Invasive versus Conservative Management in Coronary Artery Disease

  • June 2023,
  • 95;
  • DOI: https://doi.org/10.3121/cmr.2023.1806

Abstract

Background: In patients with ST-elevation myocardial infarction, immediate coronary angiography and intervention is the best practice, if an experienced laboratory is available. In non-Q-wave infarction most, but not all, studies suggest that early invasive strategy is superior to conservative management. Complete revascularization is preferred.

Methods: A literature search regarding management of coronary artery disease was conducted in PubMed between January 1985 to January 2021. Articles published in English were reviewed, and those relevant were selected by both authors. Special focus was on the ISCHEMIA trial and related articles.

Results: The utility of coronary angiography in patients with stable coronary artery disease is challenging. All patients should undergo optimal medical therapy. Patients with angina should not only receive approved anti-anginal agents but should also receive lifestyle modifications and pharmacologic therapy to control risk factors such as diabetes, hypertension, dyslipidemia, and smoking; and should consider organized physical activity programs. Low density lipoprotein should be reduced to 70 mg/dL or less. Non-invasive studies such as coronary computed tomography angiography (CCTA) are preferred. If expert CCTA is not available, then stress test, preferably with imaging, is recommended. If the results of CCTA show high risk, then coronary angiography and intervention are usually indicated. In patients with left main disease, left ventricular dysfunction, or symptoms of congestive heart failure, early invasive strategy is recommended. If none of these conditions exist, then initial medical therapy may be initiated, and invasive therapy should be utilized only if clinically indicated. In patients with chronic stable angina, continue with medical therapy and risk factor modification. If the frequency or severity of angina episodes change, coronary angiography and revascularization should be considered, as appropriate. In patients with significant renal dysfunction, angiogram may be indicated only if there is complete failure of medical therapy.

Conclusion: Optimal medical therapy should be initially utilized in all patients. Early invasive management and revascularization should be utilized in patients with left ventricular dysfunction, congestive heart failure, and failure of medical therapy. A shared decision-making process should always be utilized.

Keywords:

In 1929, Werner Forssmann performed the first case of cardiac catheterization. He introduced a urethral catheter into his own left antecubital vein and advanced the catheter to the right side of his own heart. He then walked to the radiology department to take his own chest radiograph, confirming the position of the catheter.1 It was not until three decades later that Mason Sones performed coronary angiography.2 Since that time, coronary angiography emerged as the cornerstone of the diagnosis and management of coronary artery diseases.

In 1980, Marcus A. Dewood and colleagues proved beyond a doubt that acute coronary occlusion is one of the primary causes of acute myocardial infarction. He performed coronary angiograms in 322 patients within 24 hours of the onset of myocardial infarction; 87% of patients who were studied 4 hours after the event had total coronary occlusion. This percentage decreased with time, suggesting the occurrence of spontaneous reperfusion in a minority of patients.3 This study, as well as others from the Thrombolysis In Myocardial Infarction (TIMI) study group led to treating myocardial infarction with thrombolytic therapy or with percutaneous intervention.4 If a qualified catheterization laboratory is available, then percutaneous intervention is preferred. If a patient presents to a hospital without a cardiac catheterization laboratory, then thrombolytic therapy should be immediately utilized. Patients who receive thrombolytic therapy may be transferred to a tertiary care facility for angiography if they have recurrence of cardiac ischemia or infarction.

It was William O’Neill and his group, as well as Eric Topol with his Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) group, that proved percutaneous intervention is the preferred management of infarction when a qualified cardiac catheterization laboratory is present.5 Since then, coronary angiography followed by PCI has been performed in most patients with acute coronary syndromes including acute myocardial infarction. While coronary angiography is clearly the best route in patients presenting with ST-elevation myocardial infarction and acute coronary syndromes, is it essential that it should be the initial strategy in all patients with suspected coronary artery disease? The issue of the best therapy for those that present with angina but not acute myocardial infarction remains more controversial. This report will discuss the role of angiography and revascularization therapy in patients who present with stable angina, with a focus on the ISCHEMIA trial.6

Further studies proved the benefit of percutaneous coronary intervention in patients with acute infarction. The DANAMI-2 study randomized 1,572 patients to thrombolytic therapy or coronary intervention within 12 hours of the onset of myocardial infarction. Patients who received coronary intervention had less combined endpoint of stroke, reinfarction, and death 30 days after the event.7 In a second study, patients with myocardial infarction were transferred for immediate angiography, and intervention had less incidence of stroke, reinfarction, or death compared to those who were treated with medical therapy.8 Immediate coronary stenting is the recommended strategy for ST-elevation myocardial infarction, if it can be performed in a timely manner by a competent team.

Coronary Angiography in ST-Elevation Myocardial Infarction

After the routine use of thrombolytic therapy, it was the accepted practice to perform coronary angiography in most patients who presented with an acute myocardial infarction. In 1989, the TIMI II trial was published; 3262 patients were randomly assigned to coronary angiography 18 to 48 hours after thrombolytic therapy or to angiography only if clinically indicated.9 The results were a surprise to the cardiology community. There was no significant difference in ejection fraction, reinfarction, or death between the two groups. In the invasive strategy, coronary angioplasty was attempted in only 57% of the invasive group. According to protocol, all high risk patients, such as left main equivalent, bifurcation lesions, and long lesions (among others), were excluded from intervention. No stents were utilized, allowing a very high rate of restenosis. Quite possibly, with the advances in interventional cardiology, if the study was repeated today, the results would likely favor invasive strategy. In the following decade, it became clear that immediate coronary angiography with angioplasty,10 then with stenting,11 is the preferred strategy, with far superior outcome.

Coronary Angiography in non-ST-Elevation Myocardial Infarction

Most, but not all, studies suggest that an early invasive strategy is superior to conservative medical therapy in patients with non-ST-elevation myocardial infarction.12,13 This is particularly superior in a high risk ischemia group, with low risk of invasive complications. In the FRISC-II studies, 2457 patients with acute coronary syndromes in 58 Scandinavian hospitals were randomized to early invasive or to a non-invasive strategy. Patients were followed for 3 months. Early coronary angiography was superior in patients with evidence of ischemia in the electrocardiogram or in those with elevated cardiac enzymes upon presentation. In those groups of patients with non-ST-elevation myocardial infarction, the composite risk of death, myocardial infarction, or hospital readmission was significantly less in the invasive arm.14 Similar results were shown in other large randomized, multicenter trials such as the TACTICS study15 and the RITA3 trial.16 In a single center, randomized trial, the RIDDLE-NSTEM trial, 323 patients were randomized to a very early interventional group with coronary angiography started within < 2 hours of presentation or a delayed intervention (2-72 hours) following initial presentation. The early group had less rate of death and less incidence of a new myocardial infarction.17 This benefit lasted at follow-up 3 years later.18 While meta-analysis of various studies clearly showed invasive strategy is superior to conservative medical therapy,19 it does not seem that angiogram has to be done at presentation, but it may be delayed for a day or more later, with similar reduction in combined cardiac events of reinfarction and rehospitalization.20-23 The difference in the cost of care for early versus late intervention is minimal.24 While most studies agree on the short-term benefit, it seems that in long-term follow-up of up of up to 10 years, the initial benefit is dissipated.25-27

In a real life reporting from France, 1645 patients with non-ST-myocardial infarction were followed for 3 years. Patients who were managed by invasive strategy had a reduction in cardiovascular death and total mortality at the end of 3 years of observation, compared to those patients who were initially managed with conservative medical therapy.28

It seems that the preponderance of evidence suggests that initial coronary angiogram is the preferred strategy for non-ST-elevation MI and unstable angina. While coronary angiogram can be done at presentation, it may be delayed for a day or two. Despite the addition of the angiogram, the overall cost of care is minimal when done at initial presentation. This strategy is particularly useful in patients with hemodynamic or cardiac rhythm instability, refractory angina, or to those patients with a predischarge positive stress test.29 Attempts at quantifying ischemia is challenging. Stress testing does not correlate well with actual coronary angiography. Computed tomographic coronary angiography has a better predictive diagnostic value when compared with functional stress test.30

Management in the Elderly

Guidelines recommend coronary angiography in patients with non-ST-segment infarction regardless of age.31 Both cardiologists and the elderly are hesitant to pursue invasive strategies. There is a perception that the risk may be higher, particularly as far as stroke or significant bleeding risk.

While an occasional report failed to show a benefit of early invasive study in patients older than 80 years, those reports were of a small sample size and were clearly underpowered to show any benefit.32 More than one report, however, did show a benefit with lower mortality and less future ischemic events.33,34 In the “After Eighty Study” in Norway, 457 patients over 80 years of age, with non-ST-elevation myocardial infarction and unstable angina were randomized to early invasive or conservative therapy. The early invasive group had less composite end point of death, need for urgent revascularization, and occurrence of myocardial infarction.35 There was no increase in bleeding risks in the early invasive group. In another randomized study of such patients over 70 years of age as well as with significant co-morbid conditions, those assigned to the invasive arm fared better, particularly during early follow-up.36 Therefore, early invasive strategy should be considered in the very elderly with two caveats: clear assessment of expected risk such as development of end-stage renal failure, and a special emphasis on shared decision-making after a thoughtful physician-patient discussion. These general suggestions follow guidelines for coronary artery revascularization published by the American College of Cardiology and American Heart Association.37 Most randomized studies did include patients younger than 75 years of age. The TIME study randomized 305 elderly patients with persistent angina with at least Canadian Cardiac Society Class II, despite being on antianginal therapy into optimized therapy versus revascularization. Those patients randomized to revascularization had clear improvement in the severity of angina and better quality of life.38 Thus, advanced age should not be a major factor in deciding on revascularization.

The Gender Difference

While gender differences exist in coronary artery disease,39 it seems that both men and women with non-Q wave myocardial infarction may benefit from invasive strategy, regardless of age.40-42 That is particularly true when there is an increase in serum troponin level at presentation. While many thoughtful discussions at presentation with a non-ST-elevation myocardial infarction with consideration of many variables should take place, patient sex should not influence the final discussion.

Stable Coronary Disease

The utility of coronary angiography and revascularization is challenging in stable coronary disease. Coronary angiography is clearly recommended in patients who survived sudden cardiac death and in those patients with decreased left ventricular function or congestive heart failure. It is considered inappropriate in asymptomatic patients on medical therapy, particularly those who are considered low risk group based on non-invasive testing.43 We will review a few landmark trials that addressed this challenge, with emphasis on the ISCHEMIA trial.

One of the first large trials to address medical therapy versus percutaneous coronary intervention in the management of patients with stable coronary disease was the COURAGE trial. In this study, 2287 patients with stable coronary artery disease were randomized to optimal medical therapy only versus medical therapy plus percutaneous coronary intervention. The patient population included patients with angina and with suitable anatomy for percutaneous coronary intervention. Those with persistent Canadian Cardiovascular Society Class IV, markedly positive stress test, and refractory heart failure were excluded from the study. Patients were followed for a median of 4.6 years. There was no significant difference between the two groups in cardiac mortality, nor in the combined adverse cardiovascular events.44 Of note is that the study cohort was a quite low risk group. Those with significant angina, a markedly positive stress test, ejection fraction < 30%, and any evidence of congestive heart failure were excluded from the study. Despite recruiting a low risk group, about one-third of patients crossed to the interventional group, because of a change in clinical status. Furthermore, patients were treated mostly with balloon angioplasty or bare metal stents, a practice that does not represent the current practice of mainly using advanced drug-eluting stents. Some may argue that the study conclusion may not be applicable in the current practice era, with the major advance of drug-eluting stents in the field of interventional cardiology.

In another study, 2368 patients with both stable coronary artery disease and diabetes mellitus were randomized to intensive medial therapy or to revascularization in patients with stable ischemic heart disease. Revascularization was performed with either percutaneous intervention or coronary bypass surgery. At 5-year follow-up, there was no difference between the two groups in cardiac mortality or in adverse cardiac events.45 In this particular study, however, diabetic patients who underwent coronary artery bypass surgery had a clearly better outcome when compared with the medical group. Again, the entire cohort of the study was low risk, where all the high risk patients were excluded from randomization. The majority of percutaneous coronary interventions were done with balloon angioplasty or bare metal coronary stents.

The ISCHEMIA Trial

Over more than three decades ago, a total of 14 randomized clinical trials were conducted to compare optimal medical therapy to invasive management with revascularization. The studies did not show a clear benefit of revascularization on mortality or major cardiovascular events.46 Studies, however, in general had a small cohort with medical and interventional practices that hardly reflect current advances and contemporary therapy that are used to treat coronary artery disease. There was a need to conduct a study with a large cohort that included more recent advances, including drug-eluting stents. That was the principle goal of the international trial of comparative health effectiveness of medical and invasive approaches in patients with stable coronary artery disease (the ISCHEMIA trial).47

In the ISCHEMIA trial, 5179 patients with stable coronary artery disease were randomized to an initial invasive or conservative strategy. Both groups received optimal medical therapy. Patients were followed for a median of 3.2 years. The primary outcome was a composite of myocardial infarction, unstable angina, heart failure, resuscitated cardiac arrest, or cardiovascular death. At the end of the observation period, initial invasive strategy did not improve the primary endpoint.47 The study did have some limitations, such as lower than planned power (initially it was hoped to randomize 8000 patients) that occurred in part due to smaller than expected sample size, and a lower than expected cardiac event rate. In addition, protocol adjustments were made in the middle of the study, such as changes in the inclusion criteria. While initially stress tests were supposed to include imaging, a regular ECG stress test was added to enhance recruitment. Could these limitations have impacted the conclusion? Patients in the invasive group had an event rate of 17.2% versus 29.3% in the conservative group; a numerical but not statistically significant difference.48 The study was supposed to address the value of initial invasive strategy on patients with moderate or severe ischemia on stress test. High risk patients, however, such as those with left main disease, evidence of congestive heart failure, left ventricular dysfunction with ejection fraction < 35%, and those patients with recent history of unstable angina were excluded; thus, the study results do not apply to these groups of patients.49 The definition of severe ischemia in the nuclear study was more than 10% ischemic area and in stress echo was more than two abnormal echocardiographic segments, yet some of those patients did not have obstructive coronary artery disease, suggesting that perhaps some patients did not indeed have severe disease.50

In clinical practice, the frequency of angina plays a key role in directing the patient toward invasive strategy. In patient selection for this study, those who had angina at least once daily, with no ability to increase antianginal medications, and those who did not appear to be in good compliance to receive medication, were excluded from randomization.51 Of interest is the risk for developing cardiac events was not related to the degree of ischemia or the stress test, but rather to the anatomic severity of coronary artery disease.52 In the group of patients with truly less severe coronary artery disease, one-third of patients in the conservative arm crossed over to the invasive strategy at a rate of 6.5% per year.53

Advantage of Invasive Therapy in the ISCHEMIA Trial

One of the secondary objectives of the trial was to see if there was any benefit of the invasive management on patients with stable coronary artery disease. With assessment at both early as well as late in the study period, invasive management was associated with improvement in anginal symptoms as well as quality of life.54 Findings should be discussed with patients at their initial encounter to reach the best shared decision-making. Patients should be informed that while composite cardiac events were similar between invasive and conservative groups, it seems that initial invasive strategy has an advantage in decreasing spontaneous infarction and may better reduce angina. However, since there were more procedures in the invasive arm, there were more procedure-associated myocardial infarctions. These are usually smaller in size and do not have significant long-term effects on prognosis. Spontaneous infarctions were frequent in the conservative arm and were associated with higher mortality.55 The ISCHEMIA study group investigated the incidence of ST-elevation myocardial infarction in the study group. There was statistically more incidence in the conservative group, with associated increase in total mortality, strongly suggesting a clear benefit of early invasive strategy.56

Stable coronary Artery Disease with Advanced Chronic Kidney Disease

The main ISCHEMIA trial excluded patients with severe chronic kidney disease. In a second study, 705 patients with stable coronary artery disease with moderate to severe ischemia and glomerular filtration rate < 30 ml per minute per 1.73 m2 or on dialysis were again randomized to initial invasive or conservative strategy. Chronic kidney disease patients randomized to the invasive arm had a higher incidence of stroke, more patients required dialysis, and there was higher mortality.57,58 That disappointing outcome extended to those patients who were listed in the renal transplant program.59 Invasive therapy should be reserved to total failure of conservative medical therapy in those groups patients with severe kidney disease.

Coronary Computed Tomographic Angiography (CCTA)

One of the most important clinical caveats of the ISCHEMIA trial was the utility of coronary computed tomography angiography (CCTA) in the management of patients with coronary artery disease. The study excluded those patients with left main disease or non-obstructive coronary artery disease based on the result of CCTA.60,61 In the ISCHEMIA trial, 1728 patients had both CCTA and invasive angiography. There was excellent agreement between both studies in identifying the degree of atherosclerosis in 97.1% of patients.62 That certainly exceeds the accuracy of various kinds of stress tests that are plagued by false positive and false negative results and also lacks the superiority of anatomic details offered by CCTA.63

More recently, in a clinically focused study, 3561 patients with stable chest pain and intermediate pretest probability for coronary artery disease were randomized to CCTA or invasive coronary angiography as the initial diagnostic test. The risk of major cardiovascular events during follow-up of 3.5 years was similar between both groups. The only difference was risk of procedure related risk, more in the invasive angiography group.64 These results suggest it is time for CCTA to take a more prominent role in deciding the best initial management of patients with chest pain. More papers addressed the value of CCTA in the management of patients presenting with chest pain and probable coronary artery disease. The SCOT-Heart investigators randomized 4,416 patients with stable chest paint to standard of care or standard of care plus CCTA.65 At 5 years of follow up, the group that had CCTA had lower mortality and less evidence of non-fatal infarction. Despite this clear benefit, the clinical utility of CCTA lags behind the clear evidences of the superiority of the tests. At least one report suggests that coronary calcium score may be of some value in this assessment.66 A recent meta-analysis of seven randomized studies comparing invasive versus conservative therapy in stable coronary artery disease was conducted. There was no survival advantage for patients who were randomized to initial invasive management.67 The recent introduction of FFR-CT enhanced the valued of coronary computed tomographic angiography. Patients with negative value had less rate of revascularization and a lower rate of myocardial infarction and cardiovascular death at follow up.68

Approach to Patients with Chest Pain

When encountering patients with stable coronary disease, a careful history is the initial approach. If the discomfort appears to be angina, patients with a recent history of unstable angina will benefit from initial invasive strategy. Those with ejection fraction < 35% and/or with evidence of heart failure, New York class III or IV, will benefit from invasive management as well.69 In addition, patients with left main coronary artery disease noted on CT angiography should be directed for coronary angiography and revascularization.

Every patient should be placed on optimal medical therapy (OMT). There is no need to rush stable, moderate risk patients to the catheterization laboratory.70 OMT is not only limited to guideline-directed medication. It should include lifestyle modifications as well as smoking cessation, good diabetes control, and low density lipoprotein level at 70 mg/dL or less. Also, weight loss and organized activity programs should be included.

Patients then may undergo CCTA. If there is significant left main coronary artery disease or severe proximal triple vessel coronary artery disease, invasive strategy is the best initial management. In the absence of these abnormalities, it is reasonable to continue with OMT, reserving coronary angiography to failure of medical therapy.71 A shared decision-making discussion with the patient should be undertaken; the patient should know that deferring angiogram is not unreasonable.72 They are to expect a need for coronary angiogram in about one-third of the group. There is also a chance of delayed spontaneous myocardial infarction in about 10%. Figure 1 suggests appropriate management of patients with stable coronary artery disease.

Suggested algorithm for patients presenting with chest pain and stable coronary artery disease. OMT: Optimal medical therapy. Meds, smoking cessation, daily exercise, LDL less than 70 mg/dL. CCTA: computed coronary tomographic angiography; ICA: Invasive coronary angiography.
Figure 1.

Suggested algorithm for patients presenting with chest pain and stable coronary artery disease. OMT: Optimal medical therapy. Meds, smoking cessation, daily exercise, LDL less than 70 mg/dL. CCTA: computed coronary tomographic angiography; ICA: Invasive coronary angiography.

Conclusion

Immediate coronary angiography with appropriate revascularization is the best management for ST-elevation myocardial infarction and the majority of patients with acute coronary syndromes. In those with moderate to severe ischemia at stress test and stable coronary artery disease, there is no significant difference between initial invasive therapy and OMT in long-term follow-up in mortality; however, those patients managed with early revascularization may have better quality of life, less angina, and less incidence of spontaneous myocardial infarction. Those with left main disease, low ejection fraction, or clear congestive heart failure are the main exceptions in which angiogram and appropriate revascularization be performed.

Acknowledgements

The authors are grateful to Marie Fleisner for editorial assistance with this paper.

Footnotes

  • Disclosures: Dr. Kloner’s work was supported in part by the Francis Bacon Foundation and the Pasadena Community Foundation-John and Lucille Crumb Medical Research Endowment to HMRI, and by the Marylou Ingram Endowment to HMRI. The authors have no conflicts of interest related to this work.

  • Received October 3, 2022.
  • Revision received January 25, 2023.
  • Accepted February 22, 2023.

References

  1. 1.
    ↵
    Bourassa MG. The history of cardiac catheterization. Can J Cardiol. 2005;21(12):1011-1014.
    Google ScholarPubMed
  2. 2.
    ↵
    Ryan TJ. The coronary angiogram and its seminal contributions to cardiovascular medicine over five decades. Circulation. 2002;106(6):752-756. doi:10.1161/01.CIR.0000024109.12658.D4.
    Google ScholarCrossRefFull TextPubMed
  3. 3.
    ↵
    DeWood MA, Spores J, Notske R, Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med. 1980;303(16):897-902. doi:10.1056/NEJM198010163031601.
    Google ScholarCrossRefPubMedWeb of Science
  4. 4.
    ↵
    Braunwald E. The treatment of acute myocardial infarction: the Past, the Present, and the Future. Eur Heart J Acute Cardiovasc Care. 2012;1(1):9-12. doi:10.1177/2048872612438026.
    Google ScholarCrossRefPubMed
  5. 5.
    ↵
    O’Neill W, Timmis GC, Bourdillon PD, A prospective randomized clinical trial of intracoronary streptokinase versus coronary angioplasty for acute myocardial infarction. N Engl J Med. 1986;314(13):812-818. doi:10.1056/NEJM198603273141303.
    Google ScholarCrossRefPubMedWeb of Science
  6. 6.
    ↵
    Maron DJ, Hochman JS, Reynolds HR, ; ISCHEMIA Research Group. Initial Invasive or Conservative Strategy for Stable Coronary Disease. N Engl J Med. 2020;382(15):1395-1407. doi:10.1056/NEJMoa1915922.
    Google ScholarCrossRefPubMed
  7. 7.
    ↵
    Moon JCC, Kalra PR, Coats AJS. DANAMI-2: Is primary angioplasty superior to thrombolysis in acute MI when the patient has to be transferred to an invasive centre? Int J Cardiol. 2002;85(2-3):199-201. doi:10.1016/S0167-5273(02)00183-3.
    Google ScholarCrossRefPubMedWeb of Science
  8. 8.
    ↵
    Bøhmer E, Hoffmann P, Abdelnoor M, Arnesen H, Halvorsen S. Efficacy and safety of immediate angioplasty versus ischemia-guided management after thrombolysis in acute myocardial infarction in areas with very long transfer distances results of the NORDISTEMI (NORwegian study on DIstrict treatment of ST-elevation myocardial infarction). J Am Coll Cardiol. 2010;55(2):102-110. doi:10.1016/j.jacc.2009.08.007.
    Google ScholarCrossRefFull TextPubMed
  9. 9.
    ↵
    TIMI Study Group. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) phase II trial. N Engl J Med. 1989;320(10):618-627. doi:10.1056/NEJM198903093201002
    Google ScholarCrossRefPubMedWeb of Science
  10. 10.
    ↵
    Grines CL, Browne KF, Marco J, ; The Primary Angioplasty in Myocardial Infarction Study Group. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med. 1993;328(10):673-679. doi:10.1056/NEJM199303113281001
    Google ScholarCrossRefPubMedWeb of Science
  11. 11.
    ↵
    Grines CL, Cox DA, Stone GW, ; Stent Primary Angioplasty in Myocardial Infarction Study Group. Coronary angioplasty with or without stent implantation for acute myocardial infarction. N Engl J Med. 1999;341(26):1949-1956. doi:10.1056/NEJM199912233412601.
    Google ScholarCrossRefPubMedWeb of Science
  12. 12.
    ↵
    Topol EJ. A guide to therapeutic decision-making in patients with non–ST-segment elevation acute coronary syndromes. J Am Coll Cardiol. 2003;41(4)(Suppl S):S123-S129. doi:10.1016/S0735-1097(02)02689-X.
    Google ScholarCrossRefFull Text
  13. 13.
    ↵
    Fox KAA, Clayton TC, Damman P, ; FIR Collaboration. Long-term outcome of a routine versus selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome a meta-analysis of individual patient data. J Am Coll Cardiol. 2010;55(22):2435-2445. doi:10.1016/j.jacc.2010.03.007.
    Google ScholarCrossRefFull TextPubMed
  14. 14.
    ↵
    Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators. Lancet. 1999;354(9180):708-715.
    Google ScholarCrossRefPubMedWeb of Science
  15. 15.
    ↵
    Cannon CP, Weintraub WS, Demopoulos LA, ; TACTICS (Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy)—Thrombolysis in Myocardial Infarction 18 Investigators. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001;344(25):1879-1887. doi:10.1056/NEJM200106213442501.
    Google ScholarCrossRefPubMedWeb of Science
  16. 16.
    ↵
    Fox KAA, Poole-Wilson PA, Henderson RA, ; Randomized Intervention Trial of unstable Angina Investigators. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina. Lancet. 2002;360(9335):743-751. doi:10.1016/S0140-6736(02)09894-X.
    Google ScholarCrossRefPubMedWeb of Science
  17. 17.
    ↵
    Milosevic A, Vasiljevic-Pokrajcic Z, Milasinovic D, Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients: The RIDDLE-NSTEMI Study. JACC Cardiovasc Interv. 2016;9(6):541-549. doi:10.1016/j.jcin.2015.11.018.
    Google ScholarCrossRefPubMed
  18. 18.
    ↵
    Milasinovic D, Milosevic A, Vasiljevic-Pokrajcic Z, Three-Year Impact of Immediate Invasive Strategy in Patients With Non–ST-Segment Elevation Myocardial Infarction (from the RIDDLE-NSTEMI Study). Am J Cardiol. 2018;122(1):54-60. doi:10.1016/j.amjcard.2018.03.006.
    Google ScholarCrossRef
  19. 19.
    ↵
    Mehta SR, Cannon CP, Fox KAA, Routine vs selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials. JAMA. 2005;293(23):2908-2917. doi:10.1001/jama.293.23.2908.
    Google ScholarCrossRefPubMedWeb of Science
  20. 20.
    ↵
    Badings EA, The SHK, Dambrink JHE, Early or late intervention in high-risk non-ST-elevation acute coronary syndromes: results of the ELISA-3 trial. EuroIntervention. 2013;9(1):54-61. doi:10.4244/EIJV9I1A9.
    Google ScholarCrossRefPubMed
  21. 21.
    Thiele H, Rach J, Klein N, Optimal timing of invasive angiography in stable non-ST-elevation myocardial infarction: the Leipzig Immediate versus early and late PercutaneouS coronary Intervention triAl in NSTEMI (LIPSIA-NSTEMI Trial). Eur Heart J. 2012;33(16):2035-2043. doi:10.1093/eurheartj/ehr418
    Google ScholarCrossRefPubMed
  22. 22.
    Montalescot G, Cayla G, Collet JP, Immediate vs delayed intervention for acute coronary syndromes: a randomized clinical trial. JAMA. 2009;302(9):947-954. doi:10.1001/jama.2009.1267
    Google ScholarCrossRefPubMedWeb of Science
  23. 23.
    ↵
    Mehta SR, Granger CB, Boden WE, Early versus delayed invasive intervention in acute coronary syndromes. N Engl J Med. 2009;360(21):2165-2175. doi:10.1056/NEJMoa0807986
    Google ScholarCrossRefPubMedWeb of Science
  24. 24.
    ↵
    Mahoney EM, Jurkovitz CT, Chu H, Cost and cost-effectiveness of an early invasive vs conservative strategy for the treatment of unstable angina and non-ST-segment elevation myocardial infarction. JAMA. 2002;288(15):1851-1858. doi:10.1001/jama.288.15.1851
    Google ScholarCrossRefPubMedWeb of Science
  25. 25.
    ↵
    Hoedemaker NPG, Damman P, Woudstra P, Early Invasive Versus Selective Strategy for Non-ST-Segment Elevation Acute Coronary Syndrome: The ICTUS Trial. J Am Coll Cardiol. 2017;69(15):1883-1893. doi:10.1016/j.jacc.2017.02.023
    Google ScholarCrossRefFull TextPubMed
  26. 26.
    Hirsch A, Windhausen F, Tijssen JG, Long-term outcome after an early invasive versus selective invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome and elevated cardiac troponin T (the ICTUS trial): a follow-up study. Lancet. 2007;369(9564):827-835. doi:10.1016/S0140-6736(07)60410-3
    Google ScholarCrossRefPubMedWeb of Science
  27. 27.
    ↵
    Damman P, Hirsch A, Windhausen F, Tijssen JG, de Winter RJ; ICTUS Investigators. 5-year clinical outcomes in the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) trial a randomized comparison of an early invasive versus selective invasive management in patients with non-ST-segment elevation acute coronary syndrome. J Am Coll Cardiol. 2010;55(9):858-864. doi:10.1016/j.jacc.2009.11.026
    Google ScholarCrossRefFull TextPubMed
  28. 28.
    ↵
    Puymirat E, Taldir G, Aissaoui N, Use of invasive strategy in non-ST-segment elevation myocardial infarction is a major determinant of improved long-term survival: FAST-MI (French Registry of Acute Coronary Syndrome). JACC Cardiovasc Interv. 2012;5(9):893-902. doi:10.1016/j.jcin.2012.05.008
    Google ScholarCrossRefAbstract/Full TextPubMed
  29. 29.
    ↵
    de Winter RJ, Windhausen F, Cornel JH, Early invasive versus selectively invasive management for acute coronary syndromes. N Engl J Med. 2005;353(11):1095-1104. doi:10.1056/NEJMoa044259
    Google ScholarCrossRefPubMedWeb of Science
  30. 30.
    ↵
    Sharma A, Coles A, Ksearan NK, Stress testing versus CT angiography in patients with diabetes and suspected coronary artery disease. J Am Coll Cardiol. 2019;73(8):893-902. doi:10.1016/j.jacc.2018.11.056
    Google ScholarCrossRefFull Text
  31. 31.
    ↵
    Kunniardy P, Koshy AN, Meehan G, Invasive versus conservative management in patients ≥85 years presenting with non-ST elevation myocardial infarction Intern Med J. 2021;10.1111/imj.15258. doi:10.1111/imj.15258
    Google ScholarCrossRef
  32. 32.
    ↵
    de Belder A, Myat A, Blaxill J, Revascularisation or medical therapy in elderly patients with acute anginal syndromes: the RINCAL randomised trial. EuroIntervention. 2021;17(1):67-74. doi:10.4244/EIJ-D-20-00975
    Google ScholarCrossRefPubMed
  33. 33.
    ↵
    Kolte D, Khera S, Palaniswamy C, Early invasive versus initial conservative treatment strategies in octogenarians with UA/NSTEMI. Am J Med. 2013;126(12):1076-83.e1. doi:10.1016/j.amjmed.2013.07.024
    Google ScholarCrossRefPubMed
  34. 34.
    ↵
    Reinius P, Mellbin L, Holzmann MJ, Siddiqui AJ. Percutaneous coronary intervention versus conservative treatment for non ST-segment elevation myocardial infarction in patients above 80 years of age. Int J Cardiol. 2018;267:57-61. doi:10.1016/j.ijcard.2018.05.078
    Google ScholarCrossRef
  35. 35.
    ↵
    Tegn N, Abdelnoor M, Aaberge L, Invasive versus conservative strategy in patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): an open-label randomised controlled trial. Lancet. 2016;387(10023):1057-1065. doi:10.1016/S0140-6736(15)01166-6
    Google ScholarCrossRefPubMed
  36. 36.
    ↵
    Sanchis J, Núñez E, Barrabés JA, Randomized comparison between the invasive and conservative strategies in comorbid elderly patients with non-ST elevation myocardial infarction. Eur J Intern Med. 2016;35:89-94. doi:10.1016/j.ejim.2016.07.003
    Google ScholarCrossRefPubMed
  37. 37.
    ↵
    Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published correction appears in J Am Coll Cardiol. 2022 Apr 19;79(15):1547]. J Am Coll Cardiol. 2022;79(2):e21-e129. doi:10.1016/j.jacc.2021.09.006
    Google ScholarCrossRefPubMed
  38. 38.
    ↵
    TIME Investigators. Trial of invasive versus medical therapy in elderly patients with chronic symptomatic coronary-artery disease (TIME): a randomised trial. Lancet. 2001;358(9286):951-957. doi:10.1016/S0140-6736(01)06100-1
    Google ScholarCrossRefPubMedWeb of Science
  39. 39.
    ↵
    Bairey Merz CN, Shaw LJ, Reis SE, Insights from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study: Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease. J Am Coll Cardiol. 2006;47(3 Suppl):S21-S29. doi:10.1016/j.jacc.2004.12.084
    Google ScholarCrossRefFull TextPubMed
  40. 40.
    ↵
    O’Donoghue M, Boden WE, Braunwald E, Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction: a meta-analysis. JAMA. 2008;300(1):71-80. doi:10.1001/jama.300.1.71
    Google ScholarCrossRefPubMedWeb of Science
  41. 41.
    Sui YG, Teng SY, Qian J, Gender differences in treatment strategies among patients ≥80 years old with non-ST-segment elevation myocardial infarction. J Thorac Dis. 2019;11(12):5258-5265. doi:10.21037/jtd.2019.11.55
    Google ScholarCrossRef
  42. 42.
    ↵
    Lee LC, Poh KK, Tang TP, Tan YL, Tee HW, Tan HC. The impact of gender on the outcomes of invasive versus conservative management of patients with non-ST-segment elevation myocardial infarction. Ann Acad Med Singap. 2010;39(3):168-172.
    Google ScholarPubMed
  43. 43.
    ↵
    Fihn SD, Gardin JM, Abrams J, 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons [published correction appears in Circulation. 2014 Apr 22;129(16):e462]. Circulation. 2012;126(25):3097-3137. doi:10.1161/CIR.0b013e3182776f83
    Google ScholarCrossRefFull TextPubMedWeb of Science
  44. 44.
    ↵
    Boden WE, O’Rourke RA, Teo KK, Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007;356(15):1503-1516. doi:10.1056/NEJMoa070829
    Google ScholarCrossRefPubMedWeb of Science
  45. 45.
    ↵
    BARI 2D Study Group, Frye RL, August P, A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med. 2009;360(24):2503-2515. doi:10.1056/NEJMoa0805796
    Google ScholarCrossRefPubMedWeb of Science
  46. 46.
    ↵
    Bangalore S, Maron DJ, Stone GW, Hochman JS. Routine Revascularization Versus Initial Medical Therapy for Stable Ischemic Heart Disease: A Systematic Review and Meta-Analysis of Randomized Trials. Circulation. 2020;142(9):841-857. doi:10.1161/CIRCULATIONAHA.120.048194
    Google ScholarCrossRefPubMed
  47. 47.
    ↵
    Maron DJ, Hochman JS, Reynolds HR, Initial Invasive or Conservative Strategy for Stable Coronary Disease. N Engl J Med. 2020;382(15):1395-1407. doi:10.1056/NEJMoa1915922
    Google ScholarCrossRefPubMed
  48. 48.
    ↵
    Lopes RD, Alexander KP, Stevens SR, Initial Invasive Versus Conservative Management of Stable Ischemic Heart Disease in Patients With a History of Heart Failure or Left Ventricular Dysfunction: Insights From the ISCHEMIA Trial [published correction appears in Circulation. 2020 Oct 13;142(15):e236]. Circulation. 2020;142(18):1725-1735. doi:10.1161/CIRCULATIONAHA.120.050304
    Google ScholarCrossRefPubMed
  49. 49.
    ↵
    Lopez-Sendon J, Moreno R, Tamargo J. ISCHEMIA Trial: Key Questions and Answers. Eur Cardiol. 2021;16:e34. doi:10.15420/ecr.2021.16
    Google ScholarCrossRef
  50. 50.
    ↵
    Murthy VL, Bateman TM, Chen W, Impact of the ISCHEMIA Trial on Stress Nuclear Myocardial Perfusion Imaging. J Nucl Med. 2020;61(7):962-964. doi:10.2967/jnumed.119.245399
    Google ScholarCrossRefFull TextPubMed
  51. 51.
    ↵
    Hochman JS, Reynolds HR, Bangalore S, Baseline Characteristics and Risk Profiles of Participants in the ISCHEMIA Randomized Clinical Trial [published correction appears in JAMA Cardiol. 2019 May 1;4(5):497]. JAMA Cardiol. 2019;4(3):273-286. doi:10.1001/jamacardio.2019.0014
    Google ScholarCrossRef
  52. 52.
    ↵
    Reynolds HR, Shaw LJ, Min JK, Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity. Circulation. 2021;144(13):1024-1038. doi:10.1161/CIRCULATIONAHA.120.049755
    Google ScholarCrossRefPubMed
  53. 53.
    ↵
    Mavromatis K, Boden WE. What is the Real Message of the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) Trial for Academic and Practising Cardiologists? Eur Cardiol. 2020;15:e64. doi:10.15420/ecr.2020.26
    Google ScholarCrossRef
  54. 54.
    ↵
    Spertus JA, Jones PG, Maron DJ, Health-Status Outcomes with Invasive or Conservative Care in Coronary Disease. N Engl J Med. 2020;382(15):1408-1419. doi:10.1056/NEJMoa1916370
    Google ScholarCrossRefPubMed
  55. 55.
    ↵
    Mavromatis K, Gershlick A. The Impact of the ISCHEMIA Trial on Clinical Practice: an Interventionist’s Perspective. Cardiovasc Drugs Ther. 2021;10.1007/s10557-021-07230-x. doi:10.1007/s10557-021-07230-x
    Google ScholarCrossRef
  56. 56.
    ↵
    Chaitman BR, Alexander KP, Cyr DD, Myocardial Infarction in the ISCHEMIA Trial: Impact of Different Definitions on Incidence, Prognosis, and Treatment Comparisons. Circulation. 2021;143(8):790-804. doi:10.1161/CIRCULATIONAHA.120.047987
    Google ScholarCrossRef
  57. 57.
    ↵
    Spertus JA, Jones PG, Maron DJ, Health Status after Invasive or Conservative Care in Coronary and Advanced Kidney Disease. N Engl J Med. 2020;382(17):1619-1628. doi:10.1056/NEJMoa1916374
    Google ScholarCrossRef
  58. 58.
    ↵
    Bangalore S, Maron DJ, O’Brien SM, Management of Coronary Disease in Patients with Advanced Kidney Disease. N Engl J Med. 2020;382(17):1608-1618. doi:10.1056/NEJMoa1915925
    Google ScholarCrossRefPubMed
  59. 59.
    ↵
    Herzog CA, Simegn MA, Xu Y, Kidney Transplant List Status and Outcomes in the ISCHEMIA-CKD Trial. J Am Coll Cardiol. 2021;78(4):348-361. doi:10.1016/j.jacc.2021.05.001
    Google ScholarCrossRef
  60. 60.
    ↵
    Alexander JH, Smith PK. Are We At Risk of Depriving Patients Lifesaving Cardiac Surgery?: Implications of the ISCHEMIA Trial for Coronary Artery Bypass Graft Surgery. Circulation. 2020;142(19):1797-1798. doi:10.1161/CIRCULATIONAHA.120.050524
    Google ScholarCrossRef
  61. 61.
    ↵
    Hanson CA, Patel TR, Villines TC. The New Role of Cardiac Imaging Following the ISCHEMIA Trial. Curr Treat Options Cardiovasc Med. 2021;23(6):23. doi:10.1007/s11936-021-00911-8
    Google ScholarCrossRef
  62. 62.
    ↵
    Mancini GBJ, Leipsic J, Budoff MJ, CT Angiography Followed by Invasive Angiography in Patients With Moderate or Severe Ischemia-Insights From the ISCHEMIA Trial [published correction appears in JACC Cardiovasc Imaging. 2021 Jun;14(6):1296]. JACC Cardiovasc Imaging. 2021;14(7):1384-1393. doi:10.1016/j.jcmg.2020.11.012
    Google ScholarCrossRef
  63. 63.
    ↵
    Smolka S, Desai MY, Achenbach S. After ISCHEMIA: Is coronary CTA the new gatekeeper? ISCHEMIA-Studie: Stellt die koronare CT-Angiographie künftig die Weichen? Herz. 2020;45(5):441-445. doi:10.1007/s00059-020-04962-8
    Google ScholarCrossRef
  64. 64.
    ↵
    DISCHARGE Trial Group, Maurovich-Horvat P, Bosserdt M, CT or Invasive Coronary Angiography in Stable Chest Pain. N Engl J Med. 2022;386(17):1591-1602. doi:10.1056/NEJMoa2200963
    Google ScholarCrossRefPubMed
  65. 65.
    ↵
    SCOT-HEART Investigators, Newby DE, Adamson PD, Coronary CT Angiography and 5-Year Risk of Myocardial Infarction. N Engl J Med. 2018;379(10):924-933. doi:10.1056/NEJMoa1805971
    Google ScholarCrossRefPubMed
  66. 66.
    ↵
    Money JE, Muhlestein JB, Mason S, Simplifying the ISCHEMIA trial algorithm for clinical practice: Identifying left main coronary artery disease using coronary artery calcium scans. Am Heart J. 2021;239:129-134. doi:10.1016/j.ahj.2021.05.013
    Google ScholarCrossRef
  67. 67.
    ↵
    Vij A, Kassab K, Chawla H, Invasive therapy versus conservative therapy for patients with stable coronary artery disease: An updated meta-analysis. Clin Cardiol. 2021;44(5):675-682. doi:10.1002/clc.23592
    Google ScholarCrossRef
  68. 68.
    ↵
    Patel MR, Nørgaard BL, Fairbairn TA, 1-Year Impact on Medical Practice and Clinical Outcomes of FFRCT: The ADVANCE Registry. JACC Cardiovasc Imaging. 2020;13(1 Pt 1):97-105. doi:10.1016/j.jcmg.2019.03.003
    Google ScholarCrossRefAbstract/Full TextPubMed
  69. 69.
    ↵
    Lopes RD, Alexander KP, Hochman JS, Maron DJ. Response by Lopes et al to Letter Regarding Article, “Initial Invasive Versus Conservative Management of Stable Ischemic Heart Disease Patients With a History of Heart Failure or Left Ventricular Dysfunction: Insights From the ISCHEMIA Trial”. Circulation. 2021;143(20):e961-e962. doi:10.1161/CIRCULATIONAHA.121.053672
    Google ScholarCrossRef
  70. 70.
    ↵
    Avanzas P, Kaski JC. The ISCHEMIA Trial: And the Winner Is… the Patient. Eur Cardiol. 2021;16:e10. doi:10.15420/ecr.2021.03
    Google ScholarCrossRef
  71. 71.
    ↵
    Schwarzman L, Miron-Shatz T, Maki K, Shared Decision-Making in Femoral Versus Radial Cardiac Catheterization. Am J Cardiol. 2019;124(2):190-194. doi:10.1016/j.amjcard.2019.04.014
    Google ScholarCrossRefPubMed
  72. 72.
    ↵
    Vafaei P, Naderi S, Ambrosy AP, Slade JJ. Implications of the Landmark ISCHEMIA Trial on the Initial Management of High-Risk Patients with Stable Ischemic Heart Disease. Curr Atheroscler Rep. 2021;23(11):70. doi:10.1007/s11883-021-00970-z
    Google ScholarCrossRef
Loading
PDF
Back to top

In this Issue

Clinical Medicine & Research

Clinical Medicine & Research

Vol. 21, Issue 2

1 Jun 2023

Table of Contents Cover (Photo) Index by author
  • Share

    Share This Article

    Invasive versus Conservative Management in Coronary Artery Disease
    • Clinical Medicine & Research
    • Jun 2023,
    • 21
    • (2)
    • 95-
    • 104;
    • DOI: 10.3121/cmr.2023.1806
  • Bookmark this Article

    SAVE ITEM IN SELECTED FOLDER.

Jump to

Keywords

ST-elevation myocardial infarction, STEMI, Coronary artery disease, Management