Coronary revascularisation in patients with diabetes: a chance to be better
- Correspondence to
: Professor Stephan Windecker
Department of Cardiology, Bern University Hospital, Freiburgstrasse 4, Bern 3010, Switzerland;
Commentary on: Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularisation in patients with diabetes. N Engl J Med 2012;367:2375–84.
In 2009, a pooled analysis of individual patient data from randomised clinical trials comparing percutaneous coronary interventions (PCI) with coronary artery bypass grafting (CABG) showed a survival benefit in favour of CABG.1 Techniques of both PCI and CABG evolved during the last decade with the use of drug-eluting stents (DES) and novel antiplatelet agents.
In the FREEDOM trial, patients with diabetes and multivessel coronary artery disease (CAD) were randomised with concealed allocation to PCI with DES (94% sirolimus-eluting and paclitaxel-eluting stents) or CABG. Key exclusion criteria were left main stenosis, severe heart failure, acute myocardial infarction (MI), CK>2× normal, prior cardiac surgery or PCI, previous stroke, contraindication to CABG/DES and extracardiac illness with expected survival <5 years. The primary endpoint was a composite of death, non-fatal MI and non-fatal stroke.
Between 2005 and 2010, 33 966 patients were screened; 3309 patients (9.7%) considered eligible and 1900 patients (5.6%) enrolled. The mean age was 63 years. A total of 71% of patients were men and 83% had three-vessel CAD. At 5 years, the primary endpoint occurred more frequently among patients allocated to PCI than CABG (26.6% vs 18.7%, p=0.005), which was driven by a borderline significant reduction in death (16.3% vs 10.9%, p=0.049) and a marked reduction in MI (13.9% vs 6.0%, p < 0.001) favouring CABG. Conversely, PCI was associated with a lower risk of stroke (2.4% vs 5.2%, p=0.03). Cardiovascular mortality did not differ significantly between PCI and CABG (10.9% vs 6.8%, p=0.12).
FREEDOM is the only adequately powered randomised trial comparing PCI with use of early-generation DES and CABG among patients with diabetes with multivessel CAD. It demonstrated superiority of CABG for the composite of death, MI or stroke at 5 years. This landmark trial has several strengths including its size, the simple design, the meaningful primary endpoint, the high compliance to evidence-based medications in both groups and the consistent findings across a number of subgroups—including sex, race, ejection fraction and renal function. Nevertheless, some issues deserve consideration. First, event curves began to diverge only after 2 years of follow-up, at which time an imbalance in the completeness of ascertainment of vital status between groups emerged. This was related to a higher rate of patients who withdrew from the study in the CABG arm than in the PCI arm (6.6% vs 2.0%), which may have influenced the outcome due to attrition bias. Second, the borderline difference in all-cause mortality does not appear to be driven by cardiovascular death, raising the question of mechanisms underlying the benefit of CABG over PCI. Third, the median follow-up duration was 3.8 years, but only 440 patients (23.1%) were at risk at 5 years. Longer duration of follow-up will be important to establish whether a time-dependent effect is observed with respect to outcome. Finally, new generation DES have been shown to improve long-term safety and efficacy compared with early-generation devices used in FREEDOM.2 Whether the use of new generation DES improves outcomes among patients with diabetes with complex CAD remains to be determined.
In the SYNTAX trial, PCI with paclitaxel-eluting stents resulted in increased rates of death, MI, stroke or repeat revascularisation compared with CABG (37.5% vs 24.2%, p=0.0002) among the prespecified subgroup of patients with diabetes (N=452) at 5 years.3 Notably, the SYNTAX score was predictive of cardiovascular outcomes in the overall population and in patients with diabetes, with patients with low SYNTAX scores (0–22) showing similar outcomes after PCI and CABG. FREEDOM did not confirm these findings, however, it is unclear whether the SYNTAX score was ascertained by a core laboratory.4
Taking together FREEDOM and SYNTAX, the long-term advantage of CABG over PCI with DES in terms of major adverse cardiac events—except for stroke—is evident among patients with diabetes and multivessel CAD. The latter applies to patients with complex CAD, not representing the majority of patients in everyday clinical practice. Only 6% of screened patients were finally enrolled in FREEDOM. This underscores that potential candidates for both PCI and CABG represent only a minority of cases, whereas the indication for one of the two strategies is clear in the vast majority of patients given their baseline risk profile, anatomical considerations and patient preferences.5 Robust trials such as FREEDOM undoubtedly guide informed clinical decisions and future investigations among patients with diabetes and complex CAD, since ‘FREEDOM is nothing but a chance to be better’.6