Diagnostic and Therapeutic Strategies for Stable Coronary Artery Disease Following the ISCHEMIA Trial

Until recently, coronary revascularization with coronary artery bypass grafting or percutaneous coronary intervention has been regarded as the standard choice for stable coronary artery disease (CAD), particularly for patients with a significant burden of ischemia. However, in conjunction with remarkable advances in adjunctive medical therapy and a deeper understanding of its long-term prognosis from recent large-scale clinical trials, including ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), the approach to stable CAD has changed drastically. Although the updated evidence from recent randomized clinical trials will likely modify the recommendations for future clinical practice guidelines, there are still unresolved and unmet issues in Asia, where prevalence and practice patterns are markedly different from those in Western countries. Herein, the authors discuss perspectives on: 1) assessing the diagnostic probability of patients with stable CAD; 2) application of noninvasive imaging tests; 3) initiation and titration of medical therapy; and 4) evolution of revascularization procedures in the modern era.

wherein patients were rarely categorized as high probability (>50%) for CAD in the baseline assessment. 8 The decrease in CAD prevalence in Western countries may be associated with changes in lifestyle and improvement in preventive medical therapy.
In Asian countries, the incidence of CAD varies among regions. Epidemiologic studies have demonstrated that West, South, and Central Asia have higher and increasing CAD prevalence and mortality than Western countries (Figure 1). [9][10][11][12][13] Countries in South Asia, including India, Pakistan, and Nepal, are facing an early staged CAD epidemic with an increase in premature CAD deaths, yet the proportion among total deaths is relatively low. 12 In contrast, the prevalence of CAD in countries in East Asia, such as Japan and Korea, is decreasing and is lower than in other parts of the world. 14 These geographic differences in CAD prevalence are likely related to the prevalence of risk factors and socioeconomic status in each country. 15,16 Given regional variance in the prevalence of CAD in With advances in medical therapy and revascularization techniques, outcomes in patients with stable coronary artery disease (CAD) have progressively improved.
However, unmet needs still exist between guideline recommendations and pretest probability (PTP) estimation, application of noninvasive testing, pharmacotherapy, and revascularization in Asian countries. Updated decision making and management in patients with stable CAD, including renewed evidence, should be encouraged.
CCTA ¼ coronary computed tomographic angiography; ISCHEMIA ¼ International Study of Comparative Health Effectiveness With Medical and Invasive Approaches; OMT ¼ optimal medical therapy.   23 with some alternation on the basis of institutional or regional availability. 24 CORONARY CTA AND CORONARY ARTERY CALCIUM SCORING. Coronary CTA has a high negative predictive value and is increasingly being applied in patients with stable CAD (Figure 2). In both Japanese and European clinical practice guidelines, coronary CTA is recommended as the preferred imaging modality for patients with low to intermediate PTP. 7,17 The U.S. clinical practice guidelines also emphasize the role of "guiding" treatment among these patients (    perfusion strategy was noninferior compared with the FFR strategy for high-risk patients. 22 Although availability is still limited, the diagnostic accuracy of magnetic resonance perfusion is higher than that of single-photon emission computed tomography because of superior spatial resolution, with better detectability of multivessel disease, comparable with positron emission tomography and computed tomographic perfusion (Supplemental Table 1).
These results provide strong evidence that noninvasive testing should be performed first in the management of patients with stable CAD 17 ; however, a recent study indicated that only one-third of patients who underwent PCI had preprocedural noninvasive cardiac testing including coronary CTA and functional tests in Japan, which is significantly lower than reported in Western countries. 32  Despite the introduction of coronary CTA, the annual volume of invasive coronary angiographic examinations in Japan has not changed substantially.
One possible explanation is the significant shortage of certified radiologists compared with other countries. 36 A recent survey reported that the number of computed tomographic and magnetic resonance examinations per radiologist was the highest among developed countries, and the potential work load was approximately 4 times that of other countries. 37 A paradigm shift in the approach to imaging ischemic heart disease is needed, including updated prediction and probability models, a more profound understanding of CAD, and algorithms focused on    Conversely, the use of calcium-channel blockers and nitrates has not been shown to be associated with improvement in long-term prognosis but relieves angina symptoms via its vasodilatory effects and is recommended as a second-line therapy. In Asia, however, vasospastic angina is observed rather frequently, and calcium-channel blockers and nitrates are used more frequently than in Western countries. 59 Patients with epicardial vasospasm are also known to have an increased risk for myocardial infarction. 60 The prognostic impact of calciumchannel blockers and nitrates in such patients remains unclear and requires further investigation.  Antithrombotic agents. Figure 5 shows the periopera-     68 If the low-density lipoprotein goal is not achieved even after the initiation of high-dose statin therapy, adding ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors is recommended.
Fibrate and eicosatetraenoic acid are acceptable for patients with stable CAD with hypertriglyceridemia.
As ezetimibe and eicosatetraenoic acid were associated with reduced coronary events in elderly Japanese patients, 69,70 these agents may be considered along with statin therapy to stabilize the residual risk in Asian patients with stable CAD.
LIFESTYLE MODIFICATION. In addition to OMT, lifestyle modifications, including exercise, diet modification, and smoking cessation, are fundamental for the secondary prevention of CAD. A previous study showed that smoking cessation reduced fatal CAD events even in smokers. 71 The age-adjusted prevalence of smoking in Asian countries varies, ranging from 9.6% to 45.5%. 12 Therefore, smoking cessation is a promising approach for secondary prevention in Asian countries with high smoking prevalence. We recommend the assessment of lifestyle modifications to patients every 6 months ( Figure 4).

HIGHLIGHTS
With advancements in its management, outcomes in stable CAD have progressively improved.
However, the prevalence for stable CAD differs in Asian countries, and unmet needs exist between guideline recommendations and its actual clinical application.
Decision making of stable CAD should be tailored for each patient, and we aim to provide updated information for appropriate decision-making to further improve their outcomes.