with no overall difference in the risk of all MI. The point estimate for PCI versus medical therapy for the outcome of all‐cause mortality and cardiovascular mortality paralleled that of spontaneous non‐procedural MI (incident rate ratio = 0.70; 95% CI 0.44–1.09), but was not statistically significant [23]. Another meta‐analysis of 15 trials with 14 669 patients with stable CAD that included data from the ISCHEMIA trial once again confirmed that PCI does not reduce the rates of overall mortality (relative risk = 0.98;95% CI 0.87–1.1), cardiovascular mortality or myocardial infarction, compared to medical therapy [24]. In a network meta‐analysis from 100 trials in 93 553 patients with 262 090 patient‐years of follow‐up, new generation drug eluting stents (everolimus: rate ratio 0.75, 95% CI 0.59–0.96; zotarolimus (Resolute): 0.65, 95% CI 0.42–1.00) were associated with improved survival compared with medical treatment [25]. However, balloon angioplasty (0.85, 95% CI 0.68–1.04), bare metal stents (0.92, 95% CI 0.79–1.05), or early generation drug eluting stents (paclitaxel: 0.92, 95% CI 0.75–1.12; sirolimus: 0.91, 95% CI 0.75–1.10; zotarolimus (Endeavor): 0.88, 95% CI 0.69–1.10) were not associated with improved survival compared with medical treatment. The findings suggest that there may be improved survival with new (second) generation DES but not with other PCI technology, compared with medical treatment. These reports are provocative and challenge the general dogma that PCI has no impact on mortality. The findings are especially notable because the randomized trials have generally limited the enrolment to patients with single vessel disease and have excluded high risk patients with left main disease or chronic total occlusion for whom revascularization can offer greater benefit. Thus, until further data are available and strategies for risk stratification are improved, therapeutic decisions ought to be based on guidelines, but tailored according to a combined assessment of the patient’s clinical presentation, severity of ischemia, and coronary anatomy.
Comparison of percutaneous and surgical revascularization
The available evidence suggests that PCI and CABG are equivalent for the treatment of single vessel disease. This was specifically investigated in the MASS trial at a single center in which patients with significant (>80%) proximal LAD stenosis were randomized to balloon angioplasty, CABG, or medical therapy. The data demonstrated that there was similar relief of symptoms with both forms of revascularization. However, revascularization resulted in a lower incidence of inducible ischemia compared to medical therapy alone, and all three strategies resulted in the effective treatment of limiting angina [17]. Similar findings have been reported from another small study of 134 patients with isolated proximal LAD stenosis in which angioplasty and CABG produced comparable results [26] also when the follow‐up is prolonged to 10 years [27]. Importantly, the need for repeat revascularization during follow‐up was greater with percutaneous revascularization using balloon angioplasty in both trials.
In the assessment of trials comparing surgery with PCI, an important premise is that none of these studies have specifically addressed the functional significance of the lesions treated. With respect to PCI in multivessel disease, the Fractional Flow Reserve vs Angiography for Multivessel Evaluation (FAME) trial demonstrated that a targeted strategy guided by measurement of FFR provides superior outcomes at one year compared with treatment of all vessels with visually estimated significant stenoses [28]. Several randomized clinical trials [29–34] and meta‐analyses of the data [35] have compared PCI directly with CABG for the treatment of single and multivessel disease. The studies, predominantly from the pre‐stent era, were among relatively low risk patients with multivessel disease and preserved LV function. By design, the inclusion criteria for these trials had mandated that the coronary anatomy was suitable for both forms of revascularization, thereby excluding most patients with very complex coronary anatomy or chronic total occlusions. These older trials provided important lessons, but are not directly relevant to current practice because they predated stents and the widespread use of internal mammary artery graft in CABG.
The largest of these studies is the Bypass Angioplasty Revasculari‐zation Investigation (BARI) trial in which 1829 patients were enrolled. PCI was performed with balloon angioplasty which was associated with similar frequency of death, myocardial infarction, and recurrent angina when compared with CABG during 10 years of follow‐up in the overall study population [36]. Not surprisingly, repeat revascularization was significantly less common in patients randomized to surgery. One notable finding that has influenced current practice is that cardiac mortality was significantly lower (19.4% vs 34.5%; p = 0.003) amongst diabetics requiring glucose lowering therapy who were randomized to CABG and received at least one mammary graft. Potential explanations for this observation are that CABG offers complete revascularization and hence mitigates some of the adverse impact of the greater atherosclerotic burden and “future culprit” lesions, as well as the greater likelihood of restenosis and disease progression in diabetic patients. This finding has been confirmed in a more recent study [37] but the clinical relevance and applicability of the BARI study results have been questioned by the findings from the BARI registry, which highlighted the importance of clinical judgment. The patients in the registry had clinical characteristics that were similar to those in the randomized trial, but the survival among diabetic patients was similar regardless of whether angioplasty or CABG was performed. It has been speculated that the conflicting results between the registry and the trial may have been because the treatment assignment in the registry was at the discretion of the physicians who might have selected the most appropriate form of revascularization for each patient [38].
The Arterial Reascularization Therapy Study Part I (ARTS I) and the Stent or Surgery (SoS) trials have compared bare metal stent based PCI with CABG [39,40]. In the ARTS I trial, death and myocardial infarction were similar with both treatment strategies, but, as one might expect, complete revascularization was less often achieved and repeat revascularization was more frequent with percutaneous revascularization. The results of the SoS trial were similar but, for reasons that are unclear, there was an unexpected higher mortality associated with PCI (5% vs 2%; p = 0.01), likely unrelated to treatment selection as the difference was entirely a result of non‐cardiac deaths. The long‐term results (5–6 years) of the ARTS, ERACI II, and SoS trials, and a large (7812 patients) meta‐analysis including 10 randomized trials of balloon angioplasty or stenting vs surgery with a median follow‐up of 5.9 years has been published [41–44]. In the meta‐analysis, long‐term mortality was similar after CABG and PCI in patients with multivessel CAD (hazard ratio 0.91, 95% CI 0.82–1.02; p = 0.12). CABG was associated with a significantly lower mortality in patients with diabetes (HR 0.70, 0.56–0.87; p = 0.014 for interaction) and patients aged 65 years or older (0.82, 95% CI 0.70–0.97; p = 0.002 for interaction).
DES account for vast majority of stents used for contemporary PCI around the world, but there are limited data comparing the outcomes between PCI using DES and CABG. There are three randomized clinical trials (SYNTAX, CARDia, and FREEDOM) to date [45–47]. The Synergy Between PCI with TAXUS and Cardiac Surgery (SYNTAX) trial randomized 1800 patients with three vessel and/or left main disease to either CABG or PCI after a local interventional cardiologist and cardiac surgeon at each site prospectively evaluated eligible patients and determined that equivalent anatomic revascularization could be achieved with either strategy [45]. A score of anatomic complexity (SYNTAX score: www.syntaxscore. com) was prospectively calculated. Unlike most previous trials where a small minority of patients who were screened were ultimately enrolled, almost half of the 4337 screened were randomized, with the majority of those excluded were unsuitable for PCI. The rates of death and myocardial infarction at 12 months were similar in the two groups. Stroke was significantly more frequent in the CABG group (2.2% vs 0.6%; p = 0.003) while the incidence of stent thrombosis and symptomatic graft occlusion at 12 months were similar in the two groups (3.3 and 3.4%, respectively). An increased rate of repeat revascularization in the PCI group (13.5% vs 5.9%; p < 0.001) led to an excess of major cardiac and cardiovascular events in the PCI group, with the endpoint of the trial (non‐inferiority of PCI using DES) not being met. Subgroup analysis based on the predetermined SYNTAX score showed that the negative outcome was confined to patients with high scores (>33, 10.9% in the surgical arm vs 23.4% in the PCI arm). The patients with left main disease had similar incidence of 12 month MACE in the surgical
