Acute myocardial infarction (AMI) is a serious cardiovascular disease and is a leading cause of death worldwide. In recent years, the AMI incidence and mortality has decreased significantly in America because early reperfusion and drug treatment has been standardized [
TCM has been practiced for thousands of years, and it has made great contributions to peoples’ health and wellbeing. Epidemiological data has suggested that Chinese herbal preparations may be beneficial in reducing the mortality from AMI, and TCM treatment was shown to help improve the quality of life for AMI patients [
Clinical pathways (CPs), also known as critical pathways, are management plans that display goals for patients and provide the sequence and timing of actions necessary to achieve these goals with optimal efficiency. As competition in the healthcare industry has increased, CPs have been widely implemented as a method to reduce variation in care and potentially improve healthcare quality. Cardiovascular medicine in particular is an area in which CPs have been used extensively [
In previous studies, we developed CPs based on standardized therapy for AMI Integrative Medicine. The standardized management included thrombolysis therapy, primary percutaneous coronary intervention (PCI), antiplatelet and anti-ischemic therapy, and TCM therapy (such as Astragalus injection and compound Danshen dripping pills) to benefit Qi and to activate blood. A small single-center trial suggested that the CPs could reduce the length of the hospital stay and in-hospital health care costs for patients with AMI who underwent PCI [
This trial is a multicenter, nonrandomized retrospective study in eight hospitals (Guangdong Provincial Hospital of TCM; Shuguang Hospital of Shanghai University of TCM; Yueyang Hospital of Integrated Medicine of Shanghai University of TCM; Oriental Hospital of Beijing University of TCM; Jiangsu Provincial Hospital of TCM; 3rd Affiliated Hospital of Guangxi College of TCM; Wuyi Hospital of TCM of Jiangmen city; Zhongshan Hospital of TCM) (Figure
Evaluation of clinical pathways based on integrative medicine for AMI. CPs: clinical pathways, MACE: major adverse cardiac events, AMI: acute myocardial infarction.
Inclusion criteria for this study included patients with acute myocardial infarction (onset of chest pain ≤24 h) admitted to emergency, and ages ranging from 18 to 80 years old who agreed to emergency reperfusion therapy (including intravenous thrombolysis or PCI). Exclusion criteria included serious mechanical complications (such as left ventricular free wall rupture, ventricular septal perforation, papillary muscles, and adjacent chordal rupture), concomitant diseases with aortic dissection, acute pulmonary embolism, severe liver failure, renal failure, mental illness, malignancy, hematopoietic tumor, nervous system primary diseases, and pregnancy or lactation [
In our preliminary study, we found that Qi deficiency and blood stasis were the main TCM syndromes for AMI [
Sample size was calculated using PEMS 3.1 for Windows software (Sichuan University, Chengdu). The length of in-hospital stay was considered to be one of the most important factors in the calculation of sample size. The standard deviation (SD) of the length of in-hospital stay for the conventional treatment group was 6 days [
In the study protocol, the planned sample size was 240 consecutive patients who were enrolled into the intervention groups after pathway implementation. There were 450 consecutive patients, admitted to the eight hospitals between 1 January 2008 and 31 December 2009, prior to CP implementation, who were included as a historical control group. The Guangdong Provincial Hospital of TCM planned to enroll 100 patients for the intervention group and 100 patients for the control group. Additionally, each of the other 7 hospitals planned to enroll 20 patients for the intervention group and 50 patients for the control group.
The patients in the historical control group received conventional management determined by a physician, which included Western medicine and nonstandardized TCM therapy. The patients in the intervention group were treated according to the standardized management plan as determined by the CPs. The Western medical treatment consisted of reperfusion therapy and aspirin, clopidogrel, low molecular weight heparin (LMWH),
For Qi deficiency and blood stasis, the standard TCM technique performed in the intervention group was 30 mL Astragalus injection (Astragalus, Zhengda Qingchunbao pharmaceutical company) mixed with 250 mL 5% glucose, which was infused intravenously once per day, and 10 particles of compound Danshen dripping pills (Salvia, Pseudo-ginseng, Borneol, Tasly Group) 3 times a day. Instead of Astragalus injection, Gualou Xiebai Banxia Tang (Trichosanthes 15 g, Bulbus allii macrostemonis 20 g, Pinelliae 15 g) was administered to patients with cold-phlegm syndrome, Wen Dan Tang (Poria 15 g, Dried tangerine peel 10 g, Pinellia 15 g, Caulis bambusae in taenia 15 g, Fructus aurantii 15 g) was administered for patients with heat-phlegm syndrome, 30 mL Shen Mai injection (Ginseng, Radix, Zhengda Qingchunbao pharmaceutical company) mixed with 5% glucose injection infusion was administered for Yin-deficiency, and 30 mL Shenfu (tuber, red ginseng, Sanjiu Ya pharmaceutical company) in 5% glucose intravenous infusion was administered for Yang-deficiency. All the treatments were administered for 1 week.
The primary outcome was the length of the in-hospital stay. Discharge standard, for patients to be discharged from the hospital with stable life signs (hemodynamic, electrocardiogram, and cardiac function) and without the symptoms of myocardial ischemia, was determined according to “Clinical pathways of ST-segment elevation myocardial infarction” (2009 version) by the Medical Administration of the Ministry of Health [
Between 1 January 2010 and 31 October 2010, a total of 250 consecutive patients fulfilling the inclusion criteria were initially evaluated as the intervention group, and 53 patients were excluded because of severe mechanical complications or severe liver failure and renal failure. A total of 450 patients admitted to eight hospitals from 1January 2008 to 31 December 2009 were screened for the historical control group, and 45 patients were excluded because of severe mechanical complications or concomitant diseases. As a result, there were 197 patients enrolled into the intervention group and 405 patients enrolled into the historical control group.
Of the 602 patients, 514 (85%) were admitted for ST-segment elevation myocardial infarction (STEMI) and 71 (15%) for non-ST-segment elevation myocardial infarction (NSTEMI). There were 567 patients (94%) who underwent emergency PCI and 35 patients (6%) who received intravenous thrombolysis. Patient characteristics were not significantly different between the intervention and control groups. The only exceptions were a slightly increased number of patients with a family history of coronary disease in the control group compared to the intervention group, and small increase in the number of patients in the intervention group who had hyperlipidemia or who currently smoked, compared to the control group (Table
Demographic and clinical features of patients.
Variable | Intervention group |
Historical control group |
|
|
---|---|---|---|---|
Male gender | 149 (75.6) | 308 (76.0) | 0.01 | 0.91 |
Age (yrs) | 63.42 ± 11.87 | 63.89 ± 13.20 | −0.49 | 0.63 |
Hypertension | 109 (55.3) | 214 (52.8) | 0.33 | 0.57 |
Diabetes | 37 (18.8) | 55 (13.6) | 2.77 | 0.10 |
Hyperlipidemia | 58 (29.4) | 65 (16.0) | 5.88 | 0.02 |
Previous coronary disease | 14 (7.1) | 22 (5.4) | 0.66 | 0.42 |
Previous stroke | 20 (10.2) | 34 (8.4) | 0.01 | 0.93 |
Current smoker | 106 (53.8) | 196 (48.4) | 4.96 | 0.03 |
Family history of coronary disease | 16 (8.1) | 65 (16.0) | 10.13 | 0.00 |
Clinical pattern | ||||
STEMI | 176 (89.3) | 338 (87.1) | 0.61 | 0.44 |
NSTEMI | 21 (10.7) | 50 (12.9) | ||
Cardiac function (Killips classification) | ||||
Level I | 99 (64.7) | 275 (69.1) | −0.96 | 0.34 |
Level II | 31 (20.3) | 70 (17.6) | ||
Level III | 10 (6.5) | 23 (5.8) | ||
Level IV | 13 (8.5) | 30 (7.5) | ||
Intravenous thrombolysis | 8 (4.1) | 27 (6.7) | 1.64 | 0.20 |
Emergency PCI | 189 (95.9) | 378 (93.3) | ||
Vascular lesions | ||||
Single | 64 (34.0) | 102 (30.0) | −0.37 | 0.72 |
Two branch | 56 (29.8) | 116 (34.1) | ||
Three branch | 65 (34.6) | 122 (35.9) | ||
Stenosis < 50% | 3 (1.6) | 0 (0.0) | ||
Stent implantation | 1.19 ± 0.63 | 1.25 ± 0.90 | −0.11 | 0.92 |
Values are given as number of patients (%) or mean ± SD.
STEMI: ST-segment elevation myocardial infarction; NSTEMI: non-ST-segment elevation myocardial infarction.
PCI: percutaneous coronary intervention.
Comparing the main Western medicine drug treatments in both groups, there were no statistically significantly differences among antiplatelet therapy (aspirin, clopidogrel), beta receptor blockers, ACEI (or ARB), and nitrate (
Western medicine prescribing frequency.
Variable | Intervention group |
Historical control group |
|
|
---|---|---|---|---|
Antiplatelet | 197 (100) | 402 (99) | — | 1.00* |
Low molecular weight heparin | 197 (100) | 362 (89) | — | 0.00* |
Statins | 197 (100) | 388 (96) | — | 0.01* |
|
160 (81) | 320 (79) | 0.12 | 0.72 |
ACE inhibitors |
163 (82) | 324 (80) | 0.64 | 0.42 |
Nitrate esters | 138 (70) | 276 (68) | 0.07 | 0.79 |
Antiarrhythmic drugs | 65 (33) | 79 (20) | 12.41 | 0.00 |
Values are given as number of patients (%).
*Using the exact probability method.
ACE: angiotensin-converting enzyme; ARB: angiotensin II receptor blocker.
The rate of Chinese medicine decoction use in the treatment group was significantly higher than in the control group (
Chinese medicine prescribing frequency.
Variable | Intervention group |
Historical control group |
|
|
---|---|---|---|---|
Chinese medicine therapy | 192 (97) | 342 (84) | 21.93 | 0.00 |
Compound Danshen dripping pills | 124 (63) | 9 (7) | 283.91 | 0.00 |
Qi-benefitting intravenous agents |
153 (78) | 176 (43) | 62.58 | 0.00 |
Blood-activating intravenous agents |
0 (0) | 256 (63) | — | 0.00* |
*Using the exact probability method.
The length of in-hospital stay showed a skewed distribution in both groups, and therefore a nonparametric test was used. The average length of stay in the treatment group was 3.5 days less than that of the control group, which was statistically significant (
Length of in-hospital stay.
Variable | Group |
|
|
|
|
|
---|---|---|---|---|---|---|
Length of stay |
Intervention | 197 | 9.2 ± 4.2 | 9 | 5.08 | <0.001 |
Historical | 405 | 12.7 ± 8.6 | 11 |
The average hospitalization costs had a skewed distribution in both groups, so a nonparametric test was used. In the intervention group, the average total in-hospital charges were ¥48047.3 when it was adjusted by the price index, which reduced to ¥4820.00 compared with the control group. There were statistically significant differences between intervention groups and control groups. (
In-hospital medical costs.
Variable | Group |
|
|
|
|
|
---|---|---|---|---|---|---|
Total charges (¥) | Intervention | 197 | 48047.3 ± 18929.4 | 44198.7 | 1.83 | 0.067 |
Control | 405 | 52866.0 ± 35404.4 | 46157.8 | |||
Total charges adjusted by price index (¥) |
Intervention | 197 | 46365.7 ± 18266.9 | 42651.7 | 2.94 | 0.003 |
Control | 405 | 52866.0 ± 35404.4 | 46157.8 |
The major adverse events of death, nonfatal myocardial reinfarction, stent thrombosis, and target vessel revascularization (TVR) occurred in 2.5% of patients (5 of 197) in the interventional group and in 6.9% (28 of 405) of those in the control group during hospitalization (
Individual and combined outcome measure of MACE occurrence during hospitalization.
Variable | Intervention group | Historical group |
|
---|---|---|---|
Death | 3 (1.5) | 22 (5.4) | 0.03* |
Nonfatal MI | 1 (0.5) | 1 (0.2) | 0.55* |
Stent thrombosis | 1 (0.5) | 2 (0.5) | 1.0* |
TVR | 0 (0) | 3 (0.7) | 0.56* |
| |||
Total | 5 (2.5) | 28 (6.9) | 0.03 |
*Using the exact probability method; MI: myocardial reinfarction; TVR: target vessel revascularization.
The number of patients in China who develop and present to hospitals with acute coronary syndrome will increase in the near future. China’s fee-for-service payment system has resulted in a rapid cost increase, inefficiencies, poor quality, unaffordable health care, and an erosion of medical ethics [
To standardize the AMI treatment-based integrative medicine in TCM hospitals, we conducted this study and evaluated the efficacy of CPs in eight TCM hospitals. In our study, there were more patients with hyperlipidemia or who were current smokers, and fewer patients with a family history of coronary disease in the intervention group than in the historical control group. These data indicate that, with diet and life-style changes in China, smoking and hyperlipidemia have emerged as key risk factors leading to AMI, especially for younger people.
A previous epidemiological study showed that the average length of hospital stay was from 11.6 to 13.7 days in China for the patients with AMI who were admitted to hospital within 12 h after onset of chest pain [
China’s current strategy to improve payment for health services has made some positive changes; however, the rapid increase in health expenditure and inappropriate treatment concerning individuals and governments resulting from China’s fee-for-service payment and a price schedule that overpays for drugs and high-technological diagnostics tests has led providers to overprescribe drugs and diagnostic tests [
Despite strong evidence for the benefits of AMI patient management using antiplatelet agents, LMWH and lipid-lowering therapies, reports from the CPACS study indicated that physician compliance with guideline recommendations and sustained use of medical therapy remains suboptimal [
TCM plays an important role in the current treatment of AMI especially in TCM hospitals. In the past 10 years, blood-activating had emerged as a main TCM method for treating patients with AMI, thus leading to wide prescribing of Chinese medicine intravenous preparations that are clinical blood-activating agents [
Despite wide implementation of CPs in cardiovascular disease, no controlled study has shown that CPs could reduce the incidence of the death or MACE in patients with AMI. Our research indicated that, compared with the historical group, the incidence of death and MACE during hospitalization was lower in the intervention group compared to the control group (1.5% versus 5.4%, 2.5% versus 6.9%, resp.,
Integrative medicine treatment, combining TCM and conventional medicine, has been the most representative characteristic for patients with coronary heart disease in China, especially those in TCM hospitals. We found that, in the current era of published treatment guidelines, implementation of the CPs based on the standardized therapies of integrative medicine could further improve guideline compliance and overall quality of care by reducing the length of stay and medical cost for patients with AMI in Chinese hospitals.
Although our study revealed the potential improvements in patient outcome by the development and implementation of CPs for AMI patients in China, there are several limitations of the study. First, the duration of the study period was short because of budget limitations, which leaves uncertainty in the long-term outcome of patients with AMI. Second, this study used a nonrandomized retrospective trial design, which may not fully reflect the improvement of CPs on the quality of health care due to potential changes in insurance coverage or policy. Therefore, multicenter large-scale randomized studies are needed to assess prospectively the differential effects of CPs based on integrative medicine versus CPs only based on western medicine.
None of authors received funding or research grants from the relevant drug manufacturers in this research. The authors declare that they have no conflict of interests.
All authors contributed substantially to one or more of the following activities: study design, study conduct, data analysis, interpretation of data, and writing of the manuscript.
This project was financially supported by funding from the Department of Science and Technology and the Academy of Traditional Chinese Medicine of Guangdong Province (No. 2011B032200006). The authors thank Professor Ou Aihua in the Guangdong Province Hospital of TCM for statistical analysis and assistance during the design process.