Orlando, FL - Preliminary results of two new studies reported here comparing coronary artery bypass grafting (CABG) with angioplasty/stenting in patients with multivessel disease have further fuelled the debate on how to best treat these patients. One of the studies also included a three-way comparison with drug therapy alone, which emerged as good therapeutic strategy - in the short-term at least - leaving the whole question of best practice wide open until longer-term data from the studies are compiled.

In the late 1980s/early 1990s, a series of trials comparing CABG with balloon angioplasty found they had comparable outcomes, but there was one big disadvantage of the intervention - one in three of the angioplasty patients needed a repeat procedure within a year. However, the rapid evolution of angioplasty equipment and the advent of stents had meant that complications and the need for repeat revascularizations have been much reduced and one of the new trials - SoS (stent or surgery) - was designed to assess the impact of these technological changes.

SoS is being conducted in Canada and 11 European countries, and is designed to compare CABG and stent-assisted angioplasty in more than 900 patients with multivessel disease. The primary endpoint is the need for additional revascularizations, and secondary outcomes include a composite of death or nonfatal Q-wave MI, and all-cause mortality.

Two previous studies have examined these two treatment options - the Arterial Revascularization Therapy Study (ARTS) showed equivalence of the two approaches, while the South American ERACI-II study showed a clear superiority of stent-assisted angioplasty compared with CABG surgery, although it was criticized because of the unusually high mortality rate (5%) seen in those who underwent surgery.

"Strikingly low" mortality rate with surgery in SoS

Dr Rodney Stables (Royal Liverpool University Hospital, Liverpool, UK) reported the 1-year SoS data at the ACC. These show a revascularization rate of just 17% in those undergoing percutaneous intervention - half the rate seen in older trials comparing balloon angioplasty alone with surgery. However, in direct contrast to ERACI II, the SoS data also reveal a strikingly lower mortality in the CABG patients at 1 year, just 0.8% - "beyond the wildest expectation of any surgeon," according to Stables.

However, Stables warned about reading too much into this apparent mortality benefit, noting that mortality was a secondary outcome and that the study was not designed or powered to assess mortality, so the findings "could be due to the play of chance." The death rate in the PTCA group was exactly as expected, although there were 8 cancer deaths in the angioplasty group compared with only one in the surgery group, which could have further clouded the data.

Cause of death PCI CABG Cardiac 1.6% 0.6% Other vascular 0.4% 0.2% Noncardiovascular 1.6% 0.4% Unclassified 0.4% 0% All deaths 4.1% 1.2% All deaths at 1 year 2.5% 0.8%

There were favorable outcomes and a low rate of adverse events in both the surgery and intervention groups in SoS. In fact, apart from the low mortality in the CABG group, the results "are similar to those of the ARTS study," Stables said, adding that they "support the continuing evolution of PCI." He added, "The only difference between the SoS and ERACI-II data seems to be in the performance of the surgeons."

Further analysis of SoS are being conducted - including cost/benefit assessments, quality of life measurements, and neuropsychological outcomes (see below) - all of which are expected to be reported at the ESC meeting in Stockholm in August 2001. "Only then will we know the true role of PCI in revascularization in the multivessel arena," Stables urged. He also noted that further advance such as the use of Gp IIb/IIIa inhibitors during stenting - which was quite low in SoS - and the advent of drug-eluting stents mean that the whole field is "a moving goalpost, with interventionalists always promising 'jam tomorrow.'"

Pump-head assessment built in as prospective outcome

The decision to build a prospective neuropsychological assessment into the SoS study is "one of the most important parts of this trial", commented the pioneer of angioplasty Dr Ulrich Sigwart (Royal Brompton Hospital, London, UK), during a press conference to discuss the results of SoS. He says that "most patients complain about their cognitive function after CABG surgery" and in the light of the recent publication in the NEJM about the so-called phenomenon of "pump head," the results of this part of the SoS trial will be eagerly awaited in Stockholm. Stables noted that most of the CABG patients in the SoS trial were on pump, but some were off, and thus it may be possible to do a small subgroup analysis.

The cost-benefit analyses of the SoS data is being done in conjunction with Emory University (Atlanta, GA) and three participating countries are to be studied in detail - the UK, Germany and Poland. The figures will be assessed using measures that can apply to healthcare systems around the world, Stables explained (eg how many days in intensive care, and in hospital, a patient will spend for each procedure). In this way, it is hoped that the data can be extrapolated to any situation.

MASS II - some benefit for medical therapy but surgery looks good

Meanwhile, Dr Jose Antonio Ramires (Heart Institute, Sao Paulo, Brazil) reported the other study comparing CABG with PCI (whereby 70% of patients received stents) plus the addition of a third option - medical therapy alone - at the ACC meeting. MASS II (medical, angioplasty and surgery study) randomized 611 patients with multivessel disease to one of the three treatments.

The primary endpoints of the study are: cardiac death; non-fatal acute MI and unstable angina as combined cardiac events. One-year data were presented and Ramires noted that the secondary outcomes of the study - evolution of atherosclerosis (CAD), evolution of the left ventricular function and quality of life - will not be presented until the end of the 5-year study period.

Endpoint Angioplasty Medical Surgery 1st-year further revascularization and crossover 14% 8% 0% Presence of angina after 1 year 25% 13% 6%

Although the mortality rate in the three strategies was small during the first year, in the primary endpoint of first year free of combined cardiac events, angioplasty produced the worst response during the first year, he noted. Medical therapy alone was associated with a low incidence of primary endpoints and was better than PCI in relation to the anginal status and primary endpoints, and surgical revascularization was better than medical therapy only in relation to the anginal status.

Patients treated with PCI were more likely to require further or crossover interventions than CABG patients and in terms of the combined cardiac events during the first year, CABG was significantly better than PTCA and medical treatment (p=0.00002), Ramires concluded.

Doctor - how would you treat yourself? Orlando, FL - In response to a question from a journalist during the press conference, the physicians involved in the studies were asked to say what treatment they themselves would choose if they were suffering from multivessel disease. Before replying Stables noted that "trials like SoS have to be performed but they are slightly artificial . . . they set out to create adversity." In the real world, the interventionalist and the surgeon would sit down and decide the most appropriate treatment on a case-by-case basis, he said. Nevertheless, he did not hesitate to choose angioplasty as a treatment option, particularly because he said he knew he would have an expert - Sigwart - performing the procedure. Sigwart himself commented: "None of us would like to have our chest cracked open . . . and we know that the attrition of vein grafts is substantial . . . so I would choose PTCA." He also noted that repeat bypass surgery can be difficult, and "in younger patients I always recommend a PTCA if it can be done." But when the ERACI-II data were published in January 2001, Dr Thomas Ryan (Boston Medical Center, Boston, MA) wrote an editorial saying he still believes surgery to be the better option for the majority of patients with extensive coronary disease. He told heartwire at the time that the important thing is what happens in the long-term - 3 or 5 years - and that in his opinion CABG and stenting cannot truly be compared in a randomized study because, in the real world, the patients referred to angioplasty are less sick and the majority of those with multivessel lesions will have more extensive coronary disease than can be handled by angioplasty. Ramires supports this view. He told the press conference he would choose surgery as his preferred treatment option: "You get less symptoms, less angina, less heart failure and less sudden death with surgery. Also you preserve your LVEF," he said. -LN

Lisa Nainggolan lisa@conceptis.com

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