Glycemic Control after Cardiovascular Intervention Improves CV Outcomes

[[{"type":"media","view_mode":"media_crop","fid":"60221","attributes":{"alt":"","class":"media-image media-image-right","height":"201","id":"media_crop_2743577385368","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7594","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":" ","typeof":"foaf:Image","width":"299"}}]]Improved glycemic control after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is associated with decreased long-term risk for major adverse cardiac and cerebrovascular events, according to a new study.¹ The results suggest that patients with high hemoglobin A_1c (HbA_1c) levels after PCI may be at risk for adverse events, particularly the need for repeated revascularization.

“[O]ur results suggest that glycemic control after PCI may improve long-term outcomes in patients with diabetes mellitus independent of HbA_1c level at the time of PCI. We think that our study adds new and important information on strategies for glycemic control after PCI in diabetic patients,” wrote first author Jin Kyung Hwang, MD, PhD, of Sungkyunkwan University School of Medicine (Seoul, Republic of Korea) and colleagues.¹

While research shows consistent support for the role of intensive glycemic control in decreasing microvascular complications of type 2 diabetes mellitus, whether tight glucose control can reduce macrovascular complications has been a matter of debate. Almost 25% of patients who undergo PCI have diabetes, and these patients have worse outcomes than those without diabetes.¹ Knowing how glycemic control affects outcomes could be important for the treatment of these patients. However, little evidence exists about whether glycemic control after PCI improves CV outcomes over the long term.

To investigate this issue, a single-center, observational, prospective study evaluated 980 patients with type 2 diabetes who had received PCI with DES between January 2003 and December 2011 at Samsung Medical Center (Seoul, Republic of Korea). The analysis separated patients into two groups based on American Diabetes Association criteria and 2-year HbA_1c levels: HbA_1c < 7.0 (n = 489), and HbA_1c ≥ 7.0 (n = 491). To account for baseline differences between groups, researchers also did propensity score-matching on 322 pairs of patients. The primary outcome was a composite of major adverse cardiac and cerebrovascular events (MACCE), which included cardiac death, myocardial infarction, repeated vascularization, or stroke. The median follow-up period was 5.4 years.

• 7-Year MACCE incidence:

   ♦ 25% lower risk with HbA_1c < 7.0 vs HbA_1c ≥ 7.0 (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.57-0.98; P = .03)

   ♦ HbA_1c < 7.0: 26.9%

   ♦ HbA_1c ≥ 7.0: 40.3%

• Propensity score matched analysis 7-year MACCE incidence:

    ♦ 29% lower risk with HbA_1c < 7.0 vs HbA_1c ≥ 7.0 (HR, 0.71; 95% CI, 0.52-0.97; P =.03)

    ♦ HbA_1c < 7.0: 27.5%

    ♦ HbA_1c ≥ 7.0: 37.4%

    ♦ Driven by decreased repeated revascularization procedures (19.9% vs 29.5%; HR, 0.66; 95% CI, 0.47-0.93; P = .02)

 
The authors emphasized that the benefit of improved glycemic control on long-term MACCE may have largely resulted from the decreased need for repeated revascularization procedures after PCI. In subgroup analyses, this benefit was more prominent for patients with a residual SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score of > 4 (less complete revascularization), compared with those who had a residual SYNTAX score of ≤ 4 (more complete revascularization) (P_interaction = .004). The residual SYNTAX score quantifies the degree of revascularization after PCI and may be an indicator of 5-year all-cause mortality.²

Subgroup analyses also showed a consistent relationship between glucose control and decreased long-term MACCE regardless of stent type (first generation, second generation). The results suggest that diabetes may represent the most important risk factor for re-stenosis across stent types, according to the authors.

However, these results contrast with results from three large clinical trials-ACCORD, VADT, and ADVANCE trials-which showed no benefit for intensive glucose control on major cardiovascular (CV) events.^3-5 Different enrollment criteria and baseline characteristics of study participants may explain this discrepancy, the authors pointed out. The majority of participants in the ACCORD, VADT, and ADVANCE trials had no previous CV events, while the new study included patients with established CV disease who had undergone PCI. Moreover, participants in the other three trials had higher baseline HbA_1c values and greater insulin use, and they may have had diabetes of longer duration compared with participants in this study. These differences suggest that the effect of glycemic control on CV events may vary based on patient factors such as recent CV events, glycemic control status, and duration of diabetes, according to the authors.

Study limitations

Limitations of the study include its nonrandomized observational nature and the inability to adjust for smoking status. Only patients with baseline and 2-year HbA_1c values were selected, which could have biased the study. Also, the study had limited data on lipid-lowering therapy, and information on low-density lipoprotein levels was available for only 7.7% of participants. Finally, the study lacked data on diabetes duration and new risk factors that may have developed during follow-up.

Nevertheless, the authors concluded: “Our data suggest that high HbA_1c levels 2 years after PCI may identify a population at increased risk of adverse events, especially repeat revascularization. Further study is warranted to demonstrate whether strict glucose control after PCI can improve long-term clinical outcomes in diabetic patients.”

Take-home points

• A single-center, prospective, observational study in Korea suggests that improved glycemic control after PCI with DES is associated with decreased long-term risk for MACCE

• The 7-year incidence of MACCE was 25% lower in patients with HbA_1c < 7.0 than in those with HbA_1c ≤ 7.0

• The benefit of improved glycemic control on long-term MACCE may have largely resulted from the decreased need for repeated revascularization procedures after PCI

• The results suggest that identifying patients with high HbA_1c values after PCI may target a group at risk for adverse events, particularly the need for repeated revascularization; more study is needed

References:

1. Hwang JK, Lee SH, Song YB, et al. Glycemic control status after percutaneous coronary intervention and long-term clinical outcomes in patients with type 2 diabetes mellitus. Circ Cardiovasc Interv. 2017;10:e004157. doi: 10.1161/CIRCINTERVENTIONS.116.004157.

2. Farooq V, Serruys PW, Bourantas CV, et al. Quantification of incomplete revascularization and its association with five-year mortality in the synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) trial validation of the residual SYNTAX score. Circulation. 2013;128:141-151. doi: 10.1161/CIRCULATIONAHA.113.001803.

3. Gerstein HC, Miller ME, Byington RP, et al, for Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-2559. doi: 10.1056/NEJMoa0802743.

4. Duckworth W, Abraira C, Moritz T, et al, for VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129-139. doi: 10.1056/NEJMoa0808431.

5. Patel A, MacMahon S, Chalmers J, et al, for The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560-2572. doi: 10.1056/NEJMoa0802987