Author + information
- Zachary D. Goldberger, MD⁎ ( and )
- Brahmajee K. Nallamothu, MD, MPH
- ↵⁎University of Michigan Health System, Robert Wood Johnson Clinical Scholars Program, 6312 Medical Science Building 1, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109-5604
We read with great interest the recently published meta-analysis by Costanzo et al. (1) investigating whether changes in carotid intima-media thickness (CIMT) affect major cardiovascular endpoints, including cardiovascular-related and all-cause mortality. The study was carefully executed and reported that changes in CIMT in response to drug therapy do not translate into changes in major cardiovascular events. The analysis adds to the growing understanding that although surrogate endpoints such as CIMT at baseline may be correlated with clinical outcomes, changes in these endpoints over time that result from a particular therapy may not predict future clinical events (2,3).
However, we would highlight one potential drawback in the methodology the investigators used—namely that examining the relationship between changes in CIMT and outcomes with death included as a primary endpoint is limiting, given that patients who died during follow-up cannot undergo full serial assessments of CIMT to calculate a “change.”
We recently performed a similar meta-regression analysis, looking at 28 trials of novel cardiovascular therapies to see whether changes in CIMT that result from these therapies are correlated with nonfatal myocardial infarction (MI) (4). We chose to focus our primary analysis on nonfatal MI, excluding the endpoint of death given the reason described above. Our findings raised similar concerns that changes in CIMT do not consistently predict cardiovascular events. For example, we found that for each 0.01 mm per year smaller rate of change in CIMT, the odds ratio for MI was 0.82 (95% confidence interval: 0.69 to 0.96; p = 0.018), but that no significant relationship between mean change in CIMT and nonfatal MI was noted in randomized controlled trials evaluating statin therapy or those with high CIMTs at baseline (p > 0.20 in both instances).
The results of this meta-analysis as well as others, although provocative, must be interpreted cautiously. Overall, we agree with the authors that larger clinical trials evaluating patient outcomes generally are needed to evaluate new drug therapy.
- American College of Cardiology Foundation