According to a recent publication in the Journal of the American College of Cardiology, in diabetic patients presenting with stable chest pain, a computed tomographic angiography (CTA) strategy resulted in fewer adverse cardiovascular outcomes in comparison with a functional testing strategy. The conclusions drawn from the study implied that CTA may be considered as the initial diagnostic modality in this subgroup.
To date, despite the higher prevalence and risk of coronary artery disease (CAD) in patients with diabetes, there has been limited evidence to guide clinicians in choosing among available noninvasive test (NIT) options. In the light of these considerations, the study investigators believed that this was a clinically important subgroup to assess, as the overall positive or negative results had the potential to obscure opposite findings in this important subgroup. Specifically, it was unexplored whether an anatomic approach of evaluating symptoms suggestive of CAD using coronary computed tomographic angiography (CTA) was superior in comparison to functional stress testing in altering processes of care or reducing the risk of adverse cardiovascular outcomes. To address these knowledge gaps, contemporary data from PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), a randomized trial of diagnostic evaluation strategy in stable outpatients with symptoms suggestive of CAD was utilized for a post hoc analysis. This study assessed symptomatic patients with and without diabetes to evaluate the differences in processes of care, including referral to ICA and use of CV preventative therapies, following NIT; differences in the risk of CV outcomes; and whether the risk of CV outcomes in patients with and without diabetes was different in CTA versus functional stress testing. The primary purpose of this study was to determine whether a diagnostic strategy based on CTA was superior to functional stress testing in reducing adverse cardiovascular (CV) outcomes (CV death or myocardial infarction [MI]) among symptomatic patients with diabetes.
“Sharma et al. present an elegant a priori planned subgroup analysis within the PROMISE population, stratifying participants into groups with (n ¼ 1,908) and without (n ¼ 7,058) diabetes mellitus. Compared with those without diabetes, individuals with diabetes had a higher baseline burden of CVD risk factors, and their median estimated CVD risk was almost twice that of those without diabetes. Interaction testing showed that diabetes significantly and favorably modified the relationship between the noninvasive testing strategy (coronary CTA vs. stress testing) and a composite endpoint combining cardiovascular death or MI (p-value for interaction term ¼ 0.02; adjusted hazard ratio comparing coronary CTA vs. stress testing in diabetics: 0.38; 95% confidence interval: 0.18 to 0.79; association nonsignificant in nondiabetic patients), although it did not statistically modify the association with a combined endpoint including unstable angina.”- Dr. Michael J. Blaha, M.D.
Abhinav Sharma and his colleagues reported that patients with diabetes (vs. without) were similar in age (median 61 years vs. 60 years) and sex (female 54% vs. 52%) but had a greater burden of CV comorbidities. Importantly, patients with diabetes who underwent CTA had a lower risk of CV death/MI compared with functional stress testing (CTA: 1.1% [10 of 936] vs. stress testing: 2.6% [25 of 972]; adjusted hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.79; p ¼ 0.01). However,there was no significant difference in nondiabetic patients (CTA: 1.4% [50 of 3,564] vs. stress testing: 1.3% [45 of 3,494]; adjusted hazard ratio: 1.03; 95% confidence interval: 0.69 to 1.54; p ¼ 0.887; interaction term for diabetes p-value ¼ 0.02). These findings led them to conclude that “Among a contemporary cohort of patients with symptoms suggestive of CAD requiring testing, patients with diabetes are at increased risk of CV events compared with those without diabetes; however, the absolute risk of events is still low. Patients with diabetes who were randomized to CTA rather than functional stress testing had a reduced risk of CV events compared with those randomized to functional testing.” Explaining the reason for this, Sharma et al. noted, “This finding likely arises from increased use of downstream investigations and appropriate prescription of preventative therapies that may reduce CV events (such as statins).” Although frequent subsequent invasive evaluation and more intensive medical therapy of patients with diabetes undergoing CTA might have prompted these results, there was still no doubting the fact that in evaluating stable patients with diabetes who have symptoms suggestive of CAD, physicians should consider these benefits of using CTA as the initial diagnostic strategy. : Further studies are needed to define the specific interventions that improve clinical outcomes in patients with diabetes and CAD evaluated by CTA.
“The present analysis adds to a growing body of high-quality, high-impact evidence suggesting a preeminent role of coronary CTA for the assessment of patients with new-onset chest pain of suspected coronary cause. The value of coronary CTA is likely to grow in the coming years. In selected patients, coronary CTA provides an unrivaled opportunity for more detailed analysis of both coronary anatomy and function, such as with advanced plaque characterization and computed tomography-based fractional flow reserve assessment. More research is needed on how we can best personalize medical therapy using all of the rich data available on routine coronary CTA scans.”- Dr. Miguel Cainzos-Achirica, M.D.
Speaking about the effect modification of diabetes, Dr. Pamela S. Douglas, from the Duke University School of Medicine stated, “Our findings suggest that diabetes does not modify the relationship between NIT modality and the outcome of death/MI/UAH. However, the directionality of the hazard ratio between CTA versus functional testing in patients with diabetes and those without diabetes is consistent with the results seen in the outcome of CV death/MI. These findings suggest a possible benefit of CTA over functional testing in patients with diabetes, but our study population was underpowered to detect this difference. Among patients with diabetes, the primary benefit of CTA over functional testing is to reduce the risk of CV events—specifically CV death/MI. Among patients across the spectrum of glycemic disorder, including those with pre-diabetes and those with diabetes and established CV disease, non-CV death forms a large burden of mortality. This competing cause of death may not necessarily be modified by the downstream treatments following NIT. This may have contributed to the absence of a statistically significant reduction in death/MI/UAH in CTA versus functional testing in PROMISE trial patients with diabetes despite a significant reduction in CV death/MI.” Highlighting the importance of the study findings in an accompanying editorial, Dr. Michael J. Blaha,from the Ciccarone Center for the Prevention of Cardiovascular Disease, The Johns Hopkins Hospital, Baltimore, Maryland remarked, “The present analysis adds to a growing body of high-quality, high-impact evidence suggesting a preeminent role of coronary CTA for the assessment of patients with new-onset chest pain of suspected coronary cause. The value of coronary CTA is likely to grow in the coming years. In selected patients, coronary CTA provides an unrivaled opportunity for more detailed analysis of both coronary anatomy and function, such as with advanced plaque characterization and computed tomography-based fractional flow reserve assessment. More research is needed on how we can best personalize medical therapy using all of the rich data available on routine coronary CTA scans.”
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