CTO PCI Reduces Symptoms, Improves Quality of Life: Meta-Analysis

Coronary revascularization of a chronic total occlusion (CTO) with PCI appears to significantly improve quality of life and reduce patient symptoms when compared with optimal medical therapy (OMT), according to a combined analysis of two randomized trials.

The results, which were published this week in JACC, support the use of revascularization over long-term antianginal medication in selected patients with symptomatic chronic coronary syndrome with a CTO, say investigators.

Lead researcher Gerald Werner, MD, PhD (University Heart & Vascular Center/Goethe University, Frankfurt, Germany), said that most patients with CTOs have modified their lifestyle and adapted to their symptoms, with many no longer participating in sports, physical activities, or even work. “These patients are ideal because you can really improve their quality of life,” he told TCTMD. “The average age in our population is around 60 years and they’re a large fraction of people who are limited in their work.”

The new analysis comes on the heels of the 50-patient ORBITA-CTO randomized trial that showed PCI of a single-vessel CTO significantly reduces symptoms when compared with a placebo procedure. The trial was the first to separate the “placebo effect from the true treatment effect” of CTO PCI, according to the ORBITA-CTO investigators.

In 2017, EUROCTO was the first randomized trial to show that CTO PCI reduced angina frequency and physical limitations, and improved overall quality of life, when compared with OMT. The DECISION-CTO trial, on the other hand, found that both CTO PCI and a conservative strategy with OMT were associated with significant improvements in disease-specific health status but there was no difference between the two approaches.

About 15% to 20% of lesions in patients with chronic coronary syndrome are CTOS, but the US guidelines give a relatively weak recommendation for PCI in patients with refractory angina on OMT (class 2b, level of evidence B). This reflects uncertainty around symptom relief with PCI given the disparate trial results, as well as lower success rates and a higher risk of complications with CTO PCI. In the European guidelines, CTO PCI has a class IIa recommendation (level of evidence B), meaning it can be considered, in patients with angina resistant to medical therapy.

“The problem with DECISION-CTO is the design,” said Werner. More than 70% of patients had multivessel disease, and trialists allowed PCI of these non-CTO lesions in patients assigned to medical therapy. In fact, patients in the OMT arm received an average of 2 stents compared with 2.4 stents in those assigned to PCI. “Two stents in the OMT arm is not really medical therapy,” said Werner. “They found a benefit—all the patients profited—but there was no difference between the two treatment arms in DECISION-CTO because they did a lot of PCI in the conservative arm.”

Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), agreed with such an interpretation and applauded the investigators for the new analysis focused solely on patients with a single CTO lesion.

“What people didn’t realize so much about DECISION-CTO was exactly as they say: the non-CTO PCI confounded the treatment effect,” he told TCTMD. Eliminating patients with multivessel disease isolates the patient with symptoms from a CTO lesion and shows that opening that vessel does improve quality of life and symptoms, he added.

“ORBITA-CTO is a much smaller study, but it’s important to see the data validated,” said Kirtane, adding that it was strengthened by being sham controlled.

Eliminating Multivessel CAD

The meta-analysis, performed to address the disparate results between EUROCTO and DECISION-CTO, included 518 patients (mean age 62.8 years; 82.8% male)—272 and 246 from each trial, respectively— with stable angina with a single CTO as the culprit lesion, excluding those with other significant lesions.

The overall J-CTO score was 1.81, reflective of intermediate-to-difficult CTO lesions. In the CTO group, success was 88.7% after a first attempt, rising to 92.2% after a second attempt in 15 patients. In the OMT group, 6.7% of patients crossed over to PCI in the first year.

Angina frequency and quality of life measured by the Seattle Angina Questionnaire (SAQ) improved significantly more in the PCI group by 12 months than in the OMT group. Physical limitations also appeared to improve with CTO PCI (P < 0.01 when adjusted for multiple comparison) and there was a significantly larger improvement in the SAQ summary score. The benefit was not influenced by the J-CTO score, gender, age, or the presence of diabetes. Improvements in SAQ domains considered clinically significant (physical limitation ≥ 8 points, angina frequency ≥ 20 points, and QoL ≥ 16 points) were more common in the PCI-treated patients.

For Werner, the results weren’t surprising. “I’m a CTO operator, which is a confounder, of course, in interpreting our data, but this is what we see every day,” he said. “We have a CTO program where I do two or three CTOs every day and we see the effect immediately.”

Patients with the lowest baseline SAQ score had the highest likelihood of seeing an improvement with PCI. For example, those without QoL improvements after PCI had a baseline score of 72 at baseline versus 47 in those who improved with revascularization.

In the PCI group, there were three (1.0%) non-Q-wave MIs in 283 procedures and two (0.7%) silent cerebral ischemic events after the procedure. Two patients undergoing PCI required blood transfusions for access-site bleeding. After a median of 3.1 years, there was no significant difference in the risk of cardiac death or nonfatal MI between the CTO PCI- and OMT-treated patients (2.7% vs 5.1%; P = 0.17). Stroke and hospitalization rates were also similar, but revascularization was more common in the OMT arm.  

Emmanouil S. Brilakis, MD, PhD (Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, MN), who is involved in CTO research, said these results will ring true for other operators.  

“This is something I think that the CTO community has believed from the get-go, and it's good to see all the data now coming from different avenues converging,” he told TCTMD. “Based on ORBITA-CTO, and now this combined analysis, it’s pretty clear that CTO PCI can help. That’s fairly convincing.”

A subgroup analysis of patients with a CTO in the ISCHEMIA trial also showed that the invasive strategy improved quality-of-life and hinted at a lower risk of spontaneous MI, said Brilakis. The reduction in MI, however, has not been replicated in other studies, he added, “but as far as symptoms go, which is a question asked in the meta-analysis, I think [the data] are congruent and consistent.”   

CTO Still Not For All Operators

To TCTMD, Werner said that he would like to see the guidelines strengthened, or at least clarified, for CTO PCI in patients who aren’t getting symptomatic relief with OMT. Both Werner and Brilakis noted that the 2021 US revascularization guidelines point to the two conflicting studies as one reason for the IIb recommendation.

Kirtane, on the other hand, believes the relatively weak recommendation in both guidelines is a reflection not of efficacy, but of the complexity of CTO PCI and the higher complication rate.

“At this point, when you see data like this, I think there’s a way to qualify it,” he said. “If somebody truly has severe anginal symptoms and is being treated by a high-volume CTO operator with a reasonably higher success rate and who can mitigate complications, I do think [CTO PCI] ought to be elevated [in the guidelines]. I don’t think it needs to be something thought of as a last resort.”

There are more data coming, however. The ISCHEMIA-CTO trial is currently evaluating PCI versus OMT in asymptomatic patients with significant myocardial ischemia and in those with symptoms but mild-to-moderate myocardial ischemia. However, those results aren’t expected for a couple of years.