As a cardiologist, it was not easy to accept the negative result of ORBITA Trial two years ago. Stenting an obstructed coronary does not control angina? Because of my bias towards scientific skepticism and my love affair with the null hypothesis, it was easier for me. So, at that time, I wrote a quite philosophical post analyzing the value of ORBITA. For the effect size assumed in that trial, angioplasty is not effective and we must recognize the role of placebo within the efficacy of any therapy.
As a cardiologist, I was just presented by JAMA Internal Medicine to a Chinese randomized clinical trial that supposed demonstrate the efficacy of acupuncture in controlling stable angina, as compared with sham.
Now, it is too much for me. I have to accept that stenting is not such a treatment for angina while accepting acupuncture as a valid therapy?
I could not control my bias against this Chinese trial. Yes, I was severely biased to read the trial with impartiality. But after some meditation (is the evidence for that?), I became a little more impartial and able to read the article technically.
For my surprise, I found a well written article, according to CONSORT standards, which fulfills the basic criteria for low risk of bias and random errors. It is a well dimensioned trial, with correct assumptions in sample size calculation, providing enough power to test the hypothesis and precision of confidence intervals. Methodology performed according to previous definition in clinicaltrial.gov, with no change in protocol. Conclusion based on previously defined primary end-point. Central and concealed randomization, two sham control groups (non-meridians acupuncture and simulation of acupuncture), intention-to-treat analysis, no lost of follow-up. Therefore, at a first glance, it seemed to be low risk for false positive result.
Really? What is the positive predictive value of this particular trial?
While the methodology of a trial should be evaluate in itself, its predictive value should be evaluated in the context of the pretest probability of a true hypothesis. Pretest probability depends on (1) plausibility and (2) how much previous data support the hypothesis.
First, one must consider very plausible that opening of an obstructed coronary diminishes symptoms from myocardial ischemia. Although not equivalent to the effectiveness of parachutes, improving symptoms by coronary stenting is almost obvious. On the other hand, improving symptoms from myocardial ischemia by introducing needles in a remote part of the body is less obvious.
I learned that the "meridians" are based on the trajectory of afferent nerves to be stimulated by the procedure. It gives a basic logic to acupuncture, so it is not the same as homeopathy. But nerve trajectory alone is not enough for plausibility regarding clinical efficacy. We have do go further on mechanisms.
So I asked two acupuncturists friends (hospitalist and anaesthesiologist, respectively) what is acupuncture's mechanism of action. One first gave me several different mechanisms and recognized he was not sure; the other promised to “talk to me later” … I am still waiting for the answer.
It confirms my epistemological impression that acupuncture efficacy for treating angina has low level of biological plausibility. In biology, mechanisms of disease are complex and multifactorial. On the other hand, the true mechanism of an effective treatment is related to one pathway. It seems strange, almost a miracle, that one intervention has so many beneficial pathways (imunological, anti-anti-inflamatory, improves blood flow, relaxes muscle, improves muscle mobility and more).
Regarding empirical evidence, I surprisedly found at BMJ a systematic review of randomized clinical trials testing acupuncture for stable angina, which showed consistent (no heterogeneity) positive effect of this therapy in controlling angina. However, all trials were classified as high risk of bias due to lack of blinding. High risk of bias research should not increase the pretest probability of a hypothesis being true.
Finally, people commonly use the “milenar therapy” argument in favor of acupuncture. Well, I do not know of any “milenar criteria” to be taken into account for the probability of things to be true. In fact, several myths are milenar.
Thus, we should conservatively consider the efficacy of acupuncture for controlling angina as low pretest probability of being true. I am not saying it is false, just improbable.
When we find a very good piece of evidence in favor of an improbable hypothesis, the final probability will not be high. Maybe the good evidence raises the probability to moderate, but is still needs further confirmation.
But, is it really a good evidence? I decided to compare the methodologies of the ORBITA trial against the Chinese trial. Clearly, ORBITA has a greater respect for the null hypothesis. Two issues, not evaluated by standard checklist for appraisal of evidence.
- Subjectivity of primary outcome: while ORBITA chose an objective criteria (exercise time in stress testing), Chinese chose a self-reported subjective criteria (number of angina events per week).
- Effectiveness of blinding: while ORBITA reported blinding indexes, the Chinese trial did not bother. In this case, we must consider that the acupuncturist was not blind and the patient was fully conscious. How blind it really was?
In the end, I should recognize that stenting is definitely overrated in its role for stable coronary disease. But I there is no basis for finding acupuncture the future of coronary intervention.