Stents not effective? Study sparks debate pt. 1

Posted on by Kurt Jensen

U.K. PCI study sparks U.S. debate

On Wednesday, November 1, results from the Objective Randomized Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina (ORBITA) study were published in The Lancet.

The next day, this article was published in the New York Times:

"A procedure used to relieve chest pain in hundreds of thousands of heart patients each year is useless for many of them," it began... "The new study, published in the Lancet, stunned leading cardiologists by countering decades of clinical experience. The findings raise questions about whether stents should be used so often—or at all—to treat chest pain."

Without further knowledge, the debate may start right here—the New York Times article had little in the way of medical detail to satisfy invasive cardiovascular professionals and may have further generalized results in a misleading manner.

But let's hold off on reacting, look at the debate surrounding this particular study and also place the findings in a wider context (part two). Note: this isn't the first time it has been suggested that stents are overused.

The ORBITA study and its critics

The ORBITA study randomized ~200 patients in the U.K. with stable ischemic heart disease to percutaneous coronary intervention (PCI) or to a sham procedure—where the catheter was threaded but a stent not inserted, essentially an invasive placebo—which occurred after a six-week period of intensive medical therapy optimization. Six weeks following the procedure, the effectiveness of PCI was evaluated in terms of the patients' improved exercise on a treadmill.

In an accompanying editorial in The Lancet, Dr. Rita Redberg, FACC, MSc, MD, a professor of medicine at the University of California, San Francisco, argued that "all cardiology guidelines should be revised" based on the results of this study—results that showed a statistically insignificant effect for PCI over the placebo procedure.

However, a low-risk sample, small sample size, inconclusive primary endpoint and a short-term follow-up are four common issues experts have with the study's design and its conclusions.

Patients were enrolled who had single-vessel stenosis greater than 70 percent—patients cardiac electrophysiologist Dr. John Mandrola described to The Atlantic as having "low levels of angina and [who] were low-risk in other ways."

Cardiologist Dr. Farhan J. Kwawaja further called into question the sample's relevance to U.S. guidelines and practice. "Guidelines in the U.S. would not necessarily support intervention" at this level, he said, as quoted by an article on Healthline. Mandrola argues that we can't generalize these findings to higher-risk groups.

And beyond the characteristics of the sample, many cardiologists, and an official press release from the Society of Cardiovascular Angiography and Interventions (SCAI), have argued that 200 was too small a sample size to draw conclusive findings, on top of other concerns:

"We applaud the investigators for their innovative use of a sham procedure, but we're concerned about the reliability and interpretation of the findings," said  SCAI President Kirk N. Garratt, MD, MSc, FSCAI, in the press release. "The number of patients studied was very small... The primary endpoint used, exercise tolerance, is imprecise and very subjective: patient tolerance of exercise normally varies from week to week... despite this, the improvement in exercise time among PCI patients was almost 2.5 times greater than in sham patients, suggesting PCI led to incremental improvement."

In a few detailed responses on his Twitter, Cardiologist Dr. Eric Topol, founder and director of the Scripps Translational Science Institute, also commented on the study, saying, "The trends are all in favor of PCI and suggest a woefully inadequate sample size" in addition to Beta error—or rather, a likelihood that study results showed a false negative for the effectiveness of PCI:

Dr. Topol also called into question the study's primary endpoint—another common refrain for critics of the study's design. "The exercise time selected as the primary endpoint had remarkable heterogeneity and noise (see 95% CI), even though its increment was nearly 3-fold increased with PCI," he wrote in the Twitter picture, above.

In fact, SCAI identified one of the study's secondary endpoints as the most objective measure—and favorable to PCI. "The most objective measure of ischemia relief in ORBITA was a secondary endpoint of heart performance called the DSE peak stress wall motion score index," said Dr. Garratt. "This measure significantly improved by PCI over sham treatment."

This measure of ischemia relief further reflects critics' opinions that the study was too focused on the short-term. "Of course, the placebo effect can be very powerful in the short term, but ischemia remained for these sham-treated patients" said Dr. Garratt. "Since the hearts of sham-treated patients were still struggling with ischemia, I worry about the longer term."

But before we conclude in any hard and fast way in favor of disregarding these findings, we should place this study in the context of practice and further exploratory research.

What the study does say

The study did show how a placebo effect, at least in the short term, might work for PCI with stents—and it does make sense. Dr. Mandrola painted a perfect picture as to why for The Atlantic:

"Immediately, the vessels look better on the x-ray images. The narrow area is wide open, the blood is flowing freely. 'When we tell a patient, look, we "fixed" you, this has an immense positive effect,' said John Mandrola... 'So they do the PCI, and they bring the family into the lab or show them pictures of the blockage. Everyone is happy. Doctors, nurses, patient, and family. That whole scenario creates a whirl of placebo effect. And the patient feels better.'"

But, is PCI truly not more effective than a placebo? Does this whirl of placebo effect last beyond six weeks? Despite Dr. Redberg's insistence that the results are "definitive," as she said to The Atlantic, critics' arguments and questions are strong and compelling.

Let's say the study is inconclusive, but let's not discount the value of the conversation the study has sparked. The study, especially with its uncommon use of a sham procedure, is at least cause for further exploration into the placebo effect of invasive procedures in cardiology. "This one small study should inspire confirmatory studies," Dr. Mandrola said to The Atlantic. "Confirmation is key."

And that's not all. In part two of this short blog series, we'll look deeper into the implications of this study—arguments about fee-for-service motivations, clinical research for invasive procedures and more. Join our email list to receive updates from the Alliance of Cardiovascular Professionals, like when we post part two!

Plus, celebrate the week that celebrates all cardiovascular professionals—Cardiovascular Professionals Week February 11-17! LEARN MORE HERE »

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