congestive heart failure (CHF) [hazard ratio (HR): 0.66; 95% confidence interval (CI) 0.49-0.89; p = 0.0062], lower limb ischemia requiring revascularization (HR: 0.73; 95% CI 0.54-0.98; p = 0.0367) or amputation (HR: 0.43; 95% CI 0.30-0.62; p < 0.0001), and cardiovascular death (HR: 0.67; 95% CI 0.49-0.90; p = 0.0089) when compared with the DDP4i group after PSM. The subgroup analysis revealed consistent results for CHF and major adverse limb outcomes for SGLT2i versus DPP4i among patients aged ≥ 75 years, the presence of chronic kidney disease and established cardiovascular disease was consistent with the main analysis. CONCLUSIONS: SGLT2i were associated with lower risks of CHF and adverse lower limb events compared with DPP4i among patients with T2DM and PAD in real-world practice.

Effectiveness, safety, and major adverse limb events in atrial fibrillation patients with concomitant diabetes mellitus treated with non-vitamin K antagonist oral anticoagulants.

BACKGROUND: Evidence of adverse clinical outcomes for non-vitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation (AF) and diabetes mellitus are limited. We investigated the effectiveness, safety, and major adverse limb events for NOACs versus warfarin among diabetic AF patients. METHODS: In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, we identified a total of 20,967 and 5812 consecutive AF patients with diabetes taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. We used propensity-score stabilized weighting to balance covariates across study groups. RESULTS: NOAC was associated with a lower risk of major adverse cardiovascular events (MACE) (adjusted hazard ratio (aHR):0.88; [95% confidential interval (CI) 0.78-0.99]; P = 0.0283), major adverse limb events (MALE) (aHR:0.72;[95% CI 0.57-0.92]; P = 0.0083), and major bleeding (aHR:0.67;[95% CI 0.59-0.76]; P < 0.0001) compared to warfarin. NOACs decreased MACE in patients of ≥ 75 but not in those aged < 75 years (P interaction = 0.01), and in patients with ischemic heart disease (IHD) compared to those without IHD (P interaction < 0.01). For major adverse limb events, the advantage of risk reduction for NOAC over warfarin persisted in high risk subgroups including age ≥ 75 years, chronic kidney disease, IHD, peripheral artery disease, or use of concomitant antiplatelet drugs. CONCLUSION: Among diabetic AF patients, NOACs were associated with a lower risk of thromboembolism, major bleeding, and major adverse limb events than warfarin. Thromboprophylaxis with NOACs should be considered in the diabetic AF population with a high atherosclerotic burden.

Glycemic status and risks of thromboembolism and major bleeding in patients with atrial fibrillation.

BACKGROUND: Studies specifically examining the association between glycated hemoglobin A1c (HbA1c) levels and ischemic stroke/systemic thromboembolism (IS/SE) risk in atrial fibrillation (AF) patients are limited. Here, we investigated the association between HbA1c levels and the risk of IS/SE, as well as major bleeding, among AF patients with or without oral anticoagulants (OACs). We also compared the effectiveness and safety of warfarin and direct oral anticoagulants (DOACs) in different HbA1c categories. METHODS: We utilized medical data from a multi-center healthcare provider in Taiwan, which included 34,036 AF patients with serum HbA1c data available within 3 months after AF being diagnosed. Patients were divided into seven study groups according to their HbA1c levels: < 5.4%, 5.4%-5.6%, 5.7%-5.9%, 6.0%-6.4%, 6.5%-6.9%, 7.0%-7.9%, and ≥ 8.0%. The risks of IS/SE and major bleeding were compared among the groups after adjusting for baseline stroke and bleeding risk factors. RESULTS: Compared with the patients with HbA1c level < 5.4%, IS/SE risk significantly increased at HbA1c levels higher than 6.5% [adjusted hazard ratio (HR): 1.20, 95% confidence interval (CI): 1.00-1.43 for HbA1c level 6.5%-6.9%; 1.32, (95% CI 1.11-1.57) for HbA1c level 7.0%-7.9%; and 1.48 (95% CI 1.25-1.76) for HbA1c level ≥ 8.0%]. These results were generally consistent in AF patients without OACs (n = 24,931). However, among 9105 patients receiving OACs, IS/SE risk was not higher for patients having higher HbA1c levels. The risk of major bleeding was comparable across all HbA1c categories. Compared with warfarin, DOACs were associated with lower risks of IS/SE (adjusted HR: 0.61, 95% CI 0.49-0.75) and major bleeding (adjusted HR: 0.30, 95% CI 0.21-0.42) without interactions across different HbA1c categories (all P interactions > 0.05). CONCLUSION: For AF patients, IS/SE risk significantly increased once HbA1c levels exceeded 6.5%, and OACs may attenuate these associations. Compared with warfarin, DOACs were more effective and safer across broad HbA1c categories. Therefore, in addition to prescribing DOACs when indicated, more aggressive glycemic control to achieve an HbA1c level < 6.5% may be considered for eligible AF patients and should be tested in further prospective studies.

High Nighttime Heart Rate is Associated with Increased Risk of All-Cause Mortality in Patients with Heart Failure and Reduced Ejection Fraction.

High heart rate (HR) is associated with increased risks of adverse outcomes in patients with heart failure. This study aimed to evaluate which measures of HR were associated with all-cause mortality in patients with heart failure and reduced ejection fraction (HFrEF). This study involved 741 HFrEF patients (age 65.1 ± 14.7 years, 71% male) who underwent 24 hour Holter electrocardiogram and resting electrocardiogram within 7 days between 2011 and 2015. We examined the associations of resting, 24 hour, and nighttime HRs with all-cause mortality. Nighttime and 24 hour HRs were determined as the mean HRs between 11:00 p.m. and 7:00 a.m. and over 24 hours, respectively. Nighty patients (12.1%) died during the 2-year follow-up. Resting, nighttime, and 24 hour HRs were significantly associated with all-cause mortality, also after adjusting for conventional risk factors. Resting HR did not remain as an independent factor when 24 hour HR (hazard ratio 1.10, 95% confidence interval 1.04-1.18) was included in the model. Including nighttime HR (hazard ratio 1.11, 95% confidence interval 1.05-1.17) in the model also eliminated 24 hour HR as an independent variable. Compared with the lowest quartile of nighttime HR (< 65 beats/minute), the highest quartile of nighttime HR (> 87 beats/minute) was significantly associated with a higher risk of all-cause mortality (hazard ratio 2.89, 95% CI 1.49-5.60). In conclusion, 24 hour HR and nighttime HR were significantly associated with an increased risk of mortality in patients with HFrEF. Nighttime HR appeared to be more strongly associated with all-cause mortality compared with 24 hour HR.

Real-world Comparisons of Direct Oral Anticoagulants for Stroke Prevention in Asian Patients with Non-valvular Atrial Fibrillation: a Systematic Review and Meta-analysis.

BACKGROUND: Whether four direct oral anticoagulants (DOACs) are superior to warfarin among Asians with non-valvular atrial fibrillation (NVAF) remains unclear in the real-world setting. METHODS: We searched PubMed and Medline + Journals@Ovid + EMBASE from September 17, 2009 to May 4, 2019 to perform a systematic review and meta-analysis of all observational real-world studies comparing four DOACs with warfarin specifically focused on Asian patients with NVAF. RESULTS: From the original 212 results retrieved, 18 studies were included in the meta-analysis. Overall, DOACs were associated with lower risks of thromboembolism (hazard ratio; [95% confidence interval], 0.70; [0.63-0.78]), acute myocardial infarction (0.67; [0.57-0.79]), all-cause mortality (0.62; [0.56-0.69]), major bleeding (0.59; [0.50-0.69]), intracranial hemorrhage (0.50; [0.40-0.62]), gastrointestinal bleeding (0.66; [0.46-0.95]), and any bleeding (0.82; [0.73-0.92]) than warfarin. There was statistic heterogeneity between DOACs for the risks of thromboembolism (P interaction = 0.03) and acute myocardial infarction (P interaction = 0.007) when compared to warfarin. However, all DOACs showed lower risks of thromboembolism and acute myocardial infarction than warfarin when pooling studies that compared individual DOAC with warfarin. With regard to the other outcomes when compared to warfarin, there was no statistical heterogeneity between DOACs. In addition, the effectiveness and safety of four DOACs versus warfarin persisted in the subgroups of either standard-dose or low-dose DOACs. CONCLUSIONS: The meta-analysis shows that the DOACs had greater effectiveness and safety compared to warfarin in real-world practice for stroke prevention, among Asian patients with NVAF.

Intravenous iron supplementation does not increase infectious disease risk in hemodialysis patients: a nationwide cohort-based case-crossover study.

BACKGROUND: Studies have reported conflicting findings on the infection risk posed by intravenous iron supplementation among hemodialysis (HD) patients. We used a novel study design to assess associations between intravenous iron and infectious diseases. METHODS: Patients initiating HD between 1998 and 2008 were extracted from Taiwan's National Health Insurance Research Database. Their first infectious disease in the period between 1.5 years after dialysis initiation and 2010 was identified and defined as the index date. Through the case-crossover design, the odds of exposure to intravenous iron within the 1-month period immediately preceding the index date (i.e., the case period) were compared with iron exposure in three different matched control periods for the same enrollee, thus possibly reducing some unmeasured confounders. RESULTS: A total of 1410 patients who met our enrollment criteria were extracted from incident HD patients. The odds of intravenous iron exposure during the case period versus total control periods exhibited no significant difference (odds ratio: 1.000, 95% confidence interval: 0.75-1.33). In subgroup analyses, this association remained nonsignificant across patients with diabetes mellitus, heart failure, chronic lung disease, venous catheter for HD, and higher iron load. CONCLUSIONS: We found that intravenous iron supplementation did not increase short-term infection risk among HD patients.

End-stage renal disease patients using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may reduce the risk of mortality: a Taiwanese Nationwide cohort study.

BACKGROUND: The association between the use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) and mortality in end-stage renal disease (ESRD) patients lacks sufficient evidence. AIM: To investigate the efficacy of ACEI and ARB in ESRD patients. METHODS: This nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database enrolled ESRD patients from January 1997 to December 2011. Propensity score matching provided two study groups (ACEI/ARB users vs non-users), balanced in sample size, with similar comorbidities and prescriptions. These patients were followed up from the first date of receiving dialysis until mortality, 5 years or 31 December 2013 (whichever came first). We analysed the association of the use of ACEI or ARB with cardiovascular (CV) death and all-cause mortality in patients with ESRD using the Kaplan-Meier method and time-dependent Cox models, with a robust sandwich variance method. RESULTS: After propensity score matching, all characteristics of the user of ACEI or ARB (n = 17 280) and non-user (n = 17 280) groups were appropriately balanced (P > 0.05). In the Cox proportional hazards model, the user group exhibited lower CV death and all-cause mortality with adjusted hazard ratios and 95% CI of 0.58 (0.55-0.62) and 0.47 (0.46-0.49) than the non-user group did. Furthermore, the association of ACEI/ARB use with low mortality risk was observed in all examined subgroups. CONCLUSION: In this large-scale, population-based cohort study, ESRD patients using ACEI/ARB had a lower risk of CV death and all-cause mortality than non-users did.

Low bone mineral density may be associated with long-term risk of cancer in the middle-aged population: A retrospective observational study from a single center.

BACKGROUND: It is generally understood that cancer patients are at an increased risk for osteoporosis. Additionally, recent studies have suggested a shared pathophysiological mechanism between the development of cancer and osteoporosis. The purpose of this investigation was to investigate whether low bone mineral density is associated with cancer risk. METHODS: We enrolled 8780 subjects who underwent dual-energy X-ray absorptiometry (DXA) and cancer screening from January 1, 2008-December 31, 2012 from a cohort selected from Chang Gung Health Care Center in Taiwan. The study end point was a definite pathological diagnosis of cancer or admission for cancer treatment. RESULTS: During a mean follow-up of 6.6 ± 1.5 years, 110 incident cases of cancer occurred. The overall incidence of cancer was significantly higher in those patients with a low BMD (1.3%) than in those with a normal BMD (1.0%). Multivariate Cox regression analysis showed that older age, smoking, and low BMD (hazard ratio: 1.5; 95% confidence interval: 1.0-2.3) were significant independent risk factors for cancer. CONCLUSION: Our investigation suggested that subjects with a low BMD may have a higher long-term risk of cancer compared with subjects with a normal BMD.

Crusade Microcatheter-Facilitated Reverse Wire Technique for Revascularization of Bifurcation Lesions of Coronary Arteries.

BACKGROUND: This study aims to analyze the lesion characteristics of bifurcations that required reverse wire technique and the efficacy and safety of this technique in approaching branches with a highly angulated take-off. METHODS: We enrolled patients in whom reverse wire technique was used after failed conventional antegrade wiring with the support of a Crusade catheter. The study endpoints were the technical success defined as succeeding in sending the reversely bent wire to the targeted branches without complications and the procedural success defined as succeeding in revascularization of the bifurcation lesions without complications. RESULTS: Among 158 patients with bifurcation lesions undergoing percutaneous coronary intervention using a Crusade catheter to facilitate wiring, 23 (14.6%) requiring the reverse wire technique in an attempt to access branches of the bifurcation lesions with an acutely angulated take-off were enrolled for analysis. The obtainable angle of take-off was 162.9 ± 4.7 degrees. For the parent vessel, the ostium of the targeted branch, and nontargeted branch, the minimal luminal diameters were 0.3 ± 0.5 mm, 0.4 ± 0.2 mm, and 1.8 ± 0.5 mm, respectively; the diameter stenosis were 88.8 ± 18.5%, 83.0 ± 7.3%, and 32.0 ± 14.5%, respectively. Technical and procedural success was achieved in 22 cases (96% for both). CONCLUSIONS: We showed in the present study that the reverse wire technique is effective and safe for approaching highly angulated branches of bifurcation lesions and consequently for complete revascularization of difficult bifurcation lesions.

Dipeptidyl peptidase-4 inhibitor decreases the risk of atrial fibrillation in patients with type 2 diabetes: a nationwide cohort study in Taiwan.

BACKGROUND: Whether dipeptidyl peptidase-4 inhibitor (DPP4i) is associated with a lower risk of new-onset atrial fibrillation (AF) in patients with diabetes remains unclear. This study aimed to evaluate the risk of AF associated with use of DPP4i among a longitudinal cohort of patients with diabetes. METHODS: Over a 3-year period, 480,000 patients with diabetes were analyzed utilizing Taiwan's National Health Insurance Research Database and 90,880 patients taking metformin as first-line therapy were enrolled. Patients were further divided into two groups: (1) DPP4i users: those taking DPP4i and (2) non-DPP4i users: those prescribed other hypoglycemic agents (HAs) as second-line drug. Study end point was defined by diagnosis of AF, addition of any third-line HA, or the end of the study period (December 31, 2013), whichever came first. RESULTS: A total of 16,017 DPP4i users and 74,863 non-DPP4i users were eligible for the study. For the DPP4i group, most patients were prescribed sitagliptin (n = 12,180; 76%). Among the non-DPP4i group, most patients took sulfonylurea (n = 60,606; 81%) as their second-line medication. DPP4i users were associated with a lower risk of new-onset AF compared with non-DPP4i users after propensity-score weighting (hazard ratio 0.65; P < 0.0001). Subgroup analysis showed that DPP4i user were associated with a lower risk of new-onset AF compared with non-DPP4i users in most subgroups. Multivariate analysis indicated that use of DPP4i was associated with lower risk of new-onset AF and age > 65 years, presence of hypertension, and ischemic heart disease were independent risk factors for new-onset AF. CONCLUSIONS: Among patients with diabetes prescribed with metformin, the patients with DPP4i as second HA were associated with a lower risk of AF compared with the patients with other drugs as second HAs in real-world practice.

Cardiovascular, Bleeding, and Mortality Risks of Dabigatran in Asians With Nonvalvular Atrial Fibrillation.

BACKGROUND AND PURPOSE: Whether dabigatran is associated with different risks of cardiovascular, bleeding events, and mortality from warfarin in Asian patients with nonvalvular atrial fibrillation remains unclear. METHODS: We used the Taiwan National Health Insurance Research Database to obtain 9940 and 9913 nonvalvular atrial fibrillation patients taking dabigatran and warfarin, respectively, from June 1, 2012, to December 31, 2013, as the dynamic cohort. Inverse probability of treatment weighting using propensity scores was used to balance covariates across 2 study groups. Patients were followed up until the first occurrence of any study outcome or end date of study. RESULTS: During a median follow-up period of 0.67 years, there were 526 outcomes for dabigatran group. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: ischemic stroke, 0.62 (0.52-0.73; P<0.0001); myocardial infarction, 0.67 (0.43-1.05; P=0.0803); intracranial hemorrhage, 0.44 (0.32-0.60; P<0.0001); major gastrointestinal bleeding, 0.99 (0.66-1.49; P=0.9658); all hospitalized major bleeding, 0.58 (0.46-0.74; P<0.0001); and all-cause mortality, 0.45 (0.38-0.53; P<0.0001). Dabigatran did not increase the risk of myocardial infarction or major gastrointestinal bleeding in all age groups when compared with warfarin. Total 8772 patients (88%) took a 110-mg dose in dabigatran group. The magnitude of effect for each outcome of 110-mg was comparable with that of 150-mg dose in the subgroup analysis. CONCLUSIONS: In real-world practice, dabigatran was associated with a reduced risk of ischemic stroke, intracranial hemorrhage, all hospitalized major bleeding, and all-cause mortality compared with warfarin in Asian patients with nonvalvular atrial fibrillation. Dabigatran did not increase the risk of major gastrointestinal bleeding or myocardial infarction compared with warfarin.

A comparison between angiotensin converting enzyme inhibitors and angiotensin receptor blockers on end stage renal disease and major adverse cardiovascular events in diabetic patients: a population-based dynamic cohort study in Taiwan.

BACKGROUND: Contemporary guidelines recommend angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB) for hypertensive patients with diabetes. However, there is limited data to evaluate the comparison between ACEi and ARB on end stage renal disease (ESRD) and major adverse cardiovascular events (MACE), in Asian diabetic patients. METHODS: We used the Taiwan Longitudinal Cohort of Diabetes Patients Database to perform a population-based dynamic cohort study. The comparison between ACEi and ARB on ESRD and MACE in diabetic patients was examined using the propensity score weighting method. We followed these patients until the occurrence of first study outcomes or end date of the study, whichever came first. RESULTS: There were 6898 and 12,758 patients in ACEi and ARB groups, respectively. The mean follow-up period was about 3.5 years in ESRD and 2.5 years in MACE. The incidence of ESRD was 0.44 % and 0.63 % per person-years in the ACEi and ARB group, respectively. The risk of ESRD was lower in the ACEi group than the ARB group [hazard ratio (HR) 0.69; 95 % confidence interval (CI) 0.54-0.88, P = 0.0025]. Among those without chronic kidney disease (CKD), the incidence of ESRD was 0.30 % and 0.37 % per person-years in the ACEi and ARB group, respectively. ACEi was similar to ARB in preventing ESRD for those without CKD (P = 0.11). Among those with CKD, the incidence of ESRD was 1.39 % and 2.34 % per person-years in the ACEi and ARB group, respectively. The ACEi group had a lower risk of ESRD than the ARB group (HR 0.61; 95 % CI 0.42-0.88, P = 0.008). The incidence of MACE was 9.33 % and 9.62 % per person-years in the ACEi and ARB group, respectively. There was no significant difference in the composite MACE outcome between the two groups (P = 0.42), but the ACEi group was associated with a higher risk of stroke than the ARB group (HR 1.12; 95 % CI 1.02-1.24, P = 0.02). CONCLUSIONS: ACEi compared with ARB was associated with a lower incidence of ESRD, especially in those with CKD. Though ACEi and ARB had a similar risk of composite MACE outcome, ACEi had a slightly higher incidence of stroke than ARB, among the Asian diabetic patients.

Using Rivaroxaban as Thrombolytic Treatment for a Patient of Pedal Arch Arterial Thrombosis with Suboptimal Result of Endovascular Therapy.

A 77-year-old male with subacute right foot ischemia was treated with endovascular therapy to relieve total thrombosis of the pedal arch extending from the dorsalis pedis of the anterior tibial artery into the posterior tibial artery, plantar segment. Because the procedure was only partially successful, rivaroxaban was used for thrombolytic treatment resulting in improvement of the patient's ischemic pain and avoidance of gangrenous progression and surgical amputation. This is the first report describing successful recanalization of pedal arch arterial thrombosis using rivaroxaban in a patient after suboptimal results of endovascular therapy.

Analysis of outcomes and prognostic factor in acute type A aortic dissection complicated with preoperative shock: A single-center study.

BACKGROUND: Acute type A aortic dissection (ATAAD) is a critical cardiovascular emergency that requires prompt surgical intervention for preserving life, particularly in patients with critical preoperative status. This retrospective study aimed to investigate the clinical features, early and late outcomes, and prognostic factors in patients undergoing aortic repair surgery for ATAAD complicated with preoperative shock. METHODS: Between April 2007 and July 2020, 694 consecutive patients underwent emergency ATAAD repair at our institution, including 162 (23.3%) presenting with preoperative shock (systolic blood pressure <90 mm Hg), who were classified into the survivor (n = 125) and non-survivor (n = 37) groups according to whether they survived to hospital discharge. The clinical demographics, surgical information, and postoperative complications were compared. Five-year survival and freedom from reoperation rates of survivors were analyzed using the Kaplan-Meier actuarial method. Multivariate logistic regression analysis was used to identify independent risk factors for in-hospital mortality. RESULTS: The in-hospital surgical mortality rate in patients with ATAAD and shock was 22.8%. The non-survivor group showed higher rates of preoperative cardiopulmonary resuscitation, acute myocardial infarction, and cerebral infarction, and was associated with longer cardiopulmonary bypass time, higher rates of total arch replacement and intraoperative extracorporeal membrane oxygenation implementation. The non-survivor group had higher blood transfusion volumes and rates of malperfusion-related complications. Multivariate analysis revealed that preoperative cardiopulmonary resuscitation, prolonged cardiopulmonary bypass time, and total arch replacement were risk factors for in-hospital mortality. For patients who survived to discharge, the 5-year cumulative survival and freedom from aortic reoperation rates were 75.6% (95% confidence interval, 67.6%-83.6%) and 82.6% (95% confidence interval, 74.2%-91.1%), respectively. CONCLUSIONS: Preoperative shock in ATAAD is associated with a high risk of in-hospital mortality, particularly in patients who undergo cardiopulmonary resuscitation and complex aortic repair procedures with extended cardiopulmonary bypass. However, late outcomes are acceptable for patients who were stabilized through surgical treatment and survived to discharge.