| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1997;96:4239-4245.)
© 1997 American Heart Association, Inc.
Articles |
Effect of the ACE Inhibitor Lisinopril on Mortality in Diabetic Patients With Acute Myocardial Infarction
Data From the GISSI-3 Study
From the Istituto Mario Negri, Milano (G.Z., R.L., A.P.M., M.G.F, L.S., G.T.), and the Centro Studi ANMCO, Firenze (A.P.M.), Italy.
Correspondence to Giulio Zuanetti, MD, Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea, 62, 20157 Milano, Italy. E-mail zuanetti{at}irfmn.mnegri.it
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background Mortality of diabetic patients with acute myocardial infarction (MI) remains high despite recent improvement in their management. There is a need to evaluate efficacy and safety of novel treatments of MI in this high-risk population. We evaluated whether treatment with an ACE inhibitor begun within 24 hours from the onset of symptoms is able to decrease mortality and morbidity of diabetic patients with acute MI.
Methods and Results A retrospective analysis of the data
of the GISSI-3 study in patients with and without a history of diabetes
was performed. Patients with suspected acute MI were randomized to
treatment with lisinopril (2.5 to 5 up to 10 mg/d) with or
without nitroglycerin (5 to 20 µg IV then 10 mg/d)
begun within 24 hours and continued for 6 weeks. The main end point was
mortality at 6 weeks, and the secondary end point was a combined
evaluation of mortality and severe left ventricular
dysfunction. Information on diabetic status was available for 18 131
patients (
94% of the total population enrolled), of whom 2790
patients had a history of diabetes. Treatment with
lisinopril was associated with a decreased 6-week mortality
in diabetic patients (8.7% versus12.4%; OR, 0.68; 95% CI, 0.53 to
0.86; 37±12 lives saved per 1000 treated patients), an effect that was
significantly (P<.025) higher than that observed in
nondiabetic patients. The survival benefit in diabetics was mostly
maintained at 6 months despite withdrawal from treatment at 6 weeks
(12.9% versus 16.1%; OR, 0.77; 95% CI, 0.62 to 0.95).
Conclusions Early treatment with the ACE inhibitor lisinopril in diabetic patients with acute MI is associated with a decreased 6-week mortality. This beneficial effect supports a widespread and early use of ACE inhibitors in diabetic patients with acute MI. The burden of mortality plus morbidity for ventricular dysfunction in diabetics remains clinically important and warrants further testing of novel therapeutic approaches.
Key Words: myocardial infarction • lisinopril • mortality • diabetes mellitus
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Several studies performed before the introduction of fibrinolysis as a routine treatment of patients with MI consistently showed that diabetic patients have a higher mortality in hospital and after discharge.1–4 In the past decade, the widespread use of fibrinolytic agents and aspirin led to a marked improvement in the prognosis of MI patients.5,6 However, diabetic patients remain a subgroup at high risk for mortality during evolving MI.5–7 Data from the TIMI II trial7 indicated that diabetic patients also have a high mortality when an invasive approach such as primary percutaneous transluminal coronary angioplasty is used. These data stress the importance of testing novel approaches in the treatment of these patients during the acute phase. ACE inhibitors may be of particular value in diabetic patients with acute MI. In fact, these drugs have been shown to be very effective in delaying some of the complications of diabetes mellitus, including chronic renal insufficiency,8 and they exert an early beneficial effect in patients with acute MI,9 presumably by counteracting the adrenergic10 and renin-angiotensin activation11 during acute MI that may be particularly important in diabetics with autonomic neuropathy. On the other hand, because diabetic patients have more extensive coronary atherosclerosis than nondiabetic patients,12 they may be more vulnerable to the effect of ACE inhibitors on the systemic and renal hemodynamics.13 Therefore, uncertainty exists whether the use of an ACE inhibitor during the acute phase of MI might be particularly beneficial in diabetics or, alternatively, would place them at an increased risk of hypotension and acute renal dysfunction with deleterious consequences on survival.
The purpose of this study was to evaluate whether treatment with lisinopril begun within 24 hours would be associated with a significant impact on mortality and morbidity in diabetic patients with acute MI.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Data obtained from the population enrolled in the GISSI-3 study were analyzed. The details of the design and the main results of the study were provided in the original report.14 Briefly, the GISSI-3 trial was a controlled multicenter randomized open trial in patients with acute MI with a 2x2 factorial design and four treatment groups: lisinopril (2.5 to 5 mg at randomization, 2.5 to 5 mg after 24 hours, 2.5 to 10 mg after 48 hours, then 10 mg/d for 6 weeks), nitroglycerin (5 to 20 mg/min IV infusion during the first 24 hours followed by 10 mg/d transdermally, combined therapy (lisinopril plus nitroglycerin), and no trial therapy. Patients entered the study if (1) they had chest pain with ST-segment elevation of
1 mm in any limb lead of the ECG and/or of 2 mm in any
precordial lead; (2) they were admitted to the coronary
care unit within 24 hours from the onset of symptoms; and (3) they were
considered hemodynamically stable, with a
systolic blood pressure >100 mm Hg. Exclusion criteria
were Killip class 4, high risk of further serious
hemodynamic deterioration after treatment with
vasodilators (systolic blood pressure 
100 mm Hg),
history of clinically relevant renal failure (creatinine
>2 mg/dL) or presence of life-threatening conditions in the
short term other than acute MI, or prior randomization within the
trial. Randomized treatments were withdrawn at 6 weeks in the absence of specific indications, and then patients were followed up until 6 months after randomization.
Data Collection
Information on history of diabetes, including type, ie, IDDM or
NIDDM, was collected by the attending physician during the in-hospital
stay.
Quality control of the collection of epidemiological and clinical data was performed centrally. Clinically relevant events (death, reinfarction, cerebrovascular accidents, renal dysfunction, persistent hypotension, and shock) were carefully collected in the study forms.
The main end point of the study was all-cause mortality at 6 weeks, and the secondary end point was the combined end point, ie, the number of patients who died plus the number of survivors who had late (beyond day 4 of hospital stay) clinical CHF or extensive left ventricular damage in the absence of clinical heart failure.
LVD was defined by the presence of late clinical CHF (defined as at
least two of the following: a third sound, rales, dyspnea, evidence of
pulmonary congestion at chest radiograph) or, in patients
without clinically evident CHF, by the presence of extensive left
ventricular damage, defined as either an
echocardiographic LVEF of 35% or 45% injured
myocardial segments (of the left ventricle evaluated by two-dimensional
echocardiography and divided into 11 segments). A
total of 1645 diabetic patients underwent
echocardiography with quantification of LVEF and
wall motion abnormalities, representing 66% of the total
diabetic population alive at follow-up. The summation of mortality plus
documented LVD was defined as combined end point.
Statistical Methods
For the purpose of this analysis, because the data
indicated that the systemic use of nitroglycerin did
not have any influence on mortality in this subgroup of patients,
analysis was focused on the comparison between patients
receiving lisinopril versus open control patients. The
effect of lisinopril on mortality in the different
subgroups was assessed by a test for heterogeneity.
Such a statistic is approximately distributed as a
2 with N-1 degrees of freedom, where N is the
number of subgroups.15 The Neyman-Pearson
2 statistic was used to test the statistical
significance of differences in the baseline characteristics of the
different groups of patients according to their diabetic status and in
the incidence of events. The effect of lisinopril was
evaluated by an "intention-to-treat" analysis. The
significance of the difference observed was defined as a two-tailed
value of P<.05. Results are also presented in
terms of Mantel-Haenszel-Peto ORs and their 95% CIs for the overall
nondiabetic and diabetic populations, 99% CI for subgroups of diabetic
patients. Survival estimates were calculated by the product-limit
method, and comparison between treated and control patients was done
with the log-rank test.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Information on diabetic status was available for 18 131 patients (
94% of total population enrolled in GISSI-3), of whom 2790
(15.2%) were defined as diabetics: 2.7% of patients had a history of
IDDM (n=496) and 12.5% had a history of NIDDM (n=2294).
Baseline Characteristics of Patients
Main demographic and clinical characteristics of diabetic and
nondiabetic patients enrolled in GISSI-3 are shown in Table 1
, together with the characteristics of
patients with missing information for diabetes (6% of total
population). In general, diabetic patients had a worse baseline risk
profile than nondiabetics. For example, 20.6% of diabetic patients
presented in Killip class >1, compared with 13.3% of
nondiabetics. Baseline characteristics were well balanced overall
between control and lisinopril-treated patients, without
significant differences in any of the subgroups analyzed.
|
Effect of Lisinopril on Mortality
Treatment with lisinopril was associated with a
decreased 6-week mortality in diabetic patients (8.7% versus 12.4%;
OR, 0.68; 95% CI, 0.53 to 0.86). This difference was significantly
(2 for heterogeneity=5.85,
P<.025) greater than that observed in nondiabetic patients
(5.6% versus 5.9%; OR, 0.95; 95% CI, 0.83 to 1.09) (Fig 1). These figures correspond to a 29.8%
reduction, or 37±12 lives saved per 1000 in the diabetic population,
and to a 5.0% reduction, or 3±4 lives saved per 1000 in the
nondiabetic population. The advantage was present in both IDDM
(11.8% versus 21.1%; OR, 0.51; 95% CI, 0.32 to 0.82) and NIDDM
(8.0% versus 10.6%; OR, 0.73; 95% CI, 0.55 to 0.97) patients,
corresponding to a 44.1% and 24.5% reduction, respectively. However,
because the test for heterogeneity did not show a
significant difference in this primary end point of the study between
IDDM and NIDDM patients, analysis was thereafter focused on the
diabetic population overall. Most but not all the survival gain in
diabetic patients was maintained at 6 months, despite withdrawal of the
ACE inhibitor treatment at 6 weeks: total mortality in
lisinopril-treated and control patients at 6 months was
12.9% versus 16.1% (OR, 0.77; 95% CI, 0.62 to 0.95).
Analysis of 6-week mortality in different subgroups of diabetic
patients is shown in Fig 2. It appears
that within the diabetic population, the effect is consistently
present in subgroups at different risk based on demographic and
clinical characteristics, with a nonsignificant value for
heterogeneity of the effect of lisinopril
within each subgroup.
|
|
Effect of Lisinopril on Combined End Point in
Diabetic Patients
The effect of lisinopril on the secondary end point of
mortality plus morbidity is shown in Table 2. The treatment was associated with a
lower combined end point incidence at 6 weeks both in diabetics and in
nondiabetics: 21.6% versus 24.5% (OR, 0.85; 95% CI, 0.71 to 1.01)
and 14.3% versus 15.5% (OR, 0.91; 95% CI, 0.83 to 1.00),
respectively. The less marked effect than that observed for mortality
in diabetic patients is due to the presence of a slightly higher
fraction of patients with late clinical CHF among survivors in
lisinopril-treated patients (7.2% versus 4.8%). To
further evaluate this point, data on occurrence up to 6 weeks of
clinical CHF, low (<35%) LVEF, and/or marked (45% of segment areas
affected) akinesia/dyskinesia of ventricular motion at
6-week echocardiogram were analyzed. No significant difference
was found in any of these three indexes of left ventricular
function between lisinopril and control patients. More
precisely, CHF was present in 8.5% of
lisinopril-treated and 7.3% of control patients; LVEF
<35% was present in 10.2% and 12.7% and akinesia and/or
dyskinesia 45% was present in 5.3% and 5.4%, respectively.
|
At 6 months, after treatment had been withdrawn at 6 weeks, in diabetic patients the difference in combined end point was 25.6% versus 28.9%, a nonsignificant 15±8% reduction.
Safety of Lisinopril in Diabetic Patients
One of the major issues related to the use of ACE
inhibitors during the acute phase of MI is the incidence
and clinical significance of adverse drug reactions.
The main adverse events recorded in the diabetic and nondiabetic
patients are shown in Table 3. There was
no difference in the incidence of stroke, shock, postinfarction angina,
and reinfarction, whereas treatment with lisinopril was
associated with an increased incidence of persistent hypotension and
renal dysfunction, similar to what was observed in the nondiabetic
population. Furthermore, even in the subgroup of patients who developed
persistent hypotension and/or renal dysfunction, the absolute number of
deaths was slightly lower in the lisinopril-treated
patients (6 versus 11 for renal dysfunction and 24 versus 32 for
persistent hypotension). There was no difference in the duration of
hospital stay of diabetic and nondiabetic patients discharged alive in
control and lisinopril-treated patients (15.3±7.1 versus
15.3±7.4 days for diabetics and 14.3±6.1 versus 14.2±6.1 days for
nondiabetics).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Studies performed after the advent of fibrinolysis indicate that diabetic patients continue to have a higher mortality after MI than nondiabetic patients. For example, data from the GISSI-2 study5 show a 30% to 60% higher in-hospital mortality in diabetic patients of both sexes compared with nondiabetic patients, similar to the GUSTO trial,6 in which mortality was 10.6% in diabetics and 6.2% in nondiabetics (OR, 1.79; 95% CI, 1.64 to 1.97). The search for novel therapeutic approaches in this high-risk population appears to be relevant for both its clinical and its socioeconomic implications.
Mechanisms for Increased Mortality in Diabetic Patients With Acute
MI and Potential for the Beneficial Effect of ACE Inhibitors
Several mechanisms may contribute to the increase of in-hospital
mortality in diabetic patients16,17: (1) more
extensive coronary atherosclerosis, (2)
clinical or subclinical diabetic cardiomyopathy
with systolic and/or diastolic dysfunction, (3)
alterations in the fibrinolytic system that impair reperfusion and
facilitate reocclusion after fibrinolysis, (4) diabetic
neuropathy with sympathetic/parasympathetic imbalance, and
(5) endothelial dysfunction leading to impaired
myocardial perfusion. It is impossible to identify the relative roles
of these mechanisms in mediating the increased mortality; however, ACE
inhibitors have the potential to interfere with most of
these mechanisms either directly (ie, altering the effect of the
renin-angiotensin and bradykinin systems) or indirectly
(ie, through their hemodynamic effects). These drugs
also appeared to be a promising therapeutic approach in diabetic
patients on the basis of their documented beneficial effect in
different clinical settings.8
Effect of ACE Inhibitors in Diabetic Patients Post-MI:
Long-term Studies
Several recent trials used ACE inhibitors in the
attempt to reduce mortality and morbidity in patients with LVD and/or
overt heart failure after acute MI. All these studies have shown a
significant benefit of long-term ACE-inhibitor therapy,
with a risk reduction in mortality of 19% to 27% over 2.5 to 4 years
of follow-up. Subgroup analyses of the
SAVE18 and TRACE studies19
indicate that the beneficial effect documented in the overall
population is present also when the analysis is limited to
patients with a history of diabetes, with a similar reduction in
mortality. This suggests that ACE inhibitors can be safely
administered in patients with LVD post-MI and that their beneficial
effect on mortality is similar in diabetic and nondiabetic
patients.
Efficacy and Safety of ACE Inhibitors During the Acute
Phase: Present Study
The data of this study confirm that diabetic patients have a high
mortality during the acute phase of MI. They also indicate that
treatment with the ACE inhibitor lisinopril is
associated with an 30% proportional reduction of 6-week mortality
in diabetics (8.7% versus 12.4%). This decrease of mortality is
significantly higher than that observed in nondiabetics (5%
reduction) and consistent among subgroups at different risk, on
the basis of demographic and clinical characteristics. It may be
speculated that because the effect of ACE inhibitors in the
acute setting is generally more pronounced in high-risk
patients,9 the worse baseline risk profile of
diabetic patients could have positively influenced the effect of
lisinopril. However, the statistical analysis
showed a significant positive interaction between presence of diabetes
and effect of the ACE inhibitor; also, for each subgroup,
the beneficial effect of lisinopril was
consistently higher in diabetics than in nondiabetics.
Interestingly, the beneficial effect of lisinopril in
diabetics appears to persist for the most part even after withdrawal
from treatment at 6 weeks, on the basis of the study protocol. Among
survivors, on the other hand, there was a higher percentage of patients
with severe LVD among diabetic patients treated with
lisinopril (7.2% versus 4.8%). A detailed
analysis of the incidence of symptomatic or
asymptomatic CHF in hospital did not show any difference
between lisinopril and control patients. This suggests that
the treatment might be able to decrease the
pathophysiological mechanisms leading to mortality
during the acute phase and leaves a burden of morbidity for LVD among
survivors that decreases the impact of the treatment on the combined
end point.
The incidence of most adverse events, such as stroke and reinfarction, was similar in treated and nontreated patients, and the increase in the incidence of renal dysfunction and persistent hypotension due to lisinopril, like that observed in nondiabetics, was not associated with a worsened outcome.
The overall analysis of these data clearly indicates that the use of an ACE inhibitor during the acute phase of MI in diabetic patients has a favorable risk/benefit ratio.
Limitations and Implications of the Present Study
The main limitation of this study lies in its retrospective
nature: the effect of ACE-inhibitor treatment in diabetic
patients was not a predefined analysis of
GISSI-3.20 A second limitation is that, at
variance with ad hoc studies such as DIGAMI,21 no
data on indexes of glycemic control were available. On the other hand,
it has to be acknowledged that this retrospective type of information
is and will be the only kind available for evaluating the effect of ACE
inhibitors in diabetic patients during MI, because no other
prospective studies on this topic are either ongoing or planned. In
this respect, the size of the diabetic population enrolled in GISSI-3
is by far the largest available for analysis. The question
remains whether this marked effect of lisinopril on
mortality in diabetic patients documented in GISSI-3 is
representative of a class effect of ACE
inhibitors. In this context, it is interesting to observe
that even in CONSENSUS II,22 a smaller study that
did not demonstrate a beneficial effect of ACE-inhibitor
treatment in the overall population, the subgroup of diabetic patients
experienced a trend toward a lower mortality (13.5% versus 16.7%; OR,
0.78; 95% CI, 0.51 to 1.19). A preliminary analysis of the
pooled data of CONSENSUS-II and CCS-1 trials with those of GISSI-3
recently performed by the ACE Inhibitors in MI
Collaborative Group (unpublished data, 1997) shows a trend toward a
more beneficial effect of ACE inhibitors in diabetic versus
nondiabetic patients (17.3 versus 3.2 lives saved per 1000 treated
patients). Current guidelines on the treatment of acute MI consider
mandatory the use of fibrinolysis and aspirin in all
eligible patients with acute MI.23 According to
these guidelines, early ACE-inhibitor treatment is
recommended only for selected subgroups of patients, such as those with
anterior MI or documented signs of CHF. A document from a consensus
conference9 has pointed out that the early use of
ACE inhibitors may lead to a further beneficial effect,
particularly during the early, high-risk phase. The data from the
present analysis indicate that the benefit from early ACE
inhibition appears to be particularly striking in diabetic patients,
whose overall mortality is confirmed to be higher than the nondiabetic
population. Although the quest for a specific intervention able to
reduce the increased risk associated with a preexisting diabetic
condition remains open, acute ACE inhibition appears to be specifically
recommended for the routine treatment of acute MI patients with
diabetes.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Acknowledgments |
|---|
Dr Zuanetti is a recipient of a Maurelio Caniato award fellowship. The GISSI-3 was endorsed by the Associazione Nazionale Medici Cardiologi Ospedalieri and by the Istituto di Ricerche Farmacologiche Mario Negri and was supported by a research grant from Zeneca and Schwarz-Pharma.
|
Footnotes |
|---|
Presented in part at the 45th American College of Cardiology Scientific Session, Orlando, Fla, March 24-27, 1996.
1 A complete list of collaborators and participating centers was published in Reference 14. 
Received April 30, 1997; revision received June 17, 1997; accepted July 3, 1997.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Smith JW, Marcus FI, Serokman R, for the Multicenter Postinfarction Research Group. Prognosis of patients with diabetes mellitus after acute myocardial infarction. Am J Cardiol. 1984;54:718–721.[Medline] [Order article via Infotrieve]
2. Singer DE, Moulton AW, Nathan DM. Diabetic myocardial infarction: interaction of diabetes with other preinfarction risk factors. Diabetes. 1989;38:350–357.[Abstract]
3. Stone PH, Muller JE, Hartwell T, York BJ, Rutherford JD, Parker CB, Turi ZG, Strauss W, Willerson JT, Robertson T, Braunwald E, Jaffe AS, and the MILIS Study Group. The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. J Am Coll Cardiol. 1989;14:49–57.[Abstract]
4. Savage MP, Krolewski AS, Kenien GG, Lebeis MP, Christlieb AR, Lewis SM. Acute myocardial infarction in diabetes mellitus and significance of congestive heart failure as a prognostic factor. Am J Cardiol. 1988;62:665–669.[Medline] [Order article via Infotrieve]
5. Zuanetti G, Latini R, Maggioni AP, Santoro L, Franzosi MG, for the GISSI-2 Investigators. Influence of diabetes on mortality in acute myocardial infarction: data from the GISSI-2 study. J Am Coll Cardiol. 1993;22:1788–1794.[Abstract]
6.
Lee KL, Woodlief LH, Topol EJ, Weaver D, Betriu A, Col
J, Simoons M, Aylward P, Van de Werf F, Califf RM, for the GUSTO-I
Investigators. Predictors of 30-day mortality in the era of reperfusion
for acute myocardial infarction: results from an international trial of
41 021 patients. Circulation. 1995;91:1659–1668.
7.
Mueller HS, Cohen LS, Braunwald E, Forman S, Feit F,
Ross A, Schweiger M, Cabin H, Davison R, Miller D, Solomon R, Knatterud
GL, for the TIMI Investigators. Predictors of early morbidity and
mortality after thrombolytic therapy of acute
myocardial infarction: analyses of patient subgroups in the
thrombolysis in myocardial infarction (TIMI) trial,
phase II. Circulation. 1992;85:1254–1264.
8. Laffer LMB, McGill JB, Gans DJ, on behalf of the North American Micro Albuminuria Study Group. The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria. Am J Med. 1995;99:497–504.[Medline] [Order article via Infotrieve]
9.
Latini R, Maggioni AP, Flather M, Sleight P, Tognoni
G. ACE-inhibitor use in patients with myocardial infarction:
summary of evidence from clinical trials. Circulation. 1995;92:3132–3137.
10. Schwartz PJ, Priori SG. Sympathetic nervous system and cardiac arrhythmias. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology: From Cell to Bedside. Philadelphia, Pa: WB Saunders Co; 1990:330–343.
11. Neri V, Parravicini I, Monza G, Petessio A, Roda L. Osservazioni sul comportamento dell'attività reninica plasmatica nell'infarto miocardico acuto. G Ital Cardiol. 1982;12:324–326.[Medline] [Order article via Infotrieve]
12. Woodfield SL, Lundergan CF, Reiner JS, Greenhouse SW, Thompson MA, Rorhbeck SC, Deychak Y, Simoons ML, Califf RM, Topol EJ, Ross A, for the GUSTO-I Angiographic Investigators. Angiographic findings and outcome in diabetics treated with thrombolytic therapy for acute myocardial infarction: the GUSTO-I experience. J Am Coll Cardiol. 1996;28:1661–1669.[Abstract]
13. Navis G, Faber HJ, de Zeeuw D, de Jong FE. ACE inhibitors and the kidney: a risk-benefit assessment. Drug Safety. 1996;15:200–211.[Medline] [Order article via Infotrieve]
14. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet. 1994;343:1115–1122.[Medline] [Order article via Infotrieve]
15. Yusuf S, Peto R, Lewis J, Collins R, Sleight P. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985;27:335–371.[Medline] [Order article via Infotrieve]
16. Jacoby RM, Nesto RW. Acute myocardial infarction in the diabetic patient: pathophysiology, clinical course and prognosis. J Am Coll Cardiol. 1992;20:736–744.[Abstract]
17. Zuanetti G, Latini R. Impact of pharmacological treatment on mortality after myocardial infarction in diabetic patients. J Diabetes Complications. 1997;11:131–136.[Medline] [Order article via Infotrieve]
18.
Moyé LA, Pfeffer MA, Wun CC, Davis BR, Geltman E,
Hayes D, Farnham DJ, Randall OS, Dinh H, Arnold JMO, Kupersmith J,
Hager D, Glasser SP, Biddle T, Hawkins CM, Braunwald E, for the SAVE
Investigators. Uniformity of captopril benefit in the SAVE study:
subgroup analysis. Eur Heart J. 1994;15:2–8.
19. Torp-Pedersen C, Kober L, Carlsen J, on behalf of the TRACE Study Group. Angiotensin-converting enzyme inhibition after myocardial infarction: the Trandolapril Cardiac Evaluation study. Am Heart J. 1996;132:235–243.[Medline] [Order article via Infotrieve]
20. GISSI-3: Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico. GISSI-3 study protocol on the effects of lisinopril, of nitrates, and of their association in patients with acute myocardial infarction. Am J Cardiol. 1992;70:62C–69C.[Medline] [Order article via Infotrieve]
21. Malmberg K, Rydén L, Efendic S, Herlitz J, Nicol P, Waldenström A, Wedel H, Welin L, on behalf of the DIGAMI Study Group. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI Study): effects on mortality at 1 year. J Am Coll Cardiol. 1995;26:57–65.[Abstract]
22. Swedberg K, Held P, Kjekshus J, Rasmussen K, Rydén L, Wedel H, CONSENSUS II Study Group. Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. N Engl J Med. 1992;327:678–684.[Abstract]
23. ACC/AHA Guidelines for the management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol. 1996;28:1328–1428.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  K. Parakh Diabetes and Mortality Risk After Acute Coronary Syndromes JAMA, November 28, 2007; 298(20): 2367 - 2368. [Full Text] [PDF]
|
|
|
|
 |
|
 Authors/Task Force Members, L. Ryden, E. Standl, M. Bartnik, G. V. d. Berghe, J. Betteridge, M.-J. de Boer, F. Cosentino, B. Jonsson, M. Laakso, et al. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: full text: The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD) Eur. Heart J. Suppl., June 1, 2007; 9(suppl_C): C3 - C74. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sulfi and A. D Timmis Review: Heart failure complicating acute myocardial infarction in patients with diabetes: pathophysiology and management strategies The British Journal of Diabetes & Vascular Disease, September 1, 2006; 6(5): 191 - 196. [Abstract] [PDF]
|
|
|
|
 |
|
 F. A. McAlister, W. A. Ghali, Y. Gong, J. Fang, P. W. Armstrong, and J. V. Tu Aspirin Use and Outcomes in a Community-Based Cohort of 7352 Patients Discharged After First Hospitalization for Heart Failure Circulation, June 6, 2006; 113(22): 2572 - 2578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Itoh, B. Ding, T. Shishido, N. Lerner-Marmarosh, N. Wang, N. Maekawa, B. C. Berk, Y. Takeishi, C. Yan, B. C. Blaxall, et al. Role of p90 Ribosomal S6 Kinase-Mediated Prorenin-Converting Enzyme in Ischemic and Diabetic Myocardium Circulation, April 11, 2006; 113(14): 1787 - 1798. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Daly, K. M. Fox, W. J. Remme, M. E. Bertrand, R. Ferrari, M. L. Simoons, and on behalf of the EUROPA investigators The effect of perindopril on cardiovascular morbidity and mortality in patients with diabetes in the EUROPA study: results from the PERSUADE substudy Eur. Heart J., July 2, 2005; 26(14): 1369 - 1378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. He, K. J. Way, E. Arikawa, E. Chou, D. M. Opland, A. Clermont, K. Isshiki, R. C. W. Ma, J. A. Scott, F. J. Schoen, et al. Differential Regulation of Angiotensin II-induced Expression of Connective Tissue Growth Factor by Protein Kinase C Isoforms in the Myocardium J. Biol. Chem., April 22, 2005; 280(16): 15719 - 15726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Eurich, S. R. Majumdar, R. T. Tsuyuki, and J. A. Johnson Reduced Mortality Associated With the Use of ACE Inhibitors in Patients With Type 2 Diabetes Diabetes Care, June 1, 2004; 27(6): 1330 - 1334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S.H. Bell Heart Failure: A Serious and Common Comorbidity of Diabetes Clin. Diabetes, April 1, 2004; 22(2): 61 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shimoni, M. Chuang, E. D. Abel, and David. L. Severson Gender-dependent attenuation of cardiac potassium currents in type 2 diabetic db/db mice J. Physiol., March 1, 2004; 555(2): 345 - 354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Shinozaki, K. Ayajiki, Y. Nishio, T. Sugaya, A. Kashiwagi, and T. Okamura Evidence for a Causal Role of the Renin-Angiotensin System in Vascular Dysfunction Associated With Insulin Resistance Hypertension, February 1, 2004; 43(2): 255 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Meune, J.-J. Mourad, J.-F. Bergmann, and C. Spaulding Interaction between cyclooxygenase and the renin-angiotensin-aldosterone system: rationale and clinical relevance Journal of Renin-Angiotensin-Aldosterone System, September 1, 2003; 4(3): 149 - 154. [Abstract] [PDF]
|
|
|
|
|
|
D. S.H. Bell Heart Failure: The frequent, forgotten, and often fatal complication of diabetes Diabetes Care, August 1, 2003; 26(8): 2433 - 2441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shimoni and X.-F. Liu Sex differences in the modulation of K+ currents in diabetic rat cardiac myocytes J. Physiol., July 15, 2003; 550(2): 401 - 412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Borghi, S. Bacchelli, D. D. Esposti, and E. Ambrosioni Effects of the Early ACE Inhibition in Diabetic Nonthrombolyzed Patients With Anterior Acute Myocardial Infarction Diabetes Care, June 1, 2003; 26(6): 1862 - 1868. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shimoni and X.-F. Liu Role of PKC in autocrine regulation of rat ventricular K+ currents by angiotensin and endothelin Am J Physiol Heart Circ Physiol, April 1, 2003; 284 (4): H1168 - H1181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
The Task Force on the Management of Acute Myocardi, F. Van de Werf, D. Ardissino, A. Betriu, D. V. Cokkinos, E. Falk, K. A.A. Fox, D. Julian, M. Lengyel, F.-J. Neumann, et al. Management of acute myocardial infarction in patients presenting with ST-segment elevation Eur. Heart J., January 1, 2003; 24(1): 28 - 66. [Full Text] [PDF]
|
|
|
|
|
|
M. Laakso and J. Kuusisto Diabetology for cardiologists Eur. Heart J. Suppl., January 1, 2003; 5(suppl_B): B5 - B13. [Abstract] [PDF]
|
|
|
|
 |
|
 S. P. Sedlis, D. A. Morrison, J. D. Lorin, R. Esposito, G. Sethi, J. Sacks, W. Henderson, F. Grover, K. B. Ramanathan, D. Weiman, et al. Percutaneous coronary intervention versus coronary bypass graft surgery for diabetic patients with unstable angina and risk factors for adverse outcomes with bypass: outcome of diabetic patients in the AWESOME randomized trial and registry J. Am. Coll. Cardiol., November 6, 2002; 40(9): 1555 - 1566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Chyun, V. Vaccarino, J. Murillo, L. H. Young, and H. M. Krumholz Cardiac Outcomes After Myocardial Infarction in Elderly Patients With Diabetes Mellitus Am. J. Crit. Care., November 1, 2002; 11(6): 504 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Marso Optimizing the diabetic formulary: beyond aspirin and insulin J. Am. Coll. Cardiol., August 21, 2002; 40(4): 652 - 661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. O. Bonow, W. E. Mitch, R. W. Nesto, P. T. O'Gara, R. C. Becker, L. T. Clark, S. Hunt, I. Jialal, S. E. Lipshultz, and E. Loh Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group V: Management of Cardiovascular-Renal Complications Circulation, May 7, 2002; 105 (18): e159 - e164. [Full Text] [PDF]
|
|
|
|
|
|
Y. Shimoni Inhibition of the formation or action of angiotensin II reverses attenuated K+ currents in type 1 and type 2 diabetes J. Physiol., November 15, 2001; 537(1): 83 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Erkens, O. H. Klungel, R. P. Stolk, J. A. Spoelstra, D. E. Grobbee, and H. G.M. Leufkens Cardiovascular Drug Use and Hospitalizations Attributable to Type 2 Diabetes Diabetes Care, August 1, 2001; 24(8): 1428 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kajstura, F. Fiordaliso, A. M. Andreoli, B. Li, S. Chimenti, M. S. Medow, F. Limana, B. Nadal-Ginard, A. Leri, and P. Anversa IGF-1 Overexpression Inhibits the Development of Diabetic Cardiomyopathy and Angiotensin II-Mediated Oxidative Stress Diabetes, June 1, 2001; 50(6): 1414 - 1424. [Abstract] [Full Text]
|
|
|
|
 |
|
 I S Malik, V K Bhatia, and J S Kooner Cost effectiveness of ramipril treatment for cardiovascular risk reduction Heart, May 1, 2001; 85(5): 539 - 543. [Abstract] [Full Text]
|
|
|
|
 |
|
 P. A. Lotufo, J. M. Gaziano, C. U. Chae, U. A. Ajani, G. Moreno-John, J. E. Buring, and J. E. Manson Diabetes and All-Cause and Coronary Heart Disease Mortality Among US Male Physicians Arch Intern Med, January 22, 2001; 161(2): 242 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. O'Keefe, M. Wetzel, R. R. Moe, K. Brosnahan, and C. J. Lavie Should an angiotensin-converting enzyme inhibitor be standard therapy for patients with atherosclerotic disease? J. Am. Coll. Cardiol., January 1, 2001; 37(1): 1 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hammoud, J.-F. Tanguay, and M. G. Bourassa Management of coronary artery disease: therapeutic options in patients with diabetes J. Am. Coll. Cardiol., August 1, 2000; 36(2): 355 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Cooper and C. I. Johnston Optimizing Treatment of Hypertension in Patients With Diabetes JAMA, June 28, 2000; 283(24): 3177 - 3179. [Full Text] [PDF]
|
|
|
|
|
|
J. M. Poothullil and M. I. Harris Diabetes and Decline in Heart Disease Mortality JAMA, September 22, 1999; 282(12): 1132 - 1132. [Full Text] [PDF]
|
|
|
|
|
|
I. Gustafsson, C. Torp-Pedersen, L. Kober, F. Gustafsson, P. Hildebrandt, and on behalf of the Trace Study Group Effect of the angiotensin-converting enzyme inhibitor trandolapril on mortality and morbidity in diabetic patients with left ventricular dysfunction after acute myocardial infarction J. Am. Coll. Cardiol., July 1, 1999; 34(1): 83 - 89. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Leor, H. Reicher-Reiss, U. Goldbourt, V. Boyko, S. Gottlieb, A. Battler, and S. Behar Aspirin and mortality in patients treated with angiotensin-converting enzyme inhibitors: A cohort study of 11,575 patients with coronary artery disease J. Am. Coll. Cardiol., June 1, 1999; 33(7): 1920 - 1925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chang, S. Sauereisen, M. Dlutowski, J. J. Veloski, and D. B. Nash A Cost-Effective Method to Characterize Variation in Clinical Practice Eval Health Prof, June 1, 1999; 22(2): 184 - 196. [Abstract] [PDF]
|
|
|
|
|
|
K. Malmberg, A. Norhammar, H. Wedel, and L. Ryden 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, May 25, 1999; 99(20): 2626 - 2632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Towler, M. Bidder, T. Latifi, T. Coleman, and C. F. Semenkovich Diet-induced Diabetes Activates an Osteogenic Gene Regulatory Program in the Aortas of Low Density Lipoprotein Receptor-deficient Mice J. Biol. Chem., November 13, 1998; 273(46): 30427 - 30434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Nesto and S. Zarich Acute Myocardial Infarction in Diabetes Mellitus : Lessons Learned From ACE Inhibition Circulation, January 13, 1998; 97(1): 12 - 15. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||