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Cardiology 2018Ischaemic heart disease is a major cause of death and disability worldwide, while angina represents its most common symptom. It is estimated that approximately 9 million... (Review)
Review
Ischaemic heart disease is a major cause of death and disability worldwide, while angina represents its most common symptom. It is estimated that approximately 9 million patients in the USA suffer from angina and its treatment is challenging, thus the strategy to improve the management of chronic stable angina is a priority. Angina might be the result of different pathologies, ranging from the "classical" obstruction of a large coronary artery to alteration of the microcirculation or coronary artery spasm. Current clinical guidelines recommend antianginal therapy to control symptoms, before considering coronary artery revascularization. In the current guidelines, drugs are classified as being first-choice (beta-blockers, calcium channel blockers, and short-acting nitrates) or second-choice (ivabradine, nicorandil, ranolazine, trimetazidine) treatment, with the recommendation to reserve second-line modifications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. However, such a categorical approach is currently questioned. In addition, current guidelines provide few suggestions to guide the choice of drugs more suitable according to the underlying pathology or the patient comorbidities. Several other questions have recently emerged, such as: is there evidence-based data between first- and second-line treatments in terms of prognosis or symptom relief? Actually, it seems that newer antianginal drugs, which are classified as second choice, have more evidence-based clinical data that are more contemporary to support their use than what is available for the first-choice drugs. It follows that actual guidelines are based more on tradition than on evidence and there is a need for new algorithms that are more individualized to patients, their comorbidities, and pathophysiological mechanism of chronic stable angina.
Topics: Adrenergic beta-Antagonists; Angina, Stable; Calcium Channel Blockers; Cardiovascular Agents; Chest Pain; Humans; Ivabradine; Nicorandil; Patient Selection; Practice Guidelines as Topic; Ranolazine; Treatment Outcome; Trimetazidine
PubMed: 29874661
DOI: 10.1159/000487936 -
Lancet (London, England) Jan 2018Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy.
METHODS
ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593.
FINDINGS
ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI -8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group.
INTERPRETATION
In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy.
FUNDING
NIHR Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, Philips Volcano, NIHR Barts Biomedical Research Centre.
Topics: Aged; Angina, Stable; Coronary Angiography; Coronary Stenosis; Double-Blind Method; Exercise Tolerance; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Treatment Outcome; United Kingdom
PubMed: 29103656
DOI: 10.1016/S0140-6736(17)32714-9 -
Heart (British Cardiac Society) Feb 2018The diagnostic management of patients with angina pectoris typically centres on the detection of obstructive epicardial CAD, which aligns with evidence-based treatment... (Review)
Review
The diagnostic management of patients with angina pectoris typically centres on the detection of obstructive epicardial CAD, which aligns with evidence-based treatment options that include medical therapy and myocardial revascularisation. This clinical paradigm fails to account for the considerable proportion (approximately one-third) of patients with angina in whom obstructive CAD is excluded. This common scenario presents a diagnostic conundrum whereby angina occurs but there is no obstructive CAD (ischaemia and no obstructive coronary artery disease-INOCA). We review new insights into the pathophysiology of angina whereby myocardial ischaemia results from a deficient supply of oxygenated blood to the myocardium, due to various combinations of focal or diffuse epicardial disease (macrovascular), microvascular dysfunction or both. Macrovascular disease may be due to the presence of obstructive CAD secondary to atherosclerosis, or may be dynamic due to a functional disorder (eg, coronary artery spasm, myocardial bridging). Pathophysiology of coronary microvascular disease may involve anatomical abnormalities resulting in increased coronary resistance, or functional abnormalities resulting in abnormal vasomotor tone. We consider novel clinical diagnostic techniques enabling new insights into the causes of angina and appraise the need for improved therapeutic options for patients with INOCA. We conclude that the taxonomy of stable CAD could improve to better reflect the heterogeneous pathophysiology of the coronary circulation. We propose the term 'stable coronary syndromes' (SCS), which aligns with the well-established terminology for 'acute coronary syndromes'. SCS subtends a clinically relevant classification that more fully encompasses the different diseases of the epicardial and microvascular coronary circulation.
Topics: Angina, Stable; Cardiac Imaging Techniques; Disease Management; Humans; Risk Factors
PubMed: 29030424
DOI: 10.1136/heartjnl-2017-311446 -
Journal of the American College of... Nov 2020Coronary heart disease is a chronic, systemic disease with a wide range of associated symptoms, clinical outcomes, and health care expenditure. Adverse events from... (Review)
Review
Coronary heart disease is a chronic, systemic disease with a wide range of associated symptoms, clinical outcomes, and health care expenditure. Adverse events from coronary heart disease can be mitigated or avoided with lifestyle and risk factor modifications, and medical therapy. These measures are effective in slowing the progression of atherosclerotic disease and in reducing the risk of thrombosis in the setting of plaque disruptions. With increasing effectiveness of prevention and medical therapy, the role of coronary artery revascularization has decreased and is largely confined to subgroups of patients with unacceptable angina, severe left ventricular systolic dysfunction, or high-risk coronary anatomy. There is a compelling need to allocate resources appropriately to improve prevention. Herein, we review the scientific evidence in support of medical therapy and revascularization for the management of patients with stable coronary heart disease and discuss implications for the evaluation of patients with stable angina and public policy.
Topics: Angina, Stable; Cardiovascular Agents; Disease Management; Healthy Lifestyle; Humans; Myocardial Ischemia; Review Literature as Topic; Risk Factors; Risk Reduction Behavior; Ventricular Dysfunction, Left
PubMed: 33153586
DOI: 10.1016/j.jacc.2020.08.078 -
The New England Journal of Medicine Dec 2023Percutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Percutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown.
METHODS
We conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina.
RESULTS
A total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; P<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. Acute coronary syndromes occurred in 4 patients in the PCI group and in 6 patients in the placebo group.
CONCLUSIONS
Among patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina. (Funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre and others; ORBITA-2 ClinicalTrials.gov number, NCT03742050.).
Topics: Aged; Female; Humans; Male; Middle Aged; Acute Coronary Syndrome; Angina, Stable; Cardiovascular Agents; Fractional Flow Reserve, Myocardial; Health Status; Percutaneous Coronary Intervention; Treatment Outcome; Double-Blind Method; Myocardial Ischemia
PubMed: 38015442
DOI: 10.1056/NEJMoa2310610 -
EuroIntervention : Journal of EuroPCR... Apr 2022Percutaneous coronary intervention (PCI) is frequently performed for stable angina. However, the first blinded trial, ORBITA, did not show a placebo-controlled increment... (Randomized Controlled Trial)
Randomized Controlled Trial
A double-blind randomised placebo-controlled trial of percutaneous coronary intervention for the relief of stable angina without antianginal medications: design and rationale of the ORBITA-2 trial.
Percutaneous coronary intervention (PCI) is frequently performed for stable angina. However, the first blinded trial, ORBITA, did not show a placebo-controlled increment in exercise time in patients with single-vessel disease, at 6 weeks, on maximal antianginal therapy. ORBITA-2 will assess the placebo-controlled efficacy of PCI on angina frequency in patients with single- or multivessel disease, at 12 weeks, on no antianginal therapy. ORBITA-2 is a double-blind placebo-controlled trial randomising participants with (i) angina at presentation, (ii) documented angina during the 2-week pre-randomisation symptom assessment phase, (iii) objective evidence of ischaemia, (iv) single- or multivessel disease, and (v) clinical eligibility for PCI. At enrolment, antianginals will be stopped, and angina questionnaires completed. Participants will record their symptoms on a smartphone application daily throughout the trial and will undergo exercise treadmill testing and stress echocardiography at pre-randomisation. They will then undergo coronary angiography with unblinded invasive physiology assessment. Eligible participants will then be sedated to a deep level of conscious sedation and randomised 1:1 between PCI and placebo. After the 12-week blinded follow-up period, they will return for questionnaires, exercise testing and stress echocardiography assessment. If angina becomes intolerable, antianginals will be introduced using a prespecified medication protocol. The primary outcome is an angina symptom score using an ordinal clinical outcome scale for angina. Secondary outcomes include exercise treadmill time, angina frequency, angina severity and quality of life. Trial registration: ClinicalTrials.gov: NCT03742050.
Topics: Angina, Stable; Cardiovascular Agents; Coronary Angiography; Double-Blind Method; Humans; Percutaneous Coronary Intervention; Quality of Life; Treatment Outcome
PubMed: 35156616
DOI: 10.4244/EIJ-D-21-00649 -
European Heart Journal Sep 2018To determine the ranges of pre-test probability (PTP) of coronary artery disease (CAD) in which stress electrocardiogram (ECG), stress echocardiography, coronary... (Meta-Analysis)
Meta-Analysis
The performance of non-invasive tests to rule-in and rule-out significant coronary artery stenosis in patients with stable angina: a meta-analysis focused on post-test disease probability.
AIMS
To determine the ranges of pre-test probability (PTP) of coronary artery disease (CAD) in which stress electrocardiogram (ECG), stress echocardiography, coronary computed tomography angiography (CCTA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiac magnetic resonance (CMR) can reclassify patients into a post-test probability that defines (>85%) or excludes (<15%) anatomically (defined by visual evaluation of invasive coronary angiography [ICA]) and functionally (defined by a fractional flow reserve [FFR] ≤0.8) significant CAD.
METHODS AND RESULTS
A broad search in electronic databases until August 2017 was performed. Studies on the aforementioned techniques in >100 patients with stable CAD that utilized either ICA or ICA with FFR measurement as reference, were included. Study-level data was pooled using a hierarchical bivariate random-effects model and likelihood ratios were obtained for each technique. The PTP ranges for each technique to rule-in or rule-out significant CAD were defined. A total of 28 664 patients from 132 studies that used ICA as reference and 4131 from 23 studies using FFR, were analysed. Stress ECG can rule-in and rule-out anatomically significant CAD only when PTP is ≥80% (76-83) and ≤19% (15-25), respectively. Coronary computed tomography angiography is able to rule-in anatomic CAD at a PTP ≥58% (45-70) and rule-out at a PTP ≤80% (65-94). The corresponding PTP values for functionally significant CAD were ≥75% (67-83) and ≤57% (40-72) for CCTA, and ≥71% (59-81) and ≤27 (24-31) for ICA, demonstrating poorer performance of anatomic imaging against FFR. In contrast, functional imaging techniques (PET, stress CMR, and SPECT) are able to rule-in functionally significant CAD when PTP is ≥46-59% and rule-out when PTP is ≤34-57%.
CONCLUSION
The various diagnostic modalities have different optimal performance ranges for the detection of anatomically and functionally significant CAD. Stress ECG appears to have very limited diagnostic power. The selection of a diagnostic technique for any given patient to rule-in or rule-out CAD should be based on the optimal PTP range for each test and on the assumed reference standard.
Topics: Angina, Stable; Computed Tomography Angiography; Coronary Angiography; Coronary Stenosis; Echocardiography, Stress; Electrocardiography; Humans; Magnetic Resonance Angiography; Positron-Emission Tomography; Probability; Single Photon Emission Computed Tomography Computed Tomography
PubMed: 29850808
DOI: 10.1093/eurheartj/ehy267 -
European Heart Journal Oct 2013
2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology.
Topics: Aged; Angina, Stable; Cardiac Imaging Techniques; Cardiotonic Agents; Coronary Artery Bypass; Coronary Artery Disease; Electrocardiography; Evidence-Based Medicine; Female; Humans; Male; Myocardial Revascularization; Percutaneous Coronary Intervention; Primary Health Care; Prognosis; Risk Assessment; Risk Reduction Behavior
PubMed: 23996286
DOI: 10.1093/eurheartj/eht296 -
Circulation. Cardiovascular... Apr 2023As society ages, the number of older adults with stable ischemic heart disease continues to rise. Older adults exhibit the greatest morbidity and mortality from stable... (Review)
Review
As society ages, the number of older adults with stable ischemic heart disease continues to rise. Older adults exhibit the greatest morbidity and mortality from stable angina. Furthermore, they suffer a higher burden of comorbidity and adverse events from treatment than younger patients. Given that older adults were excluded or underrepresented in most randomized controlled trials of stable ischemic heart disease, evidence for management is limited and hinges on subgroup analyses of trials and observational studies. This review aims to elucidate the current definitions of aging, assess the overall burden and clinical presentations of stable ischemic heart disease in older patients, weigh the available evidence for guideline-recommended treatment options including medical therapy and revascularization, and propose a framework for synthesizing complex treatment decisions in older adults with stable angina. Due to evolving goals of care in older patients, it is paramount to readdress the patient's priorities and preferences when deciding on treatment. Ultimately, the management of stable angina in older adults will need to be informed by dedicated studies in representative populations emphasizing patient-centered end points and person-centered decision-making.
Topics: Humans; Aged; Angina, Stable; Treatment Outcome; Myocardial Ischemia; Comorbidity; Randomized Controlled Trials as Topic
PubMed: 36916288
DOI: 10.1161/CIRCINTERVENTIONS.122.012438 -
Cardiovascular Drugs and Therapy Aug 2016Nitrates have been used to treat symptoms of chronic stable angina for over 135 years. These drugs are known to activate nitric oxide (NO)-cyclic... (Review)
Review
Nitrates have been used to treat symptoms of chronic stable angina for over 135 years. These drugs are known to activate nitric oxide (NO)-cyclic guanosine-3',-5'-monophasphate (cGMP) signaling pathways underlying vascular smooth muscle cell relaxation, albeit many questions relating to how nitrates work at the cellular level remain unanswered. Physiologically, the anti-angina effects of nitrates are mostly due to peripheral venous dilatation leading to reduction in preload and therefore left ventricular wall stress, and, to a lesser extent, epicardial coronary artery dilatation and lowering of systemic blood pressure. By counteracting ischemic mechanisms, short-acting nitrates offer rapid relief following an angina attack. Long-acting nitrates, used commonly for angina prophylaxis are recommended second-line, after beta-blockers and calcium channel antagonists. Nicorandil is a balanced vasodilator that acts as both NO donor and arterial K(+) ATP channel opener. Nicorandil might also exhibit cardioprotective properties via mitochondrial ischemic preconditioning. While nitrates and nicorandil are effective pharmacological agents for prevention of angina symptoms, when prescribing these drugs it is important to consider that unwanted and poorly tolerated hemodynamic side-effects such as headache and orthostatic hypotension can often occur owing to systemic vasodilatation. It is also necessary to ensure that a dosing regime is followed that avoids nitrate tolerance, which not only results in loss of drug efficacy, but might also cause endothelial dysfunction and increase long-term cardiovascular risk. Here we provide an update on the pharmacological management of chronic stable angina using nitrates and nicorandil.
Topics: Angina, Stable; Humans; Nicorandil; Nitrates; Nitric Oxide Donors; Vasodilator Agents
PubMed: 27311574
DOI: 10.1007/s10557-016-6668-z