Submit Manuscripts
Author Information
Subscribe/Renew
Email Alerts
Feedback
RSS Feed

About the Journal
Editorial Board & Staff

Interventions Homepage Imaging Homepage Interventions Homepage Imaging Homepage

ACC.org
Cardiosmart
Cardiosource
CVN
Imaging Library
JACC Imaging
JACC Interventions


ACC/AHA 2008 Performance Measures for Adults With ST-Elevation and Non-ST-Elevation Myocardial Infarction

ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease
cardiology careers collections past issues search home
     

J Am Coll Cardiol, 1999; 33:119-124
© 1999 by the American College of Cardiology Foundation
This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Garratt, K. N.
Right arrow Articles by Holmes, D. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Garratt, K. N.
Right arrow Articles by Holmes, D. R., Jr.

CLINICAL STUDIES

Sulfonylurea drugs increase early mortality in patients with diabetes mellitus after direct angioplasty for acute myocardial infarction

Kirk N. Garratt, MD, FACCa, Peter A. Brady, MD, MRCPa, Nancy L. Hassinger, MDa, Diane E. Grilla, Andre Terzic, MD, PhDa and David R. Holmes, Jr., MD, FACCa

a Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA

Manuscript received February 19, 1998; revised manuscript received August 10, 1998, accepted September 10, 1998.

Address for correspondence: Dr. Kirk N. Garratt, 200 First St. SW, Rochester, Minnesota 55905


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
Objectives. The purpose of this study was to examine the impact of sulfonylurea drug use on outcome in diabetic patients undergoing direct coronary angioplasty for acute myocardial infarction.

Background. Sulfonylurea drugs impair ischemic preconditioning. Whether sulfonylurea drugs affect outcome adversely in diabetic patients undergoing direct angioplasty for acute myocardial infarction is unknown.

Methods. Clinical outcomes after direct balloon angioplasty for acute myocardial infarction were evaluated in 67 diabetic patients taking oral sulfonylurea drugs and 118 diabetic patients not taking these drugs.

Results. Hospital mortality was significantly higher among diabetics treated with sulfonylurea drugs at the time of myocardial infarction (24% vs. 11%). Univariate analysis identified sulfonylurea drug, age, ventricular function, ejection fraction less than 40%, prior bypass surgery and congestive heart failure as correlates of increased in-hospital mortality. Logistic regression found sulfonylurea drug use (odds ratio 2.77, p = 0.017) to be independently associated with early mortality. Congestive heart failure, but not sulfonylurea drug use, was associated with an increased incidence of in-hospital ventricular arrhythmias. Congestive heart failure, prior bypass surgery and female gender, but not sulfonylurea drug use, were associated with late adverse events.

Conclusions. Sulfonylurea drug use is associated with an increased risk of in-hospital mortality among diabetic patients undergoing coronary angioplasty for acute myocardial infarction. This early risk is not explained by an increase in ventricular arrhythmias, but may reflect deleterious effects of sulfonylurea drugs on myocardial tolerance for ischemia and reperfusion. For surviving patients sulfonylurea drug use is not associated with an increased risk of serious late adverse events.

Abbreviations and Acronyms
  CABG = coronary artery bypass graft surgery
  CI = 95% confidence interval
  HbgA1C = glycosylated hemoglobin
  KATP = adenosine triphosphate–sensitive potassium channel
  LVEF = left ventricular ejection fraction
  MI = myocardial infarction
  OR = odds ratio

Patients with diabetes mellitus account for a large proportion of patients admitted with acute myocardial infarction (MI) and as a whole have a poorer prognosis when compared to nondiabetic patients (1–3). Moreover, diabetic patients with ischemic heart disease have a substantially worse outcome following coronary interventional procedures despite similar rates of procedural success when compared to patients without diabetes (4,5). The basis for these differences in outcome remains unresolved.

Among possible contributing factors, use of sulfonylurea hypoglycemic agents has been reported to increase cardiovascular mortality in patients with non–insulin dependent (type II) diabetes mellitus (6,7). The mechanism of action and the controversy surrounding the clinical use of sulfonylurea drugs has recently been reviewed in detail (8). Sulfonylureas, while promoting release of insulin (9–11) through blockade of metabolism regulated adenosine triphospate–sensitive potassium channel (KATP) channels present in pancreatic b-cell membranes (12,13), also block KATP channels present in cardiac cells and coronary vasculature (14–17). This action impairs ischemic preconditioning (18–20) and prevents coronary vasodilation in response to ischemia (21–23). Since ischemic preconditioning and coronary vasodilation act to protect the heart against ischemic insults (24), sulfonylurea drug action within the myocardium may increase its vulnerability to ischemia (25). Furthermore, sulfonylureas impair ischemic preconditioning during coronary angioplasty, leading to increased clinical manifestations of ischemia (26). However, there have been no clinical reports of increased mortality in patients with ischemic heart disease treated with glibenclamide, a sulfonylurea with known high affinity for myocardial KATP channels (15,16), and no data are available that address specifically outcomes in diabetic patients with MI undergoing direct coronary angioplasty while taking sulfonylurea drugs.

To address this, we examined mortality and other adverse events among diabetic patients undergoing direct balloon angioplasty for acute MI, and assessed the effects of oral sulfonylurea hypoglycemic drug use on clinical outcome.


   Methods
Top
 Abstract
 Methods
Results
 Discussion
 References
 
Patient population.   Patients with preexisting diabetes mellitus undergoing direct coronary angioplasty for treatment of acute MI between January 1985 and December 1994 were identified retrospectively from the Mayo Clinic coronary intervention database. This cutoff date was selected to assure against inclusion of patients using metformin, a nonsulfonylurea oral hypoglycemic agent available commercially in North America after December 29, 1994. Initial data for each patient were entered into the database prospectively, and follow-up data were obtained through review of medical records for all hospital and outpatient visits at Mayo Clinic and affiliated hospitals, and from a standardized questionnaire completed at 6 and 12 months following intervention, and annually thereafter. Adverse events were corroborated through review of medical records and death notices. In accordance with Minnesota law, only patients who consented to the use of their clinical records for research purposes were included in this study; the number of eligible patients not included for this reason was zero. This study was approved by the Mayo Clinic Institutional Review Board.

Medical treatment.   Patients were divided into two groups on the basis of their use of diabetic medications. Group 1 consisted of diabetic patients with acute MI taking an oral sulfonylurea drug at the time of angioplasty, and group 2 consisted of diabetic patients with acute MI not taking a sulfonylurea drug. All patients were treated with conventional doses of heparin, aspirin, beta-adrenergic blocking drugs and nitroglycerin according to established protocols for the care of patients with acute MI.

Coronary angiography and revascularization.   Coronary angiography was performed in patients immediately upon presentation with acute MI. All patients were treated with direct balloon angioplasty employing standard technique; nonballoon coronary intervention devices (atherectomy devices, lasers or stents) were not evaluated in this study. Multivessel disease was considered present when angiographic narrowing of ≥70% involving at least one major coronary artery was accompanied by a narrowing of ≥50% in at least one other artery. Procedural success was defined as improvement of >40% luminal diameter in all lesions treated. Abrupt closure was defined as reduction of anterograde coronary blood flow to Thrombolysis in Myocardial Infarction trial grade 0–1 after angioplasty. Circulatory shock was defined as systolic blood pressure <90 mm Hg or cardiac output <2.5 liters/min. Clinical success was defined as procedural success without death, Q wave MI or urgent coronary artery bypass graft surgery (CABG).

End points.   In-hospital adverse events assessed included death, serious ventricular arrhythmias (fibrillation or sustained tachycardia), procedural success and complications, recurrent Q wave MI, need for CABG or repeat angioplasty procedures and postprocedural renal insufficiency (defined as an elevation of creatinine to >2.5 mg/dl). Late events assessed included death, postdischarge MI (Q wave and non–Q wave), need for additional angioplasty procedures or CABG and presence of recurrent severe angina. Correlates of in-hospital mortality, in-hospital ventricular arrhythmias, late death and a combined late end point of death, repeat MI, recurrent severe angina, CABG or repeat target vessel angioplasty were sought.

Statistical analysis.   Demographic characteristics and in-hospital adverse events in the two patient groups were compared using chi-square and student t test as appropriate. Stepwise logistic regression was used to model correlates of in-hospital adverse events. Variables included in the model were age, presence of congestive heart failure, left ventricular ejection fraction (LVEF), LVEF <40% (as a separate discrete variable), family history of atherosclerotic heart disease, gender, glycosylated hemoglobin (HgbA1C), HgbA1C >8.5% (as a separate discrete variable), hypercholesterolemia (defined as total serum cholesterol ≥250 mg/dl), hypertension (defined as diastolic blood pressure >90 mm Hg and/or systolic blood pressure >140 mm Hg), multivessel coronary disease, prior CABG and sulfonylurea drug use. Cox proportional hazard modeling was used to develop models for late mortality, MI, severe angina and a composite of these three end points.


   Results
Top
 Abstract
 Methods
 Results
Discussion
 References
 
Baseline characteristics.   One hundred and eighty-eight diabetic patients were identified who presented with acute MI and who were treated with direct balloon angioplasty during the study period. The use of sulfonylurea agents was uncertain in three patients, so they were excluded from analysis. Of the remainder, 67 were taking oral sulfonylurea hypoglycemic agents at the time of treatment (group 1), and 118 were not (group 2); 70 group 2 patients were using insulin, and 38 were controlled without either insulin or oral hypoglycemic agents. Clinical and angiographic characteristics of both groups are summarized in Table 1. Patients in group 1 were significantly older, and had a significantly lower mean LVEF when compared with group 2 (Table 1). Other factors known to affect mortality, such as extent of disease, incidence of congestive heart failure and infarct location, were similar in the two groups.


View this table:
[in this window]
[in a new window]
  		Table 1 Patient Characteristics

 
Procedural characteristics and success.   In group 1, procedural success was achieved in 50 (74.6%) patients, which included 73 (85.9%) lesions. In group 2, procedural success was achieved in 95 (80.5%) patients, and 122 (84.1%) lesions. Overall rates of procedural success were not significantly different between the two groups. Although the incidence of circulatory shock was not significantly different, patients in group 1 required insertion of an intra-aortic balloon pump more frequently than patients in group 2 (p = 0.046) (Table 2).


View this table:
[in this window]
[in a new window]
  		Table 2 Procedural Success and Complications of Angioplasty

 
In-hospital events.   Despite similar rates of procedural success, in-hospital mortality was higher in patients from group 1 than group 2 (24% vs. 11%, p = 0.02). All early deaths were caused primarily by pump dysfunction with cardiogenic shock except for five arrhythmic deaths (two bradyarrhythmic events, three ventricular tachycardic or fibrillation events). Two patients died following emergency CABG. Logistic regression analysis found use of oral sulfonylurea agents to be associated with an increased risk of death (Table 3). Other variables associated independently with an increased risk of early mortality included LVEF, LVEF <40%, prior CABG, age and congestive heart failure. Multivariate analysis found oral sulfonylurea drug use to be independently associated with increased early mortality (Fig. 1).


View this table:
[in this window]
[in a new window]
  		Table 3 Logistic Model for In-Hospital Death

 


View larger version (10K):
[in this window]
[in a new window]
  		Figure 1 Multivariate correlates of in-hospital mortality (odds ratios and 95% confidence intervals).

 
Ventricular tachycardia or fibrillation occurred in 27% of group 1 and 22% of group 2 patients (p = NS). The presence of congestive heart failure (odds ratio [OR] = 2.77, 95% confidence interval [CI] = 1.2 to 6.60, p = 0.03) and male gender (OR = 2.53, CI = 1.04 to 6.14, p = 0.04), but not sulfonylurea drug use, were associated multivariately with an increased frequency of in-hospital ventricular fibrillation.

Rates of other adverse events, including recurrent MI and the need for additional revascularization procedures, were similar in the two groups.

Late events.   Follow-up was available for all hospital survivors. Mean follow-up was 3.8 ± 2.3 years (range: 0.1 to 9.9 years) for group 1, and 3.6 ± 2.4 years (range: <0.1 to 9.1 years) for group 2. Although repeat coronary angioplasty procedures were performed more frequently for group 2 patients during the follow-up period (17.8% vs. 46.7% within 5 years after treatment, p = 0.05), no difference in the frequency of subsequent MI (19.9% vs. 23.1% at 5 years, p = NS), need for CABG (23.3% vs. 31.7% at 5 years; p = NS) or late mortality was found between the two groups. Only congestive heart failure (relative risk = 3.10, CI = 1.47 to 6.51, p = 0.003) was associated with an increased relative risk of death during the follow-up period.

Multivariate modeling identified only prior CABG to be associated with the combined end point of late death, MI, severe angina, CABG or repeat target vessel angioplasty.


   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
This study finds that the risk of death for diabetic patients undergoing balloon angioplasty for acute MI is 2.77 times higher if they are using an oral sulfonylurea hypoglycemic agent at the time of treatment. The impact of sulfonylurea drug use on early mortality was similar to the impact of reduced LVEF or overt clinical heart failure. Thus, use of sulfonylurea drugs may represent an additional risk factor in patients undergoing coronary interventional procedures in the presence of MI.

Sulfonylureas and mortality.   Prior indication that sulfonylurea drug use may have adverse consequences in diabetic patients with cardiac disease came from epidemiological studies that demonstrated increased cardiovascular mortality among patients taking these agents (7). Although this observation generated much controversy, a similar conclusion was reached in a subsequent study that found increased mortality following MI in diabetic patients treated with sulfonylureas when compared to diabetic patients treated with insulin (6). The present study is consistent with these observations, and suggests that sulfonylurea drug use may increase mortality specifically among diabetic patients with MI undergoing acute revascularization therapy through coronary angioplasty. This increased mortality could not be explained on the basis of differences in age, ventricular function, hyperglycemic control or procedural success between diabetic patients taking and not taking these drugs.

We did not find sulfonylurea drug use to be associated with an increased incidence of ventricular arrhythmias, suggesting that the observed increased mortality was not due to an increase in electrical instability in these patients. Thus, use of sulfonylurea drugs per se appears to be associated with worse early outcome in this patient population, but the mechanisms whereby sulfonylurea drugs may increase mortality have not been defined.

Potential explanations for increased mortality with sulfonylurea drugs.   Experimentally, sulfonylureas increase infarct size and accelerate the death of hypoxic cardiomyocytes through blockade of KATP channels that mediate ischemic preconditioning in myocardium (8,27,28). Increased vulnerability of myocardium to ischemic insult in the presence of sulfonylurea drugs may have contributed to the increased mortality observed in this group of diabetic patients. Indeed, it has been demonstrated in isolated human myocardium (18) and in patients undergoing balloon angioplasty (26) that sulfonylurea drug treatment abolishes the cardioprotective efficacy of ischemic preconditioning. Although the extent of cell damage was not measured in the present study, increased ischemic myocardial injury should result in greater impairment of contractile function, which is an important known determinant of survival after acute MI (29,30). In this regard, our observations that the mean left ventricular ejection fraction was lower and requirement of intra-aortic balloon pump support was greater among patients taking sulfonylurea drugs are of interest.

Other mechanisms by which sulfonylureas may increase mortality in patients with MI include inhibition of the endogenous fibrinolytic system (31). This could be effected through enhanced production of proinsulin, which is known to stimulate endothelial production of plasminogen activator inhibitor-1 (32–34). Elevated serum levels and activity of this inhibitor have been documented in animals and diabetic patients given sulfonylurea drugs (32,35–37), and resistance to tissue-type plasminogen activator has also been observed (38,39). This effect could also be mediated by lipoprotein(a) levels, which have been observed to correlate well with plasminogen activator inhibitor-1 activity and antigen levels (35,40) among diabetic patients using sulfonylurea drugs. When metformin, an antidiabetic biguanide compound, was substituted for sulfonylurea drugs in non–insulin dependent diabetic patients the abnormalities in plasminogen activator inhibitor-1 behavior improved without changes in lipoprotein(a) levels, suggesting a direct effect from sulfonylurea drugs, although the degree of individual improvement was related to the baseline lipoprotein(a) levels (40). These are important considerations, since refractory thrombosis is a recognized cause of failed angioplasty for acute MI (41–43). However, we observed no differences in the extent of refractory thrombosis but rather found similar overall procedural success rates during coronary intervention, suggesting that the principal mechanism by which sulfonylurea drugs increased mortality was not impaired endogenous fibrinolysis.

Sulfonylureas and late events.   The finding that sulfonylurea drug use was not associated with an increased incidence of late events (other than the need for repeat balloon angioplasty) is consistent with our earlier observations (44). Unselected diabetic patients with MI treated with a variety of management strategies had similar late outcomes (2.7 ± 2.3 years) whether taking sulfonylurea drugs at the time of MI or not. This suggests either that the early mortality among diabetic patients using sulfonylurea drugs precluded the opportunity to observe late events in this group, or that the principal deleterious effects of sulfonylurea drug use are observed predominantly in the period of acute myocardial ischemia; the latter is consistent with previous studies, which indicate that the time of exposure to the drug and the state of the myocardium are important determinants of the consequences of sulfonylurea drug use (18,27,45,56).

Study limitations.   The limitations of this study include the retrospective study design, and the limited number of patients with diabetes who underwent direct balloon angioplasty during the 10-year study period. Postulates regarding the potential role of KATP channels and other possible mediators of increased mortality are consistent with, but not supported directly by, the data presented. Patients not receiving sulfonylurea drugs were not analyzed further, so no conclusions may be made regarding the potential effects of other antidiabetic treatment strategies in the setting of acute MI (including the possible impact of oral biguanide therapy). Since only balloon angioplasty was studied, the impact of other catheter-based therapies, such as coronary stents, remains unknown. 46


   References
Top
 Abstract
 Methods
 Results
 Discussion
 References
 

  1. Mak KH, Moliterno DJ, Granger CB, et al. Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. J Am Coll Cardiol. 1997;30:171–179[Abstract]
  2. Abbud ZA, Shindler DM, Wilson AC, Kostis JB. Effect of diabetes mellitus on short- and long-term mortality rates of patients with acute myocardial infarction: a statewide study. Myocardial Infarction Data Acquisition System Study Group. Am Heart J. 1995;130:51–58[CrossRef][Medline]
  3. Malmberg K, Ryden L. Myocardial infarction in patients with diabetes mellitus. Eur Heart J. 1988;9:259–264[Abstract/Free Full Text]
  4. BARI Investigators. Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. N Engl J Med. 1996;335:217–225[Abstract/Free Full Text]
  5. Stein B, Weintraub WS, Gebhart SP, et al. Influence of diabetes mellitus on early and late outcome after percutaneous transluminal coronary angioplasty. Circulation. 1995;91:979–989[Abstract/Free Full Text]
  6. Rytter L, Troelsen S, Beck-Nielsen H. Prevalence and mortality of acute myocardial infarction in patients with diabetes. Diabetes Care. 1985;8:230–234[Abstract]
  7. Klimt CR, Knatterud GL, Meinert CL, Prout TE. A study of the effects of hypoglycemic agents in vascular complications in patients with adult-onset diabetes. Diabetes. 1970;19:747–830
  8. Brady PA, Terzic A. The sulfonylurea controversy: more questions from the heart. J Am Coll Cardiol. 1998;31:950–956[Abstract/Free Full Text]
  9. Panten U, Schwanstecher M, Schwanstecher C. Sulfonylurea receptors and mechanism of sulfonylurea action. Exp Clin Endocrinol Diabetes. 1996;104:1–9[Medline]
  10. Groop L. Sulphonylureas in NIDDM. Diabetes Care. 1992;15:737–754[Abstract]
  11. Gerich JE. Oral hypoglycemic agents. N Engl J Med. 1989;321:1231–1245[Medline]
  12. Edwards G, Weston A. The pharmacology of ATP-sensitive potassium channels. Annu Rev Pharmacol Toxicol. 1993;33:597–637[CrossRef][Medline]
  13. Ashcroft SJ, Ashcroft FM. The sulphonylurea receptor. Biochim Biophys Acta. 1992;1175:45–59[Medline]
  14. Terzic A, Jahangir A, Kurachi Y. Cardiac ATP-sensitive K+ channels: regulation by intracellular nucleotides and potassium opening drugs. Am J Physiol. 1995;38:C525–C545
  15. Hamada E, Takikawa R, Ito H, et al. Glibenclamide specifically blocks ATP-sensitive K+ channel current in atrial myocytes of guinea pig heart. Jpn J Pharmacol. 1990;54:473–477[Medline]
  16. Findlay I. Inhibition of ATP-sensitive K+ channels in cardiac muscle by the sulphonylurea drug glibenclamide. J Pharmacol Exp Ther. 1992;261:540–545[Abstract/Free Full Text]
  17. Fosset M, De Weille JR, Green RD, Schmid-Antomarchi H, Lazdunski M. Antidiabetic sulphonylureas control action potential properties in heart cells via high affinity receptors that are linked to ATP-dependent K+ channels. J Biol Chem. 1988;263:7933–7936[Abstract/Free Full Text]
  18. Cleveland JC Jr, Meldrum DR, Cain BS, Banerjee A, Harkem AH. Oral sulfonylurea hypoglycemic agents prevent ischemic preconditioning in human myocardium: two paradoxes revisited. Circulation. 1997;96:29–32[Abstract/Free Full Text]
  19. Grover GJ. Protective effects of ATP-sensitive potassium-channel openers in experimental myocardial ischemia. J Cardiovasc Pharmacol. 1994;24:S18–S27
  20. Gross GJ. ATP-sensitive potassium channels and myocardial preconditioning. Basic Res Cardiol. 1995;90:85–88[CrossRef][Medline]
  21. Ming Z, Parent R, Lavallee M. ß2-Adrenergic dilation of resistance coronary vessels involves KATP channels and nitric oxide in conscious dogs. Circulation. 1996;95:1568–1576
  22. Jackson WF. Arteriolar tone is determined by activity of ATP-sensitive potassium channels. Am J Physiol. 1993;265:H1797–H1803
  23. Narishige T, Egashira K, Akatsuka Y, Takahashi T, Kasuya H, Takeshita A. Glibenclamide prevents coronary vasodilation induced by ß1-adrenoceptor stimulation in dogs. Am J Physiol. 1994;266:H84–H92
  24. Murray C, Jennings R, Reimer K. Preconditioning with ischemia: a delay in lethal injury in ischaemic myocardium. Circulation. 1986;74:1124–1136[Abstract/Free Full Text]
  25. Engler RL, Yellon DM. Sulphonylurea KATP blockade in type II diabetes and preconditioning in cardiovascular disease: time for reconsideration. Circulation. 1996;94:2297–2301[Free Full Text]
  26. Tomai F, Crea F, Gaspardone A, Versaci F, De Paulis R. Ischemic preconditioning during coronary angioplasty is prevented by glibenclamide, a selective ATP-sensitive K+ channel blocker. Circulation. 1994;90:700–705[Abstract/Free Full Text]
  27. Brady PA, Zang S, Lopez JR, Jovanovic A, Alekseev AE, Terzic A. Dual effect of glyburide, an antagonist of KATP channels, on metabolic inhibition-induced Ca2+ loading in cardiomyocytes. Eur J Pharmacol. 1996;308:343–349[CrossRef][Medline]
  28. Gross GJ, Auchampach JA. Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs. Circ Res. 1992;70:223–233[Abstract/Free Full Text]
  29. O’Murchu B, Gersh BJ, Reeder GS, Bailey KR, Holmes DR Jr. Late outcome after percutaneous transluminal coronary angioplasty during acute myocardial infarction. Am J Cardiol. 1993;72:634–639[CrossRef][Medline]
  30. Zaret BL, Wackers FJ, Terrin ML, et al. Value of radionuclide rest and exercise left ventricular ejection fraction in assessing survival of patients after thrombolytic therapy for acute myocardial infarction: results of Thrombolysis in Myocardial Infarction (TIMI) phase II study. The TIMI Study Group. J Am Coll Cardiol. 1995;26:73–79[Abstract]
  31. Heine RJ. Role of sulfonylureas in non-insulin-dependent diabetes mellitus: Part II—"The cons". Horm Metab Res. 1996;28:522–526[Medline]
  32. Juhan-Vague I, Alessi MC, Vague P. Thrombogenic and fibrinolytic factors and cardiovascular risk in non-insulin-dependent diabetes mellitus. Ann Med. 1996;28:371–380[Medline]
  33. Nordt TK, Schneider DJ, Sobel BE. Augmentation of the synthesis of plasminogen activator inhibitor type-1 by precursors of insulin. A potential risk factor for vascular disease. Circulation. 1994;89:321–330[Abstract/Free Full Text]
  34. Nordt TK, Sawa H, Fujii S, Sobel BE. Induction of plasminogen activator inhibitor type-1 (PAI-1) by proinsulin and insulin in vivo. Circulation. 1995;91:764–770[Abstract/Free Full Text]
  35. Morishita E, Asakura H, Jokaji H, et al. Hypercoagulability and high lipoprotein(a) levels in patients with type II diabetes mellitus. Atherosclerosis. 1996;120:7–14[CrossRef][Medline]
  36. Mansfield MW, Stickland MH, Grant PJ. Environmental and genetic factors in relation to elevated circulating levels of plasminogen activator inhibitor-1 in Caucasian patients with non-insulin-dependent diabetes mellitus. Thromb Haemost. 1995;74:842–847[Medline]
  37. Ito Y, Okeda T, Sato Y, Ito M, Sakata T. Plasminogen activator inhibitor-1 in nonobese subjects with non-insulin-dependent diabetes mellitus. Proc Soc Exp Biol Med. 1996;211:287–291[Abstract]
  38. Gray RP, Yudkin JS, Patterson DL. Enzymatic evidence of impaired reperfusion in diabetic patients after thrombolytic therapy for acute myocardial infarction: a role for plasminogen activator inhibitor? Br Heart J. 1993;70:530–536[Abstract/Free Full Text]
  39. McGill JB, Schneider DJ, Arfken CL, Lucore CL, Sobel BE. Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients. Diabetes. 1994;43:104–109[Abstract]
  40. Testa R, Bonfigli AR, Piantanelli L, Manfrini S, Testa I, Gregorio F. Relationship between plasminogen activator inhibitor type-1 plasma levels and the lipoprotein(a) concentrations in non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract. 1996;33:111–118[CrossRef][Medline]
  41. Hasdai D, Garratt KN, Holmes DR Jr, Berger PB, Schwartz RS, Bell MR. Coronary angioplasty and intracoronary thrombolysis are of limited efficacy in resolving early intracoronary stent thrombosis. J Am Coll Cardiol. 1996;28:361–367[Abstract]
  42. Ambrose JA, Weinrauch M. Thrombosis in ischemic heart disease. Arch Intern Med. 1996;156:1382–1394[Abstract]
  43. Oltrona L, Eisenberg PR, Lasala JM, Sewall DJ, Shelton ME, Winters KJ. Association of heparin-resistant thrombin activity with acute ischemic complications of coronary interventions. Circulation. 1996;94:2064–2071[Abstract/Free Full Text]
  44. Brady PA, Al-Suwaidi J, Kopecky SL, Terzic A. Sulphonylureas and mortality in diabetic patients with myocardial infarction. Circulation. 1998;97:709–710[Free Full Text]
  45. Brady PA, Alekseev AE, Aleksandrova LA, Gomez LA, Terzic A. A disrupter of actin microfilaments impairs sulfonylurea-inhibitory gating of cardiac KATP channels. Am J Physiol. 1996;271:H2710–H2716
  46. Brady PA, Alekseev AE, Terzic A. Operative condition-dependent response of cardiac KATP channels towards sulfonylureas. Circ Res. 1998;82:272–278[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. Marinovic, M. Ljubkovic, A. Stadnicka, Z. J. Bosnjak, and M. Bienengraeber
Role of sarcolemmal ATP-sensitive potassium channel in oxidative stress-induced apoptosis: mitochondrial connection
Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1317 - H1325.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
S. E. Inzucchi and D. K. McGuire
New Drugs for the Treatment of Diabetes: Part II: Incretin-Based Therapy and Beyond
Circulation, January 29, 2008; 117(4): 574 - 584.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
P. Ferdinandy, R. Schulz, and G. F. Baxter
Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning
Pharmacol. Rev., December 1, 2007; 59(4): 418 - 458.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. Basu, N. Charkoudian, W. Schrage, R. A. Rizza, R. Basu, and M. J. Joyner
Beneficial effects of GLP-1 on endothelial function in humans: dampening by glyburide but not by glimepiride
Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1289 - E1295.
[Abstract] [Full Text] [PDF]

Home page
 BMJHome page
D. T Eurich, F. A McAlister, D. F Blackburn, S. R Majumdar, R. T Tsuyuki, J. Varney, and J. A Johnson
Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review
BMJ, September 8, 2007; 335(7618): 497 - 497.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
A. J. Chicco, M. S. Johnson, C. J. Armstrong, J. M. Lynch, R. T. Gardner, G. S. Fasen, C. P. Gillenwater, and R. L. Moore
Sex-specific and exercise-acquired cardioprotection is abolished by sarcolemmal KATP channel blockade in the rat heart
Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2432 - H2437.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
S. Yamada, G. C. Kane, A. Behfar, X.-K. Liu, R. B. Dyer, R. S. Faustino, T. Miki, S. Seino, and A. Terzic
Protection conferred by myocardial ATP-sensitive K+ channels in pressure overload-induced congestive heart failure revealed in KCNJ11 Kir6.2-null mutant
J. Physiol., December 15, 2006; 577(3): 1053 - 1065.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. Takeda, T. Komaru, K. Takahashi, K. Sato, H. Kanatsuka, Y. Kokusho, K. Shirato, and H. Shimokawa
Beating myocardium counteracts myogenic tone of coronary microvessels: involvement of ATP-sensitive potassium channels
Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H3050 - H3057.
[Abstract] [Full Text] [PDF]

Home page
 Am J Health Syst PharmHome page
H. A. Spiller and T. S. Sawyer
Toxicology of oral antidiabetic medications
Am. J. Health Syst. Pharm., May 15, 2006; 63(10): 929 - 938.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
Z. T. Bloomgarden
Cardiovascular Disease
Diabetes Care, May 1, 2006; 29(5): 1160 - 1166.
[Full Text] [PDF]

Home page
 Cardiovasc ResHome page
R. A. Kloner and S. H. Rezkalla
Preconditioning, postconditioning and their application to clinical cardiology
Cardiovasc Res, May 1, 2006; 70(2): 297 - 307.
[Abstract] [Full Text] [PDF]

Home page
 CMAJHome page
D. S.H. Bell
Do sulfonylurea drugs increase the risk of cardiac events?
Can. Med. Assoc. J., January 17, 2006; 174(2): 185 - 186.
[Full Text] [PDF]

Home page
 HeartHome page
P. Monteiro, L. Goncalves, and L. A Providencia
Diabetes and cardiovascular disease: the road to cardioprotection
Heart, December 1, 2005; 91(12): 1621 - 1625.
[Full Text] [PDF]

Home page
 Cardiovasc ResHome page
M. Juhaszova, C. Rabuel, D. B. Zorov, E. G. Lakatta, and S. J. Sollott
Protection in the aged heart: preventing the heart-break of old age?
Cardiovasc Res, May 1, 2005; 66(2): 233 - 244.
[Abstract] [Full Text] [PDF]

Home page
 Clin. DiabetesHome page
B. Kimmel and S. E. Inzucchi
Oral Agents for Type 2 Diabetes: An Update
Clin. Diabetes, April 1, 2005; 23(2): 64 - 76.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
A. Prasad, G. W. Stone, T. D. Stuckey, C. O. Costantini, P. J. Zimetbaum, M. McLaughlin, R. Mehran, E. Garcia, J. E. Tcheng, D. A. Cox, et al.
Impact of diabetes mellitus on myocardial perfusion after primary angioplasty in patients with acute myocardial infarction
J. Am. Coll. Cardiol., February 15, 2005; 45(4): 508 - 514.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
U. Quast, D. Stephan, S. Bieger, and U. Russ
The Impact of ATP-Sensitive K+ Channel Subtype Selectivity of Insulin Secretagogues for the Coronary Vasculature and the Myocardium
Diabetes, December 1, 2004; 53(suppl_3): S156 - S164.
[Abstract] [Full Text] [PDF]

Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
W. S. Aronow
Management of the Elderly Person After Myocardial Infarction
J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2004; 59(11): 1173 - 1185.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
S. Clement, S. S. Braithwaite, M. F. Magee, A. Ahmann, E. P. Smith, R. G. Schafer, and I. B. Hirsch
Management of Diabetes and Hyperglycemia in Hospitals
Diabetes Care, February 1, 2004; 27(2): 553 - 591.
[Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
T. Ostergard, K. B. Degn, M.-A. Gall, R. D. Carr, J. D. Veldhuis, M. K. Thomsen, R. A. Rizza, and O. Schmitz
The Insulin Secretagogues Glibenclamide and Repaglinide Do Not Influence Growth Hormone Secretion in Humans but Stimulate Glucagon Secretion during Profound Insulin Deficiency
J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 297 - 302.
[Abstract] [Full Text] [PDF]

Home page
 HeartHome page
J J Meier, B Gallwitz, W E Schmidt, A Mugge, and M A Nauck
Is impairment of ischaemic preconditioning by sulfonylurea drugs clinically important?
Heart, January 1, 2004; 90(1): 9 - 12.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
X. Wang, M. Wei, P. Kuukasjarvi, J. Laurikka, O. Jarvinen, T. Rinne, E.-L. Honkonen, and M. Tarkka
Novel pharmacological preconditioning with diazoxide attenuates myocardial stunning in coronary artery bypass grafting
Eur. J. Cardiothorac. Surg., December 1, 2003; 24(6): 967 - 973.
[Abstract] [Full Text] [PDF]

Home page
 Br J AnaesthHome page
M. Zaugg, E. Lucchinetti, C. Garcia, T. Pasch, D. R. Spahn, and M. C. Schaub
Anaesthetics and cardiac preconditioning. Part II. Clinical implications
Br. J. Anaesth., October 1, 2003; 91(4): 566 - 576.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
J. F. Huizar, L. A. Gonzalez, J. Alderman, and H. S. Smith
Sulfonylureas attenuate electrocardiographic ST-segment elevation during an acute myocardial infarction in diabetics
J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1017 - 1021.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
P. A. Brady and A. Jovanovic
The sulfonylurea controversy: Much ado about nothing or cause for concern?
J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1022 - 1025.
[Full Text] [PDF]

Home page
 Circ. Res.Home page
N. L. Weintraub
Impaired Hypoxic Coronary Vasodilation and ATP-Sensitive Potassium Channel Function: A Manifestation of Diabetic Microangiopathy in Humans?
Circ. Res., February 7, 2003; 92(2): 127 - 129.
[Full Text] [PDF]