Author + information
- Antonio Colombo, MD⁎ ( and )
- Azeem Latib, MD
- ↵⁎Reprint requests and correspondence:
Dr. Antonio Colombo, EMO-GVM Centro Cuore Columbus, Via Buonarroti 48, 20145 Milan, Italy
- coronary angioplasty
- coronary artery disease
- myocardial perfusion imaging
- outcome research
- percutaneous transluminal
Percutaneous revascularization for coronary artery disease (CAD) aims to treat ischemia-producing lesions with a focus on eliminating their negative impact. However, coronary atherosclerosis is a generalized and progressive disease. Treatment of a culprit stenosis may not alter the natural history of CAD in which nonobstructive and non–ischemia-producing lesions can progress to high-grade stenoses (1). In addition, a lack of clinical data documenting the long-term impact of disease progression after successful contemporary revascularization has resulted in an underestimation of its contribution to future adverse events. Indeed, one of the most difficult questions that patients and referring physicians could ask us is: Will future adverse events arise from the vessel revascularized or from progression of atherosclerotic disease in another coronary vessel or in other segments of the treated artery? In this context, the findings of the BASKET-PRO (Basel Stent Kosten-Effektivitäts Trial–PROgression of CAD) study in this issue of the Journal are enlightening (2), as it provides important information regarding the contribution of remote disease progression, not only on late clinical events but also on new symptomatic or silent ischemia.
The investigators selected 428 patients from the BASKET study (3) with successful and complete revascularization, defined as the absence of clinical events or ischemic perfusion defects at 6 months after intervention, and followed them for 5 years. Repeat single-photon emission computed tomography (SPECT) scans were performed at 5 years on 206 patients without late follow-up events who consented to a second SPECT (35% did not). The main findings of this study were:
• Late clinical events occurred in 25.7% of patients, with a 10% incidence of death and 8.4% of myocardial infarction (MI) from 6 months to 5 years.
• Remote MI or revascularization accounted for 37.1% of the late nonfatal events.
• Event rates were lower in remote versus target-vessel areas (9.8% vs. 14.3%; p = 0.019), mostly due to a lower rate of MI in remote areas (1.9% vs. 6.3%; p = 0.002).
• Patients with target-vessel events were more likely to have both a revascularization and an MI than those with remote events were (33.3% vs. 10.5%; p < 0.01).
• New ischemic perfusion defects were detected in 23.3% and were silent in the majority (71%). Remote ischemia accounted for 37.5% of new perfusion defects in patients without events.
• No difference was detected in the frequency of remote events or new perfusion defects between drug-eluting and bare-metal stents.
We congratulate Zellweger et al. (2) for the very high rate of clinical follow-up (97%), including the large number of SPECT studies performed at 6 months and 5 years. A minor limitation of the present study is that although the investigators quantified the magnitude of events, they gave no information about the nature of these events, especially for the target vessel. Target-vessel events may occur due to the target lesion (restenosis, stent thrombosis, or neoatherosclerosis) or due to proximal or distal disease progression. Similarly, a proportion of the new target-vessel perfusion defects may indicate disease progression rather than stent failure. Thus, it is conceivable that the proportion of late events and new perfusion defects due to CAD progression has been underestimated.
There are a limited number of studies documenting the long-term natural history of CAD progression after stenting with which to compare and validate these data. In a large percutaneous coronary intervention (PCI) registry of 3,474 patients, Glaser et al. (4) reported that 6% of initially nonculprit coronary lesions will have clinical plaque progression requiring non–target-lesion PCI by 1 year. Cutlip et al. (5) provided longer-term data on 1,228 patients after implantation of second-generation bare-metal stents. Stent-related events predominated during the first year of follow-up (18.3% for target-lesion and 12.4% for non–target-lesion events), becoming less common during years 2 to 5 (average annual hazard rate: 1.7% and 6.3% for target- and non–target-lesion events, respectively). Similarly, remote-vessel and target-vessel revascularization occurred at similar rates between years 2 to 5 (average annual hazard rate: 3.5% vs. 2.4%), but about one-half of the target-vessel revascularizations were due to progression of disease at nonstented sites rather than failure of the stent and its margins. In both studies, a larger CAD burden was associated with a significantly higher risk for clinical plaque progression. In the contemporary drug-eluting stent era, Chacko et al. (6) and Leon et al. (7) reported 5-year data from the SIRIUS (Sirolimus-Eluting Stent in De Novo Native Coronary Lesions) and the 4 TAXUS (Treatment of De Novo Coronary Disease Using Paclitaxel-Eluting Stent) studies. In SIRIUS, non–target-vessel MI accounted for 28% and 17% of all MI after sirolimus-eluting and bare-metal stent implantations (6). Although, the 5-year cumulative revascularization incidence was 32.3% in the drug-eluting and 45.0% in the bare-metal stent groups, target-lesion revascularization was 12.5% and 28.8%, respectively. This finding attests to the importance of disease progression in remote coronary segments as a significant source of future adverse events. Similarly, in the pooled 5-year TAXUS data, approximately one-half of all late Q-wave MIs occurred in nonstented vessels (thus completely unrelated to the stent); and non–target-lesion revascularization contributed equally with target-lesion revascularization to the low ongoing rate of target-vessel revascularization after the first year (7). However, no data are provided in this study about the rates of remote-vessel revascularization. Finally, Alexopoulos et al. (8) attempted to characterize the etiology of nonfatal acute MI in 91 cases occurring 1 month after stent implantation (32.6% drug-eluting stents). Myocardial infarction was attributed to disease progression at another site in 46.2%, restenosis in 38.4%, and stent thrombosis in 11% of cases with a median time from PCI to MI of 27, 19, and 9 months, respectively. These 5 studies display a common thread. Disease progression may be as important as stent failure and accounts for about one-half of the adverse events during long-term follow-up. However, we should not forget that the aforementioned studies are limited by the inclusion of low-risk patients and lack the high rate of clinical follow-up seen in the BASKET-PRO study; some were retrospective; none were specifically designed to study disease progression; and all focused only on patients with events. The most distinctive feature of BASKET-PRO is the performance of SPECT scans at 5 years in patients without events in order to evaluate the magnitude and contribution of clinically significant but “silent” CAD progression.
A question that the critical observer is forced to ask, is whether surgical revascularization would have resulted in different outcomes, particularly as the majority of events were related to the target vessel? Although coronary artery bypass grafting (CABG) has no effect on disease progression in nonbypassed vessels, Kroncke et al. (9) have elegantly demonstrated that grafting a coronary artery increases the risk of disease progression 3 to 6 times; predominantly resulting in proximal (74%) rather than distal progression in arteries with patent grafts; and the majority (78%) of progression in grafted arteries was to 100% occlusion. Despite this negative effect on disease progression, an arterial bypass graft may better protect the coronary vessel by preventing future events from proximal disease progression or plaque rupture. Indeed, the 4-year data from the SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) trial recently presented by Patrick Serruys at the European Association of Cardiothoracic Surgery meeting in Lisbon should force us to take a moment of reflection. At 4 years, the rate of cardiac death and MI after revascularization in patients with multivessel disease were significantly higher after PCI versus CABG (7.6% vs. 4.3%, p = 0.004, and 8.3% vs. 3.8%, p < 0.001). A difference in major adverse cardiovascular and cerebrovascular event rates in favor of CABG was observed in patients with intermediate (23 to 32) or high SYNTAX scores (≥33), suggesting that CABG may be the standard of care in patients with complex disease, whereas PCI may be acceptable in patients with less complex disease, including the left main.
So what is the practical take-home message from this study? In patients who are successfully and completely revascularized at 6 months, 1 in 4 will have an event at 5 years and this event will be due to disease progression in 40% to 50%. In those who have not had an event, 1 in 4 will have clinically significant inducible ischemia (silent in the majority) and again this will be from disease progression in 40% to 50%. These findings underscore the importance of aggressive secondary prevention, lifestyle modification, and long-term surveillance for inducible ischemia in all patients with CAD. The fact that the majority of late events and new perfusion defects are target-vessel–related should prompt us to consider CABG for proximal diffuse disease of the left anterior descending artery. Paradoxically left main disease without much proximal and mid-left anterior descending disease may be a PCI target.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
↵⁎ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
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