Cheng-Hsueh Wu

Statins, risk of diabetes, and implications on outcomes in the general population.

OBJECTIVES This study aimed to evaluate the association of statin exposure and incident diabetes, and subsequent outcomes in the general population. BACKGROUND Cardiovascular events as consequences of atherosclerosis and diabetes are reduced by statins. However, statins are associated with excessive risk of diabetes occurrence according to clinical trial analyses. From daily-practice perspectives, it remains unclear whether statin use increases risk; prognoses of diabetes after exposure require further clarification. METHODS From Taiwan National Health Insurance beneficiaries age ≥45 years (men) and ≥55 years (women) before 2004, subjects continuously treated with statins ≥30 days during 2000 to 2003 and nonusers before 2004 were identified. Among nondiabetic individuals at the cohort entry, controls were matched to statin users on a 4:1 ratio by age, sex, atherosclerotic comorbidities, and year of their entry. Outcomes as diabetes, major adverse cardiovascular events (MACE, the composite of myocardial infarction and ischemic stroke), and in-hospital deaths were assessed. RESULTS Over a median of 7.2 years, annual rates of diabetes were significantly higher in statin users (2.4% vs. 2.1%, p < 0.001), whereas MACE (hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.68 to 0.98 for myocardial infarction; HR: 0.94; 95% CI: 0.86 to 1.03 for ischemic stroke; HR: 0.91; 95% CI: 0.84 to 0.99 for MACE]) and in-hospital mortality (HR: 0.61; 95% CI: 0.55 to 0.67]) were less. The risk-benefit analyses suggested that statin treatment was favorable in high-risk (HR: 0.89; 95% CI: 0.83 to 0.95) and secondary prevention (HR: 0.89; 95% CI: 0.83 to 0.96) populations. Among diabetic patients, prior statin use was associated with fewer MACE (HR: 0.75; 95% CI: 0.59 to 0.97). In-hospital deaths were similar in statin-related diabetes among high-risk (HR: 1.11; 95% CI: 0.83 to 1.49) and secondary prevention (HR: 1.08; 95% CI: 0.79 to 1.47) subjects compared with nondiabetic controls. CONCLUSIONS Risk of diabetes was increased after statins, but outcomes were favorable.

Sitagliptin and the risk of hospitalization for heart failure: A population-based study

BACKGROUND Saxagliptin was associated with an increased risk of hospitalization for heart failure (HHF) in diabetic patients with high cardiovascular risk. This study assessed the risk of HHF during an exposure to sitagliptin in general diabetic patients. METHODS In Taiwan National Health Insurance research database, a study of the beneficiaries aged ≥ 45 years with diabetes treated with or without sitagliptin between March 2009 and July 2011 was conducted. Patients treated with sitagliptin were matched to patients never exposed to a dipeptidyl peptidase-4 (DPP-4) inhibitor by the propensity score methodology. The outcome measures were the first and the total number of HHF, and mortality for heart failure or all causes. RESULTS A total of 8288 matched pairs of patients were analyzed. During a median of 1.5 years, the first event of HHF occurred in 339 patients with sitagliptin and 275 patients never exposed to a DPP-4 inhibitor (hazard ratio: 1.21, 95% confidence interval: 1.04-1.42, P = 0.017); all-cause mortality was similar (hazard ratio: 0.87, 95% confidence interval: 0.74-1.03, P = 0.109). The risk for HHF was proportional to exposure (hazard ratio: 1.09, 95% confidence interval: 1.06-1.11, P < 0.001 for every 10% increase in adherence to sitagliptin). Overall, there were 935 events of HHF, in which the association between the number of HHF and the adherence to sitagliptin was linear. The greatest total number of HHF occurred in the patients with the highest adherence. CONCLUSIONS The use of sitagliptin was associated with a higher risk of HHF but no excessive risk for mortality was observed.

Long-term use of angiotensin II receptor blockers and risk of cancer: A population-based cohort analysis

BACKGROUND The risk of incident cancer after angiotensin II receptor blockers (ARBs) exposure was controversially reported by analyses of clinical trials and database. We assessed the occurrence of overall and site-specific cancers among ARB users and nonusers in the cohort with indications for ARB treatment. METHODS Data were obtained from the Taiwan National Health Insurance research database. Subjects exposed to ARBs ≥ 180 days with no cancer prior to the first year of ARB initiation were identified; age-, sex-, comorbidity- and time-matched nonusers without cancer before the index date plus 1 year were selected. Incidences of overall and the most common cancers between users and nonusers were compared. RESULTS There were 42,921 subjects enrolled in each group. During the mean follow-up of 4.8 ± 2.4 years, the cumulative incidence of cancer was 4% (ARB users) and 6% (ARB nonusers) (hazard ratio: 0.58, 95% confidence intervals 0.55-0.62; P<0.001). All ARBs significantly correlated with lower rates of cancer. Malignancies from the 7 most common sites were fewer in ARB users with the relative risk reduction of 28 to 49%. ARBs were associated with a decrease in incident cancer across subgroups including prior and concomitant exposure to angiotensin-converting enzyme inhibitors. CONCLUSIONS In the cohort with indications for ARB treatment, exposure to ARBs was associated with lower risk of overall and site-specific cancers compared to nonusers. These findings reassure the safety of ARBs and support further investigations on ARBs and cancer prevention at the molecular level.

Risk of New-Onset Diabetes Mellitus Versus Reduction in Cardiovascular Events With Statin Therapy

The Food and Drug Administration recently updated the safety warning concerning the association between statin therapy and new-onset diabetes mellitus (NODM). For prediabetes, little information is available for statins on cardiovascular outcome reduction and diabetogenic consequences. This study aimed to examine the risk of NODM and the reduction of cardiovascular events and death (MACE) after statin therapy in the prediabetic subjects. The medical and pharmacy claims of the prediabetic beneficiaries were retrieved from Taiwan National Health Insurance research database. The occurrence of NODM, MACE, and morbidity indexed by hospitalizations and emergency visits was ascertained by ambulatory and inpatient database. A propensity score-matched model was constructed for statin users and nonusers. During follow-up (4.1 ± 2.5 years), NODM and MACE occurred in 23.5% and 16.7%, respectively, of nonusers and 28.5% and 12.0%, respectively, of users. Statin therapy was associated with a greater risk of NODM (hazard ratio 1.20, 95% confidence interval 1.08 to 1.32) and less risk of MACE (hazard ratio 0.70, 95% confidence interval 0.61 to 0.80), both in dose-dependent fashions. The earlier and more persistent use correlated with the greater increase in risk of NODM offset by the proportionally larger reduction in MACE. Furthermore, the early persistent users had the lowest rate of hospitalizations and emergency visits. In conclusion, our findings suggested that the relation between NODM and therapeutic advantages of statins was parallel in the prediabetic population. Treatment benefits outweighed diabetic consequences in subjects receiving the earlier and more persistent treatment.

Complexity of atrial fibrillation patients and management in Chinese ethnicity in routine daily practice: Insights from the RealiseAF Taiwanese cohort

BACKGROUND Most atrial fibrillation (AF) epidemiology described Western populations; there is a paucity of data from Chinese ethnicity. This study presented differences in patient characteristics and management strategies, and assessed the quality of life (QoL) and AF control in Taiwanese patients from RealiseAF. METHODS RealiseAF enrolled 10,523 patients internationally, in which Taiwanese cohort accounts for 7.1%. Physicians were randomly selected from a global list. Patient characteristics, management and therapeutic strategies of AF, QoL measured by the EQ-5D questionnaire, and the control of AF (in sinus rhythm, or AF with a ventricular rate ≤80 beats per minute) evaluated by electrocardiography were assessed. RESULTS Taiwanese patients were mostly outpatients (93.9%), older (70.2±11.8 years), accompanied by more comorbidities, more frequently (51.7%) in permanent AF, and symptomatic (European Heart Rhythm Association score ≥II: 81.5%) compared with the non-Taiwanese cohort. A rhythm-control strategy was less preferable to rate-control than in non-Taiwanese cohort as well as the use of class I and III antiarrhythmic drugs (AADs); 85.2% of Taiwanese patients received AADs, among which beta-blockers were the most common (46.9%). QoL was compromised (Visual Analogue Scale: 70.3±14.4; single index utility score: 0.81±0.25) and only 48.6% of the Taiwanese patients had AF controlled. CONCLUSIONS AF complexity in the Taiwanese cohort was similar to or even greater than that in the non-Taiwanese cohort. The Taiwanese patients were highly symptomatic; QoL was impaired despite the widespread use of medications and AF control was unsatisfactory. There is an apparent unmet need in AF treatment in Chinese ethnicity.

Determinants of low-density lipoprotein cholesterol goal attainment: Insights from the CEPHEUS Pan-Asian Survey

Background: Previous studies have reported that the attainment of goals for low‐density lipoprotein cholesterol (LDL‐C) are globally suboptimal, but contemporary data are scarce. The CEntralized Pan‐Asian survey on tHE Under‐treatment of hypercholeSterolemia (CEPHEUS‐PA) is the largest evaluation of pharmacological treatment for hypercholesterolemia in Asia. The study reported here analyzed the Taiwan cohort in CEPHEUS‐PA to identify the determinants of successful treatment. Methods: The patients eligible for this study were adults (≥18 years old) with hypercholesterolemia and with at least two coronary heart disease (CHD) risk factors who had been receiving lipid‐lowering drugs for at least 3 months before enrollment, without adjustment for at least 6 weeks before enrollment. Demographic and clinical information and lipid concentrations were recorded. Cardiovascular risk levels and LDL‐C targets were determined using the updated Adult Treatment Panel III. Results: In this group of 999 Taiwanese patients, 50%, 25%, and 24% had LDL‐C goals set at <70 mg/dL, <100 mg/dL, and <130 mg/dL, respectively. The overall attainment rate was 50%, with the lowest rate in patients set at the most stringent target (22%), followed by those whose therapeutic goals were <100 mg/dL (69%) and <130 mg/dL (87%). The success of LDL‐C control was lower in patients with multiple risk factors other than CHD or its equivalents than in those without these multiple risk factors (37% vs. 53%, p < 0.001), and lower in patients with metabolic syndrome than in those without (43% vs. 66%, p < 0.001). Baseline LDL‐C and cardiovascular risk were inversely associated with goal attainment, whereas treatment with statins was directly associated with the achievement of LDL‐C goals. Patients with diabetes (odds ratio 0.49, 95% confidence interval 0.29–0.84, p = 0.010) and with metabolic syndrome (odds ratio 0.15, 95% confidence interval 0.05–0.40, p < 0.001) were less likely to be treated with statins. Conclusion: This study showed that there is a discrepancy between the updated Adult Treatment Panel III recommendations for LDL‐C control and the control attained by this group of Taiwanese patients. In particular, treatment with statins was largely underused in patients with diabetes and in those with metabolic syndrome. These findings highlight the need for more intensive treatment in high‐risk patients and those with multiple risk factors, particularly patients with metabolic syndrome.

Identification and Management of Noncompliance in Atrial Fibrillation Patients Receiving Dabigatran: The Role of a Drug Monitor

Noncompliant patients might be at risk of thromboembolism because of the short half‐life and rapid offset of dabigatran etexilate. The assessment and management of dabigatran noncompliance should be optimized.

Association between serum uric acid and cardiovascular risk in nonhypertensive and nondiabetic individuals: The Taiwan I-Lan Longitudinal Aging Study

Serum uric acid level is a risk factor for cardiovascular disease (CVD). However, whether it is an independent risk factor or not remains controversial. We analyzed the association between serum uric acid level and cardiovascular risk. In total, 973 nonhypertensive and nondiabetic participants in the I-Lan Longitudinal Aging Study were eligible for this study. Subjects were divided into tertiles according to uric acid levels. The 10-year cardiovascular risk was calculated using Framingham risk score (FRS). Study subjects in the highest tertile of serum uric acid level were older, more likely to be male, and had higher systolic blood pressure, body mass index, carotid artery intima–media thickness and serum triglyceride, high-sensitivity C-reactive protein, and low-density lipoprotein cholesterol levels and lower serum high-density lipoprotein cholesterol levels (all p < 0.05). Subjects in the highest tertile had significantly higher FRS (p < 0.001). After adjusting for other risk factors, serum uric acid level remained associated significantly with the FRS (p < 0.05). In binary logistic regression analysis, the serum uric acid level was an independent predictive factor for high (≥20%) FRS (odds ratio 1.33, 95% confidence interval 1.10–1.68). These findings warrant attention to this cardiovascular risk factor in apparently healthy adults.

Clinical outcomes of percutaneous coronary intervention with rotablation in patients with acute or recent myocardial infarction

Background Although rotational atherectomy (RA) has been an accepted and widely used medical procedure for more than 15 years, the clinical outcomes of RA in high‐risk populations remain elusive. Therefore, the purpose of this study was to investigate the safety and efficacy of RA for patients with acute or recent myocardial infarction (MI), and report the short‐ and long‐term clinical outcomes in this population. Methods We enrolled patients undergoing percutaneous coronary intervention (PCI) and RA at two medical centers in Taiwan between January 2004 and December 2013. Individuals who suffered an acute MI within 30 days before RA were assigned to the MI group; the remaining subjects were assigned to the non‐MI group. Results A total of 154 subjects were enrolled in our study, among them: 47 (30.5%) had an acute MI within 30 days of RA (MI group), and the remaining 107 (69.5%) patients without MI comprised the non‐MI group. PCI and RA procedures were performed successfully in 150 patients. The 30‐day and 1‐year total death, MI, and major adverse cardiac event (MACE included all‐cause death, MI, and clinical‐driven target lesion revascularization) rates were 6.5%, 12.3%, and 15.6%, and 9.7%, 15.2%, and 30.5%, at the 30‐day and 1‐year follow‐ups, respectively. MI was identified as an independent predictor for both 30‐day MACE and total death (MACE, OR: 3.95, P = 0.006; total death, OR: 4.67, P = 0.043), and remained an independent predictor for 1‐year total death and MI (total death, HR: 4.47, P = 0.007; MI, HR: 2.62, P = 0.016). Conclusion Our study demonstrated the safety and efficacy of RA in patients with acute or recent MI, and identified MI as an independent predictor of both short‐ and long‐term outcomes.

Long-term outcome of patients with very small coronary artery disease: A comparison of drug-eluting and bare metal stents.

Background Among patients with very small vessel disease and chronic kidney disease (CKD), the comparative efficacy of bare metal stents (BMSs) versus drug‐eluting stents (DESs) is not frequently addressed. This study aimed to evaluate the long‐term outcomes of patients with very small vessel disease managed with percutaneous coronary intervention. Methods Our study included 158 consecutive patients undergoing percutaneous coronary intervention from January 2003 to December 2013. The primary end points were cardiovascular death and target vessel failure, which consisted of cardiovascular death, target vessel‐related myocardial infarction, and ischemia‐driven target vessel revascularization. Results BMSs were used in 37 patients, while DESs were utilized in 121 patients. During the mean follow‐up period of 2.7 ± 2.2 years (median 2.1 years; interquartile range, 1.3−4.2 years), the target vessel failure rate was 48.6% versus 28.1% (BMS vs. DES, p = 0.020) and the cardiovascular death rate was 27% versus 18.2% (BMS vs. DES, p = 0.241). The use of a DES (hazard ratio: 0.44, 95% confidence interval: 0.24–0.79, p = 0.006) remained the most significant predictor of target vessel failure after multivariate analysis. In CKD subgroup analysis, the benefit of a 2.25 mm DES was evident only in the subgroup with CKD, but such a benefit disappeared in those without CKD. Conclusion Compared with BMSs, implantation of DESs in a patient population with very small vessel disease effectively reduced target vessel failure. However, the beneficial effects of DESs appeared to be evident only in the subgroup with CKD.