Coronary revascularization before vascular surgery
Patients undergoing vascular surgery are at higher risk for cardiovascular events. Despite published guidelines, the exact approach to pre-operative cardiac evaluation for these patients varies significantly. The report of a VA cooperative study in last week’s NEJM looked at the value of prophylactic coronary-artery revascularization before elective major vascular surgery.
Patients undergoing elective AAA repair or surgery for PVD of the legs were referred for cardiac catheterization if they were felt to be at increased risk for cardiac complications. The exact reasons for referral were variable and included abnormal thallium stress test and high risk based on clinical criteria. Patients were then eligible for randomisation if they had significant coronary disease of at least one vessel and did not have left main disease, aortic stenosis or an EF less than 20%.
510 patients were randomized to either prophylactic revascularization (CABG or angioplasty, at the discretion of the cardiologists) or no revascularization. In the revascularization group, 99 underwent CABG, 141 angioplasty. After mean follow-up of 2.7 years there was no difference in mortality in the two groups (about 22%).
This is the first study to randomize patients to yes-or-no cardiac revascularization prior to vascular surgery. Given the improvement in medical therapy and the peri-operative use of beta-blockers (84% of patients received them in this study), the result is not surprising but is important.
There are some caveats: patients with left main disease were excluded from randomization. Thus, one cannot use these results to say that there is never a need for pre-operative coronary angiography. Furthermore, no-revascularization prior to vascular surgery is not “never” — 8% of patients randomized to this approach underwent coronary revascularization after their elective surgery.
December 19, 2004
Accupuncture for knee pain (and two other articles)
In the Annals of Internal Medicine due out on December 21 are three “alternative medicine” articles.
The lead article, effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee, randomized 570 patients with osteoarthritis of the knee to one of three interventions: a 26 week tapering schedule of acupuncture, sham acupuncture, or six 2-hour group sessions of education. The patients were evaluated at 4, 8, 14 and 26 weeks for improvement in five areas: a pain score, a function score, a global assessment score, a physical health score and a 6-minute walking distance test.
Acupuncture provided statistically significant benefit over sham acupuncture and over the education alone approach at 26 weeks in terms of the pain, function and global assessment scores. The authors conclude: “Acupuncture seems to provide improvement in function and pain relief as an adjunctive therapy for osteoarthritis of the knee when compared with credible sham acupuncture and education control groups.”
I have two comments to make about this paper. First, similarly to my remarks about the paper on effectiveness of vestibular rehabilitation for the treatment of vertigo, I would have liked to see some measure that expresses in plainer english the results of the study. What percentage of patients would, at the end of trial, consider repeating the therapy? How many would consider recommending it to their family or friends? Clearly there is a benefit, but it’s hard to contextualize that benefit, to get a handle on how clinically worthwhile it is.
A second point relates to the results themselves, presented in Table 2 of the paper. The change from baseline for all five measurements is reported for the three groups (true acupuncture, sham acupuncture and education) at weeks 4, 8, 14 and 26. Taking one example, the WOMAC pain score was approximately 8.95 at baseline in the three groups. At week 4, it improved by 2.22 in the true acupuncture group, by 1.98 in the sham acupuncture group and by 0.84 in the education group.
This means that the benefit of true acupuncture over education was 2.22-0.84 = 1.38. Similarly, the benefit of sham acupuncture over education was 1.98-0.84 = 1.14. In this case, if the benefit of true acupuncture over education was 1.38, and that of sham acupuncture over education was 1.14, then one might conclude that 1.14/1.38 = 83% of the benefit of true acupuncture was due to the placebo (sham acupuncture) effect. I realize that this may not be a statistically correct assumption, but I believe it does represent a reasonable approximation. I would love to hear what statisticians have to say about this.
At any rate, I performed the same calculation for the other results given in Table 4, and came up with the following numbers:
- For the improvement in WOMAC pain score, at weeks 4, 8, 14 and 26, the percentages of the improvement attributable to placebo acupuncture were: 83%, 74%, 55% and 59%.
- For the improvement in WOMAC function score, at weeks 4, 8, 14 and 26, the percentages attributable to placebo acupuncture were: 43%, 46%, 58% and 52%.
- For the patient global assessment score, the corresponding percentages were: 50%, 38%, 52% and 0% (no effect from sham acupuncture).
Although these numbers are derived by me and may not be strictly correct, I think they do give an idea that about half of the benefit from acupuncture in this study was due to a generic placebo effect equivalent to sham acupuncture, and about half of the effect was specific to the real treatment. That’s not a bad overall result for acupuncture, considering how important the placebo effect is pain therapy.
Two other articles from the same issue:
Acupuncture versus placebo for the treatment of chronic mechanical neck pain was a single-blind randomized study comparing acupuncture with sham electrical stimulation of acupuncture points (placebo) for chronic neck pain. Although there was a statistically significant benefit of acupuncture over the placebo, this benefit was only of modest degree and felt to be not clinically significant.
More interesting was a clinical prediction rule to identify patients with low back pain most likely to benefit from spinal manipulation. The authors used a clinical prediction rule with 5 components:
- length of current episode (component positive if < 16 days)
- symptoms below the knee (absent)
- level of fear of pain and avoidance of activity (low)
- presence of hypomobile lumbar spine segments (at least one)
- internal rotation at the hip (> 35 degrees)
When four out of five of these components were positive (about 1/3 of patients), there was a substantially better outcome with spinal manipulation than with exercise alone and also better than with spinal manipulation in the 2/3 of patients who did not score well on the prediction rule. The only problem I have with the applicability of this study is that the prediction rule was evaluated by a physical therapist. How easy it would be for primary practitioners to successfully perform the same evaluation is unclear to me.
December 15, 2004
MRI for breast imaging
Last week’s JAMA had an article on magnetic resonance imaging of the breast prior to biopsy, which evaluated the performance of MRI imaging in evaluating patients with breast abnormalities. This study found that MRI had good sensitivity but only moderate specificity for detecting cancer. The negative predictive value of MRI was only about 85%, not high enough to obviate the need for biopsy.
In the same issue is an excellent editorial by Monica Morrow from Fox Chase Cancer Center in Philadelphia, Magnetic resonance imaging in breast cancer — one step forward, two steps back?
Dr. Morrow discusses the role of MR imaging of the breast. She notes that at present there are two main scenarios in which MRI is being used: for the screening of women at high risk for breast cancer, and for supplemental evaluation of patients with abnormalities of the breast.
The screening of women at high risk, such as those with BRCA mutations, lends itself to MRI evaluation, because these women are often younger, with denser breast tissue, a situation where MRI has an advantage over conventional mammography.
On the other hand, using MRI to evaluate patients with breast abnormalities (clinical and/or mammographic) is a different matter. As demonstrated in the study, the specificity and negative predictive value of MRI are not sufficient to allow the avoidance of breast biopsy. Nevertheless, MRI is being used more and more in this context. Why? Because of the perception that it is more sensitive and can pick up multicentric lesions better than mammography. Thus, it can be used to make decisions about the appropriateness of local (breast-sparing) treatment.
Here, Dr. Morrow makes an interesting point. Although MRI can pick up multicentric cancers with greater sensitivity than mammography, she argues that the need for mastectomy in these cases is not clear. She draws a parallel to the 1970’s, when breast-sparing surgery was being investigated. At that time, pathologic studies indicated that breast cancer was often multicentric; this was used to argue against the advisability of limited surgery. However, clinical trials showed that as long as the surgical margins were clean, breast-sparing surgery plus radiation of the breast yielded excellent results. Analogously, the detection of multicentric cancers by MRI may push towards mastectomy, but without clinical trials it isn’t clear that this will yield better results.
Breast cancer is out of my area of expertise, but this editorial was short, easy to read and thought-provoking.
The situation Dr. Morrow describes reminds me a bit of a recent development in cardiology, the advent of non-invasive methods for visualizing coronary arteries (CT angiography). Visual evidence is very convincing, and there is a strong urge to act upon what we see. Paradoxically, the ability to visualize coronaries non-invasively may well increase the number of invasive procedures, as the instinct to open up tight lesions will be hard to resist. Whether this will always be the right thing to do is another question.
In both cases, seeing is believing, but belief isn’t always the best basis for action in medicine.
December 14, 2004
Ablation for atrial fibrillation — author’s reply
In my post about the recent NEJM article on ablation for atrial fibrillation, I commented that “… it is not clear to me how exactly to evaluate a comparison of an ejection fraction in atrial fibrillation (the baseline) with one obtained in normal sinus rhythm…”
The corresponding author of this article, Dr. Pierre Jais, has emailed me this reply:
I would like to thank you for your comments and interesting web site.
I just would like to emphasize that the baseline echographic EF was acquired just after the ablation procedure, in sinus rhythm, to overcome the
limititation you pointed out.Best regards.
Pierre Jais
I went back to the article, to see if I had misunderstood or misstated the methods. The description of the echocardiographic determination of ejection fraction at baseline is as follows:
Patients were routinely admitted two days before the ablation procedure for baseline evaluation. Treatment with oral anticoagulants, taken by all the patients, was stopped on admission, and treatment with all antiarrhythmic drugs, except amiodarone, was stopped for an appropriate period before ablation. Heart rate and rhythm were monitored with the use of 48-hour ambulatory electrocardiography. Transesophageal echocardiography was performed to rule out atrial thrombi, and transthoracic echocardiography was performed to evaluate cardiac structure and function. Echocardiographic measurement of the left ventricular ejection fraction was standardized with the use of Simpson’s biplane method for all patients during the initial hospitalization and subsequent visits.
From the above description, I don’t think it was unreasonable to assume that the initial EF was determined while the patients were still in atrial fibrillation.
Thus, the author’s reply represents a significant clarification.
December 11, 2004
Defibrillators post-MI — a note of caution
The use of implantable cardioverter-defibrillators for the prevention of sudden death in patients who are at high risk for but have not yet had cardiac arrest (primary prevention) is gradually expanding. A number of trials have shown mortality benefit in different populations:
- MADIT: benefit in patients with coronary disease, ejection fraction less than 35%, spontaneous nonsustained ventricular tachycardia and inducible VT with electrophysiologic testing.
- MUSTT: benefit in patients with similar criteria to MADIT, but EF less than 41%.
- MADIT II: benefit in patients with prior MI and EF less than 31%. Important study, since EPS no longer required.
- DEFINITE: patients with non-ischemic cardiomyopathy, VPC’s or NSVT, EF less than 36% had a significant reduction in arrhythmic death but only a trend towards reduction in overall mortality.
- SCD-HEFT (reported but not yet published): benefit in patients with EF ≤ 35%, both ischemic and non-ischemic, particularly in class II rather than class III CHF.
On the negative side, the CABG-PATCH trial, published in 1997, failed to demonstrate any benefit from the implantation of an ICD in patients with ejection fractions under 36% and an abnormal signal-averaged ECG who had just undergone coronary bypass surgery. It has been speculated that active ischemia is an important component of sudden death, and thus patients who had just been revascularized would not benefit as much from an ICD.
Another negative trial has just been published in this week’s NEJM: the DINAMIT trial. In this study from Germany, 674 patients with ejection fractions under 36% who had had an MI less than 40 days previously and demonstrated reduced heart-rate variability or persistent sinus tachycardia (poor prognostic signs related to autonomic system activation), were randomized to therapy with or without an ICD.
Although arrhythmic deaths were significantly reduced by the device, this was almost exactly compensated for by an increase in non-arrhythmic deaths, so the overall death rate was the same in both treatment arms. The authors speculate that in this group of patients, with decreased heart rate variability and a recent MI, the risk of non-arrhythmic, pump-failure death is high, so that ICD therapy ends up converting some arrhythmic deaths to pump failure deaths without affecting the overall outcome.
How do we reconcile these results with the MADIT II trial, in which post-MI patients with reduced LV systolic function benefited from ICD placement? It turns out that most of the MADIT patients had their MI in the remote past. In fact, in a subgroup analysis, the benefit from the ICD was limited to patients whose MI was over 18 months previous to trial entry. This meshes quite well with the data from the current study.
Why remote MI’s should benefit from ICD placement so much more than recent ones is a bit puzzling to me. One possibility is that, as indicated in the CABG PATCH trial, residual ischemia is an important contributor to sudden death risk. In that case, patients with recent MI’s are more likely to have been screened and revascularized when necessary than patients with older events. In MADIT II, patients were not systematically evaluated for ischemia prior to enrollment. Could it be that appropriate screening and treatment of residual ischemia would reduce the potential benefit of defibrillator placement?
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