Comparable 10-Year Mortality in Elderly Patients After PCI or CABG: SYNTAXES
The 5-year data suggested the mortality curves were separating in favor of surgery, but that trend didn’t hold up later on.
Revascularization with PCI might be a reasonable alternative to CABG surgery in elderly patients with complex coronary artery disease, including multivessel and left main disease, according to long-term follow-up from the SYNTAX Extended Survival trial.
At 10 years, the rates of all-cause mortality were similar between the two revascularization strategies among patients aged 70 years and older, while at 5 years, patients treated with PCI had comparable rates of major adverse cardiovascular and cerebrovascular events as those treated surgically.
“We’re currently learning a lot of things about these studies with 10-year follow-up,” senior investigator Patrick W. Serruys, MD, PhD (National University of Ireland, Galway), told TCTMD. “Many of the assumptions that I had about 10 years are really challenged by what we are finding day after day. It’s a little bit different from what we were expecting in the sense that when you see the mortality curves diverging at 5 years, like the surgeons [were concerned about], we all had expected that the curves would keep diverging over time.”
At 5 years in SYNTAX, there was no significant difference in the risk of death between surgery and PCI with a first-generation paclitaxel-eluting stent (Taxus; Boston Scientific), and while there was a thought that longer-term follow-up might ultimately favor cardiac surgery, that trend was not borne out. The 10-year results of SYNTAX were presented just 2 years ago and showed comparable all-cause mortality among patients treated surgically and those treated with PCI. There also were no significant differences in mortality between treatments for patients with multivessel disease and for those with left main CAD.
The new analysis, which is published May 31, 2021, in the Journal of the American College of Cardiology, focused on the elderly and includes follow-up for 93.8% of the original 1,800 patients with de novo three-vessel disease or left main CAD randomized to treatment with PCI or CABG surgery.
Cardiac surgeon Robbin Cohen, MD (University of Southern California, Los Angeles), who wasn’t involved in the analysis, said the highly respected SYNTAX trial was one of the studies that demonstrated CABG surgery was superior to catheter-based interventions. The 1-year results, published more than a decade ago, found that CABG was better than PCI for reducing the risk of MACCE, a benefit that was driven by a higher rate of revascularization with PCI. The 5-year results confirmed those early findings, with investigators reporting higher rates of MI and revascularization in the PCI-treated patients.
The latest 10-year results focusing on elderly patients have several limitations that limit their generalizability, he said, all of which are acknowledged by the researchers. For example, defining “elderly” as 70 years or older is somewhat arbitrary; the technology, including the use of Taxus, is no longer used; and the background medical therapy used then wasn’t as good as it is today. Most importantly, patients included in the trial were only randomized if they could be treated with either revascularization strategy.
“I do think that the biggest glitch in a study like SYNTAX is that in order to be enrolled you had to be a candidate for multivessel PCI and coronary bypass surgery,” said Cohen. “Most of the patients we see these days for surgery are really not PCI candidates. Most of them have multiple, complicated lesions or diffuse disease, or complicated left main disease, so the decision is easier to make towards surgery rather than PCI.”
Still, Cohen pointed out that coronary stent technology has improved since the first-generation devices, as have the skills of interventional cardiologists, including their ability to treat left main CAD. For that reason, he said it wouldn’t be surprising to see more elderly patients undergoing PCI for multivessel/left main CAD but hoped these new data would not be used to undermine the current team-based approach to care.
“One of the biggest questions is whether cardiologists will use data like these to bypass offering surgery,” he said. “I think that would be a mistake given how successful the concept of the heart team has been and how well we’re now working together to make the best decision for every patient. But I do think this will stimulate some interesting conversations.”
SYNTAX Conducted Between 2005 and 2007
Among 1,800 patients randomized in SYNTAX, 31.9% were older than 70 years. In these elderly patients, all-cause mortality at 10 years did not significantly differ between the PCI- and CABG-treated groups (44.1% vs 41.1%; P = 0.530). In those younger than 70 years, PCI was associated with a numerically higher death risk of borderline statistical significance (21.1% vs 16.6%; P = 0.052). The test for interaction between treatment and age was not statistically significant, however (P = 0.332).
Given the advancing age of those who were 70 years and older at the study outset, Serruys said it’s not surprising to see such a high mortality rate at 10-year follow-up. “On the other hand, you enter the trial at 70 and they’re now 80 years old and roughly 60% of these individuals are alive,” he said.
Focusing on survival within 10 years of the index procedure, elderly patients treated with PCI had a life expectancy of 7.9 years compared with 7.7 years for those undergoing CABG surgery, a nonsignificant difference. The researchers point out that the analysis might be underpowered to detect disparities in life expectancy but note that the upper bound of the confidence interval between the treatments suggests CABG might be associated with a benefit of 0.7 years, which is just 8 months over 10-year follow-up.
With respect to MACCE at 5 years, there was no difference in risk among elderly patients treated with PCI or CABG surgery (39.4% vs 35.1%; P = 0.233). In those younger than 70 years, however, PCI was associated with a higher risk of MACCE at 5 years (36.3 vs 23.0%; P < 0.001). The test for interaction between treatment and age was statistically significant (P = 0.04). In terms of quality of life at 5 years, health status was similar between the PCI and the CABG groups, with patients reporting comparable angina frequency, physical limitations, treatment satisfaction, and overall quality of life.
Personalized Care Is Key
To TCTMD, Serruys said the elderly patients in SYNTAX received fewer arterial conduits and more venous conduits than the nonelderly patients. He noted that, generally speaking, the mortality rate for CABG surgery closes in on PCI around 6-8 years, which might be the result of failing saphenous vein grafts. “We know there is a lot of saphenous vein graft attrition around 7 years,” he said. “That’s really the half-life of all these saphenous bypass grafts and might be a reason why there is no difference [in mortality].”
In terms of how these results may shape practice, Serruys emphasized individualized care, highlighting the retooled SYNTAX score, known as SYNTAX II 2020, for predicting the risk of death at 10 years (and MACCE at 5 years) in patients eligible for PCI or CABG surgery. Clinical trials, such as SYNTAX, EXCEL, and FREEDOM, give estimates of the average treatment effect, but a new score like SYNTAX 2020 provide a more personalized estimate of risk, which aids in the discussion with surgeons, interventional cardiologists, and patients, said Serruys.
Whether or not the 10-year results sway more elderly patients towards PCI over surgery, Cohen said that remains to be seen. Like Serruys, he stressed that a personalized approach to care remains the best strategy. “The heart team approach is working, and everybody’s angiogram is so different that I really think it will be a matter of individualizing every patient,” he said. “A lot of what the study implies is currently in place.”
Ravi Hira, MD (Pulse Heart Institute, Tacoma, WA), who wrote an editorial accompanying the study, points out that elderly patients are excluded from most randomized trials but says the baby-boomer generation has sparked a rise in the number of patients with multivessel CAD. He nots that a lot has changed in the 14 years since SYNTAX wrapped up, including the introduction of physiology-guided PCI, intracoronary imaging, newer-generation DES, and complete revascularization.
Ono M, Serruys PW, Hara H, et al. 10-year follow-up after revascularization in elderly patients with complex coronary artery disease. J Am Coll Cardiol. 2021;Epub ahead of print.
Hira RS. Revascularizing complex CAD in elderly patients: the coming-of-age story of percutaneous coronary intervention. J Am Coll Cardiol. 2021;Epub ahead of print.
- Serruys reports personal fees from Biosensors, Micel Technologies, Sinomedical Sciences Technology, Philips/Volcano, Xeltis, and HeartFlow.
- Cohen reports no conflicts of interest.
- Hira reports consulting for Abbott Vascular and Boston Scientific; and speaking engagements for Abiomed.