What a Sham: The Power of Placebo

The November 2, 2017 issue of The Lancet included an online first article (R. Al-Lamee et al) describing a sham-controlled trial of percutaneous coronary intervention (PCI) in the treatment of stable angina pectoris. Each year more than 500,000 PCI procedures are done for stable angina worldwide and unblinded randomized trials have shown significant relief of symptoms and improvement in exercise time.

The trial enrolled 230 patients with symptoms of angina pectoris and severe (>70%) single-vessel stenosis. Patients with left mainstem coronary disease, those with >50% stenosis of other vessels, and several other categories were excluded. After enrollment, the patients received 6 weeks of guideline-directed antianginal medical therapy (beta-blockers, calcium-channel blockers, oral nitrates), a statin, and antiplatelet therapy. Two hundred patients were randomized to undergo PCI or to have coronary catheters inserted and withdrawn with no intervention.

The primary endpoint was the difference between the groups in exercise time improvement. Unblinded randomized trials had shown improvements of 48-55 seconds. The mean pre-randomization exercise time was 490 seconds in the placebo group and 528 seconds in the PCI group. The improvements after treatment were 11.8 seconds with placebo and 28.4 seconds with PCI; the difference of 16.6 seconds in favor of PCI was not statistically significant (p=0.2).

An interventional cardiologist commenting on the trial on PBS warned against extrapolating the results too far. He pointed out that this was a small study, some of the patients at baseline had very mild angina, and all of these patients received more vigorous medical therapy than the norm in clinical practice. So PCI is not going away. But still we have to be impressed with this reminder of the awesome power of placebo.

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Comments

  1. Clifford Dacso, MD says:

    Dr. A once again goes to the heart of the matter (sorry). The rapid profusion of interventions, though, surpasses considered clinical trials. The beauty of the Lancet paper is its placebo controlled design, probably never to be replicated, certainly in the US. The study recalls the elegant 1978 paper in Circulation by Henry McIntosh and Jorge Garcia (1978;57:405-431) that reviewed 10 years of coronary artery bypass surgery and concluded that there was almost no credible evidence that it worked. I am just not sure that that the McIntosh paper changed the trajectory of cardiovascular surgery!

  2. More than twice the exercise time improvement in the treatment group. Was the study adequately powered to conclude no difference? Can’t interpret negative findings without a disclosure of the power of the study.

    • Clifford Dacso, MD says:

      From the paper: “We designed ORBITA conservatively, to detect an effect size from invasive PCI of 30 s, smaller than that of a single antianginal agent. We calculated that, from the point of randomisation, a sample size of 100 patients per group had more than 80% power to detect a between-group difference in the increment of exercise duration of 30 seconds, at the 5% significance level, using the two-sample t test of the difference between groups.”

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