Diabetes and Coronary Artery Disease: Is PCI Still an Option? 20 years after BARI, is There Reason to Believe it’s Different Now?
ACCEL | Patients with diabetes mellitus (DM) are prone to a diffuse and rapidly progressive form of atherosclerosis, which increases their likelihood of requiring revascularization. So, it should be no surprise that 30% to 35% of patients undergoing revascularization have DM.1
Presence of diabetes is associated with worse outcomes for both coronary intervention and bypass surgery and, ever since publication of the BARI (Bypass Angioplasty Revascularization Investigation) study,2 it has been thought that CABG is better than PCI for patients with DM and multivessel disease.
Is that still true? Many advances have occurred in the nearly 20 years since publication of the BARI results. Drug-eluting stents (DES), for example, are broadly used and the second-generation devices significantly reduce restenosis rates in patients with and without DM compared with bare-metal stents (BMS). In recent years, papers have shown conflicting results in terms of whether PCI remains a correlate of restenosis in patients with DM.
Recently, Stone and colleagues conducted an analysis of 18 pooled randomized trials to assess whether baseline lesion complexity affects outcomes following PCI with DES according to diabetic status.3 The study, the largest analysis to date examining DES outcomes relating to DM, suggested that freedom from repeat revascularization 1 year post-DES was comparable in patients with and without diabetes at least for simple stented lesions (TABLE). However, for patients with diabetes and complex lesions, there were significantly higher rates of repeat revascularization after DES than individuals without DM.
We also now have 5-year results from the Syntax (Synergy Between PCI with TAXUS and Cardiac Surgery) trial of patients with 3-vessel disease treated with CABG or PCI.4 The results suggest that CABG should remain the standard of care for patients with diabetes as this approach resulted in significantly lower rates of death, MI, and repeat revascularization than PCI, while stroke rates were similar. One issue that could affect the trial results: the comparator to CABG was first-generation paclitaxel-eluting stents (PES).
The aforementioned analysis by Stone and colleagues included studies of both first- and second-generation DES and was not powered to examine the impact different types of DES might have had on the interaction between DM status and lesion complexity. However, stent type was used as a variable for the propensity score match to minimize the impact of any such effects.
In this regard, although a network meta-analysis of randomized trials suggested that everolimus-eluting stents might be the safest and most efficacious in patients with DM,5 a recent nationwide study did not show substantial differences in clinical restenosis rates between different stent types in patients with DM.6 Use of EES was associated with improved outcomes compared with sirolimus-eluting stents (SES) or PES, mainly driven by lower rates of stent thrombosis and mortality. These results suggest better safety rather than efficacy with EES when compared with first-generation SES or PES.
The SYNTAX trial authors acknowledged that patients with complex CAD (intermediate or high SYNTAX scores) particularly benefit from CABG, “whereas PCI is an acceptable treatment option in patients with less complex disease (low SYNTAX scores), though at a price of significantly higher rates of repeat revascularization.”
In the Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial,7 CABG was superior to PCI in that it significantly reduced rates of death and MI, but at a cost of a higher rate of stroke: 5-year stroke rates of 2.4% in the PCI group and 5.2% in the CABG group (p=0.03). It should be noted that FREEDOM was not powered to detect a difference in all-cause mortality, but there was a higher rate in the PCI-treated group (p=0.049). Also, 94% of patients were treated exclusively with either SES or PES.
Interestingly, in a subanalysis of the FREEDOM trial, investigators reported that the rate of MACE (death, MI, or stroke) was higher in patients treated with insulin than in those not treated with insulin.8They also documented that insulin-treated patients have worse clinical outcome regardless of the treatment arm, which may either be due to more aggressive disease or an adverse effect of insulin.
The most recent data come from two studies both published at the end of March 2015. One was the Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease (BEST) study.9 The trial was terminated early due to slow enrollment, leaving 880 patients to be randomized. At 2 years, the primary endpoint (a composite of death, MI, or TVR) had occurred in 11.0% of the patients in the PCI group and in 7.9% of those in the CABG group and at a median of 4.6 years, the primary endpoint had occurred in 15.3% of the patients in the PCI group and in 10.6% of those in the CABG group (HR: 1.47; p=0.04).
The second recent paper was an observational registry study, comparing outcomes in patients with multivessel disease who underwent CABG or PCI with EES.10 Each group had 9,223 patients with similar propensity scores. The risk of death associated with PCI with everolimus-eluting stents was similar to that associated with CABG, but PCI was associated with a higher risk of MI (among patients with incomplete revascularization) and repeat revascularization but a lower risk of stroke.
The authors wrote that the choice between CABG and PCI with EES may depend on whether complete revascularization can be achieved with PCI. “If the answer is yes, the choice between PCI and CABG should be made on the basis of weighing the short-term risk of death and stroke with CABG against the long-term risk of repeat revascularization with PCI. If complete revascularization does not appear to be feasible on the basis of anatomy, our data then suggest that such patients do better with CABG.”
In an editorial accompanying these two papers, Robert A. Harrington, MD, Chair of the Department of Medicine at the Stanford University School of Medicine, wrote, “To the extent that the data from these two studies can be relied on, there are clearly tradeoffs between the two revascularization strategies that need to be discussed with patients as part of the shared decision-making process.”11
However, he added: “Although these conclusions seem reasonable on the basis of the current data, we should do better than base clinical decisions on flawed observational studies and undersized randomized trials. It should be unacceptable to have evidence voids in areas so common and so costly (in clinical and financial terms) to the public health.”
Instead, Dr. Harrington noted, we should be making shared decisions on the basis of a continuously accumulating set of data that includes randomized comparisons when appropriate.
- In direct comparisons, CABG has been shown to be associated with fewer repeat revascularizations than PCI, but questions have been raised about incremental improvements in stent technologies that might narrow the outcome gap between these two approaches.
- When comparing patients with and without diabetes, the data suggest tradeoffs between these two revascularization strategies that need to be discussed with patients as part of the shared decision-making process.
- Also, there is a need for better ways to aggregate and analyze large amounts of clinical data to better inform practice at the point of care.
- Aronson D, Edeman ER. Rev Endocr Metab Disord. 2010;11:75-86.
- The BARI Investigators, Alderman E, Bourassa M, Brooks MM, et al. Circulation. 1997;96:1761-9.
- Kedhi E, Généreux P, Palmerini T, et al. J Am Coll Cardiol. 2014;63:2111-8.
- Head SJ, Davierwala PM, Serruys PW, et al. Eur Heart J. 2014;35:2821-30.
- Bangalore S, Kumar S, Fusaro M, et al. BMJ. 2012;345:e5170.
- Kedhi E, Gomes ME, Lagerqvist B, et al. J Am Coll Cardiol Intv. 2012;5:1141-9.
- Farkouh ME, Domanski M, Sleeper LA, et al. N Engl J Med. 2012;367:2375-84.
- Dangas GD, Farkouh ME, Sleeper LA, et al. J Am Coll Cardiol. 2014;64:1189-97.
- Park SJ, Ahn JM, Kim YH, et al. N Engl J Med. 2015 26;372:1204-12.
- Bangalore S, Guo Y, Samadashvili Z, Blecker S, Xu J, Hannan EL. N Engl J Med. 2015;372:1213-22.
- Harrington RA. N Engl J Med. 2015;372:1261-3.
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