People with blocked arteries in the heart are usually told they need open heart, or bypass, surgery. The procedure, properly known as coronary artery bypass grafting (CABG), is recommended by the American Heart Association, among others, as the best way to keep blood flowing to the heart, especially if the blockage is in the arteries on the left side of the heart.
But cardiologists started to change their advice in 2016 and were encouraged to do so by groups such as the European Association for Cardio-Thoracic Surgery (EACTS), which had started to recommend that stents—tiny tubes that are pushed into a blocked artery to open it up—and CABG were both equally effective for people with mild heart blockage.
Everyone in heart medicine had been reading a game-changing piece of research, known as the EXCEL study, which claimed that stents, always the bridesmaid to CABG's bride, were just as safe and effective. In short, similar numbers of patients were dying whether they had had a stent or CABG.
The research team, led by cardiologist Gregg Stone from Columbia University Medical Center, treated 1,905 heart patients either with CABG or a stent and tracked them to see how many had died from a heart-related problem—such as a stroke or heart attack—three years later.
In that time, 14.7 percent in the CABG group and 15.4 percent in the stent group had died. Stent therapy, introduced in 1972, had suddenly come of age and was "noninferior," as the researchers said—or just as good.1
The picture was similar after five years. By then, 22 percent of patients in the stent group and 19.2 percent of those in the CABG group had died, so again the researchers concluded that there was no significant difference between the two treatments.2
Are you sure?
But other studies weren't coming up with the same results. Another major review, the NOBLE study, also tracked the health of heart patients to see how they fared after CABG or a stent.
The NOBLE researchers, from Oulu University Hospital in Finland, concluded that CABG is still the better option. After five years, 29 percent of patients in the stent group suffered major cardiac failure, including death, compared with only 19 percent in the CABG group.3
Why had these two major studies—EXCEL and NOBLE—come to such different conclusions? They weren't measuring quite the same outcomes, suggested researchers from the Aswan Heart Center in Egypt, with the NOBLE researchers also including patients who needed further treatment.4
But there was another reason, according to one of the EXCEL group's main researchers, Professor David Taggart from Oxford University: his fellow researchers had adopted a strange definition of a heart attack, and had done so halfway through the trial.
So what's a heart attack?
Dropping his bombshell statement at the EACTS 2019 conference, Taggart claimed that CABG had been set up to fail by the EXCEL researchers, who had suddenly included 'periprocedural MIs'—heart attacks that happen during or immediately following surgery—when the true measure should have been any heart-related death.
"If you look at death itself, arguably the most important outcome of this trial, there is a strong benefit of bypass grafting," he told the conference. "If you look at nonperiprocedural MI [heart attack that happens months or years after the procedure], in other words, real myocardial infarction," he continued, there was again, "a strong benefit in favor of CABG."5
By comparison, the NOBLE study had excluded fatal heart attacks that happened on the operating table. "If you look at real myocardial infarction, the ones that occur 30 days after an operation, then there was a strong benefit of CABG over stents.
"In the EXCEL trial, to equate a periprocedural biochemical definition of myocardial infarction and give it the same weight as a nonprocedural myocardial infarction was an absolute outrage in my opinion."
Although he was one of the original architects of the study, Taggart announced that he was removing his name from the report, the first time he had done so in more than 300 studies he had been involved with.
In response, Professor Stone, the principal EXCEL researcher, said Taggart had misinterpreted the data, and that the rates of death were similar in the CABG and stent groups. He said it was "the ultimate in cherry-picking" by looking at one endpoint, which the trial had not even been structured to review, from just one trial. In a later Tweet, Stone said it was "a delusion" that the definition of myocardial infarction had ever changed in the study.
Enter the BBC
All of this could have remained an academic squabble—albeit one that had profound implications for heart patients—had it not been for BBC investigators from the current affairs Newsnight program, who heard about the spat and decided to explore further. 7
Unpublished data that the BBC journalists were shown revealed there were 80 percent more deaths in the stent group, and the Data Safety Monitoring Board, which looks after the interests of patients, had also started to record more deaths among stent patients. Board members had alerted the EXCEL researchers and suggested the data should be made public—especially as guidelines were starting to favor stents—but their request was ignored.
Speaking to the BBC, Professor Nick Freemantle at University College London, who had helped shape the new guidelines, said he would never have changed them had he seen the missing data. The implications of making "a wrong recommendation" were that "patients who have received stents will have died who otherwise would have lived for longer, survived for longer, if they'd had open heart surgery," he said.
Following the broadcast, EACTS stated it is "a matter of serious concern to us that some results in the EXCEL trial appear to have been concealed and that some patients may therefore have received the wrong clinical advice." It has described its own recommendation—that stents were equally as effective for left-side artery blockage—as "unsafe."
There's money, too
There was one other factor that made Taggart and others uneasy. The EXCEL study is funded by Abbott Vascular, a stent manufacturer, and Professor Stone had disclosed he had received fees from, or held equity in, 20 private medical companies, several of which were involved in the manufacture of stents.
Another EXCEL researcher, Professor Pieter Kappetein, was now working for Medtronic, which also makes stents, as its chief medical officer. Newsnight investigators estimate that almost half of the 33 EXCEL researchers had declared receiving fees from stent manufacturers.
In his talk to EACTS 2019, Taggart revealed that the chief medical officer of the study's sponsor, Abbott Vascular, was also one of the authors. By comparison, the NOBLE study had been sponsored by a stent manufacturer, Biosensors, and had nonetheless concluded that CABG was better for heart patients.
Had financial factors influenced the EXCEL researchers? Nobody can say, but what really matters is that some of the 1.8 million stent procedures carried out last year in the US were not the best approach, and as a consequence, some patients have died when otherwise they may still have been alive today.
Of cabbages and stents
Heart bypass (coronary artery bypass graft, or CABG—pronounced 'cabbage') is one of those amazing surgical procedures that puts the doctor center-stage as a hero.
It ensures blood continues to flow to the heart when one or more coronary arteries—usually on the left side of the heart—become blocked. As its name suggests, it's a technique where one or more blocked coronary arteries are "bypassed," often by inserting an artery taken from the patient's leg that allows blood to flow around the blockage.
Until the EXCEL study (see main article), CABG was the preferred procedure for left coronary artery blockage or when all three coronary arteries are blocked. The procedure is all about re-establishing blood flow to the heart, but it doesn't prevent a heart attack or angina (chest pain).
It's complicated, expensive and dangerous, and with the rise of stents, fewer CABG procedures are being carried out. In the US, the rate has fallen by around 46 percent.
Stents, or percutaneous coronary intervention (PCI), are less invasive and dangerous and can achieve similar results, at least according to its advocates.
A coronary stent or tube is threaded into the blocked coronary artery and opens it up by pushing plaque against the artery wall.
Although stenting reduces angina, some believe its benefits have been overblown. For one, a heart attack doesn't happen when arteries narrow, but only when they are suddenly blocked—by which time, it's too late for stenting or CABG.
Complications from PCI include arrythmia, or irregular heartbeat, and blood vessel damage. And, as some critics of the EXCEL study suggest, you're more likely to die from a heart problem after a stent than following CABG.