[논문]Clopidogrel에 Proton Pump Inhibitors 병용 시 급성 관동맥 증후군 환자의 심장관련 부작용에 미치는 영향

김수현; 이유정

Clopidogrel에 Proton Pump Inhibitors 병용 시 급성 관동맥 증후군 환자의 심장관련 부작용에 미치는 영향
Influence of the Concomitant Use of Clopidogrel and Proton Pump Inhibitors on Adverse Cardiovascular Events in Korean Patients with Acute Coronary Syndrome 원문보기

한국임상약학회지 = Korean journal of clinical pharmacy, v.24 no.2, 2014년, pp.106 - 114

Abstract ▼ AI-Helper

Purpose: Recent investigations suggest that the antiplatelet effect of clopidogrel may be decreased when this medication is taken together with certain proton pump inhibitors (PPIs). However, there has been no study conducted in Korea regarding the clinical effect of clopidogrel-PPI interaction. This study targeted patients who received stents to investigate the effect of the concomitant use of clopidogrel and PPIs on the occurrence of adverse cardiovascular events in Korean patients. Methods: The patients who received a stent insertion at the Yeouido St. Mary's Hospital between January 2010 and April 2011 were included. The patients were divided into two groups, clopidogrel and clopidogrel + PPI, and followed for 12 months after the date of stent insertion using prescription history and medical records. The recurrence rates of the cardiovascular events among the two patient groups were statistically analyzed. Results: There was no difference between the two groups in the basic characteristics of the 157 patients in the clopidogrel group and the 62 patients in the clopidogrel+PPI group. Simple logistic regression showed a significantly higher rate of re-hospitalization in the clopidogrel+PPI group (OR=1.893, 95% CI 1.040-3.445, p=0.037). However, the results of the multivariate logistic regression of the variables found to have statistical significance by crosstabulation showed no significant difference in the rate of adverse cardiovascular events or re-hospitalization between the two groups. Conclusions: There was no significant difference between the clopidogrel and clopidogrel+PPI group among new patients with cardiovascular stents with respect to the occurrence of revascularization procedures, stent thrombosis, or chest pain, or with respect to the re-hospitalization rate for all cardiovascular events.

주제어

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제안 방법

First, basic patient information was analyzed to reflect the variables between the two groups. Patient gender, age, and weight and the effectiveness of stent were examined.
Fourth, based on the information from medical records, including coronary angiography records and PCI records, the number of stented vessels and the location of the treated vessel, which was classified as left main coronary (LM), left anterior descending (LAD), left circumflex (LCX), or right coronary artery (RCA), were investigated.
Second, any other medications used with clopidogrel were categorized as a β-blocker, angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), calcium channel blocker (CCB), nitrate, warfarin, or non-steroidal anti-inflammatory drug (NSAID) and then investigated.
Therefore, the present study targeted Korean patients who were admitted with acute coronary syndrome and treated with stent insertion. The patients were divided into two groups, one receiving only clopidogrel and the other receiving a PPI in addition to clopidogrel, to compare and evaluate the occurrence rates of MACEs between the two groups through retrospective analysis of prescriptions and medical records.
Univariate logistic regression analysis was performed on each of the revascularization, thrombosis, chest pain or dyspnea, and re-hospitalization groups, with PPI use as the only variable in comparing the clopidogrel-only group and the clopidogrel + PPI group.

대상 데이터

A total of 268 patients were admitted to the Cardiology Department of Yeouido St. Mary’s Hospital and underwent PCI.
Mary’s Hospital. The hospital is located in Seoul, South Korea, and is a tertiary health care facility with a 770-bed capacity.
This study targeted patients who were admitted with acute coronary syndrome and treated with a stent insertion at the Department of Cardiology of Yeouido St. Mary’s Hospital.

데이터처리

A chi-square test or Fisher’s exact test was performed for the crosstabulation analysis.
Multiple logistic regression analysis was performed on the variables found to have statistical significance on crosstabulation (p < 0.1), and Fisher’s exact test was performed to determine whether each of the PPI medications (esomeprazole, lansoprazole, and rabeprazole) had a different effect on the occurrence rate of major cardiovascular events.
Of the variables between the PPI group and the non-PPI group, two nominal variables, age and weight, were analyzed for the mean and standard deviation (SD) of each group, and an independent t-test was performed on the two groups.
The p values of categorical variables are derived from a chi-square test or Fisher's exact test.

성능/효과

Furthermore, no differences were found in the diagnosis (angina and myocardial infarction) or currently used medications between the two groups. Although no differences were found for the risk factors for acute MI, including smoking, diabetes, stroke, and history of PCI, 71.0% of the PPI group had hypertension, which was significantly higher than the 55.4% in the clopidogrel-only group (p=0.046).
Other ordinal variables underwent crosstabulation to determine the p-value. In the cases in which there were only two categories of response, such as for the variables of the presence of diabetes and the presence of hypertension, only the frequency and percentage of responses affirming the presence of the conditions were recorded. For those variables with three or more response categories, such as diagnosis and intervention location, the frequency and percentage of all of the categories were recorded.
The clopidogrel-only group and the clopidogrel + PPI group showed a significant difference in the percentage of patients with hypertension (55.4% vs. 71.0%; p=0.046), with more patients with hypertension in the group with concomitant PPI therapy. With this exception, the other basic characteristics were not significantly different between the two groups (Table 1).
The result of the analysis found that the re-hospitalization rate was 1.893 times higher in the clopidogrel + PPI therapy group (p=0.037) compared with the clopidogrel group when cases of re-hospitalization due to all adverse cardiac events were considered. However, there were no significant differences in revascularization, thrombosis, or chest pain or dyspnea between the two groups.
The results of an analysis of the factors affecting revascularization found that diabetes (p=0.060), diagnosis (p=0.088), concomitant PPI therapy (p=0.066), and betablocker therapy (p=0.004) were significantly correlated with the occurrence of revascularization at a significance level of 0.1 (Table 2). Only warfarin therapy (p=0.
The results of our study found no significant difference in basic patient characteristics, such as age, gender, and weight, between the clopidogrel-only group and the clopidogrel+ PPI group. Furthermore, no differences were found in the diagnosis (angina and myocardial infarction) or currently used medications between the two groups.
²⁷⁾ only included rabeprazole and investigated 199 patients who were prescribed only clopidogrel and 103 patients who were prescribed both rabeprazole and clopidogrel. The results of this study found no relationship between concomitant therapy using rabeprazole and clopidogrel and the risk of coronary vascular event occurrence (HR=1.28; 95% CI=0.54-3.00; p=0.56). In contrast to many studies published on the interaction between omeprazole and clopidogrel.
¹³⁾ targeted8205 patients who were admitted with acute coronary syndrome and treated with the PPIs omeprazole and rabeprazole prescribed together with clopidogrel. The results showed that the recurrence of ACS was 1.86 times higher in the clopidogrel+PPI group compared with the clopidogrel- only group (AOR=1.86; 95% CI= 1.57-2.20), and the rate of revascularization procedures was 1.49 times higher (AOR=1.49; 95% CI=1.30-2.71). Death or readmission due to side effects was also found to be 1.
Second, any other medications used with clopidogrel were categorized as a β-blocker, angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), calcium channel blocker (CCB), nitrate, warfarin, or non-steroidal anti-inflammatory drug (NSAID) and then investigated. Third, when clopidogrel and a PPI were prescribed together, the PPI medications were categorized as esomeprazole, lansoprazole, or rabeprazole (all with a hospital prescription code), and all cases of concomitant usage of more than one day were investigated.

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