Meta-analysis raises questions about ischaemia-driven revascularisation

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A meta-analysis published in JAMA Internal Medicine indicates that percutaneous coronary intervention (PCI) does not reduce the risk of death or non-fatal myocardial infarction in patients with stable coronary artery disease with myocardial ischaemia that has been identified through stress testing or fractional flow reserve (FFR). These results raise questions about the effectiveness of ischaemia-driven revascularisation.

Kathleen Stergiopoulous (Division of Cardiovascular Medicine, Department of Medicine, State University Of New York–Stony Brook School of Medicine, Stony Brook, USA) and others report that they performed a systematic review and collaborative meta-analysis of PCI vs. medical management alone in stable coronary artery disease and myocardial ischaemia because of the “equipoise” surrounding the issue. They explain that a large observation study showed that revascularisation in patients with at least moderate ischaemia was associated with fewer cardiac deaths than medical management alone but add: “Two post-hoc studies of patients enrolled in the COURAGE (Clinical outcomes using revascularisation and aggressive drug evaluation) trial with either mild or moderate-to-severe ischaemia at baseline failed to demonstrate a reduction in death or myocardial infarction in patients treated with PCI compared with those who received medical therapy.”


Stergiopoulous et al included five studies in the meta-analysis, which included COURAGE, MASS (Medicine, angioplasty, or surgery) II, and FAME (Fractional flow reserve vs. angiography for multivessel disease) 2. They reviewed data for patients who were identified as having myocardial ischaemia (through stress testing or FFR) and looked at the incidence (after a maximum of five years of follow-up) of all-cause death, non-fatal myocardial infarction, unplanned revascularisation, or angina in these patients. Of 4,064 patients in the meta-analysis, via randomisation, 2,106 received PCI and 2,048 received medical management alone.


The rate of all-cause death was not significantly different between treatment groups—6.5% for patients receiving PCI vs. 7.3% for patients receiving medical management alone (p=0.42). There were also no differences in the rates of non-fatal myocardial infarction (9.2% for PCI vs. 7.6% for medical management; p=0.06), unplanned revascularisation (18.3% vs. 28.4%; p=0.14), and recurrent or persistent angina (20.3% vs. 23.3%; p=0.67).


According to the authors, the results “strongly suggested” that the relationship between ischaemia and mortality is not altered or ameliorated by catheter-based revascularisation of obstructive flow-limiting coronary stenosis and that the genesis of late clinical events is not necessarily a consequence of the ischaemic vascular territory subtending a stenotic coronary segment “but rather due to the development of new plaque ruptures in distant coronary segments without flow-limiting stenoses.” They add the findings also “call into question the common practice of ischaemia-driven revascularisation where the presence of myocardial ischaemia routinely determines patient selection for coronary angiography and revascularisation.”


Brown told Cardiovascular News: “This meta-analysis suggests that the cardiology community reconsider the strategy of ischaemia-guided revascularisation. Many of the over 10 million stress tests performed annually in the USA are to identify ischaemia as a prelude to referral for revascularisation. If our findings are confirmed in the ongoing ISCHEMIA trial, many of these stress tests and subsequent revascularisations may be unnecessary.”

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