CRT: Is a randomized trial needed for PCI CTO?

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WASHINGTON, D.C.—While there may be enough evidence to prove the benefit of performing PCI for chronic total occlusions (CTOs), a randomized controlled trial may still be necessary to convince the naysayers, according to a Feb. 24 presentation at the Cardiovascular Research Technologies (CRT) annual meeting.

“Why it’s necessary to get on a common ground is demonstrated through the discrepant approach to treating CTOs with PCI in one three-center Canadian registry in which [the centers] were embarking on a common task,” said Gerald S. Werner, MD, PhD, of Klinikum Darmstadt in Darmstadt, Germany. At these centers, the rate of CTO PCI ranged from 1 percent to 10 and 60 percent. “Their varied approaches cannot be based in evidence, or it would have been more uniform.”

In order to assess whether there is enough evidence to support CTO PCI, he looked at three factors in his presentation:

  • Does it improve clinical outcomes?
  • Does it present an alternative to surgery?
  • Does it improve survival?

“In terms of clinical outcomes, studies have clearly shown that performing CTO PCI results in angina relief [and] quality of life is improved,” Werner noted, citing a study by Grantham et al, which assessed early health status benefits of CTO recanalization (Circ Cardiovasc Qual Outcomes 2010;3:284-290). “Even in asymptomatic patients, there seems to be a trend that successful treatment is beneficial.”

He spoke to a commonly held misperception that collaterals are not sufficient to prevent ischemia, which is “not true.”

However, the extent of ischemic burden is important, as demonstrated by Safley et al (Catheter Cardiovasc Interv 2011;78[3]337-343). The researchers found that ischemic burden is reduced following CTO PCI, and the decrease is greater at high ischemic burden. A threshold of 12.5 percent ischemic burden is suggested as a criterion for performing PCI in the setting of CTO.

“If the ischemia was less than 6 percent, sometimes the operators did more harm than good,” explained Werner. “If the ischemia was more than 12 percent of the myocardium, the procedure was beneficial.”

Also, there can be an expected improvement in left ventricular (LV) function, but only in patients with depressed LV function, he said.  

MRI is the gold standard to assess these patients. However, Werner noted that there is a gray zone where it is still challenging to see if these patients will experience a benefit or not with PCI CTO.

Does CTO PCI present an alternative to surgery? A substudy of the all-comers SYNTAX trial by Farooq et al showed that only 68 percent of the CABG arm had successfully completed angiography, and only 49 percent of the PCI arm (J Am Coll Cardiol 2013,61[3]:282-294). Those in whom CTO was not successfully treated had a significantly higher event rate in the three- to four-year follow-up.

Therefore, Werner concluded that “CABG is not the best alternative because it failed to graft many of these patients, and PCI is the better alternative because contemporary success rate is better than what was seen in the SYNTAX trial, in terms of stents and operator volume. Today, high-volume operators achieve a successful rate of more than 90 percent.”

Werner questioned whether the treatment needs to improve survival to prove its benefit. He pointed to cohort data on prognosis, but these trials only assessed failed CTO PCIs. Again, he said that much of the data is outdated, because the standard success rates of CTO PCI is much higher in Europe and the U.S.

Returning to the original question, do we need a randomized trial, Werner said that operators could look to the available evidence, which indicates improved clinical outcomes. Consequently, they should not need a randomized trial. “However, we who believe there is enough evidence are in the minority and we need to convince the majority,” said Werner, adding that a randomized trial will probably be required to do so.

Yet, he cautioned that a survival benefit may not be an appropriate endpoint. “Quality of life is important for PCI in stable coronary artery disease.”

Also, the EURO-CTO Trial is an ongoing randomized trial for this assessment. The trial, which began in 2012, intends to enroll 1,200 patients with 40 operators (greater than 80 percent success rate). This may provide enough evidence to produce PCI CTO guidelines to begin to standardize care for these patients.