Method for providing information about prognosis prediction after percutaneous coronary intervention

Abstract

The present invention relates to a method for providing information about prognosis prediction after percutaneous coronary intervention (PCI), in which provided is information indicating that among patients who have received percutaneous coronary intervention, patients with abnormal ankle-brachial index (ABI) are more likely to have poor prognosis compared to those without abnormal ABI.

Description

Methods for providing information on prognosis after percutaneous coronary intervention

[0001] The present invention relates to a method for providing information on predicting prognosis after percutaneous coronary intervention.

[0002]

[0003] Peripheral arterial disease (PAD) is associated with systemic atherosclerosis and is a major cause of atherosclerotic cardiovascular (CV) morbidity and mortality. Approximately 13% to 22% of patients with coronary artery disease (CAD) have PAD, which increases the risk of future ischemic events. Like CAD, PAD is managed through lifestyle modifications, medications, endovascular treatment, or surgery. Lifestyle modifications and medications are recommended to improve clinical outcomes. A diagnostic approach to PAD is crucial because risk stratification can provide the basis for determining the treatment modality and intensity. Patients with both CAD and PAD generally require more intensive medical management, including potent antithrombotic or lipid-lowering therapy for secondary prevention. Recently, there has been increasing interest in the role of PAD in CAD patients and its prognosis for bleeding events. The COMPASS (Cardiovascular Outcomes for People Using Anticoagulant Strategies) trial found that adjunctive use of low-dose novel oral anticoagulants to aspirin reduced ischemic events compared with aspirin alone, but increased major bleeding events in patients with PAD.

[0004] The ankle-brachial index (ABI) is a well-established method for assessing PAD, and current guidelines recommend specific criteria for an abnormal ABI (<0.9 or >1.4). Previous studies have reported that an abnormal ABI is associated with an increased risk of ischemic events. However, abnormal ABI has not been well investigated as a risk factor for ischemic and hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI).

[0005]

[0006] The purpose of the present invention is to provide a method for providing information on predicting prognosis after percutaneous coronary intervention.

[0007]

[0008] The present invention relates to a method for providing information on predicting prognosis after percutaneous coronary intervention (PCI), which provides information that patients who have an abnormal ankle-brachial index (ABI) among patients who have undergone PCI are more likely to have a poor prognosis than patients who do not have an abnormal ABI.

[0009] In the present invention, the ABI value of a patient with an abnormal ankle-brachial index may be 0.9 or less or 1.4 or more.

[0010] In the present invention, the poor prognosis may be ischemic stroke, hemorrhage, or death.

[0011]

[0012] The method of the present invention can predict the prognosis of percutaneous coronary intervention using the ankle-brachial index. Specifically, it can be determined that patients with an abnormal ABI are more likely to experience adverse outcomes, such as ischemic stroke, bleeding, and death, compared to patients without an abnormal ABI.

[0013]

[0014] Figure 1. Study flow chart. Patients who underwent percutaneous coronary intervention (PCI) participated in this study. GNUH, Gyeongsang National University Hospital; PAD, peripheral artery disease; ABI, ankle-brachial index.

[0015] Figure 2. Five-year cumulative incidence of clinical outcomes. (A) Primary endpoint: composite of all-cause death, myocardial infarction, stroke, and major bleeding. (B) All-cause death. (C) Myocardial infarction. (D) Stroke. (E) Major bleeding. ABI, ankle-brachial index.

[0016] Figure 3. Predictive discrimination model for the primary endpoint and major bleeding. (A) Primary endpoint. (B) Major bleeding. AUC, area under the curve; CI, confidence interval; ABI, ankle-brachial index. *Age > 65 years, diabetes, acute coronary syndrome, previous percutaneous coronary intervention, left ventricular ejection fraction < 50%, renal dysfunction (estimated glomerular filtration rate [eGFR] < 60 mL / min / 1.73 m2), and anemia (hemoglobin < 13 g / dL in men and < 12 g / dL in women). †Dyslipidemia, renal dysfunction (eGFR < 60 mL / min / 1.73 m2), and anemia (hemoglobin < 13 g / dL in men and < 12 g / dL in women).

[0017]

[0018] The present invention is described in detail below.

[0019]

[0020] The present invention relates to a method for providing information on predicting prognosis after percutaneous coronary intervention.

[0021] The method of the present invention can provide information that patients who have undergone percutaneous coronary intervention (PCI) and have an abnormal ankle-brachial index (ABI) are more likely to have a poorer prognosis than patients who do not have an abnormal ABI.

[0022] Percutaneous coronary intervention (PCI) is a nonsurgical procedure used to treat narrowing of the coronary arteries of the heart found in coronary artery disease. This procedure involves combining coronary angioplasty with the placement of a stent, a permanent wire mesh tube made of either drug-eluting (DES) or bare metal (BMS). A stent-delivering balloon, derived from an angioplasty catheter, is inflated with media to force contact between the stent's abutment and the vessel wall (stent deployment), widening the vessel's diameter. After accessing the bloodstream through the femoral or radial artery, the procedure uses a coronary catheter visualized on X-ray images. An interventional cardiologist can then perform coronary angioplasty using a balloon catheter, which advances the deflated balloon into the blocked artery and inflates it to relieve the narrowing. Specific devices, such as stents, can be placed to keep the vessel open. A variety of other procedures can also be performed.

[0023] The ankle brachial index (ABI) is a test used to diagnose peripheral artery disease by measuring the blood pressure of the brachial arteries and ankle arteries on both sides and calculating the change in pressure.

[0024] An ankle-brachial index of 0.9 or less or 1.4 or more may be considered abnormal.

[0025] Through statistical analysis, the inventors confirmed that among patients who underwent percutaneous coronary intervention (PCI), the group with an abnormal ankle-brachial index (ABI) had a worse prognosis than the group without an abnormal ankle-brachial index (ABI).

[0026] Accordingly, the present invention can provide information that among patients who underwent percutaneous coronary intervention (PCI), patients with an abnormal ankle-brachial index (ABI) are more likely to have a poor prognosis than patients without an abnormal ABI.

[0027] The aforementioned poor prognosis may include, for example, ischemic stroke, hemorrhage, or death. Death is not limited to any cause and may refer to death from any cause.

[0028] The above contrast can be used to compare individuals with abnormal ABI and patients with normal ABI, or to compare individuals and groups.

[0029] If necessary, the method of the present invention can further predict the prognosis by combining known factors related to the prognosis of percutaneous coronary intervention. In such cases, a more accurate prediction may be possible.

[0030] The above factors may include, but are not limited to, dyslipidemia, renal dysfunction, anemia, etc.

[0031]

[0032] The present invention will be described in more detail with reference to the following examples.

[0033]

[0034] Example

[0035] method

[0036] Participants

[0037] A total of 5,160 patients who underwent PCI at Gyeongsang National University Hospital from January 2011 to December 2016 were enrolled (Fig. 1). Exclusion criteria were as follows: 1) prior PAD treatment (n = 105), 2) absence of ABI measurement (n = 138), 3) use of oral anticoagulants at discharge (n = 87), and 4) missing post-discharge follow-up data (n = 83). Ultimately, 4,747 patients were included in the study. Clinical characteristics, symptoms, angiographic and procedural findings, discharge medications, and clinical outcome data were prospectively collected by the study coordinator. Patients were followed up regularly at 1, 6, and 12 months after the index procedure and annually thereafter. Additional information was collected from medical records or telephone interviews when necessary. The Institutional Review Board of Gyeongsang National University Hospital approved the study protocol (No. GNUH 2018-07-012) and waived the written consent requirement for access to the institutional registry. This study was conducted in accordance with Good Clinical Practice (GLP) guidelines and the principles of the Declaration of Helsinki.

[0038]

[0039] Measuring ABI and Defining Abnormal ABI

[0040] A Doppler ultrasound device (VP-1000; Colin Co., Ltd., Komake, Japan) was used to measure the ABI of each leg before PCI (or before discharge in emergency cases). The order of limb pressure measurements was as follows: first arm, first posterior tibial artery, first dorsalis pedis artery, second posterior tibial artery, second dorsalis pedis artery, and second arm. Each pressure was measured twice, and the average of these pressures was used for calculations. The ABI of each leg was calculated by dividing the higher of the posterior tibial pressure or dorsalis pedis pressure by the higher of the systolic blood pressure of the right or left arm. The lowest ABI was selected for the left and right legs. The ABI threshold for detecting PAD was 0.90 or less, and initial studies showed a sensitivity of 80% or greater and a specificity of 90% or greater. An ABI greater than 1.40 was defined as abnormal and predicted the incidence of PAD with 60–80% accuracy.

[0041]

[0042] Evaluation variables and definitions

[0043] The primary endpoint was a composite outcome of adverse clinical events, including all-cause death, myocardial infarction (MI), stroke, and major bleeding. All endpoints were described according to the Academic Research Consortium (ARC) definition. Individual components of the primary endpoint were analyzed as secondary endpoints. All-cause mortality included death from cardiac and non-cardiac causes during the follow-up period. Fatal bleeding was also assessed. MI was defined as ischemic symptoms or electrocardiographic ischemic changes with elevated cardiac troponin levels, or imaging evidence of recent viable myocardium loss or new regional wall motion abnormalities. Stroke, defined as rapid onset of focal or global neurologic deficits with signs or symptoms, was confirmed by a neurologist based on neuroimaging findings. Major bleeding was defined as ARC Type 3 or 5 hemorrhage.

[0044]

[0045] Statistical analysis

[0046] To analyze the normal distribution of continuous variables, the Kolmogorov-Smirnov test was performed. Continuous variables were expressed as mean ± standard deviation or median (interquartile range [IQR]) as appropriate, and categorical variables were expressed as frequencies and percentages. Student's unpaired t-test was used for parametric continuous variables, and the Mann-Whitney U test was used for nonparametric continuous variables. Categorical variables were compared using Pearson's chi-square test or Fisher's exact test, as appropriate. Receiver-operating characteristic (ROC) curve analysis was performed to find the optimal cutoff for continuous variables, which were then converted to dichotomous covariates. The area under the curve (AUC) was compared, and the improved discrimination power was calculated using the identified risk factors for adverse clinical reactions.

[0047] All demographic characteristics and laboratory measurements were evaluated using univariate analysis to predict clinical adverse events. Variables with a p value <0.1 in the univariate analysis were entered into multivariate Cox proportional hazards analysis to determine the independent correlates of ischemic and hemorrhagic events. Survival curves were constructed using Kaplan-Meier estimation according to the ABI and compared using the log-rank test. A p value of <0.05 was considered statistically significant, and all statistical analyses were performed using SPSS version 24.0 (SPSS Inc., Chicago, IL, USA) and Medcalc version 13.3.3.0 statistical software (Medcalc, Ostend, Belgium).

[0048]

[0049] result

[0050] Patient characteristics

[0051] Among 4,747 patients, 610 (12.9%) had an abnormal ABI (594 patients with an ABI ≤0.9 and 16 patients with an ABI >1.4). Compared with the normal ABI group, the abnormal ABI group had unique clinical characteristics, including older age, low body mass index, hypertension, diabetes, previous ischemic stroke, and chronic kidney disease (CKD) (Table 1). The clinical presentation of acute coronary syndrome (ACS), particularly acute myocardial infarction (MI), was associated with a higher proportion of abnormal ABI. The abnormal ABI group had higher white blood cell (WBC) counts and high-sensitivity C-reactive protein (hs-CRP) levels compared with the normal ABI group. The incidence of anemia, renal dysfunction, and decreased left ventricular (LV) function was also higher in the abnormal ABI group than in the normal ABI group. Angiographic and procedural findings showed that multivessel CAD occurred more frequently, and peripheral vascular grafting (PCI) was performed more frequently in the abnormal ABI group than in the normal ABI group.

[0052]

[0053]

[0054]

[0055] Association between abnormal ABI and clinical outcomes

[0056] The median follow-up period was 31.0 months (IQR, 15.3–49.7). The estimated cumulative incidence rates based on Kaplan-Meier curves were as follows: 211 all-cause deaths, 170 MIs, 112 strokes, and 153 major bleeding events. The median ABI for the general population was 1.07 (IQR, 0.99–1.13). ABI was significantly lower in each composite endpoint of clinical outcomes (primary endpoint, 0.96 ± 0.19 vs. 1.04 ± 0.13, p < 0.001; all-cause mortality, 0.91 ± 0.20 vs. 1.04 ± 0.13, p < 0.001; MI, 1.00 ± 0.17 vs. 1.04 ± 0.14, p = 0.011; stroke, 0.99 ± 0.16 vs. 1.04 ± 0.14, p = 0.010; major bleeding, 0.98 ± 0.18 vs. 1.04 ± 0.14, p = 0.001).

[0057] The number of clinical adverse events increased steadily during the follow-up period (Figure 2). Kaplan-Meier curves showed an increasing difference between the two groups. The abnormal ABI group had a higher 5-year cumulative incidence of the primary endpoint (36.0% vs. 14.5%, log-rank test, p<0.001), all-cause death (19.4% vs. 5.1%, log-rank test, p<0.001), MI (6.3% vs. 4.1%, log-rank test, p=0.013), stroke (6.2% vs. 2.7%, log-rank test, p=0.001), and major bleeding (8.9% vs. 3.7%, log-rank test, p<0.001) (Figure 2). In multivariate analysis, abnormal ABI was found to be an independent risk factor for the primary endpoint (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.74–2.80; p<0.001), all-cause mortality (HR, 3.05; 95% CI, 2.17–4.31; p<0.001), stroke (HR, 1.79; 95% CI, 1.02–3.14; p=0.042), and major bleeding (HR, 1.61; 95% CI, 1.03–2.51; p=0.034) (Table 2). When predicting the primary endpoint, abnormal ABI had a higher predictive value than the reference variables (age ≥65 years, diabetes, ACS, previous PCI, left ventricular ejection fraction <50%, renal dysfunction, and anemia) (AUC 0.674 vs. AUC 0.656, p <0.001) (Fig. 3). When abnormal ABI was combined with the reference variables (dyslipidemia, renal dysfunction, and anemia), the predictive value for major bleeding was stronger (AUC 0.597 vs. AUC 0.569, p = 0.014).

[0058]

[0059]

Claims

1. A method for predicting prognosis after percutaneous coronary intervention (PCI), which provides information that patients with an abnormal ankle-brachial index (ABI) are more likely to have a poor prognosis than patients without an abnormal ABI.

2. A method for providing information on predicting prognosis after percutaneous coronary intervention in a patient with an abnormal ankle-brachial index of claim 1, wherein the ABI value is 0.9 or less or 1.4 or more.

3. A method for providing information on predicting prognosis after percutaneous coronary intervention according to claim 1, wherein the poor prognosis is ischemic stroke, hemorrhage or death.

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