Design of the ZWOT-CASE study: an observational study on the effectiveness of an integrated programme for cardiovascular risk management compared to usual care in general practice.

BACKGROUND: Cardiovascular diseases (CVD) contribute considerably to mortality and morbidity. Prevention of CVD by lifestyle change and medication is important and needs full attention. In the Netherlands an integrated programme for cardiovascular risk management (CVRM), based on the Chronic Care Model (CCM), has been introduced in primary care in many regions in recent years, but its effects are unknown. In the ZWOT-CASE study we will assess the effect of integrated care for CVRM in the region of Zwolle on two major cardiovascular risk factors: systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-cholesterol) in patients with or at high risk of CVD. METHODS: This study is a pragmatic observational study comparing integrated care for CVRM with usual care among patients aged 40-80 years with CVD (n = 370) or with a high CVD risk (n = 370) within 26 general practices. After 1 yr follow-up, primary outcomes (SBP and LDL-cholesterol level) are measured. Secondary outcomes include lifestyle habits (smoking, dietary habits, alcohol use, physical activity), risk factor awareness, 10-year risk of cardiovascular morbidity or mortality, health care consumption, patient satisfaction and quality of life. CONCLUSION: The ZWOT-CASE study will provide insight in the effects of integrated care for CVRM in general practice in patients with CVD or at high CVD risk. TRIAL REGISTRATION: The ZWOlle Transmural Integrated Care for CArdiovaScular Risk Management Study; ClinicalTrials.gov ; Identifier: NCT03428061; date of registration: 09-02-2018; This study has been retrospectively registered.

Transfer times and outcomes in patients with ST-segment-elevation myocardial infarction undergoing interhospital transfer for primary percutaneous coronary intervention: APEX-AMI insights.

BACKGROUND: Transfer delays for primary percutaneous coronary intervention may increase mortality in patients with ST-segment-elevation myocardial infarction. We examined the association between door 1-to-door 2 (D1D2) time, a measure capturing the entire transfer process, and outcomes in patients undergoing interhospital transfer for primary percutaneous coronary intervention. METHODS AND RESULTS: We evaluated the relationship between D1D2 time and the 90-day incidence of death, shock, and heart failure in the subset of 2075 (36.1%) of 5745 patients who underwent interhospital transfer for primary percutaneous coronary intervention in the Assessment of Pexelizumab in Acute Myocardial Infarction trial. There was no significant difference in the 90-day incidence of death, shock, and heart failure between the transferred and the nontransferred groups (10.3% versus 10.2%; P = 0.89). The median difference in symptom-to-balloon time between the 2 groups was 45 minutes (229 versus 184; P<0.001). The primary outcome per 30-minute delay was higher for patients with a D1D2 time ≤150 minutes (hazard ratio, 1.19: 95% confidence interval, 1.06 to 1.33; P = 0.004) but not for D1D2 times >150 minutes (hazard ratio, 0.99: 95% confidence interval, 0.96 to 1.02; P = 0.496). The association between longer D1D2 time and worsening outcome was no longer statistically significant after multivariable adjustment. CONCLUSIONS: Longer transfer times were associated with higher rate of death, shock, and heart failure among patients undergoing interhospital transfer from primary percutaneous coronary intervention, although this difference did not persist after adjusting for baseline characteristics.

Risk of bleeding after prehospital administration of high dose tirofiban for ST elevation myocardial infarction.

BACKGROUND: In most patients with ST-elevation myocardial infarction (STEMI), antiplatelet drugs are already administrated in the ambulance, before hospital admission. We investigated the safety of prehospital initiation of a high dose of the glycoprotein IIb/IIIa inhibitor tirofiban on top of aspirin, clopidogrel and heparin. METHODS: It concerns a sub-analysis of the On-TIME 2 trial. 1398 patients were enrolled and 1275 patients (91.2%) had clinical follow up. Non CABG-related bleeding was defined according to the TIMI criteria. Logistic regression was used to determine predictors of 30-day bleeding. The independent association between bleeding and mortality (30-day and 1-year) was evaluated using Cox proportional Hazard models. RESULTS: Bleeding (major or minor) was observed in 47 patients (3.7%), with only 13 patients (1%) with major bleeding. The strongest independent determinants of bleeding were age (OR 1.05, 95% CI 1.01-1.08, p=0.011), Killip class >1 at admission (OR 2.5, 95% CI 1.2-5.3, p=0.020) and intra aortic balloon pump (IABP) use (OR 4.2, 95% CI 1.6-11.1, p=0.003). High dose tirofiban was not an independent predictor of bleeding (OR 1.7, 95% CI 0.9-3.2, p=0.116). Bleeding was associated with an increased risk of 30-day mortality (HR 5.5, 95% CI 1.6-7.8, p<0.001) and one-year mortality (HR 3.2, 95% CI 1.4-7.2, p=0.005). CONCLUSION: Prehospital use of high dose tirofiban is safe and associated with a low risk of bleeding. Age, Killip class >1, IABP use, but not high dose tirofiban are independent determinants of bleeding in STEMI patients. Bleeding is independently associated with 30-day and 1-year mortality.

Higher efficacy of pre-hospital tirofiban with longer pre-treatment time to primary PCI: protection for the negative impact of time delay.

AIMS: To evaluate the impact of longer duration of pre-hospital initiated antiplatelet and antithrombotic therapy on outcome in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: In this sub-analysis of the Ongoing Tirofiban in Myocardial Evaluation (On-TIME) 2 trial, we studied, in 1,370 patients, the effect of pre-treatment time (time from administering study medication to time of angiography) on complete ST-segment resolution (STR), initial patency and 30-day mortality. Study medication consisted of high dose tirofiban (HDT) or control (placebo or no HDT) on top of high dose clopidogrel, aspirin and unfractionated heparin. Median pre-treatment time was 55 min (44-70). Longer pre-treatment was associated with longer transportation times, longer in-hospital delay, longer total ischaemic time (all p<0.001) and higher 30-day mortality (3.6% vs. 1.8%, p=0.046). Longer HDT pre-treatment time was independently associated with increased complete STR both before (odds ratio [OR] 1.51, 95%; confidence interval [CI] 0.98-2.32; p=0.06) and after PCI (OR 1.43, 95%; CI 1.02-2.02; p=0.039) and with a significantly improved initial TIMI 2 or 3 flow (51.4% vs. 43.4%, p=0.042) and reduced 30-day mortality (2.1% vs. 5.0%, p=0.047) as compared to longer control pre-treatment. CONCLUSIONS: Longer time delay before primary PCI is associated with increased mortality. Pre-treatment with high dose tirofiban, however, may compensate for this negative effect by improving ST-segment resolution and initial patency and by reducing mortality. Further studies should be performed to confirm that this is an attractive therapy for patients with longer delays to reperfusion.

Facilitated reperfusion with prehospital glycoprotein IIb/IIIa inhibition: predictors of complete ST-segment resolution before primary percutaneous coronary intervention in the On-TIME 2 trial: correlates of reperfusion before primary PCI.

OBJECTIVE: The objective of this study is to evaluate the incidence, predictors, and outcome of complete ST-segment resolution (STR) during transportation after pretreatment with dual or triple antiplatelet therapy in the Ongoing Tirofiban in Myocardial Infarction Evaluation (On-TIME) 2 trial. METHODS: Patients with ST-segment elevation myocardial infarction were randomized in the ambulance to pretreatment with high-dose tirofiban (HDT) or to a control pretreatment (placebo or no HDT) on top of 600-mg clopidogrel, 500-mg aspirin, and 5000-IU unfractionated heparin. Complete STR was defined as ≥70% STR on the electrocardiogram obtained before percutaneous coronary intervention (PCI) as compared with the inclusion electrocardiogram. RESULTS: Complete STR before PCI occurred in 16.8% (n = 188/1121) and more frequently in the HDT group (19.0% vs 14.6%, P = .05). Independent predictors for complete STR before PCI were younger age (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.70-0.96, P = .01 per 10 year increase), fast diagnosis (OR, 0.97; 95% CI, 0.97-1.0, P = .004 per 15-minute increase time from symptom onset to diagnosis), longer pretreatment time (OR, 1.09; 95% CI, 1.03-1.16, P = .003 per 15-minute increase time start study medication to angiography), and randomization to HDT (OR, 1.39; 95% CI, 1.0-1.9, P = .05). Complete STR before PCI was associated with very low 30-day (0.5% vs 2.8%, P = .07) and 1-year (1.1% vs 5.0%, P = .019) mortality. CONCLUSIONS: Dual or triple antiplatelet pretreatment in the ambulance results in complete STR before PCI in 17% of patients. Fast ST-segment elevation myocardial infarction diagnosis, prehospital initiation of pretreatment early after symptom onset, and HDT independently predicted STR before PCI. Complete STR is associated with improved clinical outcome.

Pre-hospital administration of tirofiban in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty: a sub-analysis of the On-Time 2 trial.

AIMS: Glycoprotein IIb/IIIa blocking agents seem to improve percutaneous coronary intervention (PCI) results in patients with ST-elevation myocardial infarction (STEMI). We aimed to compare the effect of pre-hospital administration of tirofiban in STEMI patients with and without diabetes mellitus (DM) treated with primary PCI. METHODS AND RESULTS: We performed a pre-specified sub-analysis of the randomised On-Time II trial (n=984) and it's open label run-in phase (n=414), which investigated pre-hospital administration of high dose tirofiban in STEMI patients treated with primary PCI. Two-hundred and twenty (16%) diabetic patients (known DM or Hba1C ≥6.2%) were included, 101 in the placebo group and 119 in the tirofiban group. In patients with DM, randomisation to tirofiban resulted in a lower residual ST deviation (5.1±8.5 mm vs. 6.2±5.6 mm, p=0.003), a reduced infarct size (CK 1694±1925 U/L vs. CK 2040±1829 U/L, p=0.02) and a trend towards lower one-year mortality (4.6% vs. 11.6%, p=0.07). The beneficial effects of tirofiban were more pronounced in diabetic patients compared to patients without diabetes. CONCLUSIONS: Pre-hospital administration of tirofiban in diabetic STEMI patients treated with primary PCI improves ST resolution and reduces myocardial infarct size. Tirofiban seems particularly beneficial in patients with diabetes.

Prehospital triple antiplatelet therapy in patients with acute ST elevation myocardial infarction leads to better platelet aggregation inhibition and clinical outcome than dual antiplatelet therapy.

OBJECTIVE: To assess whether prehospital initiation of high-dose tirofiban in addition to high-dose clopidogrel results in more adequate inhibition of platelet aggregation (IPA) and better clinical outcome after primary percutaneous coronary intervention (PCI). METHODS: Prespecified two-centre substudy of the prospective, international, multicentre, placebo controlled Ongoing Tirofiban in Myocardial Infarction Evaluation trial 2 (On-TIME-2 trial). 648 of 964 (67%) patients in the On-TIME-2 trial with ST elevation myocardial infarction undergoing primary PCI were studied. Pre-PCI IPA after early prehospital initiation of high-bolus dose (25 µg/kg) tirofiban was compared to placebo in addition to acetylsalicylic acid, unfractionated heparin and 600 mg clopidogrel. RESULTS: IPA was measured at a median of 60 min after study medication administration. In all four tests: Fe induced platelet aggregation, ADP induced platelet aggregation, platelet function analyser (PFA)-100 (collagen-epinephrine and collagen-ADP cartridge) IPA was higher in patients pretreated with high-dose tirofiban (p<0.001 for all tests), even after >74 min of pretreatment. Patients in the highest quartile of IPA had less residual ST segment deviation 1 h post-PCI (p value for trend: p=0.001, 0.004, 0.001, 0.002 respectively). There was a significant relationship between PFA-100 (both cartridges) and major adverse cardiovascular events (MACE, p=0.028, p=0.035) and early thrombosis (p=0.009, p=0.007). CONCLUSIONS: 60 min of prehospital initiated antiplatelet treatment including high-dose tirofiban resulted in higher levels of IPA compared to pretreatment with acetylsalicylic acid and high-dose clopidogrel alone, even after longer pretreatment times. Levels of IPA were significantly related to ST resolution and MACE, including stent thrombosis. This substudy confirms the main findings of the On-TIME2 trial that clopidogrel alone is suboptimal, even at high dose and administered well in advance of primary PCI.

Effect of early, pre-hospital initiation of high bolus dose tirofiban in patients with ST-segment elevation myocardial infarction on short- and long-term clinical outcome.

OBJECTIVES: The purpose of this trial was to study the effect of a high bolus dose (HBD) of tirofiban on clinical outcome in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2) placebo-controlled, double-blind, randomized trial showed that early administration of HBD tirofiban in the ambulance improves ST-segment resolution in patients with STEMI undergoing primary percutaneous coronary intervention. The effect of early tirofiban treatment on clinical outcome is unclear. METHODS: The On-TIME 2 trial consisted of 2 phases: an open-label phase, followed by a double-blind, placebo-controlled phase. STEMI patients were randomized to either HBD tirofiban or no tirofiban (phase 1) or placebo (phase 2) in addition to aspirin, heparin, and high-dose clopidogrel. The protocol pre-specified a pooled analysis of the 2 study phases to assess the incidence of major adverse cardiac events at the 30-day follow-up and on total mortality at the 1-year follow-up. RESULTS: During a 3-year period, 1,398 patients were randomized, 414 in phase 1 and 984 in phase 2. Major adverse cardiac events at 30 days were significantly reduced (5.8% vs. 8.6%, p = 0.043). There was a strong trend toward a decrease in mortality (2.2% vs. 4.1%, p = 0.051) in patients who were randomized to tirofiban pre-treatment, which was maintained during the 1-year follow-up (3.7% vs. 5.8%, p = 0.08). No clinically relevant difference in bleeding was observed. CONCLUSIONS: Early, pre-hospital initiation of HBD tirofiban, in addition to high-dose clopidogrel, improves the clinical outcome after primary percutaneous coronary intervention in patients with STEMI. (Ongoing 2b/3a inhibition In Myocardial infarction Evaluation; ISRCTN06195297).

Tirofiban for myocardial infarction.

IMPORTANCE OF THE FIELD: Inhibition of platelet aggregation plays a key role in treatment of coronary artery disease. AREAS COVERED IN THIS REVIEW: Studies on the effects of tirofiban in patients with either ST elevation or non-ST elevation myocardial infarction are reviewed. WHAT THE READER WILL GAIN: Tirofiban is a small-molecule glycoprotein IIb/IIIa receptor inhibitor. If discontinued, the action of tirofiban is faster reversed as abciximab. The dose varied between low (bolus of 0.4 microg/kg administered over 30 min followed by an infusion of 0.10 microg/kg/min), intermediate (bolus of 10 microg/kg administered over 3 min followed by an infusion of 0.15 microg/kg/min) and high (bolus of 25 microg/kg administered over 3 min followed by an infusion of 0.15 microg/kg/min). The high-dose administration especially may be beneficial in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI). There is no indication for tirofiban in patients treated with thrombolysis. Patients with non-ST elevation myocardial infarction requiring PCI are most likely to benefit from tirofiban if they have ongoing ischemia and/or dynamic ECG changes. The risk of serious bleeding with tirofiban is low and there is a very low risk of thrombocytopenia. TAKE HOME MESSAGE: Use of tirofiban for myocardial infarction is effective and has an acceptable safety profile.

Tirofiban as adjunctive therapy for acute coronary syndromes and percutaneous coronary intervention: a meta-analysis of randomized trials.

AIMS: To perform a thorough and updated systematic review of randomized clinical trials comparing tirofiban vs. placebo or vs. abciximab. METHODS AND RESULTS: We searched for randomized trials comparing tirofiban vs. placebo or any active control. Odds ratios (OR) were computed from individual studies and pooled with random-effect methods. Thirty-one studies were identified involving 20,006 patients (12 874 comparing tirofiban vs. heparin plus placebo or bivalirudin alone, and 7132 vs. abciximab). When compared with placebo, tirofiban was associated at 30 days with a significant reduction in mortality [OR = 0.68 (0.54-0.86); P = 0.001] and death or myocardial infarction (MI) [OR = 0.69 (0.58-0.81); P < 0.001]. The treatment benefit persisted at follow-up but came at an increased risk of minor bleedings [OR = 1.42 (1.13, 1.79), P = 0.002] or thrombocytopenia. When compared with abciximab, mortality at 30 days did not differ [OR = 0.90 (0.53, 1.54); P = 0.70], but in the overall group tirofiban trended to increase the composite of death or MI [OR = 1.18 (0.96, 1.45); P = 0.11]. No such trend persisted at medium-term follow-up or when appraising studies testing tirofiban at 25 microg/kg bolus regimen. CONCLUSION: Tirofiban administration reduces mortality, the composite of death or MI and increases minor bleedings when compared with placebo. An early ischaemic hazard disfavouring tirofiban was noted when compared with abciximab in studies based on 10 but not 25 microg/kg tirofiban bolus regimen.

Defining the role of platelet glycoprotein receptor inhibitors in STEMI: focus on tirofiban.

Tirofiban is a small molecule, nonpeptide tyrosine derivative. Although similar to abciximab in that it has a high specificity and affinity for the glycoprotein (GP) IIb/IIIa receptor, tirofiban dissociates from the GP IIb/IIIa receptor more rapidly than abciximab. Additionally, the action of tirofiban is reversed within hours after completion of the infusion, whereas abciximab binds irreversibly resulting in a considerably longer effect. The efficacy of tirofiban in ST-segment elevation myocardial infarction (STEMI) has been demonstrated when administered in patients being managed with primary percutaneous coronary intervention (PCI). These trials primarily studied tirofiban utilizing the high-dose bolus regimen (25 microg/kg bolus followed by a maintenance infusion of 0.15 microg/kg/min for 18-24 hours). The On-TIME (Ongoing Tirofiban in Myocardial Infarction Evaluation) 2 trial assessed early administration of the high-dose bolus regimen of tirofiban either at the referral centre or in the ambulance, in patients being transferred to a primary PCI centre. Early use of tirofiban resulted in both a significant increase in the rate of complete resolution of ST-segment deviation pre- and post-PCI, and improvement in clinical outcomes at 30 days. Moreover, the multi-factorial MULTISTRATEGY (Multicentre Evaluation of Single High-Dose Bolus Tirofiban vs Abciximab With Sirolimus-Eluting Stent or Bare Metal Stent in Acute Myocardial Infarction) trial, which compared the high-dose bolus regimen of tirofiban with standard dose administration of abciximab administered immediately prior to PCI, revealed similar effects on myocardial perfusion, ST-segment elevation recovery and clinical outcomes between the two agents, and confirmed the safety of tirofiban when used in combination with drug-eluting stents in patients with STEMI undergoing primary PCI. These studies showed tirofiban to be a well tolerated and effective GP IIb/IIIa inhibitor. On the basis of the demonstrated benefits of the high-dose bolus regimen, tirofiban may be considered useful in the management of patients with STEMI.

Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: The most effective magnitude and timing of antiplatelet therapy is important in patients with acute ST-elevation myocardial infarction (STEMI). We investigated whether the results of primary coronary angioplasty (PCI) can be improved by the early administration of the glycoprotein IIb/IIIa blocker tirofiban at first medical contact in the ambulance or referral centre. METHODS: We undertook a double-blind, randomised, placebo-controlled trial in 24 centres in the Netherlands, Germany, and Belgium. Between June 29, 2006, and Nov 13, 2007, 984 patients with STEMI who were candidates to undergo PCI were randomly assigned to either high-bolus dose tirofiban (n=491) or placebo (N=493) in addition to aspirin (500 mg), heparin (5000 IU), and clopidogrel (600 mg). Randomisation was by blinded sealed kits with study drug, in blocks of four. The primary endpoint was the extent of residual ST-segment deviation 1 h after PCI. Analysis was by intention to treat. The trial is registered, number ISRCTN06195297. FINDINGS: 936 (95%) patients were randomly assigned to treatment after a prehospital diagnosis of myocardial infarction in the ambulance. Median time from onset of symptoms to diagnosis was 76 min (IQR 35-150). Mean residual ST deviation before PCI (10.9 mm [SD 9.2] vs 12.1 mm [9.4], p=0.028) and 1 h after PCI (3.6 mm [4.6] vs 4.8 mm [6.3], p=0.003) was significantly lower in patients pretreated with high-bolus dose tirofiban than in those assigned to placebo. The rate of major bleeding did not differ significantly between the two groups (19 [4%] vs 14 [3%]; p=0.36). INTERPRETATION: Our finding that routine prehospital initiation of high-bolus dose tirofiban improved ST-segment resolution and clinical outcome after PCI, emphasises that further platelet aggregation inhibition besides high-dose clopidogrel is mandated in patients with STEMI undergoing PCI.

ST-segment elevation resolution and outcome in patients treated with primary angioplasty and glucose-insulin-potassium infusion.

BACKGROUND: To evaluate the impact of adjunctive high-dose glucose-insulin-potassium (GIK) on ST-segment elevation resolution in patients with ST-segment elevation myocardial infarction (MI). METHODS: As part of a randomized controlled trial of GIK versus no GIK in patients treated with primary percutaneous coronary intervention (PCI) for ST-elevation MI in a tertiary referral center, we analyzed ST-segment elevation resolution. Paired electrocardiographic recordings (baseline and 3 hours after primary PCI) were available in 612 (65%) of 940 patients. RESULTS: We analyzed paired electrocardiograms of 310 patients randomized to GIK and 302 control patients. Baseline characteristics of the groups were comparable. Combined complete (>70%) and partial (30%-70%) resolution was more commonly observed in the GIK group (87%) when compared with the control group (78%), odds ratio 1.92 (95% CI 1.23-3.02, P = .004); 1-year mortality was lower in patients with combined complete and partial resolution compared with patients without resolution (3.8% vs 10.3%, P = .011). There was no difference in 1-year mortality between GIK and control patients (5.5% vs 4.3%, P = .58). CONCLUSIONS: In patients with ST-elevation MI treated with primary PCI, addition of GIK is associated with improved ST-segment elevation resolution. ST-segment elevation resolution is related to improved 1-year survival. No benefit of GIK on 1-year outcome was observed. Future trials should investigate whether GIK-induced improvement of ST-segment elevation resolution results in more favorable clinical outcome.

Achieved platelet aggregation inhibition after different antiplatelet regimens during percutaneous coronary intervention for ST-segment elevation myocardial infarction.

OBJECTIVES: To evaluate the extent of platelet aggregation inhibition in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), treated with different antiplatelet agents and dosages. BACKGROUND: The extent of platelet aggregation inhibition is an independent predictor of major cardiac events after elective PCI. In STEMI patients undergoing PCI, routine dose of antiplatelet agents may be associated with less effective platelet aggregation inhibition. METHODS: Patients were treated with clopidogrel before angiography and randomized to abciximab, tirofiban, high-dose tirofiban, or no glycoprotein (GP) IIb/IIIa inhibitor; GP IIb/IIIa inhibitor bolus, followed by maintenance infusion, was administered after angiography, but before PCI. Platelet aggregation inhibition was assessed before angiography, immediately after PCI, and 1 and 6 h afterwards. RESULTS: The total study population consisted of 112 patients. Platelet aggregation inhibition was variable for individuals and suboptimal for all agents, particularly in the periprocedural period. Only with high-dose tirofiban, mean periprocedural platelet aggregation inhibition exceeded 80%. Angiographic parameters after PCI were not different between the groups. No relationship was found between the level of platelet aggregation and parameters of PCI success (Thrombolysis In Myocardial Infarction frame count and myocardial blush grade), after combining the data from all four groups studied. CONCLUSIONS: Platelet aggregation inhibition in STEMI patients undergoing PCI, treated with antiplatelet agents, is variable and suboptimal for all agents and dosages studied. Only with high-dose tirofiban, mean periprocedural platelet aggregation inhibition exceeded 80%. However, no relationship of platelet aggregation inhibition and angiographic outcome was found in this patient cohort.

Glucose-insulin-potassium infusion as adjunctive therapy in myocardial infarction: current evidence and potential mechanisms.

BACKGROUND: In ST-elevation myocardial infarction (STEMI) there is conflicting evidence that mortality, morbidity and infarct size is reduced by therapies influencing myocardial metabolism, such as infusion of glucose-insulin-potassium (GIK). Several clinical trials with GIK have already provided insight into the magnitude of this effect. The aim of this article was to review randomized trials on adjunctive GIK infusion in STEMI. METHODS: Randomized trials comparing GIK with placebo or untreated controls in patients with STEMI were identified by electronic and manual searches. A systematic analysis of all data was performed, with regard to inclusion criteria, dose of GIK and additional use of reperfusion therapy. Thirteen trials, involving 4992 patients, were included. RESULTS: Overall, hospital mortality was 10.8% after GIK compared to 12.9% in controls (p = 0.02). GIK infusions were in particular effective when a high dose was used and if given as an adjunct to reperfusion therapy. In patients with heart failure on admission, GIK may have worse effects. In all analyzed trials, GIK infusion caused only mild adverse effects, although fluid overload may be a problem in certain patients. CONCLUSIONS: GIK may reduce mortality in patients with STEMI, particularly if a high dose is used and when GIK is administered as an adjunct to reperfusion therapy. However, all studies had a relative small sample size and additional large randomized trials are certainly needed before a definite conclusion can be made. The limited evidence currently available does not warrant GIK therapy to be applied in patients at the present time.