WO2025100587A1 - Method for providing information about prognosis prediction after percutaneous coronary intervention - Google Patents

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

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

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 with lifestyle modification, pharmacological therapy, endovascular therapy, or surgery. Of these, lifestyle modification and pharmacological therapy are recommended to improve clinical outcomes. The diagnostic approach to PAD is important because risk stratification can provide the basis for determining the mode and intensity of treatment. In general, patients with both CAD and PAD 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 the prognosis of bleeding events. The COMPASS (Cardiovascular Outcomes for People Using Anticoagulant Strategies) trial found that low-dose novel oral anticoagulants as adjuncts to aspirin reduced ischemic events but increased major bleeding events in patients with PAD compared with aspirin monotherapy.

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

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

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 underwent PCI are more likely to have a poor prognosis than patients who do not have an abnormal ABI.

In the present invention, the ABI value of a patient with an abnormal ankle-brachial index may be less than or equal to 0.9 or greater than 1.4.

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

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 abnormal ABI are more likely to have poor prognoses such as ischemic stroke, bleeding, and death than those without.

Figure 1. Flow chart of the study. Patients who underwent percutaneous coronary intervention (PCI) participated in this study. GNUH, Gyeongsang National University Hospital; PAD, peripheral artery disease; ABI, ankle brachial index.

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.

Figure 3. Predictive discrimination models 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%, impaired renal function (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, impaired renal function (eGFR <60 mL/min/1.73 m2), and anemia (hemoglobin <13 g/dL in men and <12 g/dL in women).

The present invention is described in detail below.

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

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

Percutaneous coronary intervention (PCI) is a nonsurgical procedure used to treat narrowing of the coronary arteries of the heart found in coronary artery disease. The procedure involves combining stent placement, a permanent wire mesh tube made of drug-eluting (DES) or bare metal (BMS), with angioplasty. A stent-delivering balloon from an angioplasty catheter is inflated with media to force contact between the stent’s abutment and the vessel wall (stent deployment), thus widening the vessel diameter. After accessing the bloodstream through the femoral or radial artery, the procedure is performed using a coronary catheter visualized in the blood vessel on X-ray imaging. The interventional cardiologist can then perform 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 open the vessel. A variety of other procedures can also be performed.

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.

An ankle-brachial index of 0.9 or less or 1.4 or more can be considered abnormal.

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

Accordingly, the present invention can provide information that patients who underwent percutaneous coronary intervention (PCI) and had an abnormal ankle-brachial index (ABI) are more likely to have a poor prognosis compared to patients who did not.

The above poor prognosis may be, for example, ischemic stroke, hemorrhage, or death. The above death may mean death due to any cause, and is not limited to the cause.

The above contrast can be compared between individuals (patients with abnormal ABI and patients with normal ABI) or between individuals and groups.

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

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

The present invention will be described more specifically with reference to the following examples.

Example

method

Participants

From January 2011 to December 2016, a total of 5,160 patients who underwent PCI at Gyeongsang National University Hospital were enrolled (Fig. 1). Exclusion criteria were as follows: 1) previous PAD treatment (n = 105), 2) no ABI measurement (n = 138), 3) oral anticoagulants at discharge (n = 87), and 4) missing follow-up data after discharge (n = 83). A total of 4,747 patients were ultimately 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 regularly followed-up 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 informed consent requirement for access to the institutional registry. The study was conducted in accordance with Good Clinical Practice (GLP) guidelines and the principles of the Declaration of Helsinki.

Measuring ABI and Defining Abnormal ABI

ABI of each leg was measured before PCI (before discharge in emergency cases) using a Doppler ultrasound device (VP-1000; Colin Co., Ltd., Komake, Japan). The order of limb pressure measurement 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 each pressure was used for calculation. ABI of each leg was calculated by dividing the higher of the posterior tibial pressure or the dorsalis pedis pressure by the higher of the systolic blood pressure of the right or left arm. The lowest ABI was selected from 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 more and a specificity of 90% or more. An ABI greater than 1.40 was defined as abnormal, which predicted the incidence of PAD with 60–80% accuracy.

Evaluation variables and definitions

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 death included death from cardiac and noncardiac causes during the follow-up period. We also assessed death from fatal bleeding. MI was defined as ischemic symptoms or ischemic changes on electrocardiogram with increased cardiac troponin levels, or imaging evidence of recent loss of viable myocardium or new regional wall motion abnormalities. Stroke, defined as rapid onset of focal or global neurologic deficit with signs or symptoms, was confirmed by a neurologist on the basis of neuroimaging findings. Major bleeding was defined as ARC type 3 or 5 hemorrhage.

Statistical Analysis

The Kolmogorov-Smirnov test was performed to analyze the normal distribution of continuous variables. 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 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 changed to dichotomous covariates. The area under the curve (AUC) was compared, and the improved discrimination power was calculated using the risk factors of identified adverse clinical reactions.

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 a 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).

result

Patient characteristics

Abnormal ABI was observed in 610 (12.9%) of 4,747 patients (594 patients with ABI ≤0.9 and 16 patients with 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), especially acute MI, was associated with a higher proportion of abnormal ABI. The abnormal ABI group showed 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 that PCI was performed more frequently in the abnormal ABI group than in the normal ABI group.

Association between abnormal ABI and clinical outcomes

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: 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 death, 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).

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, 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 multivariable 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). In predicting the primary endpoint, abnormal ABI had a stronger predictive value than the reference variables (age ≥65 years, diabetes, ACS, previous PCI, left ventricular ejection fraction <50%, renal dysfunction, anemia) (AUC 0.674 vs. AUC 0.656, p <0.001) (Fig. 3). The combination of abnormal ABI and reference variables (dyslipidemia, renal dysfunction, anemia) had a stronger predictive value for major bleeding (AUC 0.597 vs. AUC 0.569, p = 0.014).

Claims (3)

A method for providing information on predicting prognosis after percutaneous coronary intervention (PCI), providing information that patients with an abnormal ankle-brachial index (ABI) undergoing PCI are more likely to have a poorer prognosis than patients without an abnormal ABI. A method for providing information on predicting prognosis after percutaneous coronary intervention, wherein the ABI value of a patient with the abnormal ankle-brachial index according to claim 1 is 0.9 or less or 1.4 or more. 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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