Abstract
Background
The Taiwan Society of Cardiology (TSOC) has established multicenter registries for coronary artery disease (CAD) to investigate clinical characteristics, management and risks for mortality. However, the impacts of newly-emerged evidence-based therapies, including the use of drug-eluting stents (DESs), on patients with CAD in Taiwan remain unclear.
Methods
The Tri-Service General Hospital–Coronary Heart Disease (TSGH-CHD) registry is a single-center, prospective, longitudinal registry in Taiwan containing data from 2014-2016. Individuals who were admitted for coronary angiography were enrolled. Patient profiles, management and in-hospital outcome data were collected.
Results
We included 3352 patients: 2349 with stable angina and 1003 with acute coronary syndrome (ACS). In the stable angina group, both patients receiving stenting and those receiving medical treatment had a 0.7% mortality rate; DESs were used in 70.4% of the patients receiving stenting. In the ACS group, the patients receiving stenting and those receiving medical treatment had a 4.9% and 10.7% mortality rate, respectively; DESs were used in 63.1% of the patients receiving stenting. In the 2008-2010 Taiwan ACS registry, DESs were used in only 28% of all stenting procedures, and the estimated hospital mortality rate was 1.8%. Multivariate analysis indicated that older age, prior stroke, and cardiogenic shock on admission were associated with an increased risk of in-hospital mortality in the ACS group.
Conclusions
Compared with the Taiwan ACS cohort, the TSGH-CHD registry revealed increased DES use and increased disease complexity and severity after 2010. Although unlikely to significantly improve survival, interventionists seemed to perform high-risk procedures for complex CAD more often in the new DES era.
Keywords: Angiography, Cohort study, Coronary heart disease, Drug-eluting stent
INTRODUCTION
Coronary artery disease (CAD) remains the leading cause of mortality and morbidity worldwide, thus imposing a considerable burden on public health.1,2 In recent decades, both improved adherence to guidelines and advancements in coronary interventional therapy have improved clinical outcomes in patients with CAD.3 Several systematic health examinations and prospective observational studies on large registries have been conducted to provide data that can enhance the understanding of the characteristics of CAD patients with complex underlying comorbidities and those receiving contemporary management. Moreover, they provide crucial information about clinical outcomes over relatively long follow-up periods.4-8
Prospective randomized controlled trials, which are considered to be the gold-standard study design, provide robust evidence for establishing guidelines. However, registries may also play a major role in establishing guidelines, and they complement each other perfectly.7-10 The National Health Insurance program in Taiwan is a tremendous resource in terms of data availability, and relevant institutes in Taiwan have constructed several registries for the main cardiovascular diseases to help researchers examine the status of real-world practice, identify inadequacies in guideline implementation, and improve cardiovascular patient care.11
Data from two of these registries of acute coronary syndrome (ACS) established in 2008-2010 and 2012-2015 have shown increased trends of drug-eluting stent (DES) use in different cohorts.9,12 An increasing amount of evidence-based data on interventional therapy in CAD patients has been published, including data on the prevalence of DES use and its clinical benefits after 2010.13 However, the impacts of such evidence-based therapy on patients with CAD in Taiwan remain unclear. The Tri-Service General Hospital (TSGH) established a Coronary Heart Disease (TSGH-CHD) registry in 2014 that provides contemporary clinical profiles covering the entire spectrum of CAD and the aim of the study is to enable the cohort effect on outcomes in daily practice to be studied.
METHODS
TSGH-CHD registry and study population
TSGH is a metropolitan tertiary hospital in Taipei, Taiwan. In 2014, TSGH established the TSGH-CHD registry, a single-center, prospective, and longitudinal cohort database. Patients were eligible for enrollment in this registry if they presented with stable angina (SA) or ACS, including unstable angina (UA), ST-segment elevation myocardial infarction (STEMI), and non-STEMI (NSTEMI). All patients in this cohort were admitted to the hospital and received coronary angiography with or without coronary interventional therapy. Clinical decisions regarding pharmacologic treatment and/or therapeutic percutaneous coronary intervention (PCI) were made by the attending physicians on the basis of patients’ characteristics, clinical presentations, or coronary phenotypes. Patients were excluded if they were hospitalized without clinical suspicion of CAD (i.e., the purpose of the angiographic examination was due to pre-operative evaluation for major cardiac surgery or post-heart transplant coronary investigation).
Data acquisition
All clinical data in the TSGH-CHD registry have been thoroughly reviewed and recorded by a specialized research assistant since 2014. Data collected at baseline included the patients’ demographic characteristics, medical history, vital signs, clinical profile, and, if available, biological test results and echocardiographic findings. In addition, coronary angiography results, interventional procedures, in-hospital morbidity data, and mortality data were comprehensively evaluated from medical records.
Definition of acute coronary syndrome
Recently, the Fourth Universal Definition of Myocardial Infarction (2018) categorized acute myocardial infarction into various types on the basis of pathological, clinical, and prognostic differences.14 However, in the TSGH-CHD registry, the patients were classified as having UA, NSTEMI, and STEMI in the spectrum of ACS through conventional practice.15,16 STEMI was defined as myocardial ischemia in association with persistent ST-segment elevation or new left bundle-branch block on an electrocardiogram, and it was considered to be an indication for immediate reperfusion therapy. Diagnostic ST-segment elevation in the absence of left ventricular hypertrophy was defined as new ST-segment elevation at the J point in at least two contiguous leads as follows: new ST-segment elevation of ≥ 2 mm (0.2 mV) in men or ≥ 1.5 mm (0.15 mV) in women in leads V2 and V3 and/or ≥ 1 mm (0.1 mV) in other contiguous chest leads or limb leads. The absence of ST-segment elevation was suggestive of NSTE-ACS, including NSTEMI and UA, depending on whether cardiac biomarkers were elevated. If cardiac biomarkers were elevated and the clinical context was appropriate, NSTEMI was considered. Otherwise, the patients were considered to have UA. Obstructive CAD was defined as a coronary diameter stenosis of ≥ 50%. Cardiogenic shock was defined as systolic blood pressure of < 90 mmHg despite intravenous fluid resuscitation or the administration of inotropic agents on admission.
Study outcomes
Because only in-hospital events are available in the current stage of the TSGH-CHD registry, the main outcomes in this study for analysis were in-hospital mortality and morbidities including in-hospital stroke, major bleeding, and acute in-stent thrombosis.
Comparison with the Taiwan ACS registry
The Taiwan Society of Cardiology (TSOC) has established multicenter registries for cardiovascular diseases in the past decade, mainly including patients with ACS.11 Therefore, this provides a good opportunity to evaluate the cohort effects of medical practice by comparing a previous TSOC ACS registry and our contemporary TSGH-CHD registry. All of the baseline characteristics, clinical presentations, stent types, and in-hospital outcomes were investigated.
Statistical analysis
Data are presented as means ± standard deviations for normally distributed continuous variables and as percentages for categorical variables. Differences in the characteristics between different populations were assessed using the unpaired two-tailed Student t test or one-way analysis of variance for continuous variables, and the chi-square and Fisher’s exact tests for nominal variables. Backward stepwise logistic regression analysis of the various clinical variables was performed to determine predictors of in-hospital mortality. In addition, to assess the influence of stent types on mortality, two models were constructed. Model 1 was used for regression analysis for the entire ACS cohort, and model 2 was used for analysis for those undergoing coronary interventions with stenting. Variables with a p value of < 0.05 in the univariate models were selected for testing in the multivariate analysis. Statistical analyses were performed using SPSS (version 25.0; SPSS, Chicago, USA), and differences were considered significant at p < 0.05.
RESULTS
Baseline characteristics
A total of 3,352 patients were selected from the TSGH-CHD registry from 2014 to 2016. Figure 1 displays the inclusion and exclusion criteria of the study. Of the included patients, 2,349 (70.1%) presented with SA and 1,003 (29.9%) with ACS. Among the patients with ACS, 353 (35.2%) had STEMI, 545 (54.3%) had NSTEMI, and 105 (10.5%) had UA.
Figure 1.
Concept of the Tri-Service General Hospital–Coronary Heart Disease (TSGH-CHD) registry. The algorithm illustrates the inclusion and exclusion criteria for the TSGH-CHD registry for the period from 2014 to 2016.
Overall, the mean age was 63.5 ± 12.9 years, and 2486 (74.2%) patients were men (Table 1). Hypertension was the most common underlying comorbidity (74.6%), followed by dyslipidemia (43.8%), diabetes mellitus (37.4%), and previous history of myocardial infarction (MI) (29.1%). No significant differences were observed in age or sex between the patients with SA and those with ACS. However, the proportions of traditional cardiovascular risk factors (e.g., hypertension, dyslipidemia, prior history of MI, and underlying status of uremia) were higher in the patients with SA than in those with ACS. Laboratory data revealed that the patients with SA had lower serum levels of low-density lipoprotein cholesterol and higher serum levels of high-density lipoprotein cholesterol than the patients with ACS. The prevalence of cardiogenic shock on admission was 12.2% in the ACS group.
Table 1. Clinical characteristics of patients, stratified by coronary artery disease types in TSGH-CHD registry.
| Overall (N = 3,352) | ACS (N = 1,003) | Stable angina (N = 2,349) | |
| Demographic data | |||
| Age (years) | 63.5 ± 12.9 | 63.9 ± 13.9 | 63.3 ± 12.5 |
| Gender (male, %) | 2,486 (74.2) | 747 (74.5) | 1,739 (74.0) |
| Smoking (ex/current) | 172 (5.1)/1377 (41.1) | 31 (3.1)/476 (47.5) | 141 (6.0)/901 (38.4) |
| Hypertension (N, %) | 2,501 (74.6) | 678 (67.6) | 1,823 (77.6)* |
| Diabetes mellitus (N, %) | 1,253 (37.4) | 367 (36.6) | 886 (37.7) |
| Dyslipidemia (N, %) | 1,469 (43.8) | 323 (32.2) | 1,146 (48.8)* |
| Prior MI (N, %) | 975 (29.1) | 197 (19.6) | 778 (33.1)* |
| Prior stroke/TIA (N, %) | 316 (9.4) | 107 (10.7) | 209 (8.9) |
| Prior HF (N, %) | 453 (13.5) | 133 (13.3) | 320 (13.6) |
| Prior AF/AFL (N, %) | 229 (6.8) | 55 (5.5) | 174 (7.4) |
| PAOD (N, %) | 123 (3.7) | 33 (3.3) | 90 (3.8) |
| Uremia (N, %) | 374 (11.2) | 93 (9.3) | 281 (12.0)* |
| Laboratory data | |||
| Hemoglobin (g/dL) | 13.2 ± 2.4 | 13.1 ± 2.7 | 13.2 ± 2.2 |
| Creatinine (mg/dL) | 1.9 ± 2.4 | 1.9 ± 2.4 | 1.9 ± 2.4 |
| Total cholesterol (mg/dL) | 163.2 ± 41.3 | 162.5 ± 42.6 | 163.5 ± 40.7 |
| HDL-C (mg/dL) | 41.0 ± 11.0 | 38.8 ± 10.7 | 41.9 ± 11.0* |
| LDL-C (mg/dL) | 100.8 ± 34.2 | 103.5 ± 36.3 | 99.5 ± 33.1* |
| Triglyceride (mg/dL) | 142.4 ± 96.2 | 140.0 ± 105.5 | 144.0 ± 91.7 |
| Clinical presentation on admission | |||
| Cardiogenic shock (N, %) | NA | 122 (12.2) | NA |
ACS, acute coronary syndrome; AF/AFL, atrial fibrillation/atrial flutter; HDL-C, high-density lipoprotein cholesterol; HF, heart failure; LDL-C, low-density lipoprotein cholesterol; MI, myocardial infarction; NA, not applicable; PAOD, peripheral arterial occlusive disorder; TIA, transient ischemia attack; TSGH-CHD, Tri-Service General Hospital–Coronary Heart Disease.
* Indicates significant difference between ACS and stable angina group, p < 0.05.
Coronary lesions and procedural characteristics
Table 2 presents the coronary angiographic findings. Overall, 285 (8.5%) patients had angiographically documented left main coronary artery lesions. The left anterior descending coronary artery (LAD) was the most commonly stenosed coronary artery. The prevalence rates of triple-vessel disease (TVD), chronic total occlusion, and ostial lesions were higher in the patients with ACS than in those with SA. Nevertheless, the prevalence of in-stent restenosis lesions was higher in the patients with SA than in those with ACS.
Table 2. Characteristics of clinical presentation, coronary lesions and stent types, stratified by coronary artery disease types in TSGH-CHD registry.
| Overall (N = 3,352) | ACS (N = 1,003) | Stable angina (N = 2,349) | |
| Coronary lesion data | |||
| LM lesion (N, %) | 285 (8.5) | 102 (10.2) | 183 (7.8)* |
| LAD lesion (N, %) | 2,637 (78.7) | 868 (86.5) | 1,769 (75.3)* |
| LCX lesion (N, %) | 1,792 (53.5) | 620 (61.8) | 1,172 (49.9)* |
| RCA lesion (N, %) | 1,977 (59.5) | 698 (69.6) | 1,279 (54.4)* |
| Presence of TVD (N, %) | 1,356 (40.5) | 490 (48.9) | 866 (36.9)* |
| Presence of CTO lesion (N, %) | 580 (17.3) | 197 (19.6) | 383 (16.3)* |
| Presence of ostial lesion (N, %) | 1,017 (30.3) | 361 (36.0) | 656 (27.9)* |
| Presence of ISR lesion (N, %) | 308 (9.2) | 75 (7.5) | 233 (9.9)* |
| Overall (N = 1,675) | ACS (N = 669) | Stable angina (N = 1,006) | |
| Stent types, based on patients with stenting | |||
| BMS (N, %) | 481 (28.7) | 239 (35.7) | 242 (24.1)* |
| DES (N, %) | 1130 (67.5) | 422 (63.1) | 708 (70.4)* |
| BVS (N, %) | 127 (7.6) | 35 (5.2) | 92 (9.1)* |
ACS, acute coronary syndrome; BMS, bare-metal stent; BVS, bioresorbable vascular scaffold; CTO, chronic total occlusion; DES, drug-eluting stent; ISR, in-stent restenosis; LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; LM, left main coronary artery; RCA, right coronary artery; TSGH-CHD, Tri-Service General Hospital–Coronary Heart Disease; TVD, triple-vessel disease.
* Indicates significant difference between ACS and stable angina group, p < 0.05.
Most of the patients (66.7% of the ACS group and 42.8% of the SA group) underwent PCI with stent placement, as revealed by the TSGH-CHD registry (Figure 2). Notably, the percentage of patients undergoing coronary artery bypass grafting (CABG) was higher in the ACS group than in the SA group (8.3% vs. 4.7%). DES use was more common than bare-metal stent (BMS) use in both the ACS and SA groups (63.1% and 70.4%, respectively; Table 2). Furthermore, 5.2% of the patients with ACS received bioabsorbable scaffold placement during coronary revascularization.
Figure 2.
Distribution of therapeutic intervention in the Tri-Service General Hospital–Coronary Heart Disease (TSGH-CHD) registry. The pie chart indicates the proportion of patients receiving different therapeutic interventions in the TSGH-CHD registry. ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; POBA, plain old balloon angioplasty.
In-hospital outcomes
Table 3 shows the in-hospital mortality and complication rates stratified by the type of CAD and different therapeutic interventions. The overall in-hospital mortality rates in the entire population, ACS group, and SA group were 2.8%, 7.5%, and 0.9%, respectively. In the patients with SA, the in-hospital mortality rate was 0.7% both in those who received medical treatment and in those who received PCI and stenting. However, in the patients with ACS, the in-hospital mortality rate was higher in those who received medical treatment than in those who received PCI and stenting (10.7% vs. 4.9%). There were significant differences in in-hospital morbidities between the patients with ACS and those with SA: the patients with ACS had a longer hospital stay (mean 9.2 vs. 4.9 days), higher risk of in-hospital stroke (0.6 vs. 0.1%), and higher incidence of major bleeding episodes (2.0 vs. 0.3%). Table 3 presents detailed information regarding different therapeutic interventions in the study groups. No significant differences in in-hospital stroke or major bleeding were noted between the four therapeutic interventions. Notably, the patients who underwent CABG had the longest hospital stay and in-hospital mortality in both ACS and SA groups. Only two patients had acute in-stent thrombosis in the SA group: one patient had multiple bioabsorbable scaffold placements with poor medication compliance, and the other had clopidogrel resistance, who was eventually referred for CABG. Additional subgroup analyses of clinical outcomes in the patients with ACS according to treatment modality is presented in Supplement Table 1. The in-hospital mortality rates in the patients with STEMI and NSTEMI were higher than in those with UA (9.9% and 7.0% vs. 1.9%). Among the patients with STEMI and NSTEMI, the in-hospital mortality rates were higher in the patients who received medical treatment and plain old balloon angioplasty (POBA) only compared to those who received PCI and stenting. The clinical strategy of medical treatment or POBA only in those with ACS may indicate the presence of non-coronary etiologies, and the concomitant comorbidities may have been associated with poor clinical outcomes.
Table 3. In-hospital mortality and morbidities, stratified by coronary artery disease types and interventions in TSGH-CHD registry.
| Overall (N = 3,352) | Medical treatment (N = 1,222) | POBA only (N = 261) | PCI with stent (N = 1,675) | CABG (N = 194) | |
| TSGH-CHD registry population (N = 3,352) | |||||
| Hospital stay (days) | 6.2 ± 11.7 | 4.7 ± 8.8 | 5.6 ± 9.5 | 5.8 ± 12.6 | 20.3 ± 13.3# |
| In-hospital mortality | 95 (2.8%) | 25 (2.0%) | 14 (5.4%) | 40 (2.4%) | 16 (8.2%)# |
| In-hospital stroke | 8 (0.2%) | 3 (0.2%) | 0 (0.0%) | 4 (0.2%) | 1 (0.5%) |
| Major bleeding | 28 (0.8%) | 3 (0.2%) | 3 (1.1%) | 19 (1.1%) | 3 (1.5%) |
| Overall (N = 1,003) | Medical treatment (N = 168) | POBA only (N = 83) | PCI with stent (N = 669) | CABG (N = 83) | |
| ACS population (N = 1,003) | |||||
| Hospital stay (days) | 9.2 ± 14.9 | 9.3 ± 15.3 | 8.1 ± 10.3 | 8.0 ± 15.1 | 19.0 ± 13.6# |
| In-hospital mortality | 75 (7.5%) | 18 (10.7%) | 12 (14.5%) | 33 (4.9%) | 12 (14.5%)# |
| In-hospital stroke | 6 (0.6%) | 2 (1.2%) | 0 (0.0%) | 3 (0.4%) | 1 (1.2%) |
| Major bleeding | 20 (2.0%) | 2 (1.2%) | 3 (3.6%) | 13 (1.9%) | 2 (2.4%) |
| Overall (N = 2,349) | Medical treatment (N = 1,054) | POBA only (N = 178) | PCI with stent (N = 1,006) | CABG (N = 111) | |
| Stable angina population (N = 2,349) | |||||
| Hospital stay (days) | 4.9 ± 9.7* | 3.9 ± 6.9 | 4.4 ± 8.9 | 4.3 ± 10.3 | 21.2 ± 13.1# |
| In-hospital mortality | 20 (0.9%)* | 7 (0.7%) | 2 (1.1%) | 7 (0.7%) | 4 (3.6%)# |
| In-hospital stroke | 2 (0.1%)* | 1 (0.1%) | 0 (0.0%) | 1 (0.1%) | 0 (0.0%) |
| Major bleeding | 8 (0.3%)* | 1 (0.1%) | 0 (0.0%) | 6 (0.6%) | 1 (0.9%) |
ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; CAD, coronary artery disease; PCI, percutaneous coronary intervention; POBA, plain old balloon angioplasty; TSGH-CHD, Tri-Service General Hospital–Coronary Heart Disease.
* Indicates significant difference between ACS and stable angina group, p < 0.05. # Indicates significant difference between four groups with different therapeutic interventions.
Supplement Table 1. Subgroup analyses of in-hospital mortality and morbidities in TSGH-CHD ACS population.
| Overall (N = 353) | Medical treatment (N = 44) | POBA only (N = 18) | PCI with stent (N = 267) | CABG (N = 24) | |
| STE-ACS population | |||||
| Hospital stay (days) | 8.3 ± 15.5 | 10.0 ± 13.8 | 5.1 ± 5.6 | 7.1 ± 15.8 | 20.4 ± 15.3* |
| In-hospital mortality | 35 (9.9%) | 5 (11.4%) | 6 (33.3%) | 21 (7.9%)0 | 3 (12.5%)* |
| In-hospital stroke | 3 (0.8%) | 1 (2.3%) | 0 (0.0%) | 1 (0.4%) | 1 (4.2%) |
| Major bleeding | 10 (2.8%) | 1 (2.3%) | 0 (0.0%) | 8 (3.0%) | 1 (4.1%) |
| Overall (N = 545) | Medical treatment (N = 93) | POBA only (N = 56) | PCI with stent (N = 344) | CABG (N = 52) | |
| NSTE-ACS population | |||||
| Hospital stay (days) | 10.4 ± 15.3 | 11.0 ± 17.9 | 9.6 ± 11.7 | 9.0 ± 15.0 | 19.1 ± 13.4* |
| In-hospital mortality | 38 (7.0%) | 13 (14.0%) | 6 (10.7%) | 11 (3.2%) | 8 (15.4%)* |
| In-hospital stroke | 2 (0.4%) | 1 (1.1%) | 0 (0.0%) | 1 (0.3%) | 0 (0.0%) |
| Major bleeding | 9 (1.7%) | 1 (1.1%) | 2 (3.6%) | 5 (1.5%) | 1 (1.9%) |
| Overall (N = 105) | Medical treatment (N = 31) | POBA only (N = 9) | PCI with stent (N = 58) | CABG (N = 7) | |
| UA population | |||||
| Hospital stay (days) | 5.8 ± 9.3 | 3.5 ± 2.7 | 4.7 ± 4.4 | 6.3 ± 11.5 | 13.6 ± 7.5 |
| In-hospital mortality | 2 (1.9%) | 0 (0.0%) | 0 (0.0%) | 1 (1.7%) | 1 (14.3%) |
| In-hospital stroke | 1 (1.0%) | 0 (0.0%) | 0 (0.0%) | 1 (1.7%) | 0 (0.0%) |
| Major bleeding | 1 (1.0%) | 0 (0.0%) | 1 (11.1%) | 0 (0.0%) | 0 (0.0%) |
CABG, coronary artery bypass grafting; NSTE-ACS, non-ST elevation acute coronary syndrome; PCI, percutaneous coronary intervention; POBA, plain old balloon angioplasty; STE-ACS, ST-elevation acute coronary syndrome; UA, unstable angina.
* Indicates significant difference between four groups with different therapeutic interventions.
Table 4 provides a summary of the results of univariate and multivariate logistic regression analysis of the predictors of in-hospital mortality in the patients with ACS. The univariate analysis revealed that in the patients with ACS, older age, previous history of stroke, previous history of heart failure, underlying uremia status, peripheral arterial occlusive disorders, and the presence of cardiogenic shock on admission were associated with a relatively high risk of in-hospital mortality. The multivariate analysis indicated that only older age, previous history of stroke, and presence of cardiogenic shock were independent risk factors for in-hospital mortality. In model 2, which assessed the influence of stent types on in-hospital mortality, the multivariate regression analysis revealed no significant association between DES use and the risk of in-hospital mortality in the patients with ACS who underwent coronary interventions and stenting (Table 4).
Table 4. Univariate and multivariate logistic regression analysis for predictors of in-hospital mortality in ACS patients.
| ACS (N = 1003) | Univariate analysis | Multivariate analysis | Model 2 multivariate analysis* | |||
| OR (95% CI) | p value | OR (95% CI) | p value | OR (95% CI) | p value | |
| Age (years) | 1.05 (1.03-1.07) | < 0.001 | 1.05 (1.03-1.08) | < 0.001 | 1.12 (1.08-1.17) | < 0.001 |
| Male gender | 0.71 (0.43-1.18) | 0.183 | ||||
| Hypertension | 1.45 (0.85-2.48) | 0.176 | ||||
| DM | 1.32 (0.82-2.12) | 0.257 | ||||
| Dyslipidemia | 0.81 (0.48-1.36) | 0.419 | ||||
| Prior MI | 1.22 (0.69-2.14) | 0.494 | ||||
| Prior stroke | 2.73 (1.52-4.89) | 0.001 | 2.04 (1.09-3.81) | 0.025 | 2.65 (1.03-6.85) | 0.044 |
| Prior HF | 2.23 (1.27-3.93) | 0.005 | 1.13 (0.60-2.14) | 0.702 | 1.25 (0.47-3.30) | 0.658 |
| Prior AF/AFL | 1.25 (0.49-3.25) | 0.641 | ||||
| Uremia | 2.22 (1.17-4.22) | 0.014 | 1.80 (0.88-3.68) | 0.111 | 1.31 (0.37-4.60) | 0.675 |
| PAOD | 2.90 (1.16-7.27) | 0.023 | 1.55 (0.56-4.34) | 0.401 | 0.78 (0.07-8.40) | 0.837 |
| Cardiogenic shock | 3.78 (2.21-6.45) | < 0.001 | 4.44 (2.51-7.86) | < 0.001 | 5.99 (2.41-14.89) | < 0.001 |
| Presence of TVD | 1.36 (0.95-2.19) | 0.199 | ||||
| DES use* | 0.36 (0.18-0.74) | 0.006 | 0.54 (0.24-1.21) | 0.133 |
ACS, acute coronary syndrome; AF/AFL, atrial fibrillation/atrial flutter; CI, confidence interval; DES, drug-eluting stent; DM, diabetes mellitus; HF, heart failure; MI, myocardial infarction; OR, odds ratio; PAOD, peripheral arterial occlusive disorder; TVD, triple-vessel disease.
* Model 2 indicates that only patients undergoing coronary intervention with stenting (N = 669) are analyzed.
Comparison of profiles between the TSGH-CHD registry and the Taiwan ACS registry
Two Taiwan ACS registries were created from an observational, prospective cohort study at 39 centers in Taiwan from 2008 to 2010 and at 24 hospitals from 2012 to 2015. Unlike these two registries, the TSOC ACS registry II only included ACS patients who received PCI with stenting during hospitalization (Table 5). The ACS patients in the two ACS registries and those in the TSGH-CHD registry had similar characteristics with respect to age, sex, hypertension, diabetes mellitus, dyslipidemia, and prior stroke. However, the patients in the TSGH-CHD registry had a higher prevalence of previous heart failure than those in the two TSOC ACS registries. The population in the TSGH-CHD ACS registry had a lower percentage of STEMI (35.2% vs. 52.3% and 54.9%) and a higher percentage of NSTEMI (54.3% vs. 33.9% and 45.1%), and they also had a considerably higher in-hospital mortality rate (7.5% vs. 1.8%). DES was more commonly used in the TSGH-CHD ACS registry than in the TSOC ACS registry I and II (63.1% vs. 24.9% and 50.9%, respectively). The higher referral rate for CABG in the TSGH-CHD ACS registry compared to the TSOC ACS registry I and II (8.3% vs. 3.3% and 0.2%) may indicate the severity and complexity of CAD in the TSGH-CHD registry. The rates of in-hospital stroke and major bleeding were similar between the TSOC ACS registry I and TSGH-CHD ACS registry.
Table 5. Comparison between several Taiwan ACS registries.
| TSOC ACS registry I | TSOC ACS registry II | TSGH-CHD ACS registry | |
| Study period | 2008-2010 | 2012-2015 | 2014-2016 |
| Study design | multi-center* | multi-center* | single-center |
| Patient number (N) | 3183 | 2,357# | 1003 |
| Baseline characteristics | |||
| Age (years) | 63.1 ± 13.6 | 61.8 ± 12.8 | 63.9 ± 13.9 |
| Women | 22.0% | 17.7% | 25.5% |
| Hypertension | 64.0% | 63.7% | 67.6% |
| Diabetes mellitus | 36.0% | 34.3% | 36.6% |
| Dyslipidemia | 39.1% | 44.5% | 32.2% |
| Prior myocardial infarction | 41.1% | 9.1% | 19.6% |
| Prior heart failure | 5.4% | 5.5% | 13.3% |
| Prior stroke | 9.0% | 6.1% | 10.7% |
| Characteristics of ACS | |||
| STEMI | 52.3% | 54.9% | 35.2% |
| NSTEMI | 33.9% | 45.1% | 54.3% |
| UA | 12.2% | 0% | 10.5% |
| Left main lesion | 3.2% | NA | 10.5% |
| Treatment modalities | |||
| DES implantation | 24.9% | 50.9% | 63.1% |
| CABG referral | 3.3% | 0.2% | 8.3% |
| Clinical outcomes | |||
| In-hospital mortality | 1.8% | NA | 7.5% |
| In-hospital stroke | 0.4% | NA | 0.6% |
| Major bleeding | 1.8% | NA | 2.0% |
* 39 hospitals in Taiwan participated in the TSOC ACS registry I and 24 hospitals participated in the TSOC ACS registry II. # In TSOC ACS registry II, only ACS patients who received PCI with stenting during hospitalization were included.
ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; DES, drug-eluting stent; NA, not available; NSTEMI, non-ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; TSOC, Taiwan Society of Cardiology; TSGH-CHD, Tri-Service General Hospital–Coronary Heart Disease; UA, unstable angina.
DISCUSSION
The TSGH-CHD registry is a single-center, prospective, longitudinal observational cohort database, and data collection for this registry is still ongoing. We conducted this study to provide contemporary clinical profiles of short-term in-hospital outcomes in the entire spectrum of CAD patients in this registry. We demonstrated an increased prevalence of DES use in the settings of SA and ACS.
SA population in the TSGH-CHD registry
Most of the existing cardiovascular-specific registries focus on patients with ACS, and few available datasets reflect the characteristics of patients with stable CAD, and the definition of stable CAD varies.17-20 Using the TSGH-CHD registry, we assessed demographic data, outcomes, and treatment strategies, and compared them with those in other published registries. The Chronic Ischemic Cardiovascular Disease (CICD)-PILOT registry provides information on a broad spectrum of patients with chronic ischemic heart disease across Europe.21 After comparing the elective PCI subgroup in the CICD-PILOT registry with the PCI subgroup (both with and without stent placement) of the SA population in the TSGH-CHD registry (Supplement Table 2), we observed that the baseline characteristics of age, sex, and history of hypertension were similar; however, we identified a numerically higher rate of diabetes and lower rate of dyslipidemia in our population. Notably, the rates of dual antiplatelet prescriptions at discharge were similar between the two registries, but the rates of RAS blockers, beta-blockers, and statin prescriptions were considerably lower in our population. These findings suggest the existence of a gap in the implementation of evidence-based secondary prevention medication in our clinical practice, indicating potential suboptimal treatment of patients with SA after elective PCI.
Supplement Table 2. Comparison between TSGH-CHD stable angina population and CICD-PILOT registry.
| TSGH-CHD stable angina population (PCI subgroup, N = 1,184) (2014-2016) | CICD-PILOT registry (Elective PCI subgroup, N = 933) (2013-2014) | |
| Baseline characteristics | ||
| Age (years) | 64.57 ± 11.53 | 66.2 ± 10.1 |
| Male gender | 79.8% | 71.5% |
| Hypertension | 82.3% | 84.1% |
| DM | 43.9% | 27.2% |
| Dyslipidemia | 54.1% | 78.9% |
| Current smoker | 42.5% | 49.8% |
| Prior MI | 45.8% | 49.0% |
| Prior HF | 13.2% | NA |
| Prior stroke | 9.7% | 14.3% |
| Prior AF | 5.9% | NA |
AF, atrial fibrillation; DM, diabetes mellitus; HF, heart failure; MI, myocardial infarction, NA, not available.
In our study, the in-hospital mortality rate was 0.9% in all patients with SA and only 0.7% in the patients with SA who underwent PCI and stenting during hospitalization. Similarly, Narins et al. reported an in-hospital mortality rate of 0.39% in a large cohort of patients who underwent more than 100,000 elective PCI procedures in New York.22 Another noteworthy finding is that only 4.7% of the SA population and 5.5% of the subgroup of those with significant obstructive CAD (at least one coronary stenosis ≥ 50%) were referred for CABG after coronary angiography, despite the high prevalence of TVD (36.9%). In the Eastern Taiwan-Coronary Heart Disease (ET-CHD) registry, 1997-2003, almost 24.0% of the patients were treated with CABG.23 Although we did not have Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) scores, which indicates the severity of coronary atherosclerosis and serves as a decision-making tool in interventional cardiology,24,25 the decreasing trend in CABG referrals may reflect advanced in equipment for interventional cardiology and technical skills of interventionists, which may enable them to address more complex CAD cases.26,27
ACS population in the TSGH-CHD registry
Our study revealed that the patients with ACS had different types of coronary lesions compared to those with SA (more TVD, chronic total occlusion, and ostial lesions but less in-stent restenosis). The overall in-hospital mortality rate was 7.5% in the ACS population: 4.9% among those who received PCI and stenting, 10.7% among those who received medical treatment only, and 14.5% among those who underwent CABG. Older age, previous history of stroke, and cardiogenic shock on admission were independent factors for in-hospital mortality.
We compared the ACS population in two TSOC ACS registries with that in the TSGH-CHD ACS registry.9,12 First, an increase in DES placement was noted in the contemporary TSGH-CHD ACS registry compared with the TSOC ACS registry I (63.1% vs. 24.9%). In another Taiwan multicenter ACS registry established in the early DES era (2012--2015) which included information on only patients undergoing PCI for STEMI and NSTEMI,12 the prevalence of DES use was 51%, which is between that observed in the TSGH-CHD registry and the Taiwan ACS registry from 2008-2010. Increasing evidence suggests that DESs can reduce the rates of restenosis and target lesion revascularization compared with BMSs; hence, DESs are generally considered the stents of choice in the ACS setting.13,28,29 Sung et al. demonstrated that DES implantation may offer more favorable long-term cardiovascular outcomes and survival benefits compared with BMS implantation.30 In the present study, DES use in the ACS patients at a high risk of mortality tended to have the clinical benefit of reducing in-hospital mortality (odds ratio = 0.54), although the corresponding results obtained in the multivariate analysis were statistically nonsignificant (p = 0.133). These findings indicate the evolution from BMSs to first-generation DESs and then to second-generation DESs currently, a trend that is consistent with the recommendations of cardiac societies that new-generation DESs should be prioritized over BMSs because of their superior safety and efficacy profiles.16,31,32
Second, the in-hospital mortality rate was 7.5% in the ACS population in the TSGH-CHD registry and 4.9% in the patients who received primary PCI, which are significantly higher than that in Taiwan ACS registry for 2008-2010 (approximately 1.8%). The extremely high mortality rate (14.5%) in the ACS patents who underwent CABG, the higher referral rate for CABG (8.3% vs. 3.3%), higher prevalence of left main coronary artery lesions (10.2% vs. 3.2%) and TVD (48.9%) in the TSGH-CHD ACS registry compared to those in the TSOC ACS registry I highlight the complexity of CAD in the TSGH-CHD registry, which partly explains the higher mortality rate in in ACS patients in the registry. Moreover, cardiogenic shock at admission occurred in 2.2%-7.7% of the patients with acute MI, which was an independent risk factor for mortality in our registry.33 In our ACS population, the rate of cardiogenic shock at admission was 12.2%, which is considerably higher than that in other large ACS registries worldwide. Additionally, the TSGH-CHD ACS registry contained a higher proportion of patients who received medical treatment only compared with those in the TSOC ACS registry I from 2008-2010 (16.7% vs. 12.3%), which led to the high mortality rate (10.7%) in our registry. Finally, regarding the cause of death, the incidence of noncardiac death was 24.0% in our ACS population, which is higher than that in the TSOC ACS registry I (16.1%). Data from the Asia-Pacific region have reported an ACS-related mortality rate of approximately 5% during hospitalization.10 Taken together, the evidence shows a higher in-hospital mortality rate in our population.
Study limitations
Several limitations of this single-center, observational, nonrandomized cohort study should be considered. The TSGH-CHD registry contains regional data only, and some discrepancies may exist in different areas in Taiwan. Another limitation is the lack of definitive proof of links between current clinical practices and the outcomes. Moreover, the issue of selection bias may exist in our registry, because we enrolled patients with the most severe initial presentations, including shock, and even those with out-of-hospital cardiac arrest. Most of them died within 24 h after presenting at the emergency department. We believe that some patients with myocardial injury unrelated to coronary stenosis may have been included in our cohort. Nevertheless, this situation may provide clinical information that closely reflects real-world practice. Lastly, the clinical data of SYNTAX scores, which represents the severity of CAD, were also lacking in our registry.
CONCLUSIONS
In conclusion, we conducted this study using the TSGH-CHD registry to provide the contemporary clinical profiles of hospitalized patients with SA and ACS. Our study indicated an increased prevalence of DES use in Taiwan after 2010. Moreover, interventionists seemed to attempt high-risk procedures for complex CHD more often in the DES era, although this may not have significantly improved survival. This study also revealed some discrepancies with other registries in Taiwan and gaps between clinical practice and recommendations. Finally, we are confident that our findings will enhance clinicians’ awareness, improve routine clinical management, and guide future research.
Acknowledgments
This work is supported by grants from Tri-Service General Hospital (TSGH-C108-024, TSGH-D-109039 to C.-H. W). This manuscript was edited by Wallace Academic Editing.
CONFLICT OF INTEREST
All the authors have full access to and take responsibility for the integrity of the data. All the authors declare no conflict of interest.
REFERENCES
- 1.O’Kelly BF, Massie BM, Tubau JF, et al. Coronary morbidity and mortality, pre-existing silent coronary artery disease, and mild hypertension. Ann Intern Med. 1989;110:1017–1026. doi: 10.7326/0003-4819-110-12-1017. [DOI] [PubMed] [Google Scholar]
- 2.Ohira T, Iso H. Cardiovascular disease epidemiology in Asia. Circ J. 2013;77:1646–1652. doi: 10.1253/circj.cj-13-0702. [DOI] [PubMed] [Google Scholar]
- 3.Herrington W, Lacey B, Sherliker P, et al. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circ Res. 2016;118:535–546. doi: 10.1161/CIRCRESAHA.115.307611. [DOI] [PubMed] [Google Scholar]
- 4.Tsai WC, Wu KY, Lin GM, et al. Clinical characteristics of patients less than forty years old with coronary artery disease in Taiwan: a cross-sectional study. Acta Cardiol Sin. 2017;33:233–240. doi: 10.6515/ACS20161026A. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Roth GA, Johnson C, Abajobir A, et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol. 2017;70:1–25. doi: 10.1016/j.jacc.2017.04.052. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Lopez AD, Mathers CD, Ezzati M, et al. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006;367:1747–1757. doi: 10.1016/S0140-6736(06)68770-9. [DOI] [PubMed] [Google Scholar]
- 7.Budaj A, Brieger D, Steg PG, et al. Global patterns of use of antithrombotic and antiplatelet therapies in patients with acute coronary syndromes: insights from the Global Registry of Acute Coronary Events (GRACE). Am Heart J. 2003;146:999–1006. doi: 10.1016/S0002-8703(03)00509-X. [DOI] [PubMed] [Google Scholar]
- 8.Cheng CI, Chen CP, Kuan PL, et al. The causes and outcomes of inadequate implementation of existing guidelines for antiplatelet treatment in patients with acute coronary syndrome: the experience from Taiwan Acute Coronary Syndrome Descriptive Registry (T-ACCORD Registry). Clin Cardiol. 2010;33:e40–e48. doi: 10.1002/clc.20730. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Shyu KG, Wu CJ, Mar GY, et al. Clinical characteristics, management and in-hospital outcomes of patients with acute coronary syndrome - observations from the Taiwan ACS Full Spectrum Registry. Acta Cardiol Sin. 2011;27:135–144. [Google Scholar]
- 10.Chan MY, Du X, Eccleston D, et al. Acute coronary syndrome in the Asia-Pacific region. Int J Cardiol. 2016;202:861–869. doi: 10.1016/j.ijcard.2015.04.073. [DOI] [PubMed] [Google Scholar]
- 11.Wu CK, Juang JMJ, Chiang JY, et al. The Taiwan Heart Registries: its influence on cardiovascular patient care. J Am Coll Cardiol. 2018;71:1273–1283. doi: 10.1016/j.jacc.2018.02.006. [DOI] [PubMed] [Google Scholar]
- 12.Li YH, Chiu YW, Cheng JJ, et al. Changing practice pattern of acute coronary syndromes in Taiwan from 2008 to 2015. Acta Cardiol Sin. 2019;35:1–10. doi: 10.6515/ACS.201901_35(1).20180716B. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Valgimigli M, Tebaldi M, Borghesi M, et al. Two-year outcomes after first- or second-generation drug-eluting or bare-metal stent implantation in all-comer patients undergoing percutaneous coronary intervention: a pre-specified analysis from the prodigy study (prolonging dual antiplatelet treatment after grading stent-induced intimal hyperplasia study). JACC Cardiovasc Interv. 2014;7:20–28. doi: 10.1016/j.jcin.2013.09.008. [DOI] [PubMed] [Google Scholar]
- 14.Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction. J Am Coll Cardiol. 2018;72:2231–2264. doi: 10.1016/j.jacc.2018.08.1038. [DOI] [PubMed] [Google Scholar]
- 15.Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;64:e139–e228. doi: 10.1016/j.jacc.2014.09.017. [DOI] [PubMed] [Google Scholar]
- 16.Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2018;39:119–177. doi: 10.1093/eurheartj/ehx393. [DOI] [PubMed] [Google Scholar]
- 17.Daly CA, Clemens F, Lopez Sendon JL, et al. The initial management of stable angina in Europe, from the Euro Heart Survey. Eur Heart J. 2005;26:1011–1022. doi: 10.1093/eurheartj/ehi109. [DOI] [PubMed] [Google Scholar]
- 18.Sorbets E, Greenlaw N, Ferrari R, et al. Rationale, design, and baseline characteristics of the CLARIFY registry of outpatients with stable coronary artery disease. Clin Cardiol. 2017;40:797–806. doi: 10.1002/clc.22730. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Steg G, Bhatt DL, Wilson PWF, et al. One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA. 2007;297:1197–1206. doi: 10.1001/jama.297.11.1197. [DOI] [PubMed] [Google Scholar]
- 20.Bhatt DL, Eagle KA, Ohman EM, et al. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. JAMA. 2010;304:1350–1357. doi: 10.1001/jama.2010.1322. [DOI] [PubMed] [Google Scholar]
- 21.Komajda M, Weidinger F, Kerneis M, et al. EURObservational Research Programme: The Chronic Ischaemic Cardiovascular Disease Registry: pilot phase (CICD-PILOT). Eur Heart J. 2016;37:152–160. doi: 10.1093/eurheartj/ehv437. [DOI] [PubMed] [Google Scholar]
- 22.Narins CR, Ling FS, Fischi M, et al. In-hospital mortality among women undergoing contemporary elective percutaneous coronary intervention: a reexamination of the gender gap. Clin Cardiol. 2006;29:254–258. doi: 10.1002/clc.4960290606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Lin GM, Li YH, Lin CL, et al. Gender differences in the impact of diabetes on mortality in patients with established coronary artery disease: a report from the Eastern Taiwan integrated health care delivery system of Coronary Heart Disease (ET-CHD) registry, 1997-2006. J Cardiol. 2013;61:393–398. doi: 10.1016/j.jjcc.2013.02.007. [DOI] [PubMed] [Google Scholar]
- 24.Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary artery bypass brafting for severe coronary artery disease. N Engl J Med. 2009;360:961–972. doi: 10.1056/NEJMoa0804626. [DOI] [PubMed] [Google Scholar]
- 25.Bundhun PK, Yanamala CM, Huang F. Percutaneous coronary intervention, coronary artery bypass surgery and the SYNTAX score: a systematic review and meta-analysis. Sci Rep. 2017;7:43801. doi: 10.1038/srep43801. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Holmes DR, Taggart DP. Revascularization in stable coronary artery disease: a combined perspective from an interventional cardiologist and a cardiac surgeon. Eur Heart J. 2016;37:1873–1882. doi: 10.1093/eurheartj/ehw044. [DOI] [PubMed] [Google Scholar]
- 27.Doenst T, Haverich A, Serruys P, et al. PCI and CABG for treating stable coronary artery disease: JACC review topic of the week. J Am Coll Cardiol. 2019;73:964–976. doi: 10.1016/j.jacc.2018.11.053. [DOI] [PubMed] [Google Scholar]
- 28.Feinberg J, Nielsen EE, Greenhalgh J, et al. Drug-eluting stents versus bare-metal stents for acute coronary syndrome. Cochrane Database Syst Rev. 2017;8:CD12481. doi: 10.1002/14651858.CD012481.pub2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Sabate M, Cequier A, Iñiguez A, et al. Everolimus-eluting stent versus bare-metal stent in ST-segment elevation myocardial infarction (EXAMINATION): 1 year results of a randomised controlled trial. Lancet. 2012;380:1482–1490. doi: 10.1016/S0140-6736(12)61223-9. [DOI] [PubMed] [Google Scholar]
- 30.Sung SH, Chen TC, Cheng HM, et al. Comparison of clinical outcomes in patients undergoing coronary intervention with drug-eluting stents or bare-metal stents: a nationwide population study. Acta Cardiol Sin. 2017;33:10–19. doi: 10.6515/ACS20160608A. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Palmerini T, Biondi-Zoccai G, Della Riva D, et al. Clinical outcomes with drug-eluting and bare-metal stents in patients with ST-segment elevation myocardial infarction: evidence from a comprehensive network meta-analysis. J Am Coll Cardiol. 2013;62:496–504. doi: 10.1016/j.jacc.2013.05.022. [DOI] [PubMed] [Google Scholar]
- 32.Li YH, Wang YC, Wang YC, et al. 2018 guidelines of the Taiwan Society of Cardiology, Taiwan Society of Emergency Medicine and Taiwan Society of Cardiovascular Interventions for the management of non ST-segment elevation acute coronary syndrome. J Formos Med Assoc. 2018;117:766–790. doi: 10.1016/j.jfma.2018.06.002. [DOI] [PubMed] [Google Scholar]
- 33.Thiele H, Ohman EM, Desch S, et al. Management of cardiogenic shock. Eur Heart J. 2015;36:1223–1230. doi: 10.1093/eurheartj/ehv051. [DOI] [PubMed] [Google Scholar]