ACCEL | Individuals with diabetes mellitus (DM) are much more likely to have CAD, which is a major factor in their poorer long-term outcomes, including poorer outcomes after revascularization. Add in the fact that myocardial infarction (MI) is often the first symptom of CAD, more effective screening might be useful in high-risk, asymptomatic patients, such as routine screening for CAD by cardiac CT angiography.

Screening of asymptomatic patients for a potentially life-threatening disease is an intuitively attractive example of personalized medicine. It is also consistent with the concept of an ounce of prevention being worth a pound of cure. Therefore, investigators enrolled 900 patients with type 1 or type 2 DM (of at least 3 years duration) randomized 1:1 to CAD screening with CCTA-directed therapy or to guidelines-directed optimal diabetes care. All participants had diabetes but no signs or symptoms of CVD.

The rationale for this study was based on prior attempts to assess screening for asymptomatic CAD that have been limited to noninvasive tests that only detect myocardial ischemia, with variable sensitivity and specificity, and without a structured approach to therapy. CCTA provides the opportunity to noninvasively evaluate both the extent and severity of coronary atherosclerosis.

Optimal diabetes care was recommended for all controls and CCTA patients with normal coronary artery scans. Targets included a hemoglobin A1c < 7.0%, low-density lipoprotein (LDL) < 100 mg/dL, and systolic blood pressure (BP) < 130 mm Hg. Aggressive risk factor reduction was recommended for all CCTA patients with at least some documented CAD, with an emphasis on diet and exercise. Targets for these patients were: LDL < 70 mg/dL, high-density lipoprotein (HDL) > 50 mg/dL, triglycerides < 150 mg/dL, A1c < 6%, and systolic BP < 120 mm Hg.

Save the Imaging

“Among asymptomatic patients with type 1 or type 2 diabetes, screening for coronary artery disease by CCTA did not reduce the composite rates of all-cause mortality, nonfatal MI, or hospitalization for unstable angina at 4 years (TABLE) despite differential use of coronary interventions and favorable trends in lipids and blood pressure,” said Joseph Muhlstein, MD, University of Utah, Murray, Utah.

The good news is that aggressive risk-factor management worked. Despite finding moderate-to-severe CAD in 1 of every 5 study participants, as well as a high Agatston score in 4 out of 10 asymptomatic patients with DM, the event rates in both arms were low, for an approximately 0.5% annual rate of MI.¹

Dr. Muhlstein said the results reinforce the importance of aggressive risk factor and lifestyle modification in these patients. Pamela Douglas, MD, Duke Clinical Research Institute, Durham, North Carolina, agreed: “Nationally, fewer than 10% of diabetics are at goal for all cardiovascular prevention targets and this means there is a tremendous gap for risk reduction outside of the clinical trial population, which is perhaps the largest message from this trial.”

As suggested by the authors, the most likely explanation for the negative findings in this study was the excellent baseline medical therapy in these patients. In an editorial accompanying the publication of the trial results, Raymond J. Gibbons, MD, Mayo Clinic, Rochester, Minnesota, wrote that the negative results may reflect the inability to successfully implement the more aggressive therapy recommended for patients with abnormal CCTA findings.² The changes in BP and LDL cholesterol values from baseline to 1 year among patients randomized to CCTA did not differ significantly from those changes among patients in the well-managed control group.

Although studies like this are often characterized as “negative,” Dr. Gibbons pointed to several important messages. Future trials of cardiac imaging in asymptomatic patients with diabetes should be larger and focused on an enriched study population at higher risk. “A more important and more currently applicable message is that guideline-directed medical therapy for hypertension and hyperlipidemia is effective in asymptomatic patients with diabetes and should be implemented more consistently,” said Dr. Gibbons. The investigators, he wrote, have set a new published standard for what is achievable in patients with diabetes with respect to blood pressure control and lipid-lowering therapy and, when therapy is applied this effectively, patients with diabetes are no longer at high risk for major cardiovascular events.

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References

1. Muhlestein JB, Lappé DL, Lima JA, et al. JAMA. 2014;312:2234-43.
2. Gibbons RJ. JAMA. 2014;312:2219-20.

Keywords: CardioSource WorldNews Interventions

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