CardioExchange Archive

I recently heard a physician quote a paper from JACC to justify pursuing revascularization in an asymptomatic patient who was scheduled for major vascular surgery. This article is worth a close look in your journal club, even though it was published in 2009.

In their discussion, the authors summarize their findings as follows: “For patients in preparation for major vascular surgery, the present study shows that a strategy of ‘prophylactic’ coronary artery angiography for all patients at medium-high risk, followed by coronary revascularization as needed, is more effective in curbing the rate of post-operative cardiac events and death than is a conservative strategy of coronary angiography and revascularization performed on the basis of a positive noninvasive test.”

Your group should evaluate the quality of the study, particularly whether it is strong enough to affect practice.

The Design

The trial, from Italy, consecutively enrolled 208 patients (mean age, 74) who were scheduled for elective surgical treatment of major vascular disease and who had a revised cardiac risk index (RCRI) ≥2. The participants were randomized either to a selective strategy whereby noninvasive test results would guide the decision about angiography or to compulsory angiography. The researchers powered the study for a 10% reduction in the long-term and 30-day rates of major adverse cardiovascular events (MACE).

The Findings

As expected, the revascularization rate was higher in the compulsory-angiography group than in the selective-angiography group (58% vs. 40%). The two groups did not differ significantly in the MACE rate at 30 days, although it trended lower with the compulsory strategy (2.8% vs. 4.8%). At a mean follow-up of 58 months, the compulsory group had significantly better survival and freedom from cardiovascular events. The 4-year freedom from events was 87% in the compulsory group and 70% in the selective group (relative risk reduction, 59%; P=0.04).

My Analysis

First, I am amazed that every patient who met this study’s inclusion criteria was enrolled. (The article says that 672 patients were screened and that 464 had an RCRI <2. Note that 672 – 464 = 208, the number enrolled and randomized.) This trial may be the first ever in which all eligible patients opted to participate and gave informed consent. 100% participation — mighty impressive.

Second, is the result plausible? Revascularization was performed in 19 more patients in the compulsory group than in the discretionary group (61 vs. 42). The absolute difference in events at 4 years is 17%. For this intervention to be responsible for this difference, practically every person in the compulsory group who underwent revascularization would have had to derive a MACE benefit (angiography in its own right would not be expected to have an important effect on cardiac events and mortality). That is, the compulsory strategy produced 19 more revascularization procedures and prevented about 19 more cardiac events at 4 years. Is such an effect even possible, especially given the likelihood that some members of the selective group would eventually cross over and undergo catheterization and revascularization in a 4-year period? According to the published data, the number needed to treat for revascularization to achieve benefit in this trial was just about 1!

Finally, the JACC article does not list any registration of the study at clinicaltrials.gov, and a search at the site reveals no record of the trial, suggesting that it was never registered. Given that omission, it’s impossible to determine what the researchers declared about the study before it was performed.

A Better Source of Data

This amounts to merely an interesting pilot study whose results cannot trump those from the Coronary Artery Revascularization Prophylaxis (CARP) trial. In CARP, 510 patients in the U.S. were randomized to revascularization or no revascularization before major vascular surgery. No benefit of revascularization was demonstrated — either overall in the main trial or, as a CARP substudy showed, in the highest-risk subgroup. The bottom line is that the study from Italy should not be used as a justification for compulsory angiography or revascularization before vascular surgery.

What are your thoughts about this study? What would you say to a colleague who tried to justify an intervention based on its findings?