Martha Gulati, Phillip D Levy, Debabrata Mukherjee, Ezra Amsterdam, Deepak L Bhatt, Kim K Birtcher, Ron Blankstein, Jack Boyd, Renee P Bullock-Palmer, Theresa Conejo, Deborah B Diercks, Federico Gentile, John P Greenwood, Erik P Hess, Steven M Hollenberg, Wael A Jaber, Hani Jneid, José A Joglar, David A Morrow, Robert E O'Connor, Michael A Ross, Leslee J Shaw
2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
Circulation. 2021 Nov 30;144(22):e368-e454. doi: 10.1161/CIR.0000000000001029. Epub 2021 Oct 28.
Abstract/Text
AIM: This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients.
METHODS: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered. Structure: Chest pain is a frequent cause for emergency department visits in the United States. The "2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain" provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. This guideline presents an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated, and shared decision-making with patients is recommended.
Juhani Knuuti, William Wijns, Antti Saraste, Davide Capodanno, Emanuele Barbato, Christian Funck-Brentano, Eva Prescott, Robert F Storey, Christi Deaton, Thomas Cuisset, Stefan Agewall, Kenneth Dickstein, Thor Edvardsen, Javier Escaned, Bernard J Gersh, Pavel Svitil, Martine Gilard, David Hasdai, Robert Hatala, Felix Mahfoud, Josep Masip, Claudio Muneretto, Marco Valgimigli, Stephan Achenbach, Jeroen J Bax, ESC Scientific Document Group
2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes.
Eur Heart J. 2020 Jan 14;41(3):407-477. doi: 10.1093/eurheartj/ehz425.
Abstract/Text
Peter F Cohn, Kim M Fox, Caroline Daly
Silent myocardial ischemia.
Circulation. 2003 Sep 9;108(10):1263-77. doi: 10.1161/01.CIR.0000088001.59265.EE.
Abstract/Text
Roxy Senior, Harmony R Reynolds, James K Min, Daniel S Berman, Michael H Picard, Bernard R Chaitman, Leslee J Shaw, Courtney B Page, Sajeev C Govindan, Jose Lopez-Sendon, Jesus Peteiro, Gurpreet S Wander, Jaroslaw Drozdz, Jose Marin-Neto, Joseph B Selvanayagam, Jonathan D Newman, Christophe Thuaire, Johann Christopher, James J Jang, Raymond Y Kwong, Sripal Bangalore, Gregg W Stone, Sean M O'Brien, William E Boden, David J Maron, Judith S Hochman, ISCHEMIA Research Group
Predictors of Left Main Coronary Artery Disease in the ISCHEMIA Trial.
J Am Coll Cardiol. 2022 Feb 22;79(7):651-661. doi: 10.1016/j.jacc.2021.11.052.
Abstract/Text
BACKGROUND: Detection of ≥50% diameter stenosis left main coronary artery disease (LMD) has prognostic and therapeutic implications. Noninvasive stress imaging or an exercise tolerance test (ETT) are the most common methods to detect obstructive coronary artery disease, though stress test markers of LMD remain ill-defined.
OBJECTIVES: The authors sought to identify markers of LMD as detected on coronary computed tomography angiography (CTA), using clinical and stress testing parameters.
METHODS: This was a post hoc analysis of ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), including randomized and nonrandomized participants who had locally determined moderate or severe ischemia on nonimaging ETT, stress nuclear myocardial perfusion imaging, or stress echocardiography followed by CTA to exclude LMD. Stress tests were read by core laboratories. Prior coronary artery bypass grafting was an exclusion. In a stepped multivariate model, the authors identified predictors of LMD, first without and then with stress testing parameters.
RESULTS: Among 5,146 participants (mean age 63 years, 74% male), 414 (8%) had LMD. Predictors of LMD were older age (P < 0.001), male sex (P < 0.01), absence of prior myocardial infarction (P < 0.009), transient ischemic dilation of the left ventricle on stress echocardiography (P = 0.05), magnitude of ST-segment depression on ETT (P = 0.004), and peak metabolic equivalents achieved on ETT (P = 0.001). The models were weakly predictive of LMD (C-index 0.643 and 0.684).
CONCLUSIONS: In patients with moderate or severe ischemia, clinical and stress testing parameters were weakly predictive of LMD on CTA. For most patients with moderate or severe ischemia, anatomical imaging is needed to rule out LMD. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).
Copyright © 2022 American College of Cardiology Foundation. All rights reserved.
Mehmet K Aktas, Volkan Ozduran, Claire E Pothier, Richard Lang, Michael S Lauer
Global risk scores and exercise testing for predicting all-cause mortality in a preventive medicine program.
JAMA. 2004 Sep 22;292(12):1462-8. doi: 10.1001/jama.292.12.1462.
Abstract/Text
CONTEXT: The usefulness of exercise stress test results and global cardiovascular risk systems for predicting all-cause mortality in asymptomatic individuals seen in clinical settings is unclear.
OBJECTIVES: To determine the validity for prediction of all-cause mortality of the Framingham Risk Score and of a recently described European global scoring system Systematic Coronary Risk Evaluation (SCORE) for cardiovascular mortality among asymptomatic individuals evaluated in a clinical setting and to determine the potential prognostic value of exercise stress testing once these baseline risks are known.
DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 3554 asymptomatic adults between the ages of 50 and 75 years who underwent exercise stress testing as part of an executive health program between October 1990 and December 2002; participants were followed up for a mean of 8 years.
MAIN OUTCOME MEASURES: Global risk based on the Framingham Risk Score and the European SCORE. Prospectively recorded exercise stress test result abnormalities included impaired physical fitness, abnormal heart rate recovery, ventricular ectopy, and ST-segment abnormalities. The primary end point was all-cause mortality.
RESULTS: There were 114 deaths. The c-index, which corresponds to receiver operating characteristic curve values, and the Akaike Information Criteria found that the European SCORE was superior to the Framingham Risk Score in estimating global mortality risk. In a multivariable model, independent predictors of death were a higher SCORE (for 1% predicted increase in absolute risk, relative risk [RR], 1.07; 95% confidence interval [CI], 1.04-1.09; P<.001), impaired functional capacity (RR, 2.95; 95% CI, 1.98-4.39; P<.001), and an abnormal heart rate recovery (RR, 1.59; 95%, 1.04-2.41; P =.03). ST-segment depression did not predict mortality. Among patients in the highest tertile from the SCORE, an abnormal exercise stress test result, defined as either impaired functional capacity or an abnormal heart rate recovery, identified a mortality risk of more than 1% per year.
CONCLUSION: Exercise stress testing when combined with the European global risk SCORE may be useful for stratifying risk in asymptomatic individuals in a comprehensive executive health screening program.
Philip Greenland, Joseph S Alpert, George A Beller, Emelia J Benjamin, Matthew J Budoff, Zahi A Fayad, Elyse Foster, Mark A Hlatky, John McB Hodgson, Frederick G Kushner, Michael S Lauer, Leslee J Shaw, Sidney C Smith, Allen J Taylor, William S Weintraub, Nanette K Wenger, Alice K Jacobs, American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
Circulation. 2010 Dec 21;122(25):e584-636. doi: 10.1161/CIR.0b013e3182051b4c. Epub 2010 Nov 15.
Abstract/Text
C J Pepine, P F Cohn, P C Deedwania, R S Gibson, E Handberg, J A Hill, E Miller, R G Marks, U Thadani
Effects of treatment on outcome in mildly symptomatic patients with ischemia during daily life. The Atenolol Silent Ischemia Study (ASIST)
Circulation. 1994 Aug;90(2):762-8.
Abstract/Text
BACKGROUND: Detection of asymptomatic ischemia in patients with coronary artery disease has been associated with increased risk for adverse outcome, but treatment of patients with asymptomatic ischemia remains controversial. Accordingly, the purpose of this study was to determine if treatment reduces adverse outcome in patients with daily life ischemia.
METHODS AND RESULTS: A multicenter, randomized, double-blind, placebo-controlled study of asymptomatic or minimally symptomatic outpatients with daily life silent ischemia due to coronary artery disease was conducted. The primary outcome measure was event-free survival at 1 year by Kaplan-Meier analysis. Events were death, resuscitated ventricular tachycardia/fibrillation, myocardial infarction, hospitalization for unstable angina, aggravation of angina, or revascularization. The secondary outcome was ischemia during ambulatory ECG monitoring at 4 weeks. Three hundred six outpatients with mild or no angina (Canadian Cardiovascular Society class I or II), abnormal exercise tests, and ischemia on ambulatory monitoring were randomized to receive either atenolol (100 mg/d) or placebo. After 4 weeks of treatment, the number (mean +/- SD, 3.6 +/- 4.2 versus 1.7 +/- 4.6 episodes, P < .001) and average duration (30 +/- 3.3 versus 16.4 +/- 6.7 minutes, P < .001) of ischemic episodes per 48 hours of ambulatory monitoring decreased in atenolol- compared with placebo-assigned patients (4.4 +/- 4.6 to 3.1 +/- 6.0 episodes and 36.6 +/- 4.1 to 30 +/- 5.5 minutes). Event-free survival improved in atenolol-treated patients (P < .0066), who had an increased time to onset of first adverse event (120 versus 79 days) and fewer total first events compared with placebo (relative risk, 0.44; 95% confidence intervals, 0.26 to 0.75; P = .001). There was a nonsignificant trend for fewer serious events (death, resuscitation from ventricular tachycardia/fibrillation, nonfatal myocardial infarction, or hospitalization for unstable angina) in atenolol-treated patients (relative risk, 0.55; 95% confidence intervals, 0.22 to 1.33; P = .175). The most powerful univariate and multivariate correlate of event-free survival was absence of ischemia on ambulatory monitoring at 4 weeks. Side effects were mild and generally similar comparing atenolol- and placebo-treated patients, although bradycardia was more frequent with atenolol.
CONCLUSIONS: Atenolol treatment reduced daily life ischemia and was associated with reduced risk for adverse outcome in asymptomatic and mildly symptomatic patients compared with placebo.
T Von Arnim
Prognostic significance of transient ischemic episodes: response to treatment shows improved prognosis. Results of the Total Ischemic Burden Bisoprolol Study (TIBBs) follow-up.
J Am Coll Cardiol. 1996 Jul;28(1):20-4.
Abstract/Text
OBJECTIVES: The Total Ischemic Burden Bisoprolol Study (TIBBS) follow-up examined cardiac event rates in relation to transient ischemia and its treatment.
BACKGROUND: It is unclear whether transient ischemia on the ambulatory electrocardiogram has prognostic implications in stable angina and whether medical treatment can improve the prognosis.
METHODS: The TIBBS trial was an 8-week, randomized, controlled comparison of the effects of bisoprolol and nifedipine on transient ischemic episodes in patients with stable angina pectoris. Of the 545 patients screened, 520 (95.4%) could be followed up. Rates of cardiac and noncardiac death, nonfatal acute myocardial infarction, hospital admission for unstable angina and need for coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty were recorded.
RESULTS: A total of 145 events occurred in 120 (23.1%) of 520 patients. Patients with more than six episodes had an event rate of 32.5% compared with 25.0% for patients with two to six episodes and 13.2% for patients with less than two episodes (p < 0.001). Hard events (death, acute myocardial infarction, hospital admission for unstable angina pectoris) were more frequent in patients with two or more ischemic episodes (12.2% vs. 4.7%, p = 0.0049). Patients with a 100% response rate of transient ischemic episodes during the TIBBS trial had a 17.5% event rate at 1 year compared with 32.3% for non-100% responders (p = 0.008). Patients receiving bisoprolol during the TIBBS tria had a lower event rate (22.1%) at 1 year than patients randomized to nifedipine (33.1%, p = 0.033).
CONCLUSIONS: In patients with stable angina pectoris, frequent episodes of transient ischemia are a marker for an increased event rate. A 100% response to medical treatment reduces the event rate. The greater reduction of ischemia with bisoprolol than nifedipine during the TIBBS trial translated into an improved outcome at 1 year.
H J Dargie, I Ford, K M Fox
Total Ischaemic Burden European Trial (TIBET). Effects of ischaemia and treatment with atenolol, nifedipine SR and their combination on outcome in patients with chronic stable angina. The TIBET Study Group.
Eur Heart J. 1996 Jan;17(1):104-12.
Abstract/Text
OBJECTIVE: To study the relationship between presence or absence of ischaemic events on Holter monitoring and occurrence of a hard or hard+soft endpoint.
DESIGN: A randomized double-blind parallel group study of atenolol, nifedipine and their combination, with ambulatory monitoring off-treatment and after 6 weeks of randomized treatment and prospective follow-up of 2 years on average.
SETTING: Europe.
SUBJECTS: 682 men and women with a diagnosis of chronic stable angina and who were not being considered for surgery.
MAIN OUTCOME: Hard endpoints were cardiac death, nonfatal myocardial infarction and unstable angina; soft endpoints were coronary artery bypass surgery, coronary angioplasty and treatment failure.
RESULTS: The study showed no evidence of an association between the presence, frequency or total duration of ischaemic events on Holter monitoring, either on or off treatment, and the main outcome measures. There was a non-significant trend to a lower rate of hard endpoints in the group receiving combination therapy. Compliance, as measured by withdrawal from trial medication, was clearly poorest in the nifedipine group with similar withdrawal rates in the atenolol and combination therapy groups.
CONCLUSION: The recording of ischaemic events in 48 h Holter monitoring failed to predict hard or hard+soft endpoints in patients with chronic stable angina.
L Forslund, P Hjemdahl, C Held, S V Eriksson, I Björkander, N Rehnqvist
Prognostic implications of ambulatory myocardial ischemia and arrhythmias and relations to ischemia on exercise in chronic stable angina pectoris (the Angina Prognosis Study in Stockholm [APSIS]).
Am J Cardiol. 1999 Nov 15;84(10):1151-7.
Abstract/Text
The prognostic significance of ambulatory ischemia, alone and in relation to ischemia during exercise was assessed in 686 patients (475 men) with chronic stable angina pectoris taking part in the Angina Prognosis Study In Stockholm (APSIS), who had 24-hour ambulatory electrocardiographic registrations and exercise tests at baseline (n = 678) and after 1 month (n = 607) of double-blind treatment with metoprolol or verapamil. Ambulatory electrocardiograms were analyzed for ventricular premature complexes and ST-segment depression. During a median follow-up of 40 months, 29 patients died of cardiovascular (CV) causes, 27 had a nonfatal myocardial infarction, and 89 underwent revascularization. Patients with CV death had more episodes (median 5 vs. 1; p<0.01) and longer median duration (24 vs. 3 minutes; p<0.01) of ST-segment depression than patients without events. For those who had undergone revascularization, the duration was also longer (12 vs. 3 minutes; p<0.05). In a multivariate Cox model including sex, history of previous myocardial infarction, hypertension, and diabetes, the duration of ST-segment depression independently predicted CV death. When exercise testing was included, ambulatory ischemia carried additional prognostic information only among patients with ST-segment depression > or =2 mm during exercise. When the treatment given and treatment effects on ambulatory ischemia were added to the Cox model, no significant impact on prognosis was found. Ventricular premature complexes carried no prognostic information. Thus, in patients with stable angina pectoris, ischemia during ambulatory monitoring showed independent prognostic importance regarding CV death. Ambulatory electrocardiographic monitoring and exercise testing provide complementary information, but only among patients with marked ischemia during exercise. Treatment reduced ambulatory ischemia, but the short-term treatment effects did not significantly influence prognosis.
A J Moss, R E Goldstein, W J Hall, J T Bigger, J L Fleiss, H Greenberg, M Bodenheimer, R J Krone, F I Marcus, F J Wackers
Detection and significance of myocardial ischemia in stable patients after recovery from an acute coronary event. Multicenter Myocardial Ischemia Research Group.
JAMA. 1993 May 12;269(18):2379-85.
Abstract/Text
OBJECTIVE: To determine the clinical significance of silent and symptomatic myocardial ischemia detected by noninvasive testing in stable postcoronary patients.
DESIGN: Cohort study with a mean 23-month follow-up.
SETTING: Ambulatory outpatients after recent hospitalization for an acute coronary event.
PATIENTS: Nine hundred thirty-six patients (76% male; mean age, 58 years) who were clinically stable 1 to 6 months after hospitalization for acute myocardial infarction or unstable angina.
INTERVENTIONS: Noninvasive testing involved rest, ambulatory, and exercise electrocardiograms and stress thallium-201 scintigraphy.
MAIN OUTCOME MEASURES: Cox regression analysis was used to evaluate the risk (hazard ratio) of first recurrent primary events (cardiac death, nonfatal infarction, or unstable angina) or restricted events (cardiac death or nonfatal infarction) associated with ischemic noninvasive test results.
RESULTS: ST segment depression on the rest electrocardiogram was the only noninvasive test variable that identified a significantly increased risk (P = .05) for first recurrent primary events (hazard ratio; 95% confidence limits): rest electrocardiogram ST depression (1.5; 1.00, 2.25); ambulatory electrocardiogram ST depression (0.86; 0.49, 1.51); exercise electrocardiogram ST depression (1.13; 0.82, 1.56); and stress thallium-201 reversible defects (1.3; 0.96, 1.74). Test results were similar for first recurrent restricted events, and in patients with and without angina. Significantly increased risk (P < .05) was noted when exercise-induced ST depression occurred in patients who also had reduced exercise duration (hazard ratio, 3.4) or when reversible thallium-201 defects occurred in patients who also had increased lung uptake (hazard ratio, 2.8). Each high-risk subset made up less than 3% of the population and contained less than 6% of patients with first primary events.
CONCLUSION: Detection of silent or symptomatic myocardial ischemia by non-invasive testing in stable patients 1 to 6 months after an acute coronary event is not useful in identifying patients at increased risk for subsequent coronary events.
W J Rogers, M G Bourassa, T C Andrews, B D Bertolet, R S Blumenthal, B R Chaitman, S A Forman, N L Geller, A D Goldberg, G B Habib
Asymptomatic Cardiac Ischemia Pilot (ACIP) study: outcome at 1 year for patients with asymptomatic cardiac ischemia randomized to medical therapy or revascularization. The ACIP Investigators.
J Am Coll Cardiol. 1995 Sep;26(3):594-605.
Abstract/Text
OBJECTIVES: This report discusses the outcome at 1 year in patients in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study.
BACKGROUND: Comparative efficacy of medical therapy versus revascularization in treatment of asymptomatic ischemia is unknown. The ACIP study assessed the ability of three treatment strategies to suppress ambulatory electrocardiographic (ECG) ischemia to determine whether a large-scale trial studying the impact of these strategies on clinical outcomes was feasible.
METHODS: Five hundred fifty-eight patients with coronary anatomy amenable to revascularization, at least one episode of asymptomatic ischemia on the 48-h ambulatory ECG and ischemia on treadmill exercise testing were randomized to one of three treatment strategies: 1) medication to suppress angina (angina-guided strategy, n = 183); 2) medication to suppress both angina and ambulatory ECG ischemia (ischemia-guided strategy, n = 183); or 3) revascularization strategy (angioplasty or bypass surgery, n = 192). Medication was titrated atenolol-nifedipine or diltiazem-isosorbide dinitrate.
RESULTS: The revascularization group received less medication and had less ischemia on serial ambulatory ECG recordings and exercise testing than those assigned to the medical strategies. The ischemia-guided group received more medication but had suppression of ischemia similar to the angina-guided group. At 1 year, the mortality rate was 4.4% in the angina-guided group (8 of 183), 1.6% in the ischemia-guided group (3 of 183) and 0% in the revascularization group (overall, p = 0.004; angina-guided vs. revascularization, p = 0.003; other pairwise comparisons, p = NS). Frequency of myocardial infarction, unstable angina, stroke and congestive heart failure was not significantly different among the three strategies. The revascularization group had significantly fewer hospital admissions and nonprotocol revascularizations at 1 year. The incidence of death, myocardial infarction, nonprotocol revascularization or hospital admissions at 1 year was 32% with the angina-guided medical strategy, 31% with the ischemia-guided medical strategy and 18% with the revascularization strategy (p = 0.003).
CONCLUSIONS: After 1 year, revascularization was superior to both angina-guided and ischemia-guided medical strategies in suppressing asymptomatic ischemia and was associated with better outcome. These findings require confirmation by a larger scale trial.
Paul Erne, Andreas W Schoenenberger, Dieter Burckhardt, Michel Zuber, Wolfgang Kiowski, Peter T Buser, Paul Dubach, Therese J Resink, Matthias Pfisterer
Effects of percutaneous coronary interventions in silent ischemia after myocardial infarction: the SWISSI II randomized controlled trial.
JAMA. 2007 May 9;297(18):1985-91. doi: 10.1001/jama.297.18.1985.
Abstract/Text
CONTEXT: The effect of a percutaneous coronary intervention (PCI) on the long-term prognosis of patients with silent ischemia after a myocardial infarction (MI) is not known.
OBJECTIVE: To determine whether PCI compared with drug therapy improves long-term outcome of asymptomatic patients with silent ischemia after an MI.
DESIGN, SETTING, AND PARTICIPANTS: Randomized, unblinded, controlled trial (Swiss Interventional Study on Silent Ischemia Type II [SWISSI II]) conducted from May 2, 1991, to February 25, 1997, at 3 public hospitals in Switzerland of 201 patients with a recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease. Follow-up ended on May 23, 2006.
INTERVENTIONS: Percutaneous coronary intervention aimed at full revascularization (n = 96) or intensive anti-ischemic drug therapy (n = 105). All patients received 100 mg/d of aspirin and a statin.
MAIN OUTCOME MEASURES: Survival free of major adverse cardiac events defined as cardiac death, nonfatal MI, and/or symptom-driven revascularization. Secondary measures included exercise-induced ischemia and resting left ventricular ejection fraction during follow-up.
RESULTS: During a mean (SD) follow-up of 10.2 (2.6) years, 27 major adverse cardiac events occurred in the PCI group and 67 events occurred in the anti-ischemic drug therapy group (adjusted hazard ratio, 0.33; 95% confidence interval, 0.20-0.55; P<.001), which corresponds to an absolute event reduction of 6.3% per year (95% confidence interval, 3.7%-8.9%; P<.001). Patients in the PCI group had lower rates of ischemia (11.6% vs 28.9% in patients in the drug therapy group at final follow-up; P = .03) despite fewer drugs. Left ventricular ejection fraction remained preserved in PCI patients (mean [SD] of 53.9% [9.9%] at baseline to 55.6% [8.1%] at final follow-up) and decreased significantly (P<.001) in drug therapy patients (mean [SD] of 59.7% [11.8%] at baseline to 48.8% [7.9%] at final follow-up).
CONCLUSION: Among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00387231.
William E Boden, Robert A O'Rourke, Koon K Teo, Pamela M Hartigan, David J Maron, William J Kostuk, Merril Knudtson, Marcin Dada, Paul Casperson, Crystal L Harris, Bernard R Chaitman, Leslee Shaw, Gilbert Gosselin, Shah Nawaz, Lawrence M Title, Gerald Gau, Alvin S Blaustein, David C Booth, Eric R Bates, John A Spertus, Daniel S Berman, G B John Mancini, William S Weintraub, COURAGE Trial Research Group
Optimal medical therapy with or without PCI for stable coronary disease.
N Engl J Med. 2007 Apr 12;356(15):1503-16. doi: 10.1056/NEJMoa070829. Epub 2007 Mar 26.
Abstract/Text
BACKGROUND: In patients with stable coronary artery disease, it remains unclear whether an initial management strategy of percutaneous coronary intervention (PCI) with intensive pharmacologic therapy and lifestyle intervention (optimal medical therapy) is superior to optimal medical therapy alone in reducing the risk of cardiovascular events.
METHODS: We conducted a randomized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers. Between 1999 and 2004, we assigned 1149 patients to undergo PCI with optimal medical therapy (PCI group) and 1138 to receive optimal medical therapy alone (medical-therapy group). The primary outcome was death from any cause and nonfatal myocardial infarction during a follow-up period of 2.5 to 7.0 years (median, 4.6).
RESULTS: There were 211 primary events in the PCI group and 202 events in the medical-therapy group. The 4.6-year cumulative primary-event rates were 19.0% in the PCI group and 18.5% in the medical-therapy group (hazard ratio for the PCI group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P=0.62). There were no significant differences between the PCI group and the medical-therapy group in the composite of death, myocardial infarction, and stroke (20.0% vs. 19.5%; hazard ratio, 1.05; 95% CI, 0.87 to 1.27; P=0.62); hospitalization for acute coronary syndrome (12.4% vs. 11.8%; hazard ratio, 1.07; 95% CI, 0.84 to 1.37; P=0.56); or myocardial infarction (13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P=0.33).
CONCLUSIONS: As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy. (ClinicalTrials.gov number, NCT00007657 [ClinicalTrials.gov].).
Copyright 2007 Massachusetts Medical Society.
BARI 2D Study Group, Robert L Frye, Phyllis August, Maria Mori Brooks, Regina M Hardison, Sheryl F Kelsey, Joan M MacGregor, Trevor J Orchard, Bernard R Chaitman, Saul M Genuth, Suzanne H Goldberg, Mark A Hlatky, Teresa L Z Jones, Mark E Molitch, Richard W Nesto, Edward Y Sako, Burton E Sobel
A randomized trial of therapies for type 2 diabetes and coronary artery disease.
N Engl J Med. 2009 Jun 11;360(24):2503-15. doi: 10.1056/NEJMoa0805796. Epub 2009 Jun 7.
Abstract/Text
BACKGROUND: Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established.
METHODS: We randomly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy. Primary end points were the rate of death and a composite of death, myocardial infarction, or stroke (major cardiovascular events). Randomization was stratified according to the choice of percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) as the more appropriate intervention.
RESULTS: At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no significant difference in primary end points between the revascularization group and the medical-therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Adverse events and serious adverse events were generally similar among the groups, although severe hypoglycemia was more frequent in the insulin-provision group (9.2%) than in the insulin-sensitization group (5.9%, P=0.003).
CONCLUSIONS: Overall, there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision. (ClinicalTrials.gov number, NCT00006305.)
2009 Massachusetts Medical Society
David J Maron, Judith S Hochman, Harmony R Reynolds, Sripal Bangalore, Sean M O'Brien, William E Boden, Bernard R Chaitman, Roxy Senior, Jose López-Sendón, Karen P Alexander, Renato D Lopes, Leslee J Shaw, Jeffrey S Berger, Jonathan D Newman, Mandeep S Sidhu, Shaun G Goodman, Witold Ruzyllo, Gilbert Gosselin, Aldo P Maggioni, Harvey D White, Balram Bhargava, James K Min, G B John Mancini, Daniel S Berman, Michael H Picard, Raymond Y Kwong, Ziad A Ali, Daniel B Mark, John A Spertus, Mangalath N Krishnan, Ahmed Elghamaz, Nagaraja Moorthy, Whady A Hueb, Marcin Demkow, Kreton Mavromatis, Olga Bockeria, Jesus Peteiro, Todd D Miller, Hanna Szwed, Rolf Doerr, Matyas Keltai, Joseph B Selvanayagam, P Gabriel Steg, Claes Held, Shun Kohsaka, Stavroula Mavromichalis, Ruth Kirby, Neal O Jeffries, Frank E Harrell, Frank W Rockhold, Samuel Broderick, T Bruce Ferguson, David O Williams, Robert A Harrington, Gregg W Stone, Yves Rosenberg, ISCHEMIA Research Group
Initial Invasive or Conservative Strategy for Stable Coronary Disease.
N Engl J Med. 2020 Apr 9;382(15):1395-1407. doi: 10.1056/NEJMoa1915922. Epub 2020 Mar 30.
Abstract/Text
BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain.
METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction.
RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32).
CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
Copyright © 2020 Massachusetts Medical Society.
C Richard Conti, Anthony A Bavry, John W Petersen
Silent ischemia: clinical relevance.
J Am Coll Cardiol. 2012 Jan 31;59(5):435-41. doi: 10.1016/j.jacc.2011.07.050.
Abstract/Text
Myocardial ischemia can occur without overt symptoms. In fact, asymptomatic (or silent) ST-segment depression during ambulatory electrocardiogram monitoring occurs more often than symptomatic ST-segment depression in patients with coronary artery disease. Initial studies documented that silent ischemia provided independent prediction of adverse outcomes in patients with known and unknown coronary artery disease. The ACIP (Asymptomatic Cardiac Ischemia Pilot Study) enrolled patients in the 1990s and found that revascularization was better than medical therapy in reducing silent ischemic episodes and possibly cardiovascular (CV) events. However, the more recent COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial found similar CV event rates between patients treated with optimal medical therapy alone and those treated with optimal medical therapy plus percutaneous revascularization. Therefore, in the current era, medical therapy appears to be as effective as revascularization in suppressing symptomatic ischemia and preventing CV events. COURAGE was not designed to evaluate changes in the frequency of silent ischemia. Therefore, silent ischemia may persist despite current-era treatment and might still identify patients with increased risk of CV events. Also, silent ischemia is likely to occur frequently in heart transplant patients with denervated hearts and coronary allograft vasculopathy, and future study aimed at improving the management of silent ischemia in this population is warranted. Additionally, future research is warranted to study the effect of newer medical therapies such as ranolazine or selected use of revascularization (for example, guided by fractional flow reserve) in those patients with persistent silent ischemia despite optimal current-era medical therapy.
Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Ciro Indolfi, Alberto Polimeni, Annalisa Mongiardo, Salvatore De Rosa, Carmen Spaccarotella
Old unsolved problems: when and how to treat silent ischaemia.
Eur Heart J Suppl. 2020 Nov;22(Suppl L):L82-L85. doi: 10.1093/eurheartj/suaa141. Epub 2020 Nov 18.
Abstract/Text
Silent myocardial ischaemia (SMI) is defined as objective evidence of ischaemia without angina (or equivalent symptoms) in the presence of coronary artery disease, differing from silent coronary artery disease. Silent myocardial ischaemia represents the majority of episodes of myocardial ischaemia at Holter monitoring. During transient myocardial ischaemia, the symptoms appear after the contraction anomalies of the left ventricle and after the ECG changes. The cause of silent myocardial ischaemia is still not well established. The severity and duration of ischaemia have been theorized as important elements in the SMI mechanism. Another possible mechanism responsible for SMI is represented by changes in the perception of painful stimuli with an increased pain threshold. Finally, a neuronal dysfunction of the diabetic, in post-infarction or a cardiac neuronal 'stunning' could play a role in SMI. In the pre-stent era, the SMI was associated with a worse prognosis. In patients with diabetes mellitus, SMI seems to be more represented because autonomic dysfunction is present in this category of patients. In conclusion, SMI is more frequent than symptomatic ischaemia. However, despite the presence of countless studies on the subject, it is not clear today whether medical therapy has equalized the risk and what the real prognosis of SMI is.
Published on behalf of the European Society of Cardiology. © The Author(s) 2020.
S E Epstein, A A Quyyumi, R O Bonow
Myocardial ischemia--silent or symptomatic.
N Engl J Med. 1988 Apr 21;318(16):1038-43. doi: 10.1056/NEJM198804213181606.
Abstract/Text
Lawrence H Young, Frans J Th Wackers, Deborah A Chyun, Janice A Davey, Eugene J Barrett, Raymond Taillefer, Gary V Heller, Ami E Iskandrian, Steven D Wittlin, Neil Filipchuk, Robert E Ratner, Silvio E Inzucchi, DIAD Investigators
Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial.
JAMA. 2009 Apr 15;301(15):1547-55. doi: 10.1001/jama.2009.476.
Abstract/Text
CONTEXT: Coronary artery disease (CAD) is the major cause of mortality and morbidity in patients with type 2 diabetes. But the utility of screening patients with type 2 diabetes for asymptomatic CAD is controversial.
OBJECTIVE: To assess whether routine screening for CAD identifies patients with type 2 diabetes as being at high cardiac risk and whether it affects their cardiac outcomes.
DESIGN, SETTING, AND PATIENTS: The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study is a randomized controlled trial in which 1123 participants with type 2 diabetes and no symptoms of CAD were randomly assigned to be screened with adenosine-stress radionuclide myocardial perfusion imaging (MPI) or not to be screened. Participants were recruited from diabetes clinics and practices and prospectively followed up from August 2000 to September 2007.
MAIN OUTCOME MEASURE: Cardiac death or nonfatal myocardial infarction (MI).
RESULTS: The cumulative cardiac event rate was 2.9% over a mean (SD) follow-up of 4.8 (0.9) years for an average of 0.6% per year. Seven nonfatal MIs and 8 cardiac deaths (2.7%) occurred among the screened group and 10 nonfatal MIs and 7 cardiac deaths (3.0%) among the not-screened group (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.44-1.88; P = .73). Of those in the screened group, 409 participants with normal results and 50 with small MPI defects had lower event rates than the 33 with moderate or large MPI defects; 0.4% per year vs 2.4% per year (HR, 6.3; 95% CI, 1.9-20.1; P = .001). Nevertheless, the positive predictive value of having moderate or large MPI defects was only 12%. The overall rate of coronary revascularization was low in both groups: 31 (5.5%) in the screened group and 44 (7.8%) in the unscreened group (HR, 0.71; 95% CI, 0.45-1.1; P = .14). During the course of study there was a significant and equivalent increase in primary medical prevention in both groups.
CONCLUSION: In this contemporary study population of patients with diabetes, the cardiac event rates were low and were not significantly reduced by MPI screening for myocardial ischemia over 4.8 years.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00769275.
Duk-Woo Park, Do-Yoon Kang, Jung-Min Ahn, Sung-Cheol Yun, Yong-Hoon Yoon, Seung-Ho Hur, Cheol Hyun Lee, Won-Jang Kim, Se Hun Kang, Chul Soo Park, Bong-Ki Lee, Jung-Won Suh, Jung Han Yoon, Jae Woong Choi, Kee-Sik Kim, Si Wan Choi, Su Nam Lee, Seung-Jung Park, POST-PCI Investigators
Routine Functional Testing or Standard Care in High-Risk Patients after PCI.
N Engl J Med. 2022 Sep 8;387(10):905-915. doi: 10.1056/NEJMoa2208335. Epub 2022 Aug 28.
Abstract/Text
BACKGROUND: There are limited data from randomized trials to guide a specific follow-up surveillance approach after myocardial revascularization. Whether a follow-up strategy that includes routine functional testing improves clinical outcomes among high-risk patients who have undergone percutaneous coronary intervention (PCI) is uncertain.
METHODS: We randomly assigned 1706 patients with high-risk anatomical or clinical characteristics who had undergone PCI to a follow-up strategy of routine functional testing (nuclear stress testing, exercise electrocardiography, or stress echocardiography) at 1 year after PCI or to standard care alone. The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years. Key secondary outcomes included invasive coronary angiography and repeat revascularization.
RESULTS: The mean age of the patients was 64.7 years, 21.0% had left main disease, 43.5% had bifurcation disease, 69.8% had multivessel disease, 70.1% had diffuse long lesions, 38.7% had diabetes, and 96.4% had been treated with drug-eluting stents. At 2 years, a primary-outcome event had occurred in 46 of 849 patients (Kaplan-Meier estimate, 5.5%) in the functional-testing group and in 51 of 857 (Kaplan-Meier estimate, 6.0%) in the standard-care group (hazard ratio, 0.90; 95% confidence interval [CI], 0.61 to 1.35; P = 0.62). There were no between-group differences with respect to the components of the primary outcome. At 2 years, 12.3% of the patients in the functional-testing group and 9.3% in the standard-care group had undergone invasive coronary angiography (difference, 2.99 percentage points; 95% CI, -0.01 to 5.99), and 8.1% and 5.8% of patients, respectively, had undergone repeat revascularization (difference, 2.23 percentage points; 95% CI, -0.22 to 4.68).
CONCLUSIONS: Among high-risk patients who had undergone PCI, a follow-up strategy of routine functional testing, as compared with standard care alone, did not improve clinical outcomes at 2 years. (Funded by the CardioVascular Research Foundation and Daewoong Pharmaceutical; POST-PCI ClinicalTrials.gov number, NCT03217877.).
Copyright © 2022 Massachusetts Medical Society.
Panagiotis Xaplanteris, Stephane Fournier, Nico H J Pijls, William F Fearon, Emanuele Barbato, Pim A L Tonino, Thomas Engstrøm, Stefan Kääb, Jan-Henk Dambrink, Gilles Rioufol, Gabor G Toth, Zsolt Piroth, Nils Witt, Ole Fröbert, Petr Kala, Axel Linke, Nicola Jagic, Martin Mates, Kreton Mavromatis, Habib Samady, Anand Irimpen, Keith Oldroyd, Gianluca Campo, Martina Rothenbühler, Peter Jüni, Bernard De Bruyne, FAME 2 Investigators
Five-Year Outcomes with PCI Guided by Fractional Flow Reserve.
N Engl J Med. 2018 Jul 19;379(3):250-259. doi: 10.1056/NEJMoa1803538. Epub 2018 May 22.
Abstract/Text
BACKGROUND: We hypothesized that fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease.
METHODS: Among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization.
RESULTS: A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34 to 0.63; P<0.001). The difference was driven by urgent revascularizations, which occurred in 6.3% of the patients in the PCI group as compared with 21.1% of those in the medical-therapy group (hazard ratio, 0.27; 95% CI, 0.18 to 0.41). There were no significant differences between the PCI group and the medical-therapy group in the rates of death (5.1% and 5.2%, respectively; hazard ratio, 0.98; 95% CI, 0.55 to 1.75) or myocardial infarction (8.1% and 12.0%; hazard ratio, 0.66; 95% CI, 0.43 to 1.00). There was no significant difference in the rate of the primary end point between the PCI group and the registry cohort (13.9% and 15.7%, respectively; hazard ratio, 0.88; 95% CI, 0.55 to 1.39). Relief from angina was more pronounced after PCI than after medical therapy.
CONCLUSIONS: In patients with stable coronary artery disease, an initial FFR-guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long-term outcome with medical therapy alone. (Funded by St. Jude Medical and others; FAME 2 ClinicalTrials.gov number, NCT01132495 .).
Etienne Puymirat, Guillaume Cayla, Tabassome Simon, Philippe G Steg, Gilles Montalescot, Isabelle Durand-Zaleski, Alicia le Bras, Romain Gallet, Khalife Khalife, Jean-François Morelle, Pascal Motreff, Gilles Lemesle, Jean-Guillaume Dillinger, Thibault Lhermusier, Johanne Silvain, Vincent Roule, Jean-Noel Labèque, Grégoire Rangé, Grégory Ducrocq, Yves Cottin, Didier Blanchard, Anaïs Charles Nelson, Bernard De Bruyne, Gilles Chatellier, Nicolas Danchin, FLOWER-MI Study Investigators
Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction.
N Engl J Med. 2021 Jul 22;385(4):297-308. doi: 10.1056/NEJMoa2104650. Epub 2021 May 16.
Abstract/Text
BACKGROUND: In patients with ST-elevation myocardial infarction (STEMI) who have multivessel disease, percutaneous coronary intervention (PCI) for nonculprit lesions (complete revascularization) is superior to treatment of the culprit lesion alone. However, whether complete revascularization that is guided by fractional flow reserve (FFR) is superior to an angiography-guided procedure is unclear.
METHODS: In this multicenter trial, we randomly assigned patients with STEMI and multivessel disease who had undergone successful PCI of the infarct-related artery to receive complete revascularization guided by either FFR or angiography. The primary outcome was a composite of death from any cause, nonfatal myocardial infarction, or unplanned hospitalization leading to urgent revascularization at 1 year.
RESULTS: The mean (±SD) number of stents that were placed per patient for nonculprit lesions was 1.01±0.99 in the FFR-guided group and 1.50±0.86 in the angiography-guided group. During follow-up, a primary outcome event occurred in 32 of 586 patients (5.5%) in the FFR-guided group and in 24 of 577 patients (4.2%) in the angiography-guided group (hazard ratio, 1.32; 95% confidence interval, 0.78 to 2.23; P = 0.31). Death occurred in 9 patients (1.5%) in the FFR-guided group and in 10 (1.7%) in the angiography-guided group; nonfatal myocardial infarction in 18 (3.1%) and 10 (1.7%), respectively; and unplanned hospitalization leading to urgent revascularization in 15 (2.6%) and 11 (1.9%), respectively.
CONCLUSIONS: In patients with STEMI undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization at 1 year. However, given the wide confidence intervals for the estimate of effect, the findings do not allow for a conclusive interpretation. (Funded by the French Ministry of Health and Abbott; FLOWER-MI ClinicalTrials.gov number, NCT02943954.).
Copyright © 2021 Massachusetts Medical Society.
William F Fearon, Frederik M Zimmermann, Bernard De Bruyne, Zsolt Piroth, Albert H M van Straten, Laszlo Szekely, Giedrius Davidavičius, Gintaras Kalinauskas, Samer Mansour, Rajesh Kharbanda, Nikolaos Östlund-Papadogeorgos, Adel Aminian, Keith G Oldroyd, Nawwar Al-Attar, Nikola Jagic, Jan-Henk E Dambrink, Petr Kala, Oskar Angerås, Philip MacCarthy, Olaf Wendler, Filip Casselman, Nils Witt, Kreton Mavromatis, Steven E S Miner, Jaydeep Sarma, Thomas Engstrøm, Evald H Christiansen, Pim A L Tonino, Michael J Reardon, Di Lu, Victoria Y Ding, Yuhei Kobayashi, Mark A Hlatky, Kenneth W Mahaffey, Manisha Desai, Y Joseph Woo, Alan C Yeung, Nico H J Pijls, FAME 3 Investigators
Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery.
N Engl J Med. 2022 Jan 13;386(2):128-137. doi: 10.1056/NEJMoa2112299. Epub 2021 Nov 4.
Abstract/Text
BACKGROUND: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking.
METHODS: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed.
RESULTS: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group.
CONCLUSIONS: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.).
Copyright © 2021 Massachusetts Medical Society.
Divaka Perera, Tim Clayton, Peter D O'Kane, John P Greenwood, Roshan Weerackody, Matthew Ryan, Holly P Morgan, Matthew Dodd, Richard Evans, Ruth Canter, Sophie Arnold, Lana J Dixon, Richard J Edwards, Kalpa De Silva, James C Spratt, Dwayne Conway, James Cotton, Margaret McEntegart, Amedeo Chiribiri, Pedro Saramago, Anthony Gershlick, Ajay M Shah, Andrew L Clark, Mark C Petrie, REVIVED-BCIS2 Investigators
Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction.
N Engl J Med. 2022 Oct 13;387(15):1351-1360. doi: 10.1056/NEJMoa2206606. Epub 2022 Aug 27.
Abstract/Text
BACKGROUND: Whether revascularization by percutaneous coronary intervention (PCI) can improve event-free survival and left ventricular function in patients with severe ischemic left ventricular systolic dysfunction, as compared with optimal medical therapy (i.e., individually adjusted pharmacologic and device therapy for heart failure) alone, is unknown.
METHODS: We randomly assigned patients with a left ventricular ejection fraction of 35% or less, extensive coronary artery disease amenable to PCI, and demonstrable myocardial viability to a strategy of either PCI plus optimal medical therapy (PCI group) or optimal medical therapy alone (optimal-medical-therapy group). The primary composite outcome was death from any cause or hospitalization for heart failure. Major secondary outcomes were left ventricular ejection fraction at 6 and 12 months and quality-of-life scores.
RESULTS: A total of 700 patients underwent randomization - 347 were assigned to the PCI group and 353 to the optimal-medical-therapy group. Over a median of 41 months, a primary-outcome event occurred in 129 patients (37.2%) in the PCI group and in 134 patients (38.0%) in the optimal-medical-therapy group (hazard ratio, 0.99; 95% confidence interval [CI], 0.78 to 1.27; P = 0.96). The left ventricular ejection fraction was similar in the two groups at 6 months (mean difference, -1.6 percentage points; 95% CI, -3.7 to 0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, -1.7 to 3.4). Quality-of-life scores at 6 and 12 months appeared to favor the PCI group, but the difference had diminished at 24 months.
CONCLUSIONS: Among patients with severe ischemic left ventricular systolic dysfunction who received optimal medical therapy, revascularization by PCI did not result in a lower incidence of death from any cause or hospitalization for heart failure. (Funded by the National Institute for Health and Care Research Health Technology Assessment Program; REVIVED-BCIS2 ClinicalTrials.gov number, NCT01920048.).
Copyright © 2022 Massachusetts Medical Society.
Rasha Al-Lamee, David Thompson, Hakim-Moulay Dehbi, Sayan Sen, Kare Tang, John Davies, Thomas Keeble, Michael Mielewczik, Raffi Kaprielian, Iqbal S Malik, Sukhjinder S Nijjer, Ricardo Petraco, Christopher Cook, Yousif Ahmad, James Howard, Christopher Baker, Andrew Sharp, Robert Gerber, Suneel Talwar, Ravi Assomull, Jamil Mayet, Roland Wensel, David Collier, Matthew Shun-Shin, Simon A Thom, Justin E Davies, Darrel P Francis, ORBITA investigators
Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial.
Lancet. 2018 Jan 6;391(10115):31-40. doi: 10.1016/S0140-6736(17)32714-9. Epub 2017 Nov 2.
Abstract/Text
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.
Copyright © 2018 Elsevier Ltd. All rights reserved.
