December 14, 2007 (Durham, NC) - After five years of sluggish enrollment, the Surgical Treatment for Ischemic Heart Failure (STICH) has finally finished enrolling patients in its two-pronged study. Results from hypothesis one of the trial will be released in late 2008 or early 2009; results from hypothesis two will likely take until 2011, researchers now say.
According to Dr Eric Velazquez (Duke University, Durham, NC), one of the lead investigators for STICH, the trial enrolled a total of 2136 patients with coronary artery disease and left ventricular systolic dysfunction; 1212 patients have been enrolled in hypothesis one--optimal medical therapy vs CABG--and 1000 have been enrolled in hypothesis two--CABG vs CABG plus surgical ventricular reconstruction (SVR). A small proportion of patients who were randomized to CABG in hypothesis one were also randomized in hypothesis two.
As previously reported by heartwire , the complexity of STICH's design, along with entrenched physician biases, has plagued the NHLBI-funded study from the outset. As Dr Milton Packer (UT Southwestern, Dallas, TX) commented to heartwire back in 2004: "It would be fair to say that the majority of cardiologists act as if the answer being sought by this trial is already known and, in fact, have been acting that way for years."
On the one hand, surgeons have grown increasingly confident--despite a lack of incontrovertible evidence--that SVR, which surgically reshapes the ventricle to exclude nonfunctional myocardium, on top of CABG is superior to CABG alone in heart failure patients with low EF. On the other hand, despite the fact that recent trials like OAT and COURAGE have supported a role for medical therapy alone, albeit in different patient populations, many physicians are already convinced that revascularization is superior to drugs alone in patients with heart failure related to CAD.
True Equipoise
In an interview with heartwire , Velazquez described trying to drum up support and increase enrollment in STICH by visiting prominent academic medical centers, presenting three hypothetical cases, and asking a mixed group of cardiologists and cardiovascular surgeons how the patients should be managed. "In the same institution, in the same division, there was a complete host of variances in terms of their answers," he said. "STICH is unusual in that we've really had to continuously educate ourselves and our peers about the equipoise that really does exist. A lot of people have had very strong convictions and we've had to go to a lot of effort to continue to remind people that viability imaging is great, but if you look at the data carefully, it is concerning that we're using it in the way we are."
Similarly, although surgical techniques have evolved, so has medical therapy, Velazquez points out. "Surgery was last studied in a comparative way with medical therapy in the late 1970s, before we even had ACE inhibitors. And none of these patients who have heart failure or low EF were ever studied. In the surgical community there has been this uptake of SVR that I frankly think is a little troubling because the data on this are limited."
Protocol Amendments
According to Velazquez, a number of protocol amendments, described in the December 2007 issue of the Journal of Thoracic and Cardiovascular Surgery [1], helped investigators to complete the trial . Changes included a reduction in the number of patients required for hypothesis one and a loosening of requirements for radionuclide stress imaging studies, blood tests, and follow-up schedule.
To heartwire , Velazquez also emphasized that a change in study duration will ensure that the study provides meaningful answers. Patient follow-up was initially to close at the end of December 2008; however, a May 2006 protocol amendment, approved by the trial's data and safety monitoring board and the NHLBI, now means that STICH will be end-point driven (400 primary events in the hypothesis-one cohort).
"This means STICH will be a definitive trial," Velazquez stated. "We will answer the question."
Velazquez also explained that the STICH steering committee underestimated the number of countries and sites it would need to reach its target enrollment. Initially, investigators planned to enroll STICH patients in three countries only--the US, Italy, and Canada--but the trial was ultimately expanded to 26 countries and 127 sites. Three countries, however, contributed a single patient.
A number of things in the US were likely barriers to enrollment, beyond physician biases, Velazquez noted. For one, he said, patients tend to get a diagnostic catheterization then head immediately to intervention. "That goes against enrolling patients who are complicated into these types of strategy trials, because you kind of have to stop the train. You have to be able to have a system in place where you have coinvestigators across multiple disciplines of surgical, medical, heart failure, and interventional, who stop and say, 'wait'. The train is going at this speed, but we have to slow it down, approach this patient, and find out what is the best option, and as an initial strategy offer medical therapy."
A concurrent trend in the US, Velazquez added, is declining surgical revascularization procedures. "As this trial was starting, the stent era was in full swing, and all of a sudden surgical volumes were dropping. And then we were asking surgeons to allow randomization between surgery or not giving surgery at all, and that may have hit hard."
This problem was less of an issue in Canada and Europe, he added.
An End to Anecdotes and Gut Feeling
For obvious reasons, the STICH trial is unblinded. Asked if he has his own predictions about the trial outcome based on what he's seen in his own patients, Velazquez adamantly denied having any inkling of how things might turn out, and pointed out that personal observation is precisely the kind of thing that hindered STICH from the get-go.
"We don't want to just have personal anecdotes, we want to have evidence in a population that we can generalize from," Velazquez said. "There were some folks who felt very uncomfortable with the idea of enrolling their patients, and when they were randomized to medical therapy, they wished they had been offered surgery. But those patients are doing well and I see them in clinic." On the other hand, he continued, there were other high-risk patients who were eligible for enrollment in STICH because surgery was technically feasible, but they were the types of patients to whom surgeons would typically not have offered surgery outside of a randomized trial. "But those patients got through surgery fine and, four years later, are doing very well. Would they have done just as well on medical therapy? I don't know that. That's why we do trials."
Velazquez EJ, Lee KL, O'Connor CM, et al. The rationale and design of the Surgical Treatment for Ischemic Heart Failure (STICH) trial. J Thorac Cardiovasc Surg 2007; 134:1540-1547.
The complete contents of Heartwire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.
Heartwire from Medscape © 2007 Medscape
Cite this: Shelley Wood. STICH Finally Finishes Enrollment - Medscape - Dec 14, 2007.
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