Abstract
Background: Percutaneous coronary intervention (PCI) is one of the most performed interventions for ischemic heart diseases. In Hong Kong, the total number of patient discharges and deaths for ischemic heart diseases in 2009 was 33,363, including 4,360 deaths. There are over 5,000 cases of PCI yearly. This study aimed to compare clinical, economic, and humanistic outcomes among patients receiving drug-eluting stent (DES) or bare metal stent (BMS) in Hong Kong.
Methods: Patients who received stent implantation between September 15, 2009 and October 11, 2010 in Prince of Wales Hospital, Hong Kong, were recruited and followed for 18 months. Occurrence of major adverse cardiac events (cardiac death, non-fatal MI, TLR and TVR) was employed as the clinical outcome measurements. Improvement in quality-of-life by stent interventions was measured as quality-adjusted life-year (QALY). EQ-5D questionnaire was adopted to assess the QALY gained. Cost-utility analysis and cost-effectiveness analysis for BMS and DES were employed as the economic outcome measurement.
Results: Six hundred and eighty-four patients (DES = 402; BMS = 282) were included. From 0–18 months, TLR rate (2.7% vs 3.5%, p = .549) and TVR rate (3.7% vs 6.4%, p = .111) were lower in the DES group, but without statistical significance. EQ VAS (71.06 ± 14.56 vs 71.07 ± 16.57, p = .998) and utility score (0.81 ± 0.17 vs 0.78 ± 0.16, p = .162) were comparable between DES and BMS group. Overall, the cost per QALY gained was HKD + 1,178,100 and ICER was HKD + 187,000 (1USD = 7.8 HKD).
Conclusions: No significant difference in TVR, TLR rates, EQ VAS, and utility score was found between the DES and BMS group. The higher cost of index procedure for the DES group was found to be partly offset by reduced cost of follow-up, offering cost-effectiveness in ACS patients, predominantly in STEMI patients. DES was recommended for STEMI patients.
Background
Percutaneous Coronary Intervention (PCI) is one of the most performed interventions for the management of ischemic heart diseases worldwide. The first percutaneous trans-luminal coronary angioplasty (PTCA) in 1977 was subject to early re-occlusion and restenosisCitation1. The introduction of a stent in 1987Citation2 led to a significant decrease in early re-occlusion events and rate of re-vascularization proceduresCitation3. The traditional bare metal stent (BMS) is a tiny wire mesh tube which helps keep arteries open, restores normal blood flow and, therefore, minimizes the chance of a heart attack or stroke. However, repeat revascularization still occurred in 15–20% of patients receiving BMSCitation4. Stent restenosis is also a major drawback for coronary stentsCitation5.
In 2001, drug-eluting stent (DES) was introducedCitation2. Anti-proliferative drugs are delivered locally through the polymer coated on the stent surface to inhibit neointimal proliferation of the vessel wall. This can then reduce the risk of restenosis. Literature reported that DES offers an absolute risk reduction of 10–15% in terms of restenosisCitation1,Citation6. It has been found to offer a better clinical outcome (e.g. occurrence of major adverse cardiac events, MACE) than BMS as wellCitation6–9. However, the rate of very-late stent thrombosis in DMS was found to be higherCitation10,Citation11.
In Hong Kong, the total number of patients discharged from ischemic heart diseases in 2009 was 33,363, including 4,360 deathsCitation12. There are ∼5000 cases of PCI performed annuallyCitation13, in which 70% of the cases involve DESCitation13. The high volume of PCI indicates that there may be a significant impact on medical cost when different types of stents are employed.
Humanistic and economic outcome are usually evaluated by incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life year (QALY) gained. Results from literatures are mixedCitation14–21. Furthermore, most of the studies were conducted in western populations and there is only limited data for the Asian/Chinese population. This study is to offer an evidence-based real world evaluation in clinical, humanistic, and economic outcomes between DES and BMS in a Chinese population.
Methods
This was a prospective observational study conducted in a public hospital in Hong Kong. Patients who received stent implantation in the Cardiac Catheterization Laboratory, Prince of Wales Hospitals between September 15, 2009 and October 11, 2010 were recruited and followed for 18 months. Subjects should have received either DES or BMS at physician’s discretion. Patients who received more than one type of stents were excluded from the study. Subject data were collected via the Clinical Management System of Hospital Authority.
Patient demographic data, medical records, reasons for PCI, lesion characteristics, stent characteristics, re-hospitalization, and follow-up records within the study period were retrieved. Occurrence of major adverse cardiac events (MACE) was recorded. MACE includes cardiac death, non-fatal myocardial infarction (non-fatal MI), target vessel revascularization (TVR), and target lesion revascularization (TLR)Citation22. Re-hospitalization and follow-up records were also evaluated. Foci of analyses were divided according to the disease sub-types, including ST-segment elevation myocardial infarction (STEMI), unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI), and non-acute coronary syndrome patients (non-ACS). Cox regression analysis was performed to identify the potential risk factors of occurrence of MACE based on their age, gender, past medical histories, risk factors, lesion, and stent characteristics. A propensity score was estimated using a logistics regression model in which the treatment status was regressed on patients’ past medical history (CVA, IHD, MI, PVD, PCI, CABG) and risk factors (Hypertension, Dyslipidemia, Diabetes, Congestive Heart Failure, Family History, and Current Smoker) for cardiovascular diseases. Patients with BMS and DES implanted were then matched by greedy matching without replacement with a caliper of 0.000,1.
Quality-adjusted life-year (QALY) was estimated by the improvement in QoL brought by cardiac stent interventionsCitation23–25. The EQ-5D questionnaire was adopted for the assessment of the improvementCitation23–25 and it comprises two parts, namely the EQ visual analog scale (VAS) and EQ-5D descriptive systemCitation26. The EQ VAS reflects one’s own health status on a scale of 0–100, while the EQ-5D descriptive system records patient’s health status in five areas: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The outcome evaluation was conducted by telephone interviews. The response to the EQ-5D descriptive system was converted into a utility score according to the Japan EQ-5D value set by time trade-off (TTO) valuation techniqueCitation26,Citation27.
Medical costs required for PCI procedures were evaluated. They included cost of index procedure (PCI, medications, hospitalization) and cost of follow-up (medical consultations, out-patient visits, emergency visits, any repeat procedures, and use of clopidogrel after stent procedures). The unit costs of the above items were collected from HA drug formulary and Hong Kong Government Gazette 2003.
Cost-utility analysis (cost per QALY gained) and cost-effectiveness analysis (ICER) for BMS and DES were employed as the economic outcome measurement:
where ΔC = difference in total costs and ΔUS = difference in utility scores.
ICER of DES over BMS to prevent one MACE was calculated as:
where ΔC = difference in total costs and ΔUS = difference in numbers of MACE.
According to the World Health Organization (WHO)Citation28, a therapy is considered to be very cost-effective if the cost per QALY gained is smaller than the GDP per capita, cost-effective for the cost per QALY gained to be greater than the GDP per capita, but smaller than three times of the GDP per capita, and not cost-effective when the cost per QALY gained is greater than three times of the GDP per capita.
Discrete data will be reported in frequency and percentage while continuous data will be reported in mean ± standard deviation (SD). The retrieved data were compared using two-sample t-test and Chi-square test or Fisher’s exact test for continuous and categorical data, respectively. Data with a p-value <0.05 were considered as statistically significant. All data analyses were performed using SPSS 22.
Results
Baseline characteristics
Seven hundred and twenty-seven subjects were recruited. Forty-three subjects who received both DES and BMS were excluded and, therefore, 684 subjects were included in the final analysis. Among them, 402 (58.8%) subjects received DES, while 282 (41.2%) received BMS. The majority of patients were male (n = 533, 77.9%). The mean age was 64.7 ± 11.0. More than 80% (n = 575, 84.1%) of the recruited subjects had dyslipidemia and nearly 40% (n = 271, 39.6%) suffered from diabetes mellitus.
When comparing the risk factors between BMS and DES groups, there were significantly more patients with hypertension in the DES group (69.7% vs 61.0%, p = .019), but the proportion of current smokers was higher in the BMS group (29.1% vs 19.9%, p = .005). It was also found that a hist of MI was more common in the DES group (46.5% vs 41.0%, p = .002). Concerning angiographic characteristics, there were significantly more subjects in the BMS group with an ejection fraction less than 35% (9.6% vs 3.7%, p = .002), while there were more subjects in the DES group with ejection fraction more than 55% (65.6% vs 35.1%, p = .004). All baseline characteristics are listed in .
Table 1. Baseline characteristics.
Clinical outcomes
Prior to the propensity score matched analysis, non-fatal MI was found to be less in the DES group (2.2% vs 5.3%, p = .031), while the DES group demonstrated a significantly lower rate of non-fatal MI at 18-month follow-up (2.1% vs 6.9%, p = .025), and a lower percentage of total A&E visits (53.8% vs 72.9%, p < .001) and cardiac hospitalization (31.3% vs 42.2%, p = .036) for UA/NSTEMI patients. In non-ACS patients, those with DES implanted also demonstrated a significantly longer mean time to cardiac death within 18 months (4.22 ± 0.02 months vs 1.09 ± 1.04 months, p = .035). However, after propensity score matched analysis, no statistically significant outcomes were identified in the above-mentioned categories. All the clinical outcomes were summarized in .
Table 2. Clinical outcomes.
Cox Regression Analysis revealed that the types of stent (HR = 0.46; p = .004 for univariate analysis; HR = 0.30; p = 0.041 for multivariate analysis) and family history (HR = 8.40; p = .047 for univariate analysis; HR = 103.22; p = .022 for multivariate analysis) were two significant factors associated with the MACE occurrence. Detailed results of analysis were summarized in .
Table 3. Factors associated with the occurrence of MACE.
Humanistic outcomes
Throughout the 18-month follow-up, changes in EQ VAS for both DES and BMS groups were approximately the same, ∼40% increase without any statistical significance. The changes in utility score measured by EQ-5D descriptive system were also similar for both DES and BMS groups (+39.66% vs +34.48%, p = .162).
Among STEMI, UA/NSTEMI and non-ACS patients, the percentage of increase of utility score in DES group patients was the highest in STEMI patients, followed by UA/NSTEMI patients and non-ACS patients (+70.00% vs +45.45% vs +24.62%). Regarding the humanistic outcome of non-ACS patients at 18 months, DES patients showed a rise of utility score of 24.62%, which was worse than that of BMS patients (+25.00%). summarized all the humanistic outcomes of the study.
Table 4. Humanistic outcomes.
Economic outcomes
All cost data are listed in . At 18 months, the total cost was higher in the DES group but without statistical significance (p = .187). For the cost of follow-up, it was significantly lower in the DES group at 18 months (p = .032). Among the cost of follow-up, cost of hospitalization was always significantly lower in the DES group, but the cost of clopidogrel was significantly higher in the DES group.
Table 5. Economic outcomes.
For the STEMI and UA/NSTEMI patients, there were no significant differences in the total cost throughout the 18-month study period. The cost of index procedure was higher in the DES group. The difference was significant in the UA/NSTEMI group (HKD 96,380 ± 40,413 vs 78,150 ± 36,762, p < .001), but not in the STEMI group. The cost of follow-up was substantially lower in the DES group in both the STEMI group and the UA/NSTEMI group.
For the non-ACS patients, the total cost was significantly higher in the DES group throughout the study (HKD 117,020 ± 64,192 vs HKD 86,383 ± 64,689, p = .001). The cost of index procedure was significantly higher in the DES group (HKD 84,870 ± 30,023 vs HKD 59,580 ± 21,071, p < .001).
The cost utility analysis revealed that DES is dominant (i.e. less costly but more effective) to BMS at 18 months in the STEMI group (HKD −32,200/QALY) but vice versa in the non-ACS group (HKD −1,838,220/QALY). The cost per QALY gained of DES was HKD +119,000 for UA/NSTEMI group at 18 months.
Concerning the cost-effectiveness, DES was also found to be dominant in STEMI patients (ICER: HKD −247,962). For UA/NSTEMI patients, the ICER was HKD +68,654 at 18 months. On the other hand, ICER for DES group in non-ACS patients at 18 months (HKD: 2,042,467) was far greater than three times of the GDP per capita in Hong Kong and is, therefore, not considered as cost-effective.
Discussion
TAXUS IV TrialCitation6, SIRIUS TrialCitation7, ENDEAVOR II TrialCitation14, Kastrati et al.Citation8 and Roiron et al.Citation9 have shown that patients who received DES had reduced MACE and TVR rates, but no significant differences in death and recurrent MI rates. Our study, however, found that there was no significant reduction in MACE and TVR rates, which are inconsistent with the above studies. Despite the imbalance baseline characteristics between BMS and DES groups, the results of Cox regression analysis demonstrated that the types of stent employed in PCI remained an important factor of MACE occurrence. The mean time to cardiac death at 18 months was significantly longer in DES patients (7.55 months vs 1.40 months), but further research is warranted to confirm this finding, due to the limitations of the current study.
BASKET trial showed a higher total cost in DES patients at 6 months (€10,544 ± 6,849 vs €9,639 ± 9,067, p = .0001)Citation17 due to the significant higher cost of index procedure. Similar to BASKET trial, the cost of index procedure of the current study was higher in the DES group (HKD 95,510 ± 40,946 vs HKD 78,011 ± 38,829, p < .001), but this was offset by the lower cost of subsequent follow-up in the DES group. As a result, the differences in total cost between BMS and DES at 18 months was not statistically significant, and this is consistent with other studiesCitation21,Citation29.
The higher follow-up cost in the BMS group in STEMI patients was mainly related to the higher cost of hospitalization and repeated PCI. Therefore, the use of DES in STEMI patients was cost-saving in both MACE prevention and QALY gained perspectives. As for UA/NSTEMI patients, due to the relatively low incremental cost, the use of DES is also considered cost-effective in both cost-utility and cost-effectiveness analysis. On the contrary, for non-ACS patients, not only the cost of index procedure, but the cost of follow-up was also higher in the DES group. The relatively small differences in the MACE between both groups and the lack of improvement of EQ VAS and utility scores, coupled with the high total cost, make DES an unfavorable choice of stent in the non-ACS group of patients. BASKET TrialCitation17, Brophy et al.Citation16, Neyt et al.Citation18, Bischof et al.Citation19, Filion et al.Citation20, and Ong et al.Citation29 have shown that using DES in unselected patients is not cost-effective, while Hung et al.Citation30 have demonstrated that the use of DES is not cost-effective in patients with stable angina.
The current study was limited by several factors. In addition to the limitations bounded by the observational nature in a single center, the relatively short follow-up duration (18 months) after stent procedure may not be sufficient to demonstrate the true underlying cost-effectiveness of DES in different groups of patients. A meta-analysis reported that drug-eluting stents appeared to increase the risk for late thrombosis at 1 year or above after coronary revascularizationCitation10. There were overseas studies which compared the effect of DES and BMS at a follow-up period up to 5 yearsCitation31–33. It is believed a longer study period would reflect a more accurate and reliable effect of the two types of stents in the Chinese population of Hong Kong. The small sample size also accounted for the unusual findings in the regression analysis, in which family history and LVEF between 35–55% carry a significance risk of MACE but not in other factors like number of lesions and LVEF <35%. Patients’ compliance and duration of dual anti-platelet therapy, use of statin, the appropriateness of the procedure, the types of stent used (first generation vs second generation DES) and some of the baseline past medical history of patients may pose a significant impact on the clinical outcomes, but these factors were not evaluated in this study.
Conclusion
Despite the lack of a statistically significant difference in MACE occurrence between DES and BMS, DES was found to be cost-effective in ACS patients, particularly in STEMI patients. It is recommended for STEMI patients to receive DES in spite of the potential higher cost of the index procedure.
Transparency
Declaration of funding
This study was supported by the School of Pharmacy, The Chinese University of Hong Kong.
Declaration of financial/other relationships
The authors reported no conflict of interest. JME peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Acknowledgments
The study was approved by the Ethics Committee, CUHK-New Territories East Cluster, Hospital Authority, Hong Kong.
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