Jia-Rou Liu

Simvastatin-ezetimibe combination therapy is associated with a lower rate of major adverse cardiac events in type 2 diabetics than high potency statins alone: A population-based dynamic cohort study.

BACKGROUND Recent trials have shown a reduction in the risk of major adverse cardiac events (MACE) with simvastatin-ezetimibe therapy in patients with acute coronary syndrome. The potential benefits of simvastatin-ezetimibe for patients at a lower risk of MACE are unclear. This study aimed to investigate the differences of MACE risk between patients with type 2 diabetes mellitus (DM) using simvastatin-ezetimibe or high potency statins. METHODS This population-based dynamic cohort study used data from the Taiwan National Health Insurance Database. The study subjects were patients with type 2 DM, aged between 40 and 75 years. The simvastatin-ezetimibe group took simvastatin-ezetimibe only, and the statin group took atorvastatin or rosuvastatin but not simvastatin or ezetimibe. The two groups were matched for age, gender, medication date, DM diagnosis date, hypertension, and cardiovascular complications. The outcome variable was new-onset MACE. Univariate and multivariate survival analyses were performed. RESULTS A total of 20,485 patients (53% male; 4099 in the simvastatin-ezetimibe group and 16,396 in the statin group) were included, with a mean age of 59.1 years. In a total of 37,388 person-years, 1100 patients developed new-onset MACE. The annual incidence rate of new-onset MACE was lower in the simvastatin-ezetimibe group (2.61%) than that in the statin group (3.02%) (p=0.0476). After Cox regression analysis, simvastatin-ezetimibe use was independently associated with a lower risk of MACE (HR, 0.77; 95% confidence interval 0.66-0.90). CONCLUSIONS Compared to high potency statins alone, simvastatin-ezetimibe therapy was associated with a lower incidence of MACE in patients with type 2 DM.

Hyperthyroid and Hypothyroid Status Was Strongly Associated with Gout and Weakly Associated with Hyperuricaemia

Objectives The aim of this study was to estimate the risk of hyperuricaemia and gout in people with hypothyroid or hyperthyroid status. Methods This study analyzed data from individuals who participated in health screening programs at Chang Gung Memorial Hospital in northern Taiwan (2000–2010). Participants were categorized as having euthyroid, hypothyroid, or hyperthyroid status according to their thyroid-stimulating hormone (TSH) levels. Multinomial logistic regression models were used to calculate the odds ratios (95% CI) for hyperuricaemia and gout in participants with thyroid dysfunction compared to euthyroid participants. Results A total of 87,813 (euthyroid, 83,502; hypothyroid, 1,460; hyperthyroid, 2,851) participants were included. The prevalence of hyperuricaemia was higher in hyperthyroid subjects (19.4%) than in euthyroid subjects (17.8%) but not in hypothyroid subjects (19.3%). The prevalence of gout was significantly higher in both hypothyroid (6.0%) and hyperthyroid (5.3%) subjects than in euthyroid subjects (4.3%). In men, hypothyroid or hyperthyroid status was not associated with hyperuricaemia. However, hypothyroid or hyperthyroid status was associated with ORs (95% CI) of 1.47 (1.10–1.97) and 1.37 (1.10–1.69), respectively, for gout. In women, hypothyroid status was not associated with hyperuricaemia or gout. However, hyperthyroid status was associated with ORs (95% CI) of 1.42 (1.24–1.62) for hyperuricaemia and 2.13 (1.58–2.87) for gout. Conclusions Both hyperthyroid and hypothyroid status were significantly associated with gout and weakly associated with hyperuricaemia. A thyroid function test for gout patients may by warranted.

Young Male Patients with Atrial Fibrillation and CHA2DS2-VASc Score of 1 May Not Need Anticoagulants: A Nationwide Population-Based Study

Background It is unclear whether oral anticoagulants are beneficial for atrial fibrillation (AF) patients with low CHA2DS2-VASc score. Age could be important in determining the risk of thromboembolism in low risk AF patients (CHA2DS2-VASc score of 1 for male or 2 for female). Methods The Taiwan National Health Insurance Research Database (NHIRD) was used and 27,521 AF patients with CHA2DS2-VASc score of 1 (male) or 2 (female) not receiving anticoagulants were acquired as the study cohort, which were classified into three age groups: 20–49, 50–64, and 65–74 years. The clinical endpoint was the occurrence of ischemic thromboembolism within one year of follow up. Results During the follow-up of 0.94 ± 0.19 years, 385 (2.19%) male patients experienced ischemic thromboembolism, with annual rate of 2.32%. The annual risk ranged from 1.29%, 2.43% to 2.77% for male patients aged 20–49, 50–64 and 65–74 years respectively. Of the female patients, 218 (2.20%) experienced clinical event with annual rate of 2.32%. The annual risk increased from 1.87%, 2.28% to 2.64% for female patients aged 20–49, 50–64 and 65–74 years respectively. There was no difference in risk between the male patients aged 20–49 years with CHA2DS2-VASc score of 1 and overall male patients with CHA2DS2-VASc score of 0. (P = 0.631) The female patients aged 20–49 years with CHA2DS2-VASc score of 2 was associated with a higher risk of thromboembolic events than overall female patients with CHA2DS2-VASc score of 1 (HR = 1.93; P = 0.008). Conclusions Age is important in determining the risk of thromboembolism in AF patients with single risk factor. In male patients <50 years old with CHA2DS2-VASc score of 1, the risk of ischemic thromboembolism was low. Considering the benefits and the risk of bleeding, oral anticoagulation therapy may not be favorable in these patients.

Dialysis Patients with Implanted Drug-Eluting Stents Have Lower Major Cardiac Events and Mortality than Those with Implanted Bare-Metal Stents: A Taiwanese Nationwide Cohort Study.

Objective To investigate the efficacy and long-term clinical benefits of DES for dialysis patients. Background It is unclear whether percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation is associated with lower rates of major adverse cardiovascular events (MACE) or mortality compared to bare-metal stents (BMS). Methods From a nationwide cohort selected from Taiwan’s National Health Insurance Research Database, we enrolled 2,835 dialysis patients who were hospitalized for PCI treatment with stent implantation from Dec 1, 2006. Follow-up was from the date of index hospitalization for PCI until the first MACE, date of death, or December 31, 2011, whichever came first. Results A total of 738 patients (26.0%) had DES implanted, and 2,097 (74%) had BMS implanted. The medium time to the first MACE was 0.53 years (interquartile range: 0.89 years; range: 0–4.62 years). At 1-year follow-up, patients treated with BMS had significantly, non-fatal myocardial infarction (MI), all-cause mortality, and composite MACE compared to those treated with DES. The overall repeat revascularization with coronary artery bypass graft (CABG), non-fatal MI, all-cause mortality, and composite MACE were significantly lower in patients treated with DES than those treated with BMS. Multivariate cox regression analysis showed that older age, history of diabetes, history of heart failure, history of stroke, and DES vs. BMS were independent significant predictors of MACE. Conclusions DES implantation conferred survival benefits in dialysis patients compared with BMS implantation.

Risk of Cardiovascular Ischemic Events After Surgical Castration and Gonadotropin-Releasing Hormone Agonist Therapy for Prostate Cancer: A Nationwide Cohort Study

Purpose Our aim was to determine whether cardiovascular (CV) risk in patients with prostate cancer (PCa) differs between those who receive androgen-deprivation therapy by surgical castration and those who receive gonadotropin-releasing hormone agonist (GnRHa) therapy. Patients and Methods By using the Taiwan National Health Insurance Research Database, we analyzed data from 14,715 patients with PCa diagnosed from January 1, 1997, through December 31, 2011. The patients were treated with bilateral orchiectomy or GnRHa therapy. We used inverse probability of treatment weighting with propensity scores to adjust for the imbalance in covariate baseline values between these two groups. Cox regression models were used to identify risk factors for myocardial infarction (MI), ischemic stroke (IS), and cardiac-related complications. Results Overall, 3,578 patients with PCa (24.3%) underwent bilateral orchiectomy and 11,137 patients (75.7%) received GnRHa therapy. Both groups had a similar risk of CV ischemic events (ie, MI or IS; hazard ratio, 1.16; 95% CI, 0.97 to 1.38) during a median follow-up time of 3.3 years. However, during the first 1.5 years of follow-up, there were higher CV ischemic events in the orchiectomy group than in the GnRHa group (hazard ratio, 1.40; 95% CI, 1.04 to 1.88), particularly in patients who were ≥ 65 years of age, had hypertension, had a Charlson comorbidity index score ≥ 3, and had a previous history of MI, IS, or coronary heart disease. Conclusion Compared with bilateral orchiectomy, use of GnRHa does not increase the risk of CV ischemic events in patients with PCa. Nonetheless, orchiectomy is associated with higher rates of CV ischemic events in older patients and those with a history of CV comorbidities within 1.5 years of initiating androgen-deprivation therapy. These findings can help clinicians decide on the optimal castration strategy for individual patients.

Metformin is associated with fewer major adverse cardiac events among patients with a new diagnosis of type 2 diabetes mellitus: A propensity score-matched nationwide study

Abstract Early type 2 diabetes mellitus (DM) may only require lifestyle modifications for glycemic control without the need for oral hypoglycemic agents (OHAs). Metformin is believed to improve cardiovascular outcomes in patients with DM, and it is considered to be a first-line therapy. However, it is unclear whether metformin is beneficial for patients with a new diagnosis of DM compared to those who do not need OHAs for glycemic control. Data were obtained from a population-based health care database in Taiwan. Patients with a new diagnosis of DM were enrolled if they received metformin monotherapy only between 1999 and 2010. A 4:1 propensity score-matched cohort of patients with a new diagnosis of DM who did not take OHAs or insulin during follow-up was also enrolled. The primary study endpoint was the occurrence of major adverse cardiovascular events (MACEs). The time to the endpoints was compared between groups using Cox proportional hazards models. A total of 474,410 patients with DM were enrolled. During a mean 5.8 years of follow-up, the incidence of MACEs was 1.072% (1072 per 100,000 person-years) in the metformin monotherapy group versus 1.165% in the lifestyle modification group (those who did not take OHAs) (P < .001). After adjusting for confounders, metformin independently protected the DM patients from MACEs (hazard ratio: 0.83, P < .001). The metformin group also had an improved MACE-free survival profile from year 1 to year 12 (P < .001). In addition to lifestyle modifications, the patients with a new diagnosis of DM treated with metformin monotherapy had a lower MACE rate than those who did not take OHAs. Our findings suggest that metformin may be given early to patients with a new diagnosis of DM, even when they do not need OHAs for glycemic control.

The Association of Ursodeoxycholic Acid Use With Colorectal Cancer Risk: A Nationwide Cohort Study

AbstractData from preclinical studies suggest that ursodeoxycholic acid (UDCA) has a chemopreventive effect on colorectal cancer (CRC) development, but no large observational study has examined this possibility.The aim of this study was to investigate the association of UDCA use with CRC risk in a nationwide population-based cohort.This nationwide population-based cohort study used data from the Taiwan National Health Insurance Research Database for the period from 2000 through 2010. This study included data from 7119 Taiwanese adults who received ≥28 cumulative defined daily doses (cDDDs) of UDCA and 14,238 patients who did not receive UDCA (<28 cDDDs). UDCA nonusers were matched 1:2 for age, sex, enrollment date, and presence of chronic liver disease, viral hepatitis, cholelithiasis, and alcoholic liver disease. The 2 cohorts were followed until December 31, 2010 or occurrence of CRC. Cox proportional hazards regression with robust Sandwich variance estimator, which can cooperate with matching design, was used to examine the association between UDCA use and CRC risk.During 109,312 person-years of follow-up (median, 5 years), 121 patients had newly diagnosed CRC: 28 UDCA users (76.7 per 100,000 person-years) and 93 nonusers (127.7 per 100,000 person-years) (log-rank test, P = 0.0169). After multivariate adjustment for age, UDCA use was associated with a reduced risk of CRC (hazard ratio, 0.60; 95% confidence interval [CI], 0.39–0.92). The adjusted hazard ratios were 0.55 (95% CI, 0.35–0.89), 0.89 (95% CI, 0.36–2.20), and 0.63 (95% CI, 0.16–2.53) for patients with 28 to 180, 181 to 365, and >365 cDDDs, respectively, relative to nonusers.UDCA use was associated with reduced risk of CRC in a cohort mainly comprising patients with chronic liver diseases. However, further studies are needed to determine the optimal dosage of UDCA.

Suicide death rates in patients with cardiovascular diseases – A 15-year nationwide cohort study in Taiwan

BACKGROUND The literature on suicide mortality rates in patients with cardiovascular diseases (CVDs) is limited. METHODS Taiwan National Health Insurance Research Database and Taiwan Death Registry were retrieved for patients with the 5 CVDs: congestive heart failure (CHF), acute myocardial infarction (AMI), ischemic stroke (IS), hemorrhagic stroke (HS), and pacemaker implantation (PMI) between January 1, 2001, and December 31, 2015. We excluded patients younger than 15 years old. The primary outcome was suicidal death. The standardized mortality ratio (SMR) was used to compare the risk of suicidal death in the 5 CVDs to the general population. RESULTS From 2001 to 2015, there were 212,206 patients with CHF, 178,894 patients with AMI, 475,359 patients with IS, 189,555 patients with HS, and 64,173 patients with PMI. The suicide death rate per 100,000 person-year, 95% CI was 59.6 (54.5-64.8) for those with CHF, 44.6 (40.1-49.1) for AMI, 57.6 (54.7-60.5) for IS, 44.6 (40.2-49.0) for HS, 54.0 (45.9-62.0) for PMI, and 20.3 (20.1-20.4) for the general population. Patients with CHF patients had the highest SMR (2.10), followed by IS (1.96), PMI (1.86), HS (1.65), and AMI (1.46). The SMRs for patients with CVDs peaked at year 2 after the diagnosis, declined for patients with AMI, IS, and HS, increased and decreased for PMI alternately, and reached very similar values all five CVDs after 10th year after the diagnosis. CONCLUSIONS Patients with acute CVD with AMI, IS, and HS had suicide death rates peaked early after diagnosis, but patients with chronic CVD with CHF and PMI had suicide death rates that increased progressively. In addition, patients with PMI, CHF, IS had highest association with psychiatric illness and patients with PMI who were of young to middle age had highest suicide death rate.

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

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.