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Erschienen in: Cardiovascular Drugs and Therapy 3/2015

01.06.2015 | ORIGINAL ARTICLE

The Effect of Metformin Use on Left Ventricular Ejection Fraction and Mortality Post-Myocardial Infarction

verfasst von: Amjad Abualsuod, Joshua J. Rutland, Thomas E. Watts, Summit Pandat, Robert Delongchamp, Jawahar L. Mehta

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 3/2015

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Abstract

Background

Animal studies showed that the use of metformin after myocardial infarction (MI) resulted in a protective effect on cardiac myocytes. In this study, we examined the effect of metformin in patients with diabetes mellitus (DM) on left ventricular ejection fraction (LVEF) and post-MI mortality.

Methods

We reviewed charts of patients with MI admitted to the UAMS medical center. Baseline characteristics and 12-month follow up data were collected. Patients were classified into three groups: Control group- no DM (n = 464), Metformin group- DM + MI (n = 88) and No-Metformin group- DM + MI (n = 168). First, we compared Metformin and No-Metformin groups to the Control group. Second, we performed propensity-score matching in patients with DM, and compared Metformin to No-Metformin groups.

Results

All-cause 30-day and 12-month mortality was significantly higher in the No-Metformin group compared to controls (13.5 vs 9.3 % p = 0.03 at 30 days, 23.7 vs 15.9 % p = 0.03 at 12 months). However, all-cause 30-day and 12-month mortality were similar in the Controls and Metformin group (9.3 vs 6.8 % p = 0.93 at 30 days, 15.9 vs 11.4 % p = 0.97 at 12 months). Mean LVEF on presentation (45 % in the three groups) and at follow up (47.84, 46.38 and 43.62 % in Control, Metformin, and No-Metformin groups, respectively) were not statistically different. There were no significant differences in regard to re-hospitalization, re-intervention, new stroke, CHF development, new MI, or identifiable arrhythmias. Metformin was an independent predictor of lower 30-day and 12-month all-cause mortality in patients with DM (HR 0.25, p = 0.02 and HR 0.32, p = 0.01, respectively). In the matched analysis, 30-day all-cause mortality was significantly higher in the No-Metformin compared to the Metformin group (21.1 vs 8.8 %, p = 0.05). However the difference in 12-month all-cause mortality did not reach statistical significance (24.6 vs 15.8 %, p = 0.15).

Conclusion

This proof-of-concept study shows that use of metformin in patients with DM is associated with lower 30-day all-cause mortality and tendency for a lower 12-month all-cause mortality following MI without discernible improvement in LVEF.
Literatur
1.
Zurück zum Zitat Kochanek KD, Xu JQ, Murphy SL, Miniño AM, Kung HC. Deaths: final data for 2009. National vital statistics reports. 2011;60. Kochanek KD, Xu JQ, Murphy SL, Miniño AM, Kung HC. Deaths: final data for 2009. National vital statistics reports. 2011;60.
2.
Zurück zum Zitat Jhund PS, McMurray JJ. Heart failure after acute myocardial infarction: a lost battle in the war on heart failure? Circulation. 2008;118(20):2019–21.PubMedCrossRef Jhund PS, McMurray JJ. Heart failure after acute myocardial infarction: a lost battle in the war on heart failure? Circulation. 2008;118(20):2019–21.PubMedCrossRef
3.
Zurück zum Zitat Roussel R, Travert F, Pasquet B, Wilson PW, Smith Jr SC, Goto S, et al. Metformin use and mortality among patients with diabetes and atherothrombosis. Arch Intern Med. 2010;170(21):1892–9.PubMedCrossRef Roussel R, Travert F, Pasquet B, Wilson PW, Smith Jr SC, Goto S, et al. Metformin use and mortality among patients with diabetes and atherothrombosis. Arch Intern Med. 2010;170(21):1892–9.PubMedCrossRef
4.
Zurück zum Zitat UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352(9131):854–65.CrossRef UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352(9131):854–65.CrossRef
5.
Zurück zum Zitat Gæde P, Lund-Andersen H, Parving H, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358(6):580–91.PubMedCrossRef Gæde P, Lund-Andersen H, Parving H, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358(6):580–91.PubMedCrossRef
6.
Zurück zum Zitat Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353(25):2643–53.PubMedCrossRef Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353(25):2643–53.PubMedCrossRef
7.
Zurück zum Zitat Eurich DT, Majumdar SR, McAlister FA, Tsuyuki RT, Johnson JA. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care. 2005;28(10):2345–51.PubMedCrossRef Eurich DT, Majumdar SR, McAlister FA, Tsuyuki RT, Johnson JA. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care. 2005;28(10):2345–51.PubMedCrossRef
8.
Zurück zum Zitat Aguilar D, Chan W, Bozkurt B, Ramasubbu K, Deswal A. Metformin use and mortality in ambulatory patients with diabetes and heart failure. Circ Heart Fail. 2011;4(1):53–8.PubMedCentralPubMedCrossRef Aguilar D, Chan W, Bozkurt B, Ramasubbu K, Deswal A. Metformin use and mortality in ambulatory patients with diabetes and heart failure. Circ Heart Fail. 2011;4(1):53–8.PubMedCentralPubMedCrossRef
9.
Zurück zum Zitat Johnson JA, Majumdar SR, Simpson SH, Toth EL. Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes. Diabetes Care. 2002;25(12):2244–8.PubMedCrossRef Johnson JA, Majumdar SR, Simpson SH, Toth EL. Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes. Diabetes Care. 2002;25(12):2244–8.PubMedCrossRef
10.
Zurück zum Zitat Hong J, Zhang Y, Lai S, Lv A, Su Q, Dong Y, et al. Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes Care. 2013;36(5):1304–11.PubMedCentralPubMedCrossRef Hong J, Zhang Y, Lai S, Lv A, Su Q, Dong Y, et al. Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes Care. 2013;36(5):1304–11.PubMedCentralPubMedCrossRef
11.
Zurück zum Zitat Ali S, Fonseca V. Overview of metformin: special focus on metformin extended release. Expert Opin Pharmacother. 2012;13(12):1797–805.PubMedCrossRef Ali S, Fonseca V. Overview of metformin: special focus on metformin extended release. Expert Opin Pharmacother. 2012;13(12):1797–805.PubMedCrossRef
12.
Zurück zum Zitat Soraya H, Khorrami A, Garjani A, Maleki-Dizaji N, Garjani A. Acute treatment with metformin improves cardiac function following isoproterenol induced myocardial infarction in rats. Pharmacol Rep. 2012;64(6):1476–84.PubMedCrossRef Soraya H, Khorrami A, Garjani A, Maleki-Dizaji N, Garjani A. Acute treatment with metformin improves cardiac function following isoproterenol induced myocardial infarction in rats. Pharmacol Rep. 2012;64(6):1476–84.PubMedCrossRef
13.
Zurück zum Zitat Cittadini A, Napoli R, Monti MG, Rea D, Longobardi S, Netti PA, et al. Metformin prevents the development of chronic heart failure in the SHHF rat model. Diabetes. 2012;61(4):944–53.PubMedCentralPubMedCrossRef Cittadini A, Napoli R, Monti MG, Rea D, Longobardi S, Netti PA, et al. Metformin prevents the development of chronic heart failure in the SHHF rat model. Diabetes. 2012;61(4):944–53.PubMedCentralPubMedCrossRef
14.
Zurück zum Zitat Yin M, van der Horst IC, van Melle JP, Qian C, van Gilst WH, Sillje HH, et al. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure. Am J Physiol Heart Circ Physiol. 2011;301(2):H459–68.PubMedCrossRef Yin M, van der Horst IC, van Melle JP, Qian C, van Gilst WH, Sillje HH, et al. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure. Am J Physiol Heart Circ Physiol. 2011;301(2):H459–68.PubMedCrossRef
15.
Zurück zum Zitat Andersson C, Sogaard P, Hoffmann S, Hansen PR, Vaag A, Major-Pedersen A, et al. Metformin is associated with improved left ventricular diastolic function measured by tissue Doppler imaging in patients with diabetes. Eur J Endocrinol. 2010;163(4):593–9.PubMedCrossRef Andersson C, Sogaard P, Hoffmann S, Hansen PR, Vaag A, Major-Pedersen A, et al. Metformin is associated with improved left ventricular diastolic function measured by tissue Doppler imaging in patients with diabetes. Eur J Endocrinol. 2010;163(4):593–9.PubMedCrossRef
16.
Zurück zum Zitat Lexis CP, van der Horst IC, Lipsic E, Wieringa WG, de Boer RA, van den Heuvel AF, et al. Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial. JAMA. 2014;311(15):1526–35. Lexis CP, van der Horst IC, Lipsic E, Wieringa WG, de Boer RA, van den Heuvel AF, et al. Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial. JAMA. 2014;311(15):1526–35.
17.
18.
Zurück zum Zitat Bosi E. Metformin–the gold standard in type 2 diabetes: what does the evidence tell us? Diabetes Obes Metab. 2009;11 Suppl 2:3–8.PubMedCrossRef Bosi E. Metformin–the gold standard in type 2 diabetes: what does the evidence tell us? Diabetes Obes Metab. 2009;11 Suppl 2:3–8.PubMedCrossRef
19.
Zurück zum Zitat King P, Peacock I, Donnelly R. The UK prospective diabetes study (UKPDS): clinical and therapeutic implications for type 2 diabetes. Br J Clin Pharmacol. 1999;48(5):643–8.PubMedCentralPubMedCrossRef King P, Peacock I, Donnelly R. The UK prospective diabetes study (UKPDS): clinical and therapeutic implications for type 2 diabetes. Br J Clin Pharmacol. 1999;48(5):643–8.PubMedCentralPubMedCrossRef
20.
Zurück zum Zitat El Messaoudi S, Rongen GA, de Boer RA, Riksen NP. The cardioprotective effects of metformin. Curr Opin Lipidol. 2011;22(6):445–53.PubMedCrossRef El Messaoudi S, Rongen GA, de Boer RA, Riksen NP. The cardioprotective effects of metformin. Curr Opin Lipidol. 2011;22(6):445–53.PubMedCrossRef
21.
Zurück zum Zitat Whittington HJ, Hall AR, McLaughlin CP, Hausenloy DJ, Yellon DM, Mocanu MM. Chronic metformin associated cardioprotection against infarction: not just a glucose lowering phenomenon. Cardiovasc Drugs Ther. 2013;27(1):5–16.PubMedCrossRef Whittington HJ, Hall AR, McLaughlin CP, Hausenloy DJ, Yellon DM, Mocanu MM. Chronic metformin associated cardioprotection against infarction: not just a glucose lowering phenomenon. Cardiovasc Drugs Ther. 2013;27(1):5–16.PubMedCrossRef
22.
Zurück zum Zitat Lexis CP, Wieringa WG, Hiemstra B, van Deursen VM, Lipsic E, van der Harst P, et al. Chronic metformin treatment is associated with reduced myocardial infarct size in diabetic patients with ST-segment elevation myocardial infarction. Cardiovasc Drugs Ther. 2013. Lexis CP, Wieringa WG, Hiemstra B, van Deursen VM, Lipsic E, van der Harst P, et al. Chronic metformin treatment is associated with reduced myocardial infarct size in diabetic patients with ST-segment elevation myocardial infarction. Cardiovasc Drugs Ther. 2013.
23.
Zurück zum Zitat Meaney E, Vela A, Samaniego V, Meaney A, Asbun J, Zempoalteca JC, et al. Metformin, arterial function, intima-media thickness and nitroxidation in metabolic syndrome: the mefisto study. Clin Exp Pharmacol Physiol. 2008;35(8):895–903.PubMedCrossRef Meaney E, Vela A, Samaniego V, Meaney A, Asbun J, Zempoalteca JC, et al. Metformin, arterial function, intima-media thickness and nitroxidation in metabolic syndrome: the mefisto study. Clin Exp Pharmacol Physiol. 2008;35(8):895–903.PubMedCrossRef
24.
Zurück zum Zitat Matsumoto K, Sera Y, Abe Y, Tominaga T, Yeki Y, Miyake S. Metformin attenuates progression of carotid arterial wall thickness in patients with type 2 diabetes. Diabetes Res Clin Pract. 2004;64(3):225–8.PubMedCrossRef Matsumoto K, Sera Y, Abe Y, Tominaga T, Yeki Y, Miyake S. Metformin attenuates progression of carotid arterial wall thickness in patients with type 2 diabetes. Diabetes Res Clin Pract. 2004;64(3):225–8.PubMedCrossRef
25.
Zurück zum Zitat Preiss D, Lloyd SM, Ford I, McMurray JJ, Holman RR, Welsh P, et al. Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial. Lancet Diab Endo. 2013. Preiss D, Lloyd SM, Ford I, McMurray JJ, Holman RR, Welsh P, et al. Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial. Lancet Diab Endo. 2013.
26.
Zurück zum Zitat Kao J, Tobis J, McClelland RL, Heaton MR, Davis BR, Holmes Jr DR, et al. Relation of metformin treatment to clinical events in diabetic patients undergoing percutaneous intervention. Am J Cardiol. 2004;93(11):1347–50.PubMedCrossRef Kao J, Tobis J, McClelland RL, Heaton MR, Davis BR, Holmes Jr DR, et al. Relation of metformin treatment to clinical events in diabetic patients undergoing percutaneous intervention. Am J Cardiol. 2004;93(11):1347–50.PubMedCrossRef
27.
Zurück zum Zitat 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(2):668–77.PubMedCentralPubMedCrossRef 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(2):668–77.PubMedCentralPubMedCrossRef
28.
Zurück zum Zitat Malmberg K, Norhammar A, Wedel H, Ryden L. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the diabetes and insulin-glucose infusion in acute myocardial infarction (DIGAMI) study. Circulation. 1999;99(20):2626–32.PubMedCrossRef Malmberg K, Norhammar A, Wedel H, Ryden L. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the diabetes and insulin-glucose infusion in acute myocardial infarction (DIGAMI) study. Circulation. 1999;99(20):2626–32.PubMedCrossRef
29.
Zurück zum Zitat Mellbin LG, Malmberg K, Norhammar A, Wedel H, Ryden L. DIGAMI 2 investigators. Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the diabetes mellitus insulin-glucose infusion in acute myocardial infarction (DIGAMI) 2 study. Diabetologia. 2011;54(6):1308–17.PubMedCrossRef Mellbin LG, Malmberg K, Norhammar A, Wedel H, Ryden L. DIGAMI 2 investigators. Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the diabetes mellitus insulin-glucose infusion in acute myocardial infarction (DIGAMI) 2 study. Diabetologia. 2011;54(6):1308–17.PubMedCrossRef
30.
Zurück zum Zitat Burla AK, Lobato NS, Fortes ZB, Oigman W, Neves MF. Cardiac fibrosis and vascular remodeling are attenuated by metformin in obese rats. Int J Cardiol. 2013;165(3):483–7.PubMedCrossRef Burla AK, Lobato NS, Fortes ZB, Oigman W, Neves MF. Cardiac fibrosis and vascular remodeling are attenuated by metformin in obese rats. Int J Cardiol. 2013;165(3):483–7.PubMedCrossRef
31.
Zurück zum Zitat Soraya H, Farajnia S, Khani S, Rameshrad M, Khorrami A, Banani A, et al. Short-term treatment with metformin suppresses toll like receptors (TLRs) activity in isoproterenol-induced myocardial infarction in rat: are AMPK and TLRs connected? Int Immunopharmacol. 2012;14(4):785–91.PubMedCrossRef Soraya H, Farajnia S, Khani S, Rameshrad M, Khorrami A, Banani A, et al. Short-term treatment with metformin suppresses toll like receptors (TLRs) activity in isoproterenol-induced myocardial infarction in rat: are AMPK and TLRs connected? Int Immunopharmacol. 2012;14(4):785–91.PubMedCrossRef
32.
Zurück zum Zitat Attia SM, Helal GK, Alhaider AA. Assessment of genomic instability in normal and diabetic rats treated with metformin. Chem Biol Interact. 2009;180(2):296–304.PubMedCrossRef Attia SM, Helal GK, Alhaider AA. Assessment of genomic instability in normal and diabetic rats treated with metformin. Chem Biol Interact. 2009;180(2):296–304.PubMedCrossRef
33.
Zurück zum Zitat Metcalfe A, Neudam A, Forde S, Liu M, Drosler S, Quan H, et al. Case definitions for acute myocardial infarction in administrative databases and their impact on in-hospital mortality rates. Health Serv Res. 2013;48(1):290–318.PubMedCentralPubMedCrossRef Metcalfe A, Neudam A, Forde S, Liu M, Drosler S, Quan H, et al. Case definitions for acute myocardial infarction in administrative databases and their impact on in-hospital mortality rates. Health Serv Res. 2013;48(1):290–318.PubMedCentralPubMedCrossRef
Metadaten
Titel
The Effect of Metformin Use on Left Ventricular Ejection Fraction and Mortality Post-Myocardial Infarction
verfasst von
Amjad Abualsuod
Joshua J. Rutland
Thomas E. Watts
Summit Pandat
Robert Delongchamp
Jawahar L. Mehta
Publikationsdatum
01.06.2015
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 3/2015
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-015-6601-x

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