ORBITA trial and the placebo control | The Body of Evidence

ORBITA trial and the placebo control

 

A hotly debated trial at a recent cardiology conference has many people questioning the value of opening up blocked arteries in patients with stable angina.

While the evidence for acute heart attacks is pretty clear, what to do with these low risk patients is not. Enter the ORBITA trial, a rare placebo controlled trial of a common intervention.

Read the story here: http://montrealgazette.com/opinion/opinion-orbita-angioplasty-trial-provides-food-for-thought


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If you've been following the news lately, you may have heard about the ORBITA trial. Its publication in The Lancet has caused quite a stir because its main result shows that opening up blocked arteries in the heart has little benefit for people with stable angina.

Angioplasty, the ballooning open of blocked cardiac arteries, has been a staple of cardiovascular care since it was developed in the late 1970s. In the acute setting, meaning when someone has a heart attack, angioplasty has been shown to reduce death rates and prevent complications and is widely considered standard of care.

But over the past decade, studies have suggested that for stable patients with chronic angina,routinely ballooning blocked arteries did not in fact prevent heart attacks or prolong life. Nevertheless, angioplasty was still used for patients with ongoing symptoms because early studies like the ACME trial showed that it helped relieve chest pain.

But the ORBITA trial has challenged this view because it did one thing differently: It used a sham procedure for its control arm. Rather than compare angioplasty (plus putting stents in the clogged arteries) to medical therapy, the ORBITA trial compared angioplasty to a sham procedure where patients thought they were getting an angiogram, but the arteries were not actually unblocked.

There are ethical challenges to using sham surgeries in research, but they do serve the key purpose of identifying procedures that work solely through the placebo effect. In 1959, patients with angina were often sent for surgery to tie off the internal mammary artery. It was only after Leonard Cobb performed his famous sham surgery trial that the practice was shown to be ineffective. Similarly, renal artery denervation was supposed to be a surgical cure for high blood pressure and was already being widely used in Europe, before the SIMPLICITY-HTN3 trial compared it to a sham procedure and found that the earlier successes seemed to be purely due to the placebo response. The examples are not limited to cardiology. In patients with arthritis of the knee, arthoscopic surgery performed no better than a sham placebo surgery, despite its widespread popularity at the time.

There are criticisms that can be levelled against the ORBITA trial, as there can be against all trials. It was relatively short, lasting only six weeks. But as the accompanying editorial in The Lancet points out, the short duration probably favoured angioplasty, since its benefits are usually immediate, whereas medications only show their benefit in the long term. It was also a smallish trial of only 230 patients, though it was just as large as the positive ACME study that had 212. Finally, it only enrolled patients with a single blocked artery, and so it is possible, though speculative, that higher-risk patients with more severe disease might benefit from the procedure.

Of course, everyone's individual medical history is different and exceptions to the rule will always exist. But the findings of ORBITA cast doubt on how effective routine angioplasty truly is in stable, low-risk patients. The study's accompanying editorial has suggested that its place in the guidelines be downgraded to reflect these new findings.

But the important take away message from ORBITA is a more general one. It underscores how important the placebo response can be, even in surgical cases. Without Cobb's 1959 study we might still be sending patients to have their mammary arteries tied off, and without SIMPLICITY-HTN3 we might be spending millions of dollars on invasive procedures to treat high blood pressure when relatively cheap medications work just as well. But beyond the issue of cost, invasive procedures carry risks of complications. If we are going to recommend these procedures to patients, we must be certain of their value and remember the old adage of primum non nocere, first do no harm.