Chronic coronary syndrome: A review of the literature

Salman Hussain; Maraam AlRashed; Rajesh Rajan; Mohammed Al-Jarallah; Peter A Brady; Biji Soman; Raja Dashti

doi:10.4103/ACCJ.ACCJ_21_20

REVIEW ARTICLE

Year : 2021 | Volume : 3 | Issue : 1 | Page : 3-7

Chronic coronary syndrome: A review of the literature

Salman Hussain¹, Maraam AlRashed², Rajesh Rajan³, Mohammed Al-Jarallah³, Peter A Brady⁴, Biji Soman⁵, Raja Dashti³
¹ Faculty of Medicine, Royal College of Surgeons In Ireland, Dublin, Ireland
² Faculty of Medicine, Kuwait University, Kuwait City, Kuwait
³ Department of Cardiology, Sabah Al Ahmed Cardiac Centre, Kuwait City, Kuwait
⁴ Department of Cardiology, Illinois Masonic Medical Center, Chicago, IL, USA
⁵ Department of Cardiology, Milton Keynes Hospital, Milton Keynes, England, UK

Date of Submission	08-Jul-2020
Date of Decision	15-Aug-2020
Date of Acceptance	26-Aug-2020
Date of Web Publication	15-Sep-2020

Correspondence Address:
Dr. Rajesh Rajan
Department of Cardiology, Sabah Al Ahmed Cardiac Centre, Kuwait City - 13001
Kuwait

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ACCJ.ACCJ_21_20

Abstract

Chronic coronary syndrome (CCS) is a newly proposed entity by the European Society of Cardiology that replaces stable coronary artery disease (CAD), which is defined as a progressive process of plaque accumulation in coronary circulation with associated functional changes. CCS has replaced stable CAD to raise awareness that despite the clinically silent nature of the disease, there are progressive pathological changes occurring in the coronary arteries. This has allowed clinicians to review the current various diagnostic modalities, methods of risk stratifying patients based on different models and the various management options available, including lifestyle modifications, pharmacological therapies, and revascularization. With the emergence of this new entity, great emphasis has been placed on the consolidation of our comprehension of the dynamic character of the disease and the preventative actions that aim to reduce the cardiovascular disease burden.

Keywords: Chronic coronary syndrome, coronary circulation, revascularization

How to cite this article:
Hussain S, AlRashed M, Rajan R, Al-Jarallah M, Brady PA, Soman B, Dashti R. Chronic coronary syndrome: A review of the literature. Ann Clin Cardiol 2021;3:3-7

How to cite this URL:
Hussain S, AlRashed M, Rajan R, Al-Jarallah M, Brady PA, Soman B, Dashti R. Chronic coronary syndrome: A review of the literature. Ann Clin Cardiol [serial online] 2021 [cited 2023 Mar 26];3:3-7. Available from: http://www.onlineacc.org/text.asp?2021/3/1/3/295112

Introduction

Chronic coronary syndrome (CCS) is a newly described classification devised by the European Society of Cardiology (ESC) to replace the term “Stable Coronary Artery Disease (CAD).” The main reason for effecting the change is the term is thought to better describe the disease process and encompass a wider spectrum of clinical, pharmacological, and pathophysiological entities. Using this new lexicon, the disease atherosclerosis manifests as CAD is categorized into Acute Coronary Syndrome (ACS) and CCS.^[1] Since this is a relatively new entity, the profile of CCS patients has significantly evolved, challenging clinicians and researchers to have a deeper grasp on the nature of the disease and as a result, develop newer methods of assessing, diagnosing, risk stratifying, and managing patients that fall into the category of CCS.^[2],[3]

Definition of Chronic Coronary Syndrome

The main focus of introducing the concept of CCS is on the fact that CAD is a continuous phenomenon involving intravascular plaque aggregation and progression. It has different evolutionary phases.^[1],[3]

According to the 2019 ESC guidelines, patients fall into the category of CCS according to the following clinical presentations:^[1]

Patient with CAD suspicion and stable angina symptoms with/without dyspnea
New-onset heart failure with or without reduced ejection fraction in patients with suspected CAD
Those with stabilized symptoms, both symptomatic and asymptomatic within a year of ACS or latest revascularization
Patients with or without symptoms more than 1 year after the initial diagnosis or revascularization
Patients with angina and nonobstructive CAD or suspected microvascular/vasospastic disease
Asymptomatic patients where screening detects CAD.

Patients that present with unstable angina symptoms would be classified as part of the ACS category and follow a different clinical assessment route. Since the disease is dynamic, there is substantial overlap between low-risk unstable angina patients and CCS patients. In addition, many CCS patients may experience episodes of unstable angina, thus proving a challenge to many clinicians in practice.^[1]

Since CCS is a newly proposed entity that involves a wider spectrum of CAD patients, literature is lacking regarding different aspects of this entity, representing a potential area of future clinical research focus. However, the majority of the data and evidence can be extrapolated from studies and clinical trials previously done on stable CAD patients and re-assed for implications involving patients with CCS.

Initial Assessment and Diagnosis

A thorough history is essential to both establishing a diagnosis of CAD and differentiating between chronic or stable and acute or unstable symptoms consistent with angina. A major group of patients with CAD do not present with the classical anginal symptoms or chest pain, while only 10%–15% of patients have typical anginal symptoms.^[4] Comorbidities and risk factors, which include dyslipidemia, hypertension, family history of cardiovascular disease, obesity, lifestyle factors (lack of exercise and unhealthy eating habits), and smoking, should all be addressed. Every patient with a suspicion of CAD should undergo basic laboratory testing (full blood count, thyroid hormone levels, lipid profile, and fasting plasma glucose), resting electrocardiogram (ECG), and resting echocardiography.^[1] The utilization of further non-invasive (anatomical or functional) or invasive evaluation (i.e., invasive coronary angiogram) is based on the findings of the initial assessment.^[1]

The most commonly used functional non-invasive tests include: ECG, stress cardiac magnetic resonance (CMR), stress echocardiography, and positron emission topography (PET).

Anatomical noninvasive tests include coronary computed tomography angiography (CCTA).

The decision to proceed with specialized imaging depends on the risk stratification of patients using the pretest probability (PTP) model that takes into account age, gender, anginal symptoms, and the available hospital facilities.^[5] This model has been revised in the current guidelines and re-evaluated data from previous PTP models used in older guidelines.^[5],[6],[7] This model recommends that patients in high-risk groups (>85%) undergo invasive diagnostic modalities, whereas, in low-risk patients (<15%), no routine testing is recommended. For patients in the intermediate-risk group (15%–85%), noninvasive testing is recommended, although no specific imaging modality is preferred.^[1],[8] This is in large part due to the wide availability of some techniques (CCTA or stress echocardiography) or the low technical demands (stress ECG), whereas other modalities are limited by their technical requirements and the lack of availability (CMR or PET).^[8],[9]

Management of Chronic Coronary Syndrome

Lifestyle changes

A key element of CCS patient management is to emphasize the importance of risk factor control (smoking, hypertension, diabetes, dyslipidemia, and lifestyle factors), reduce symptoms, and improve overall prognosis,^[1],[10] Smoking cessation significantly reduces mortality and improves prognosis.^[11] Evidence suggests that the most effective method to achieve this is a combination of behavioral and pharmacological approaches.^[12]

Robust epidemiological evidence exists to support that regular exercise significantly reduces cardiovascular risk factors, including blood pressure, glucose intolerance, and blood lipids.^[13] A meta-analysis demonstrated the superiority of non-drug approaches as compared to drug-based approaches in diabetes prevention, with no major increase in overall cardiovascular mortality or myocardial infarction (MI).^[14],[15] Furthermore, several studies have shown that obesity is linked to higher cardiovascular events risk. Thus, bodyweight reduction and adoption of a healthy eating habit are associated with fewer unfavorable clinical outcomes and a decrease in overall cardiovascular events and mortality.^{[16],[17],[18]}

Pharmacological therapy

Pharmacological therapies aim to relieve symptoms and control the main cardiovascular risk factors such as hyperlipidemia, diabetes mellitus, and hypertension.^[1]

Anti-ischemic drugs

Many anti-ischemic drugs that improved anginal symptoms had little or no impact on preventing adverse cardiovascular events. In the REACH Registry, a retrospective study of 21860 patients reported that in patients with CAD, beta-blockers (BB) did not decrease cardiovascular death.^[19] While the use of Calcium Channel Blockers (CCBs) has not been proven to minimize mortality, they may be useful as a first-line treatment option in managing a subset of CAD patients.^[20] Patients with left ventricular systolic dysfunction or patients undergoing Coronary Artery Bypass Graft (CABG) who use BB are less likely to experience adverse cardiovascular events and exhibit reduced long-term mortality.^[21] Angiotensin-converting Enzyme (ACE) inhibitors are favored in those with hypertension, diabetes, heart failure, and in high-risk patients.^[1] However, the use of ACE inhibitors in stable CAD patients without heart failure was not associated with an incremental benefit when compared to active controls.^[22]

Anti-thrombotic therapy

Antithrombotic therapy is important in CCS patients who are at elevated risk of ischemic events or with previous MI. The current recommendation for anti-thrombotic therapy is the combination of aspirin and an oral P2Y12 inhibitor, dual antiplatelet therapy (DAPT).^[1] While there are no studies that evaluate the optimal length of DAPT use in CCS patients undergoing percutaneous coronary intervention (PCI), recommendations are based on data from subgroups of patients in relevant randomized controlled trials. Six months of DAPT therapy establishes the balance of significant benefit in secondary prevention and reduction in stent thrombosis without a significant increase in bleeding events.^[23] Further studies might be needed in CCS patients to establish the optimal length of treatment.

Dyslipidemia

Patients with CCS should be considered for statin treatment irrespective of their low density lipoprotein (LDL) levels.^[1] Newer lipid reducing agents such as proprotein convertase subtilisin/Kexin type 9 inhibitors have demonstrated impressive results in various clinical trials in reducing cholesterol, particularly LDL levels, thereby reducing the risk of cardiovascular events significantly.^[24] While short-term safety is established, long-term safety is unknown to this date, which has limited their use in practice.^[25]

Revascularization versus optimal medical therapy

The ideal approach toward patients with CCS continues to prove controversial in regard to the use of PCI and optimal medical therapy as compared to only optimal medical therapy.^[26] Various studies have reported a more favorable outcome with the incorporation of PCI, particularly fractional flow reserve (FFR)-guided PCI. FFR is a pressure wire-based index that is undergone to determine the probability of stenosis to produce an infarction using coronary angiography.^[27],[28] However, patients with non-ischemic stenosis did not receive added benefit compared to optimal medical therapy alone. Similar observations were made in the FAME 2 clinical trial.^[29]

Data from the COURAGE and ISCHEMIA trials suggested that despite improvement in anginal symptoms with revascularization through PCI, the risk of cardiovascular death or MI did not reduce significantly when compared with optimal medical therapy. The role of invasive therapy in CCS patients needs to be reconsidered.^[30],[31]

Discussion

The primary purpose in adopting the term CCS is to better reflect the dynamic process of CAD and to distinguish from ACSs allowing for more targeted research and clinical approaches.

The current method for risk stratifying patients with CCS is the PTP model.^[1] Numerous sources of data suggest that PTP could greatly overestimate the actual prevalence of the disease.^[32] Data obtained from the PROMISE trial showed that 50% of patients classified as intermediate risk, were reclassified to a PTP < 15%.^[8]

Incorporating the cardiovascular risk factors like the coronary calcium score into the basic PTP model would make it more robust and risk stratification more reliable.^[33] Coronary artery calcium score provides robust prognostic information and accurately predicts the presence of CAD.^[34] There is some evidence based on data derived from the CONFIRM registry on the use of a machine learning model that utilizes the various clinical factors in addition to the calcium score to accurately estimate CAD on CCTA.^[35]

A newer model based on biomarkers (ABC model) which utilizes A (age), B (biomarkers that include pro-B-type natriuretic peptide, high sensitivity cardiac troponin T and LDL) and C (clinical variables including diabetes, peripheral arterial disease, and smoking) has been shown to be very effective in predicting cardiovascular death in stable CAD patients.^[36] This can be especially important in patients with the long-standing diagnosis of CCS. Further research is needed to verify whether this model can be implemented clinically.

The utilization of CCTA rule out anatomical CAD because of its high negative predictive value^[8] has resulted in a decrease in the need for invasive coronary angiography in most clinical scenarios.^[37] However, CCTA only provides information on the presence or absence of CAD along with the degree of stenosis but does not provide information on the significance of the stenosis and extent of ischemia. Impairment in the microcirculation also has the potential to induce ischemia, or result in MI, even without significant stenosis.^{[1],[38],[39]} Thus, the clinical relevance of stenosis highly depends on the ischemia burden of the coronary microcirculation, which can be assessed by the perfusion and viability studies using noninvasive imaging modalities such as stress CMR and PET.^[8],[38] Incorporation of stress CMR into clinical decision pathways was shown to exhibit a lower incidence of PCI as compared to FFR-guided angiography without an increase in non-favorable clinical outcomes.^[40] This information will influence the way CCS patients are assessed and guide the decision of whether or not a more aggressive management option is necessary.

The combination of revascularization (PCI or CABG) and optimal medical therapy has always played a central role in managing stable CAD patients.^[1] Data drawn from the FAME-2 trial revealed that with the use of FFR-guided PCI, there was a decrease in the utilization of antianginal medication and as a result, a reduction in the associated side effects, along with an increase in the quality of life, with the exception of patients with non-ischemic stenosis.^[41] However, other studies, including meta-analyses, have reported no^{[31],[42],[43],[44]} or only minimal incremental benefit^[45] of the combination of PCI with optimal medical therapy when compared to only optimal medical therapy.

However, recent evidence from published data suggest that in patients with stable CAD, patients with left main or multivessel disease, who underwent CABG for revascularization, had lower cardiovascular and MI risk when compared with those on optimal medical therapy alone. Similarly, those in whom, the left main or multivessel disease was excluded and had PCI with the newer generation drug-eluting stents (DES) had a lower risk of MI when compared with those on optimal medical therapy alone, a risk reduction which was not evident with the earlier generation DES.^[46]

Since it is well established that dysfunction in the microcirculation also have the potential to result in ischemia, and that epicardial vessel stenosis or obstructions are not the sole cause of ischemia, directing treatment to epicardial disease alone is not ideal in treating CCS patients.^[39] This could potentially change the algorithm of CCS management, where revascularization may be reserved for patients who fail to improve and continue to be symptomatic with optimal medical therapy, and subsequently have a lower quality of life. The method of revascularization could also be tailored to the specific subset of patients, in which there is the maximal benefit and least possible complications.

There is little evidence regarding long-term outcomes in those with a long-established CCS. The CLARIFY registry, a prospective observational study that addressed this issue, reported that previous MI and anginal symptoms were major factors contributing to the worse prognosis. History of previous MI with or without angina had poor prognosis when compared with those without previous MI. However, among those with anginal symptoms, poor outcome was limited only to those with previous MI.^[2] Another study demonstrated that silent ischemia alone is not associated with adverse cardiovascular outcomes, and as a result, management should not be based on anti-ischemic treatment alone.^[47]

There is a knowledge gap regarding the use of risk stratification scores to critically assess different CCS patients and the follow-up time intervals, which are yet to be determined.^[1]

The combination of CCB and BB has not demonstrated superiority over monotherapy in stable CAD patients.^[48] The combination of anti-ischemic drugs most effective in the varying clinical scenario is debatable. In addition, it is also unclear whether the combination of CCBs and BB provide better relief of anginal symptoms as compared to the use of long-acting nitrates with either CCB or BB. The current guidelines state that the recommendations are only potential combinations and not formal recommendations.^[1] This highlights a large gap in evidence, and further research is encouraged to study the various potential drug combinations.

Conclusion

The classification of CCS is a welcome addition that better describes a wide range of related conditions under a single category. This has the potential to benefit research and clinical practice through improved recognition of patients that require earlier and more intensive treatment versus those patients with milder disease that could benefit from more conservative management options. By summarizing and collating the current evidence, we are able to identify gaps where further research needs to be focused.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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