Endocrinol Metab.  2021 Oct;36(5):977-987. 10.3803/EnM.2021.1046.

The Effects of Glucose Lowering Agents on the Secondary Prevention of Coronary Artery Disease in Patients with Type 2 Diabetes

Affiliations
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 2Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
  • 3Department of Biostatistics, Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea

Abstract

Background
Patients with diabetes have a higher risk of requiring repeated percutaneous coronary intervention (PCI) than non-diabetic patients. We aimed to evaluate and compare the effects of anti-diabetic drugs on the secondary prevention of myocardial infarction among type 2 diabetes mellitus patients.
Methods
We analyzed the general health check-up dataset and claims data of the Korean National Health Insurance Service of 199,714 participants (age ≥30 years) who underwent PCIs between 2010 and 2013. Those who underwent additional PCI within 1 year of their first PCI (n=3,325) and those who died within 1 year (n=1,312) were excluded. Patients were classified according to their prescription records for glucose-lowering agents. The primary endpoint was the incidence rate of coronary revascularization.
Results
A total of 35,348 patients were included in the study. Metformin significantly decreased the risk of requiring repeat PCI in all patients (adjusted hazard ratio [aHR], 0.77). In obese patients with body mass index (BMI) ≥25 kg/m2, patients treated with thiazolidinedione (TZD) exhibited a decreased risk of requiring repeat revascularization than those who were not treated with TZD (aHR, 0.77; 95% confidence interval, 0.63 to 0.95). Patients treated with metformin showed a decreased risk of requiring revascularization regardless of their BMI. Insulin, meglitinide, and alpha-glucosidase inhibitor were associated with increased risk of repeated PCI.
Conclusion
The risk of requiring repeat revascularization was lower in diabetic patients treated with metformin and in obese patients treated with TZD. These results suggest that physicians should choose appropriate glucose-lowering agents for the secondary prevention of coronary artery disease.

Keyword

Diabetes mellitus; Coronary artery disease; Secondary prevention; Percutaneous coronary intervention

Reference

1. Kannel WB, McGee DL. Diabetes and cardiovascular disease: the Framingham study. JAMA. 1979; 241:2035–8.
Article
2. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998; 339:229–34.
Article
3. Riche DM, Valderrama R, Henyan NN. Thiazolidinediones and risk of repeat target vessel revascularization following percutaneous coronary intervention: a meta-analysis. Diabetes Care. 2007; 30:384–8.
4. Center for Drug Evaluation and Research (CDER). Guidance for industry: diabetes mellitus-evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes [Internet]. Silver Spring;US Food and Drug Administration: 2008. [cited 2021 Sep 3]. Available from: https://www.fda.gov/media/71297/download .
5. Hinnen D, Kruger DF. Cardiovascular risks in type 2 diabetes and the interpretation of cardiovascular outcome trials. Diabetes Metab Syndr Obes. 2019; 12:447–55.
6. Toh S, Hampp C, Reichman ME, Graham DJ, Balakrishnan S, Pucino F, et al. Risk for hospitalized heart failure among new users of saxagliptin, sitagliptin, and other antihyperglycemic drugs: a retrospective cohort study. Ann Intern Med. 2016; 164:705–14.
Article
7. Marx N, Rosenstock J, Kahn SE, Zinman B, Kastelein JJ, Lachin JM, et al. Design and baseline characteristics of the CARdiovascular outcome trial of LINAgliptin versus glimepiride in type 2 diabetes (CAROLINA(R)). Diab Vasc Dis Res. 2015; 12:164–74.
8. Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomized controlled trial. Lancet. 2005; 366:1279–89.
9. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007; 356:2457–71.
Article
10. Noh J. The diabetes epidemic in Korea. Endocrinol Metab (Seoul). 2016; 31:349–53.
Article
11. Hampp C, Borders-Hemphill V, Moeny DG, Wysowski DK. Use of antidiabetic drugs in the U.S., 2003–2012. Diabetes Care. 2014; 37:1367–74.
Article
12. Asakura Y, Suzuki M, Nonogi H, Haze K, Sato A, Inada H, et al. Restenosis after percutaneous transluminal coronary angioplasty in patients with non-insulin-dependent diabetes mellitus (NIDDM). J Cardiovasc Risk. 1998; 5:331–4.
Article
13. Chung JW, Park YS, Seo JE, Son Y, Oh CW, Lee CH, et al. Clinical impact of dysglycemia in patients with an acute myocardial infarction. Diabetes Metab J. 2021; 45:270–4.
Article
14. Hwang JK, Lee SH, Song YB, Ahn J, Carriere K, Jang MJ, 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.
Article
15. Scheen AJ, Paquot N. Metformin revisited: a critical review of the benefit-risk balance in at-risk patients with type 2 diabetes. Diabetes Metab. 2013; 39:179–90.
Article
16. Kao J, Tobis J, McClelland RL, Heaton MR, Davis BR, Holmes DR Jr, et al. Relation of metformin treatment to clinical events in diabetic patients undergoing percutaneous intervention. Am J Cardiol. 2004; 93:1347–50.
Article
17. Gallwitz B. Clinical use of DPP-4 inhibitors. Front Endocrinol (Lausanne). 2019; 10:389.
Article
18. Chaturvedi N, Eastwood S. Prescribing by ethnicity: (im)precision medicine? Diabetes Care. 2020; 43:1687–9.
Article
19. Wang MT, Lin SC, Tang PL, Hung WT, Cheng CC, Yang JS, et al. The impact of DPP-4 inhibitors on long-term survival among diabetic patients after first acute myocardial infarction. Cardiovasc Diabetol. 2017; 16:89.
Article
20. Connelly KA, Zhang Y, Advani A, Advani SL, Thai K, Yuen DA, et al. DPP-4 inhibition attenuates cardiac dysfunction and adverse remodeling following myocardial infarction in rats with experimental diabetes. Cardiovasc Ther. 2013; 31:259–67.
Article
21. Kalogeris T, Bao Y, Korthuis RJ. Mitochondrial reactive oxygen species: a double edged sword in ischemia/reperfusion vs preconditioning. Redox Biol. 2014; 2:702–14.
Article
22. Nakamura T, Iwanaga Y, Miyaji Y, Nohara R, Ishimura T, Miyazaki S, et al. Cardiovascular efficacy of sitagliptin in patients with diabetes at high risk of cardiovascular disease: a 12-month follow-up. Cardiovasc Diabetol. 2016; 15:54.
Article
23. Kim YG, Hahn S, Oh TJ, Kwak SH, Park KS, Cho YM. Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and non-Asians: a systematic review and meta-analysis. Diabetologia. 2013; 56:696–708.
Article
24. Cai Y, Zeng T, Wen Z, Chen L. Ethnic differences in efficacy and safety of alogliptin: a systematic review and meta-analysis. Diabetes Ther. 2018; 9:177–91.
Article
25. Erdmann E, Dormandy JA, Charbonnel B, Massi-Benedetti M, Moules IK, Skene AM, et al. The effect of pioglitazone on recurrent myocardial infarction in 2,445 patients with type 2 diabetes and previous myocardial infarction: results from the PROactive (PROactive 05) Study. J Am Coll Cardiol. 2007; 49:1772–80.
26. Tordjman J, Chauvet G, Quette J, Beale EG, Forest C, Antoine B. Thiazolidinediones block fatty acid release by inducing glyceroneogenesis in fat cells. J Biol Chem. 2003; 278:18785–90.
Article
27. Law RE, Goetze S, Xi XP, Jackson S, Kawano Y, Demer L, et al. Expression and function of PPARgamma in rat and human vascular smooth muscle cells. Circulation. 2000; 101:1311–8.
Article
28. Law RE, Meehan WP, Xi XP, Graf K, Wuthrich DA, Coats W, et al. Troglitazone inhibits vascular smooth muscle cell growth and intimal hyperplasia. J Clin Invest. 1996; 98:1897–905.
Article
29. Takagi T, Yamamuro A, Tamita K, Yamabe K, Katayama M, Mizoguchi S, et al. Pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus: an intravascular ultrasound scanning study. Am Heart J. 2003; 146:E5.
Article
30. Choi D, Kim SK, Choi SH, Ko YG, Ahn CW, Jang Y, et al. Preventative effects of rosiglitazone on restenosis after coronary stent implantation in patients with type 2 diabetes. Diabetes Care. 2004; 27:2654–60.
Article
31. Coleman RL, Scott CA, Lang Z, Bethel MA, Tuomilehto J, Holman RR. Meta-analysis of the impact of alpha-glucosidase inhibitors on incident diabetes and cardiovascular outcomes. Cardiovasc Diabetol. 2019; 18:135.
Article
32. Dagenais GR, Lu J, Faxon DP, Kent K, Lago RM, Lezama C, et al. Effects of optimal medical treatment with or without coronary revascularization on angina and subsequent revascularizations in patients with type 2 diabetes mellitus and stable ischemic heart disease. Circulation. 2011; 123:1492–500.
Article
33. Dangas GD, Farkouh ME, Sleeper LA, Yang M, Schoos MM, Macaya C, et al. Long-term outcome of PCI versus CABG in insulin and non-insulin-treated diabetic patients: results from the FREEDOM trial. J Am Coll Cardiol. 2014; 64:1189–97.
34. Roumie CL, Greevy RA, Grijalva CG, Hung AM, Liu X, Murff HJ, et al. Association between intensification of metformin treatment with insulin vs sulfonylureas and cardiovascular events and all-cause mortality among patients with diabetes. JAMA. 2014; 311:2288–96.
Article
35. Currie CJ, Poole CD, Evans M, Peters JR, Morgan CL. Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes. J Clin Endocrinol Metab. 2013; 98:668–77.
Article
36. Gamble JM, Simpson SH, Eurich DT, Majumdar SR, Johnson JA. Insulin use and increased risk of mortality in type 2 diabetes: a cohort study. Diabetes Obes Metab. 2010; 12:47–53.
Article
37. Bell DS, Patil HR, O’Keefe JH. Divergent effects of various diabetes drugs on cardiovascular prognosis. Rev Cardiovasc Med. 2013; 14:e107–22.
Article
38. Hanefeld M, Frier BM, Pistrosch F. Hypoglycemia and cardiovascular risk: is there a major link? Diabetes Care. 2016; 39(Suppl 2):S205–9.
Article
39. Willey CJ, Andrade SE, Cohen J, Fuller JC, Gurwitz JH. Polypharmacy with oral antidiabetic agents: an indicator of poor glycemic control. Am J Manag Care. 2006; 12:435–40.
40. Ko SH, Han K, Lee YH, Noh J, Park CY, Kim DJ, et al. Past and current status of adult type 2 diabetes mellitus management in Korea: a National Health Insurance Service Database analysis. Diabetes Metab J. 2018; 42:93–100.
Article
41. Schnell O, Ryden L, Standl E, Ceriello A. D&CVD EASD Study Group. Updates on cardiovascular outcome trials in diabetes. Cardiovasc Diabetol. 2017; 16:128.
Article
42. Kim JY, Kim SJ, Nam CM, Moon KT, Park EC. Changes in prescription pattern, pharmaceutical expenditure and quality of care after introduction of reimbursement restriction in diabetes in Korea. Eur J Public Health. 2018; 28:209–14.
Article
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