Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease
Key result
Initial CTA cuts CV death or MI ~62% vs. functional testing in diabetic patients.
- aHR 0.38
- 95% CI 0.18-0.79
- P=0.01
- n=8,966
Why the study?
The optimal noninvasive test for patients with diabetes and stable symptoms of CAD is unknown.
Does an initial diagnostic strategy of CTA reduce adverse cardiovascular outcomes compared to functional stress testing in symptomatic patients with diabetes and suspected CAD?
Key Points
- To evaluate whether an initial diagnostic strategy of coronary computed tomographic angiography is superior to functional stress testing in reducing cardiovascular death or myocardial infarction in symptomatic patients with diabetes.
- Secondary analysis of the PROMISE randomized clinical trial (NCT01174550) evaluating symptomatic outpatients with suspected coronary artery disease randomized to computed tomographic angiography versus functional stress testing.
- Included 1,908 patients with diabetes (936 randomized to CTA, 972 to functional stress testing) and 7,058 patients without diabetes (3,564 randomized to CTA, 3,494 to functional stress testing).
- In patients with diabetes, computed tomographic angiography significantly reduced cardiovascular death or myocardial infarction compared with functional stress testing (1.1% [10/936] vs. 2.6% [25/972]; aHR 0.38, 95% CI 0.18–0.79; p=0.01).
- In patients without diabetes, cardiovascular death or myocardial infarction rates were similar between arms (1.4% [50/3,564] vs. 1.3% [45/3,494]; aHR 1.03, 95% CI 0.69–1.54; p=0.887; interaction p=0.02).
Study Design
Type
RCT (n=8,966)
Randomization
Randomized to initial anatomical testing with 64-slice multi-detector CTA or functional testing
Multicenter
Yes
Structured PICO
Does an initial diagnostic strategy of CTA reduce adverse cardiovascular outcomes compared to functional stress testing in symptomatic patients with diabetes and suspected CAD?
P
Population
8,966 stable outpatients with symptoms suggestive of CAD (including 1,908 with diabetes) randomized to initial CTA versus functional stress testing, followed for a median of 2 years.
I
Intervention
Initial anatomical testing with 64-slice multi-detector coronary computed tomographic angiography (CTA)
C
Comparator
Functional testing of the local physician's choice (exercise ECG, stress nuclear imaging, or stress echocardiogram)
O
Outcome
Cardiovascular death or myocardial infarction (MI)hard clinical
Main Result
Hazard Ratio: 0.38 (95% CI 0.18–0.79)
Absolute Event Rate: 1.1% vs 2.6%
p-value: p=0.01
In patients with diabetes and stable symptoms of CAD, an initial strategy of CTA rather than functional stress testing may significantly reduce the risk of cardiovascular death or MI.
Limitations
- Post-hoc analysis
- Small number of events for CV death/MI in patients with diabetes
- Presence of diabetes not formally established by HbA1c or fasting glucose testing
- Lack of data on glycemic control and antihyperglycemic medications during the trial
- Lack of data on risk factor control during the trial
- Small number of events
- Presence of diabetes not formally established by HbA1c or fasting glucose
- Data on glycemic control during trial not available
- Data on risk factor control during the trial not collected
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The author's conclusion that among patients with diabetes, CTA 'resulted' in fewer adverse CV outcomes comes from their observation that patients with diabetes who underwent CTA rather than functional testing had a lower risk for CV death or MI, but they found no such difference in patients without diabetes. They reported a P value of.02 for interaction with diabetes. The event rates in Table 11 in the supplement expose the core problem with this conclusion. In patients with diabetes, the rate of MI was only 0.2% in the CTA arm vs 1.3% in patients who had a functional stress test; this difference drove the 'positive' finding. But that same table shows that the number of MIs in the CTA arm was 3.5-fold lower in patients with diabetes than in those without diabetes. Think about that; how is it possible that people with diabetes had 3.5-fold fewer MIs than those without diabetes? It is not.”
“Of the 20% of the population who were diabetic, they had a significantly better outcome. It was late after randomization, which is what we would expect to the case. It was a huge reduction, 62%, in some pretty hard endpoints, cardiovascular death and MI. We're not talking about squishy endpoints. The obvious conclusion is that these patients are sicker and the ability to better identify coronary artery stenosis and do something about it in these patients, whether it's revascularization or statins and aspirin, really can have an impact on subsequent events.”
FHFrank HarrellStatistics professor, Vanderbilt University
“Sample sizes for overall randomized trials are just barely adequate (if that); sample sizes are not adequate for subgroup analyses that effectively reduce the already minimal sample size.”
Implication
CTA may be preferred initially over functional testing in symptomatic diabetics; extends PROMISE to this subgroup but needs dedicated confirmation.
Abstract
Background: The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown. Objective: To assess whether a diagnostic strategy based on coronary computed tomographic angiography (CTA) is superior to functional stress testing in reducing adverse cardiovascular (CV) outcomes (CV death or myocardial infarction [MI]) among symptomatic patients with diabetes. Methods: The Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE; NCT01174550) was a randomized trial evaluating an initial strategy of CTA versus functional testing in stable outpatients with symptoms suggestive of CAD. We compared CV outcomes in patients with diabetes (n=1,908 [21%]) and without diabetes (n=7,058 [79%]) based on their randomization to CTA or functional testing. Results: Patients with diabetes (vs. without) were similar in age (median 61 vs. 60 years) and sex (female 54% vs. 52%) but had a greater burden of CV comorbidities. Patients with diabetes who underwent CTA had a lower risk of CV death/MI, compared to functional stress testing (CTA, 1.1% [10/936] vs. stress testing, 2.6% [25/972]; adjusted hazard ratio [aHR] 0.38, 95% CI 0.18–0.79; p=0.01). There was no significant difference in non-diabetics (CTA, 1.4% [50/3,564] vs. stress testing, 1.3% [45/3,494]; aHR 1.03, 95% CI 0.69–1.54, p=0.887; interaction term for diabetes p-value=0.02). Conclusions: In diabetics presenting with stable chest pain, a CTA strategy resulted in fewer adverse CV outcomes than a functional testing strategy. CTA may be considered as the initial diagnostic strategy in this subgroup.
Discussion
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Cite This Study
Sharma et al. (2019) conducted an RCT in Stable outpatients with symptoms suggestive of CAD (n=8,966). Coronary computed tomographic angiography (CTA) vs. Functional stress testing was evaluated on CV death or myocardial infarction [MI] (aHR 0.38, 95% CI 0.18-0.79, p=0.01). In symptomatic patients with diabetes, an initial diagnostic strategy of CTA reduced the risk of cardiovascular death or myocardial infarction by 62% compared to functional stress testing (aHR 0.38, 95% CI 0.18-0.79, p=0.01).