Does CAD screening curb risk of heart disease in asymptomatic diabetes?

Noninvasive coronary artery disease (CAD) screening decreased cardiac events in asymptomatic diabetic patients by 27% when compared with standard care, according to a recent systematic review and meta-analysis published in the European Heart Journal.

“This endpoint reduction was mainly driven by lower rates of non-fatal myocardial infarction (-35%) and HF hospitalizations (-39%), although both findings fell short of statistical significance when assessed separately,” wrote corresponding author Oliver Gaemperli, MD, and colleagues at University Heart Centre, University Hospital Zurich, Zurich, Switzerland.

High cardiovascular risk in patients with asymptomatic diabetes has elicited great interest in the early detection of silent CAD by clinicians. In addition to the exercise electrocardiogram test (EET), recent imaging innovations in noninvasive CAD screening modalities include  stress echocardiography (SE), stress radionuclide myocardial perfusion imaging (MPI), coronary artery calcium scoring (CACS), and computed tomography coronary angiography (CTCA).

Nevertheless, experts debate whether pre-emptive coronary revascularization and intensification of medical therapy based on routine CAD screening ameliorates clinical outcomes in asymptomatic diabetic patients.

“Experts favoring screening refer to the improvement of risk classification and the reduction of scintigraphic CAD progression with invasive treatment,” wrote Dr. Gaemperli and colleagues. “However, opponents advocate optimal medical treatment without screening because revascularization has not convincingly been demonstrated to reduce cardiovascular events in diabetic patients.”

Additionally, initial randomized controlled trials were unable to demonstrate any prognostic benefit of noninvasive CAD screening, which may be due to undersampling and statistical type II error secondary to lower event rates than expected.

The primary endpoint for this study was categorized as “any cardiac event,” which was a composite of cardiac death, non-fatal myocardial infarction, unstable angina, or heart failure hospitalization.

Secondary endpoints of this study included all-cause death, coronary revascularization, and medication use.

In their analysis, the researchers included 5 randomized controlled trials involving 3,299 patients of whom 5.7% (n=189) presented with any cardiac event during a mean follow-up period of 4.1 years. Mean age in these studies ranged between 60.1 and 63.9 years, and the proportion of men in these studies ranged between 52% and 80%. Noninvasive CAD screening was evaluated using EET, SE, MP, CTCA with CACS, or some combination.

The researchers found that non-invasive CAD screening significantly reduced the risk of any cardiac event by 27% (relative risk [RR] 0.73, 95% CI 0.55–0.97, P = 0.028]. Of note, the number of patients needed to screen to prevent one cardiac event was 56.

This finding was mediated by reductions in non-fatal myocardial infarction (RR 0.65, 95% CI 0.41–1.02, P = 0.062) and heart failure hospitalization (RR 0.61, 95% CI 0.33–1.10, P = 0.100).

Among secondary endpoints, noninvasive CAD screening did not significantly affect cardiac death (RR 0.92, 95% CI 0.53–1.60, P = 0.77) and unstable angina (RR 0.73, 95% CI 0.41–1.31, P = 0.29). Medication use did not significantly change, although there appeared an upward trend in statin use (RR 1.05, 95% CI 0.99–1.10, P = 0.092).

During their systematic review, the researchers also identified two relevant non-randomized controlled trials with appropriate control groups that demonstrated decreases in cardiovascular events in asymptomatic diabetes patients screened with either MPI or EET with or without SE. When the researchers included these trials in their meta-analysis, they found a more substantial decrease of any cardiac event by 42% (RR 0.58, 95% CI 0.37–0.91, P = 0.017), which was driven by a significant reduction of non-fatal myocardial infarction (RR 0.52, 95% CI 0.32–0.84, P = 0.008).

The strengths of this study include low risk of bias in the sampled studies, high-quality evidence, and detailed outcome assessments. One possible limitation of this study is that different noninvasive CAD screening modalities were used—although with the exception of EET, these imaging tests have proven highly sensitive and specific with respect to CAD.

“The present systematic review and meta-analysis suggests a reduction of cardiac events with the use of a CAD screening strategy in asymptomatic diabetic patients,” the authors concluded. “These results should encourage further research into this issue by design of larger, appropriately sized randomized trials to address the exact magnitude of the effect in specific subgroups.”