A recent meta-analysis published in JAMA by Stergiopoulos et al. compared the effects of PCI and medical treatment (MT) combined, with MT alone in patients with stable coronary artery disease (CAD) and objectively documented myocardial ischemia. Of interest, they concluded that in patients with stable CAD and objectively documented myocardial ischemia, PCI and MT combined was not associated with a reduction in death, nonfatal MI, unplanned revascularization, or angina compared with MT alone (see Results below).

The meta-analysis included data obtained from  MEDLINE, Cochrane and PubMed databases from 1970 to November 2012. Hence randomized clinical trials of PCI and MT vs MT alone for stable coronary artery disease in which stents and statins were used in more than 50% of patients were included in the analysis. For studies in which myocardial ischemia diagnosed by stress testing or fractional flow reserve was required for enrolment, descriptive and quantitative data were extracted from the published report. For studies in which myocardial ischemia was not a requirement for enrolment, the authors provided data for only those patients with ischemia determined by stress testing prior to randomization. In 5 trials including 5286 patients, myocardial ischemia was diagnosed in 4064 patients by exercise stress testing, nuclear or echocardiographic stress imaging or fractional flow reserve. Clinical outcomes analyzed included: death from any cause, nonfatal myocardial infarction (MI), unplanned revascularization and angina. Follow-up ranged from 231 days to 5 years (median, 5 years). The respective event rates for PCI with MT vs MT alone for death were 6.5% and 7.3% (OR, 0.90 [95% CI, 0.71-1.16); for nonfatal MI, 9.2% and 7.6% (OR, 1.24 [95% CI, 0.99-1.56]); for unplanned revascularization, 18.3% and 28.4% (OR, 0.64 [95% CI, 0.35-1.17); and for angina, 20.3% and 23.3% (OR, 0.91 [95% CI, 0.57-1.44]).

MAIN RESULTS: Odds Ratio, PCI vs Medical Therapy

 Outcome

Odds ratio

95% CI

 Death

0.90

0.71–1.16

 Nonfatal MI

1.24

0.99–1.56

 Unplanned revascularization

0.64

0.35–1.17

 Angina

0.91

0.57–1.44

 Reference

1. Percutaneous Coronary Intervention Outcomes in Patients With Stable Obstructive Coronary Artery Disease and Myocardial Ischemia A Collaborative Meta-analysis of Contemporary Randomized Clinical Trials Kathleen Stergiopoulos, MD, PhD; William E. Boden, MD; Pamela Hartigan, PhD; Sven Möbius-Winkler, MD; Rainer Hambrecht, MD; Whady Hueb, MD, PhD; Regina M. Hardison, MS; J. Dawn Abbott, MD; David L. Brown, MDJAMA Intern Med. doi:10.1001/jamainternmed.2013.12855 Published online December 2, 2013.

Cardio Debate Expert Comments

The principal finding of this meta-analysis of 5 randomized clinical trials which included a German trial published in 2004, MASS II , COURAGE , BARI 2D  and FAME 2, in patients with stable obstructive CAD and myocardial ischemia documented by stress testing or FFR is that a strategy of initial PCI in combination with MT results in no significant reduction in mortality, nonfatal MI, unplanned revascularization, or angina compared with MT alone. These findings are unique in that this is the first meta-analysis limited to patients with documented, objective, findings of myocardial ischemia, almost all of whom underwent treatment with intracoronary stents and disease-modifying secondary prevention therapy.

I agree with the authors that the results strongly suggest that the relationship between ischemia and mortality is not altered or ameliorated by catheter-based revascularization of obstructive, flow-limiting, coronary stenoses. The lack of clinical benefit from PCI in patients with inducible ischemia suggests that the genesis of late clinical events is not necessarily a consequence of the ischemic vascular territory subtended by a stenotic coronary segment but rather due to the development of new plaque ruptures in other coronary segments without flow-limiting stenoses.  Of importance, these findings call into question the common practice of ischemia-guided revascularization (either using non invasive testing techniques or FFR) where the presence of myocardial ischemia routinely determines patient selection for coronary angiography and revascularization.

However, the study has limitations i.e. the analysis carried out by the authors could not distinguish between patients who had small amounts of ischemia from those with larger ischemic territories. This issue will be definitively addressed by the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) Trial (www.clinicaltrials.gov Identifier NCT01471522), funded by the National Heart, Lung, and Blood Institute. This study of 8000 patients with at least moderate myocardial ischemia will compare the effect of MT combined with revascularization with that of MT alone on cardiovascular death and MI. Until the study is published, we need to consider optimal medical treatment as an option at least as good as PCI+MT based on current data.