Poor Diabetes Control Associated with Poorer Coronary Stent Outcomes

By Jeffrey Zimmet, MD, PhD

SYNOPSIS: In this large, observational study of diabetic patients with coronary stents, poorer glycemic control as measured by hemoglobin A1c was associated with stepwise hazard for stent failure over a period of more than six years, primarily driven by in-stent restenosis.

SOURCE: Santos-Pardo I, Andersson Franko M, Lagerqvist B, et al. Glycemic control and coronary stent failure in patients with type 2 diabetes mellitus. J Am Coll Cardiol 2024;84:260-272.

Diabetes mellitus confers a well-described increased risk for developing significant coronary artery disease. After clinically important coronary disease has been diagnosed, moreover, patients with diabetes have a higher mortality than those without. Guidelines suggest that people with diabetes with multivessel coronary disease are better treated with coronary artery bypass grafting rather than percutaneous coronary intervention (PCI) because of higher rates of recurrent ischemic events and intermediate term mortality among patients treated by PCI.

Despite these guidelines, people with diabetes frequently are treated with coronary stents in real world practice. Recurrent ischemic events involving a coronary stent, generally captured in research studies as target lesion revascularization (TLR), have been suggested to be higher in persons with diabetes compared to those without. However, to date, little research has investigated the connection between glycemic control in patients with diabetes and stent failure events.

To this end, the investigators in this study leveraged data from a large national healthcare registry to assess whether glycemic control, rather than simply a yes-or-no answer regarding the presence of diabetes, correlates with the risk of stent failure following PCI. They focused on a time period during which second-generation drug-eluting stents were used. A total of 52,457 adult patients with a diagnosis of type 2 diabetes who received a coronary stent in Sweden between the beginning of 2010 and the end of 2020 were assessed. After excluding patients with missing hemoglobin (Hb) A1c or covariate data, the final cohort comprised 24,411 patients, in whom 29,029 stents had been implanted. The average age was 68 years and 26% were female. A majority (75%) had stents implanted in the setting of acute coronary syndromes (ACS) and 40% had multivessel disease. At a median follow-up of 6.4 years, 1,873 cases of stent failure were recorded. Of these, 1,159 were cases of in-stent restenosis (ISR), while the remaining 771 cases were stent thrombosis (ST).

In the primary analysis, the main finding was that the risk of stent failure increased stepwise with HbA1c. Using a simple cut point of HbA1c of 7%, patients above this threshold had a hazard ratio of 1.28 for stent failure, compared with those with an HbA1c below 7%. The rate of stent failure was nearly twice as high (15.6% vs. 8.9%) for patients with an HbA1c above 10%, compared with those in the 6.1% to 7% range. This result was independent of other measured clinical and procedural risk factors and was not modified by the presence or absence of insulin use. Interestingly, the link between glycemic control and stent performance was stronger for younger patients (age < 65 years) than for older ones.

The authors concluded that poorer glycemic control among patients with diabetes receiving second-generation drug-eluting coronary stents in de novo lesions was associated with higher rates of stent failure, primarily driven by ISR.

Commentary

The current study represents the best available data to date on the relationship between glycemic control and stent failure in people with diabetes who have coronary disease. What questions remain unanswered, and how should these conclusions affect clinical practice?

One crucial question is whether this truly represents a modifiable risk factor. In other words, would attempts at tighter glycemic control in the direct aftermath of a coronary stent (most here were implanted for ACS, so pre-PCI optimization of diabetes control would not be possible) result in improved stent outcomes? One of the clear strengths of this study is the longitudinal assessment of HbA1c. However, it does not really address the issue of whether early post-PCI glycemic control is paramount (as some prior smaller studies have suggested), or if this effect is gradual over time. It also is possible that this relationship applies mostly to the HbA1c at the time the stent was implanted, and that downstream attempts to better control blood sugar have lesser influence.

Should the HbA1c, in addition to the simple diagnosis of diabetes, further influence the decision regarding surgical vs. percutaneous revascularization? Despite current guideline recommendations, a majority of patients with diabetes who have multivessel disease continue to be treated with PCI. The implementation of a more granular approach to patients with diabetes by a heart team involving both cardiologists and surgeons seems a reasonable direction to proceed.

Jeffrey Zimmet, MD, PhD, is Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center.