Korea Acute Myocardial Infarction Registry

The Korea Acute Myocardial Infarction Registry (KAMIR) is a Korean prospective multicenter online registry designed to reflect the “real-world” practice in Asian patients presenting with AMI in the DES era, with support from the Korean Circulation Society since November 2005. Online registry of AMI (at www.kamir.or.kr) has been performed at 41 university or community hospitals that are high-volume centers with facilities for primary PCI and onsite cardiac surgery. Before the initiation of the KAMIR study, several investigator meetings were held, and a practical steering committee from major enrolled hospitals was selected to standardize care given in clinical practice as well as the study protocol to minimize the differences in medical care among the different hospitals and across the different time periods. Data were collected at each site by a trained study coordinator using a standardized case report form. Standardized definitions of all patient-related variables and clinical diagnoses were used. The study protocol was approved by the ethics committee at each participating institution. Data were registered and submitted from individual institutions via password-protected Internet-based electronic case report forms. We enrolled patients who were suffering from AMI, including both STEMI and non-STEMI. Patients were diagnosed with STEMI when they had new or presumed new ST-segment elevation of at least 1 mm seen in any location or new left bundle-branch block on the index or subsequent ECG with at least 1 positive cardiac biochemical marker of necrosis (including creatine kinase-MB and troponin I and T).

Study Population

From November 2005 to December 2007, a total of 13 632 patients were diagnosed with AMI. In the present study, we retrospectively enrolled patients with acute STEMI who underwent primary PCI (PCI performed within 24 hours after the symptom onset) with DES. The criteria for exclusion included non-STEMI, STEMI undergoing primary PCI with bare metal stent or balloon angioplasty only, STEMI undergoing selective PCI or conservative treatment without PCI, Killip grade IV cardiac function, contraindication to antithrombotic agents, known bleeding disorders, thrombocytopenia (<100×10⁹/L), administration of oral anticoagulants, administration of thrombolytic or fibrinolytic medications for STEMI, infarction related to the grafted vessel, severe hepatic or renal dysfunction (serum creatinine >2 mg/dL), and estimated life expectancy of <12 months.

Patients were divided into 2 groups: a dual antiplatelet therapy group (aspirin plus clopidogrel; dual group; n=2569) and a triple antiplatelet therapy group (aspirin plus clopidogrel plus cilostazol; the triple group; n=1634). Loading doses of aspirin and clopidogrel were administered immediately after the patients agreed to receive PCI. The loading and maintenance doses were 200 and 100 mg QD for aspirin and 300 to 600 and 75 mg QD for clopidogrel. Cilostazol was given right after the PCI procedure; its loading and maintenance doses were 200 and 100 mg BID, respectively. According to the KAMIR study design, AMI patients when discharged were prescribed medicines for 1 month, after which the first follow-up was performed. Dual antiplatelet therapy was administered to all patients for ≥6 months as per existing guidelines. Cilostazol was administered to the triple antiplatelet therapy group for at least 1 month after the index procedure. After discontinuation of cilostazol, the patients in the triple group received dual antiplatelet therapy.

PCI Procedure and Medical Treatment

Diagnostic angiography and PCI were performed after unfractionated heparin (50 to 70 U/kg) was administered. Coronary angiography was performed through the femoral or radial artery. During the procedure, patients received unfractionated heparin to maintain an activated clotting time of >250 seconds. Stents were deployed after prior balloon angioplasty, and the administration of platelet glycoprotein IIb/IIIa receptor blockers was left to the decision of the individual operator. A successful PCI procedure was defined as the achievement of an angiographic minimum stenosis diameter reduction to <30% in the presence of Thrombolysis in Myocardial Infarction grade III flow.

During the in-hospital period, patients received medical treatment that included β-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, and statins. After discharge, the patients continued receiving the same kinds of medications that they received in hospital except some intravenous or temporary medications.

Study Definitions and Clinical Follow-Up

The records of cardiovascular risk factors and past history (age, sex, hypertension, dyslipidemia, smoking, diabetes mellitus, family history of coronary heart disease, prior myocardial infarction, chronic heart failure and prior cerebrovascular disease, peripheral arterial disease) were dependent mainly on the patient’s self-report, but the final records were left to the physician’s discretion after he or she comprehensively considered the patient’s self-report and the in-hospital examination results. All deaths were considered cardiac deaths if noncardiac death could be excluded. Recurrent myocardial infarction was defined as recurrent symptoms with new ST-segment elevation or re-elevation of cardiac markers to at least twice the upper limit of normal. Target lesion revascularization (TLR) was defined as ischemia-induced PCI of the target lesion resulting from restenosis or reocclusion within the stent or in the adjacent 5 mm of the distal or proximal segment. Total major adverse cardiac events (MACEs) were defined as the composite of all-cause death, nonfatal myocardial infarction, and repeated PCI or coronary artery bypass grafting. Major bleeding was defined as any intracranial bleeding, bleeding associated with the need for blood transfusion, or any other clinically relevant bleeding as judged by the investigator.

Patients were required to visit the outpatient clinic of the cardiology department at the end of the first month, every 6 months after the PCI procedure, and when angina-like symptoms occurred. The 6-month clinical follow-up was done at a median of 173 days (interquartile range, 147 to 206 days). Therefore, in the present study, we collected the clinical follow-up data at 8 months (240 days) to ensure that all patients finished their 6-month follow-up. The incidences of major bleeding events and various MACEs, in hospital and at 8 months, were evaluated between the dual and triple groups.

Statistical Analysis

For continuous variables, differences between groups were evaluated by unpaired ttest or Mann-Whitney rank-sum test. For discrete variables, differences were expressed as counts and percentages and were analyzed with χ² (or Fisher exact) test between groups as appropriate. To adjust for potential confounders, a propensity score analysis was performed using the logistic regression model, testing the propensity to receive triple rather than dual antiplatelet therapy. We tested all available variables that could be of potential relevance: age, sex, Killip class on admission, cardiovascular risk factors (hypertension, dyslipidemia, smoking, diabetes mellitus, family history of coronary heart disease), prior myocardial infarction, chronic heart failure and prior cerebrovascular disease, peripheral arterial disease, stent type, number of diseased vessels, and cardiovascular medications (glycoprotein IIb/IIIa receptor blockers, heparins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β-blockers, calcium channel blockers, and statins). The logistic model by which the propensity score was estimated showed good predictive value (C statistic=0.753). Multivariable Cox regression analysis was then performed using the propensity score, antiplatelet therapies (triple versus dual), and the aforementioned variables to determine the impact of the different antiplatelet therapies on in-hospital and 8-month clinical outcomes. In addition, the effects of the different antiplatelet therapies on 8-month clinical outcomes were further evaluated in different subgroups of patients, including old (≥65 years of age), young (<65 years of age), male, female, diabetic, and nondiabetic patients. Cox regression models adjusted for propensity score and the aforementioned variables were used to assess odds ratios for various MACEs in these different subgroups of patients. All continuous variables were described as mean±SD. All analyses were 2-tailed, with clinical significance defined as values of P<0.05. All statistical processes were done with SPSS 13.0 (Statistical Package for the Social Sciences, SPSS-PC Inc, Chicago, Ill).

Study Strengths and Limitations

The strengths of the KAMIR study include its prospective design and large multicenter population base. The registry provides a comprehensive view of the contemporary treatments and outcomes in the Asian patients with AMI in the era of DES.

The present study has some limitations. First, although there is a large number of subjects in the present study, because of the nonrandomized nature of the registry study, there were baseline differences in several important prognostic factors between our primary comparison groups. Although we included most confounders in the multivariable Cox regression model, including propensity score to control the baseline biases, it is possible that some potential confounders might have crept in. However, this multicenter registry may help complete the picture gained from randomized trials, which usually have highly selected patients treated in a nonroutine setting. Second, in the present study, we divided patients into different antiplatelet therapies on the basis of their in-hospital, discharge, and follow-up medical records, but we did not collect information on adverse reactions to cilostazol during the follow-up period. However, we have detailed information on the major and minor bleeding events, mortality, and recurrent myocardial infarction, which also are very important components of safety profiles and can help us understand the main safety profiles of cilostazol.²⁶ Fortunately, a recent study showed that the adverse reactions in patients who received triple antiplatelet therapy were similar to those who received dual therapy.¹⁸ Third, because we did not collect data on cardioactive medications, including β-blockers, statins, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers, during the follow-up period, this also might be a confounding factor.

KAMIR Investigators

The complete list of KAMIR Investigators follows: Myung Ho Jeong, MD; Young Jo Kim, MD; Chong Jin Kim, MD; Myeong Chan Cho, MD; Young Keun Ahn, MD; Jong Hyun Kim, MD; Shung Chull Chae, MD; Seung Ho Hur, MD; In Whan Seong, MD; Taek Jong Hong, MD; Dong Hoon Choi, MD; Jei Keon Chae, MD; Jae Young Rhew, MD; Doo Il Kim, MD; In Ho Chae, MD; Jung Han Yoon, MD; Bon Kwon Koo, MD; Byung Ok Kim, MD; Myoung Yong Lee, MD; Kee Sik Kim, MD; Jin Yong Hwang, MD; Seok Kyu Oh, MD; Nae Hee Lee, MD; Kyoung Tae Jeong, MD; Seung Jea Tahk, MD; Jang Ho Bae, MD; Seung Woon Rha, MD; Keum Soo Park, MD; Kyoo Rok Han, MD; Tae Hoon Ahn, MD; Moo Hyun Kim, MD; Ju Young Yang, MD; Chong Yun Rhim, MD; Hyeon Cheol Gwon, MD; Seong Wook Park, MD; Young Youp Koh, MD; Seung Jae Joo, MD; Soo Joong Kim, MD; Dong Kyu Jin, MD; Jin Man Cho, MD; Jeong Gwan Cho, MD; Wook Sung Chung, MD; Yang Soo Jang, MD; Ki Bae Seung, MD; and Seung Jung Park, MD.