Elsevier

The Lancet

Volume 394, Issue 10206, 12–18 October 2019, Pages 1325-1334
The Lancet

Articles
Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial

https://doi.org/10.1016/S0140-6736(19)31997-XGet rights and content

Summary

Background

The Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial was a non-inferiority trial that compared percutaneous coronary intervention (PCI) using first-generation paclitaxel-eluting stents with coronary artery bypass grafting (CABG) in patients with de-novo three-vessel and left main coronary artery disease, and reported results up to 5 years. We now report 10-year all-cause death results.

Methods

The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension of follow-up of a multicentre, randomised controlled trial done in 85 hospitals across 18 North American and European countries. Patients with de-novo three-vessel and left main coronary artery disease were randomly assigned (1:1) to the PCI group or CABG group. Patients with a history of PCI or CABG, acute myocardial infarction, or an indication for concomitant cardiac surgery were excluded. The primary endpoint of the SYNTAXES study was 10-year all-cause death, which was assessed according to the intention-to-treat principle. Prespecified subgroup analyses were performed according to the presence or absence of left main coronary artery disease and diabetes, and according to coronary complexity defined by core laboratory SYNTAX score tertiles. This study is registered with ClinicalTrials.gov, NCT03417050.

Findings

From March, 2005, to April, 2007, 1800 patients were randomly assigned to the PCI (n=903) or CABG (n=897) group. Vital status information at 10 years was complete for 841 (93%) patients in the PCI group and 848 (95%) patients in the CABG group. At 10 years, 248 (28%) patients had died after PCI and 212 (24%) after CABG (hazard ratio 1·19 [95% CI 0·99–1·43], p=0·066). Among patients with three-vessel disease, 153 (28%) of 546 had died after PCI versus 114 (21%) of 549 after CABG (hazard ratio 1·42 [95% CI 1·11–1·81]), and among patients with left main coronary artery disease, 95 (27%) of 357 had died after PCI versus 98 (28%) of 348 after CABG (0·92 [0·69–1·22], pinteraction=0·023). There was no treatment-by-subgroup interaction with diabetes (pinteraction=0·60) and no linear trend across SYNTAX score tertiles (ptrend=0·20).

Interpretation

At 10 years, no significant difference existed in all-cause death between PCI using first-generation paclitaxel-eluting stents and CABG. However, CABG provided a significant survival benefit in patients with three-vessel disease, but not in patients with left main coronary artery disease.

Funding

German Foundation of Heart Research (SYNTAXES study, 5–10-year follow-up) and Boston Scientific Corporation (SYNTAX study, 0–5-year follow-up).

Introduction

Several randomised trials1, 2, 3, 4, 5, 6, 7, 8 have compared coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with simple balloon angioplasty, bare metal stents, or drug-eluting stents for the treatment of multivessel or left main coronary artery disease, but no significant differences in survival were demonstrated. Results from a pooled analysis of individual patient data9 from 11 trials and 11 518 patients suggested that all-cause death was significantly lower after CABG versus PCI at 5-year follow-up (9·2% vs 11·2%; hazard ratio [HR] 1·20 [95% CI 1·06–1·37], p=0·0038). However, the mean age of the patient population was 65 years, and thus the overall life expectancy of most patients exceeded this follow-up time. Longer-term follow-up beyond 5 years is required to determine the relative effectiveness of PCI versus CABG. The Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial compared PCI with paclitaxel-eluting stents versus CABG in 1800 patients with de-novo three-vessel disease and left main coronary artery disease, and reported similar survival among patients in the PCI and CABG groups after 5 years of follow-up (13·9% all-cause death in the PCI group vs 11·4% all-cause death in the CABG group, p=0·10).5, 10, 11 This study, the SYNTAX Extended Survival (SYNTAXES) study, examined all-cause death after 10 years of follow-up in patients randomly assigned to PCI or CABG in the SYNTAX trial.

Research in context

Evidence before this study

We searched PubMed for articles published in English between database inception and July 24, 2019, with the following search terms: “percutaneous coronary intervention”, “stents”, “coronary artery bypass grafting”, and “random*”. Randomised controlled trials and meta-analyses comparing percutaneous coronary intervention (PCI) using stents versus coronary artery bypass grafting (CABG) in patients with three-vessel or left main coronary artery disease were included. An individual patient data meta-analysis reported that mortality outcomes favoured CABG over PCI at 5-year follow-up in patients with multivessel disease, particularly those with diabetes and more complex coronary artery disease, whereas no significant difference was identified in patients with left main coronary artery disease. It was concluded that longer-term follow-up would be required to better define mortality differences between revascularisation strategies. In our search, we only found two randomised controlled trials reporting survival outcomes at 10 years after PCI versus CABG. In the MASS II trial, patients with multivessel disease had a 10-year all-cause death rate of 24·9% after PCI versus 25·1% after CABG (p=0·089). However, PCI was done with bare metal stents and about 40% of patients had two-vessel disease, and no patients with left main coronary artery disease were included. In the LE MANS trial, which included only patients with left main coronary artery disease (n=105), 10-year all-cause death was 21·6% after PCI versus 30·2% after CABG (p=0·41). However, the sample size was small and only 35% of PCI procedures were performed with (first-generation) drug-eluting stents. The search did not identify studies reporting outcomes in patients with de-novo three-vessel and left main coronary artery disease randomly assigned to PCI with drug-eluting stents or CABG.

Added value of this study

The current study is the first randomised trial that reports complete 10-year data on all-cause death in patients with de-novo three-vessel and left main coronary artery disease after PCI with drug-eluting stents versus CABG. It provides important insights into the relative effectiveness of PCI versus CABG regarding the most robust and clinically relevant outcome—all-cause death. At 10 years, no significant difference was found in all-cause death between PCI using first-generation paclitaxel-eluting stents and CABG. However, CABG provided a significant survival benefit in patients with three-vessel disease, but not in patients with left main coronary artery disease. These findings can aid decision making for patients with coronary artery disease who require PCI or CABG, accounting for differences in cardiovascular risk factors, coronary lesion complexity (eg, SYNTAX score), and the presence of three-vessel or left main coronary artery disease.

Implications of all the available evidence

Patients with complex, three-vessel coronary artery disease who require revascularisation should undergo CABG as it results in significantly lower all-cause death than PCI. In selected patients with left main coronary artery disease, PCI is a suitable alternative to CABG and provides similar 10-year survival.

Section snippets

Study design and patients

The SYNTAX trial (NCT00114972) was a multicentre, randomised controlled trial done in 85 hospitals across 18 North American and European countries, with the aim of assessing non-inferiority of PCI with paclitaxel-eluting stents versus CABG in patients with de-novo three-vessel disease and left main coronary artery disease for the primary endpoint of major adverse cardiac or cerebrovascular events at 1 year. The rationale, design, and 1-year primary endpoint results of the SYNTAX trial have been

Results

From March, 2005, to April, 2007, 1800 patients were randomly assigned to undergo PCI with paclitaxel-eluting stents (n=903) or CABG (n=897; figure 1). Clinical and angiographic characteristics were well matched between groups (table). Further details about the procedural characteristics of the patients included in this study have been published previously1, 5 and are included in the appendix (p 8).

Information on 10-year survival was collected between March 1, 2017, and June 17, 2019. Two

Discussion

The SYNTAX trial reported similar survival in patients with de-novo three-vessel and left main coronary artery disease randomly assigned to PCI with paclitaxel-eluting stents versus CABG after 5 years of follow-up. The SYNTAXES study is the first study to assess 10-year survival after PCI with drug-eluting stents versus CABG. At 10-year follow-up, the proportions of all-cause deaths between PCI and CABG were similar. Prespecified subgroup analyses identified that CABG resulted in significantly

Data sharing

The SYNTAX Extended Survival study hereby declares that no data will be made available to others.

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