Selection of glycoprotein IIb/IIIa inhibitors for upstream use in patients with diabetes experiencing unstable angina or non-ST segment elevation myocardial infarction. What have we learned in the last 10 years? (original) (raw)
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Circulation, 2000
on behalf of the PRISM-PLUS Investigators Background-Diabetic patients who present with unstable angina or non-ST-elevation myocardial infarction suffer a substantially greater incidence of subsequent infarction or death compared with nondiabetic patients. The present study was undertaken to examine whether diabetic patients in the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study appeared to benefit from platelet glycoprotein IIb/IIIa receptor-mediated inhibition of platelet aggregation by tirofiban. Methods and Results-Of the 1570 PRISM-PLUS patients treated with either tirofiban plus heparin (nϭ773) or heparin alone (nϭ797), Ϸ23% in each treatment group were diabetic. A comparison of treatment outcomes in the diabetic subgroup revealed that the combination therapy compared with heparin alone was associated with reductions in the incidence of the composite primary end point of death, myocardial infarction (MI), or refractory ischemia at 2, 7, 30, and 180 days (7.7% versus 8.3%, 14.8% versus 21.8%, 20.1% versus 29.0%, and 32.0% versus 39.9%, respectively; PϭNS) and in the incidence of MI or death (0.0% versus 3.1%, Pϭ0.03; 1.2% versus 9.3%, Pϭ0.005; 4.7% versus 15.5%, Pϭ0.002; and 11.2% versus 19.2%, Pϭ0.03). Tests for quantitative interaction between tirofiban therapy and diabetic status were significant. Conclusions-The addition of tirofiban to heparin and aspirin appears effective in the prevention of major ischemic events, particularly MI or death, in diabetic patients presenting with unstable angina and non-ST-elevation MI. (Circulation. 2000;102:2466-2472.)
Diabetes Mellitus and Acute Coronary Syndrome: Lessons From Randomized Clinical Trials
Current diabetes reports, 2012
Diabetes mellitus is a major independent risk factor for acute coronary syndrome (ACS). In addition, diabetic patients with ACS suffer from increased mortality compared to their nondiabetic peers. Driven by multiple pathophysiological disturbances, such patients are predisposed to a proinflammatory, prothrombotic state, which may lead to plaque rupture. To counteract this more complex biology, several therapies and strategies have emerged, with some having unique preferential benefits in this population. Antiplatelet agents such as aspirin and clopidogrel have long been standard of care. Dose adjustment of these therapies remains the subject of continued research. Along with medical therapy, ACS diabetic patients preferentially benefit from primary percutaneous intervention compared to fibrinolysis. However, with advances in reperfusion techniques, the optimal strategy has yet to be determined. With these differences in ACS treatment responses, diabetic individuals may not just be a...
Journal of The American College of Cardiology, 1993
Objectives. This study was designed to assess outcome in patients with diabetes who received thrombolytic therapy and to determine whether differences in angiographic characteristics may account for the worse outcome observed in diabetic patients.Background. Patients with diabetes are known to have a worse outcome after acute myocardial infarction than that of patients without diabetes.Methods. Clinical and angiographic characteristics of the 148 patients with diabetes and the 923 patients without diabetes in the Thrombolysis and Angioplasly in Myocardial Infarction (TAMI) trials were examined and analyzed.Results. Patients with diabetes tended to be older (median age 59 vs. 56 years) and to have a higher incidence of hypertension and hyperlipidemia and a lower incidence of cigarette smoking. Patients with diabetes had significantly more severe anatomic disease (66% vs. 46% had multivessel disease, p < 0.0001), similar global left ventricular ejection fraction (49% vs. 51%) and worse noninfarct zone ventricular function (−0.13 vs. 0.32 SD/chord, p = 0.02) than that of nondiabetic patients. Angiographic patency rates at 90 min after thrombolytic therapy were similar in patients with and without diabetes (initial 90-min patency 71% vs. 70%). Diabetic patients had nearly twice the in-hospital mortality rate (11% vs. 6%, p < 0.02) and a higher incidence of pulmonary edema (11% vs. 4%, p = 0.001). Diabetic women had an especially high in-hospital mortality rate (21%). No retinal hemorrhages were observed. Although diabetes as an unadjusted variable was predictive of in-hospital (p < 0.02) and long-term (p = 0.003) mortality, after adjustment for baseline clinical and angiographic characteristies, diabetes was not found to have an independent influence on mortality.Conclusions. Patients with diabetes after myocardial infarction have a worse outcome than that of patients without diabetes despite similar rates of infarct vessel patency. However, diabetes was not found to be an independent risk factor for increased mortality. These findings suggest that diabetes itself is not a major risk factor for poor early outcome after thrombolytic therapy for myocardial infarction; rather, the secondary effects such as more extensive coronary artery disease account for the worse outcome.
Thrombosis Research, 2014
Type 2 diabetes mellitus (T2DM) is associated with higher rates of thrombotic complications in patients with coronary artery disease (CAD) despite optimal medical therapy. Thrombus area was measured in T2DM and non-diabetic patients receiving aspirin and clopidogrel 7-10 days after troponin positive Non ST-elevation acute coronary syndrome (NSTE-ACS). Secondly, we assessed response to clopidogrel in naive patients with T2DM and stable CAD in a randomised controlled trial. Thrombus area was measured by Badimon chamber and platelet reactivity by VerifyNow ®. In T2DM patients presenting with NSTE-ACS, thrombus area was greater compared to non-diabetic patients (mean ± SD, 20,512 ± 12,567 [n=40] vs. 14,769 ± 8,531 [n=40] µm 2 /mm, p=0.02) Clopidogrel decreased thrombus area among stable CAD patients with T2DM (mean ± SD, Clopidogrel [n=45]: 13,978 ± 5,502 to 11,192 ± 3,764 µm 2 /mm vs. placebo [n=45]: 13,959 ± 7,038 to 14,201 ± 6,780 µm 2 /mm, p<0.001, delta values: clopidogrel vs. placebo, mean
European Journal of Preventive Cardiology, 2019
Background: Diabetes mellitus, largely type 2, affects nearly 10% of the global adult population according to the World Health Organization. Diabetes is an independent risk factor for atherosclerotic cardiovascular diseases, including coronary artery disease. Diabetes patients experience a two to threefold increased incidence of coronary artery disease, despite improved metabolic control and management of other cardiovascular risk factors. Discussion: Platelet abnormalities and activation as well as reduced antiplatelet drug responsiveness characterise diabetes mellitus. Mechanisms linking diabetes to platelet and vascular abnormalities, atherogenesis and atherosclerotic cardiovascular disease are still only partially known, highlighting the unique complexity of the pro-atherogenic clinical scenario and its treatment. Consistently, a higher residual cardiovascular risk characterises patients with diabetes compared with those without, in spite of improved antiplatelet and antithrombotic treatment combinations. Randomised clinical trials aimed at optimising antiplatelet treatment specifically in patients with diabetes are lacking, both in acute and chronic coronary artery disease settings. Thus, patients with diabetes are treated with regimens validated in studies including only variable proportions of diabetes patients. Myocardial revascularisation appears to confer a comparable relative benefit between diabetes patients and patients without diabetes, and generally coronary artery bypass grafting has a better outcome in diabetes mellitus versus peripheral coronary intervention. New glucoselowering drugs have been shown to reduce the incidence of major cardiovascular events in secondary prevention. Type 1 diabetes mellitus remains less explored than type 2 in this context. Conclusion: Diabetes-tailored antithrombotic strategies in acute and chronic coronary artery disease remain an unmet clinical need, requiring ad-hoc trials and precision pharmacological strategies.
Atherosclerosis, 2009
Background: It has been shown that, among patients with ST-segment elevation myocardial infarction (STEMI), diabetes is associated with a significantly higher mortality. The aim of the current study was to investigate the impact of diabetes on myocardial perfusion and mortality among STEMI patients treated with primary angioplasty and glycoprotein IIb-IIIa inhibitors. Methods: Our population is represented by a total of 1662 patients undergoing primary angioplasty for STEMI included in 11 randomized trials. Myocardial perfusion was evaluated by angiography (n = 1324) or postprocedural ECG (n = 1371). Distal embolization was defined as an abrupt "cutoff" in the main vessel or one of the coronary branches of the infarct-related artery, distal to the angioplasty site (data available in 1181 patients). Results: Diabetes was observed in a total of 281 patients (16.9%). Diabetic patients were older, with a larger prevalence of female gender, hypertension, hypercholesterolemia, advanced killip class at presentation and multivessel disease. Diabetes was associated with impaired postprocedural TIMI 3 flow (82% vs 90%, p < 0.001), MBG 2-3 (60.1% vs 74.2%, p < 0.001), complete ST-segment resolution (43.2% vs 60%, p < 0.001) and more distal embolization (16.4% vs 10.1%, p < 0.0001). The association with impaired MBG and distal embolization was confirmed after correction for baseline confounding factors. Diabetes was associated with significantly impaired mortality (12.6% vs 3.9%, HR = 3.0 [1.84-4.89], p < 0.001), that persisted even after correction for baseline confounding factors , p = 0.001).
Journal of Clinical Medicine
Purpose: To investigate the prognostic significance of diabetes mellitus (DM) in patients with high risk acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (pPCI) in the era of potent antithrombotics. Methods: Data from 1230 ST-segment elevation myocardial infarction (STEMI) patients enrolled in the PRAGUE-18 (prasugrel vs. ticagrelor in pPCI) study were analyzed. Ischemic and bleeding event rates were calculated for patients with and without diabetes. The independent impact of diabetes on outcomes was evaluated after adjustment for outcome predictors. Results: The prevalence of DM was 20% (N = 250). Diabetics were older and more often female. They were more likely to have hypertension, hyperlipoproteinemia, multivessel coronary disease and left main disease, and be obese. The primary net-clinical endpoint (EP) containing death, spontaneous nonfatal MI, stroke, severe bleeding, and revascularization at day 7 occurred in 6.1% of patients with, a...
Heart, 1993
infarction and has been shown to reduce Objective-To compare the activity of mortality' 2 and improve left ventricular funcplasminogen activator inhibitor (PAI-1) tion.3 However, not all patients treated wvch in diabetic and non-diabetic patients thrombolytic therapy have successful reperfuadmitted with acute myocardial-infarc-sion of the thrombosed artery and therapy is tion and to determine whether PAI-i further limited by reocclusion and reinfarcactivity influences reperfusion after tion in 10-25% of patients.4 The reasons for thrombolytic therapy. the resistance to lysis and the occurrence of Design-Prospective study of patients reocclusion are unclear. Factors such as admitted with acute myocardial infircplatelet activation associated with thrombolytion. SiS,56 and the procoagulant effects of plasmin7 Setting-District general hospital. probably contribute. In addition recent evi-Main outcome measures-Reperfusion dence suggests that the fibrinolytic system, assessed by time to peak release of crea-and in particular plasminogen activator tine kinase-MB isoenzyme. inhibitor (PAI-I), may be important. Both Results-Baseline PAI-1 activity and Sane et al8 and Barbash et a19 showed a relaantigen concentrations were significantly tion between raised PAI-activity on admishigher in diabetic patients (n = 45) than sion with acute myocardial infarction and in non-diabetic patients (n = 110) (24-6 reduced likelihood of a patent infarct related (6.9) v 18'6 (7.9) AU/ml (AU = arbitrar artery after thrombolytic therapy with recomunits) (p = 0-0001) and 58*8 (13.1-328-8) v binant tissue plasminogen activator. 41'0 (10.9-125.4) nglml (p = 0.004). Time Increased activity of PAI-1 has also been to peak release of creatine kinase-MB shown to predict the recurrence of infarction was calculated in 123 (80Yo)-patients. In in young survivors of myocardial infarction.'0 98 who received thrombolytic therapy the In diabetic patients mortality and morbidmedian time to peak enzyme release was ity from acute myocardial infarction are 15.5 h (7.5-24 h) in diabetic patients (n high."' 12 Non-insulin-dependent diabetic = 26) and 12 h (5-26 h) in non-diabetic patients have previously been reported to patients (n = 72) (p = 0.005). In those have increased PM-i activity,"3'4 which may with a time to peak release of A 12 h, play a part in determining the outcome from indicating likely successful reperfusion, myocardial infarction. PAI-1 activity was 17-5 (7 8) AU/ml com-We studied admission levels of PAI-I pared with 228 :(7:7) AU/ml in those with activity and outcome from thrombolytic thera dme to peak release of->12 h-(p = apy for acute myocardial infarction in 155 0001).-In multiple regression analysis patients, both diabetic and non-diabetic, both diabetes :(p = 0.0001) and PAI-i admitted to a district general hospital. The activity at admission (p = 0.029) were aims of this study were to determnme whether independently related to successfil (a) PAI-I activity influences the response to reperfusion. In 13 patients with evidence thrombolytic therapy and (b) whether PAI-i of reinfarction in hospital PAM-i activity activity is higher in diabetic patients with on day 3 was 26*7 (6.4) AU/ml compared acute myocardial infarction than in non-diawith 21*7 :(6.3) AU/ml in those without betic patients-a factor that might influence evidence of reinfrction (p = 0.032). the outcome of thrombolytic therapy in Department of Conclusion-Both raised PAI-i activity diabetic patients. Medicine, University on admission and diabetes were associ-College London Medical Sol, ated withadured likelihood of enzy-Whittington Hospital, matic £vidOceitc of reperfision after Patients and methods London thrombolytic therapy.;.:Increased PAM-1 Over a two year period we studied 155 activity on day-3 was associated with an patients admitted witi acute myocardial Department of increased risk of reinfction. Diabetic-infarction to the Whittington Hospital. They Cardiology, Whittiuaton Hospital. patients had-higher PMI-i activity on-accounted for 60% of all admissions with Londbn admission., Ths may partly explain their acute myocardial infarction over the period. D L P §UC27SO1-reduced likelihood of reperfusion. Patients were excluded if an initial blood Correspondence to: sample was not obtained before the adminis-Dr RP-Oray; Deparent of sp o Cardi&Mogy,VWhittington (Br HeartJ 1993;70:530-536) tration of thrombolytic therapy, if they pre-HosOgtal, HighgateHill, sented more than 24 hours after the onset of London Nf9 5N.. Thrombolytic therapy is now the treatment of chest pamin,-or if myocardial infarction was not Accepted for publication choice for paents with acute myocardial confirmed by World Health Organisation
Catheterization and Cardiovascular Interventions, 2008
Objective:We assessed the outcomes in diabetic patients undergoing percutaneous coronary intervention (PCI) using sirolimus-eluting stents (SES) as a function of treatment with glycoprotein (GP) IIb/IIIa inhibitors.We assessed the outcomes in diabetic patients undergoing percutaneous coronary intervention (PCI) using sirolimus-eluting stents (SES) as a function of treatment with glycoprotein (GP) IIb/IIIa inhibitors.Methods and Results:Of 551 diabetic patients treated with a SES in nine trials (RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS, REALITY, SVELTE, DIRECT, SIRIUS 2.25, and SIRIUS 4.0), 187 patients (33.9%) were administered GP IIb/IIIa inhibitors during PCI. GP IIb/IIIa blockade was associated with lower rates of myocardial infarction (MI) at 30 days (1.1% vs. 3.3%, P = 0.12) and at 1 year (1.1% vs. 4.7%, P = 0.04), and composite endpoint of cardiac death/MI at 1 year (2.2% vs. 6.2%, P = 0.05). Benefit from GP IIb/IIIa inhibitors was confined to 128 insulin-treated diabetics who had remarkable reduction in MI (0.0% vs. 6.3%, P = 0.04) and cardiac death/MI at 30 days (0.0% vs. 7.6%, P = 0.05) and at 1-year (0.0% vs. 13.4%, P = 0.01 and 0.0% vs. 15.7%, P = 0.0005, respectively). When treated with GP IIb/IIIa inhibitors, insulin-requiring diabetics had similar rates of 1-year death/MI when compared with the nondiabetic patients (0% vs. 4.7%, P = 0.13, respectively). There were no significant differences in outcomes as a function of GP IIb/IIIa blockade in diabetics not treated with insulin.Of 551 diabetic patients treated with a SES in nine trials (RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS, REALITY, SVELTE, DIRECT, SIRIUS 2.25, and SIRIUS 4.0), 187 patients (33.9%) were administered GP IIb/IIIa inhibitors during PCI. GP IIb/IIIa blockade was associated with lower rates of myocardial infarction (MI) at 30 days (1.1% vs. 3.3%, P = 0.12) and at 1 year (1.1% vs. 4.7%, P = 0.04), and composite endpoint of cardiac death/MI at 1 year (2.2% vs. 6.2%, P = 0.05). Benefit from GP IIb/IIIa inhibitors was confined to 128 insulin-treated diabetics who had remarkable reduction in MI (0.0% vs. 6.3%, P = 0.04) and cardiac death/MI at 30 days (0.0% vs. 7.6%, P = 0.05) and at 1-year (0.0% vs. 13.4%, P = 0.01 and 0.0% vs. 15.7%, P = 0.0005, respectively). When treated with GP IIb/IIIa inhibitors, insulin-requiring diabetics had similar rates of 1-year death/MI when compared with the nondiabetic patients (0% vs. 4.7%, P = 0.13, respectively). There were no significant differences in outcomes as a function of GP IIb/IIIa blockade in diabetics not treated with insulin.Conclusion:In this analysis, outcomes of insulin requiring diabetic patients undergoing PCI with SES were considerably improved with adjunctive GP IIb/IIIa inhibitors by decreasing the rates of MI and composite endpoint of cardiac death/MI. © 2008 Wiley-Liss, Inc.In this analysis, outcomes of insulin requiring diabetic patients undergoing PCI with SES were considerably improved with adjunctive GP IIb/IIIa inhibitors by decreasing the rates of MI and composite endpoint of cardiac death/MI. © 2008 Wiley-Liss, Inc.