High Bolus Dose Research Articles

Short-term outcomes of tirofiban use in primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction (STEMI)

Introduction: When patients suffering from acute ST-elevation myocardial infarction (STEMI) undergo for percutaneous coronary intervention, tirofiban is mostly prescribed. Objective: In this study, patients undergoing for primary percutaneous coronary intervention for ST-segment elevation myocardial infarction were evaluated to determine the impact of a high bolus dose (HBD) of tirofiban on clinical outcomes. Methods: This study included 272 acute STEMI patients aged less than 79 years, admitted to the Hayatabad Medical Complex hospital, Peshawar from April 2021 to February 2022. According to the random number table, these patients were divided into four groups: the control group (n= 65), low-dose group (n=69), medium-dose group (n=71) and high-dose group (n=67). Results: After percutaneous coronary intervention, the high-dose group experienced higher rates of corrected TIMI frame count (CTFC), Thrombolysis In Myocardial Infarction (TIMI) grade 3, and total frequency of ST-segment resolution greater than 50% than the other 3 groups while compared to the low- dose group as well as control group, the CTFC were greater in the medium dose group. Furthermore, the LVEF of the medium-dose group was much better than that of the low-dose group. Compared to other groups, the left ventricular end-diastolic and end-systolic dimensions of the high-dose group remained suggestively elevated.

Primary Percutaneous Coronary Intervention with High-Bolus Dose Tirofiban: The FASTER (Favorite Approach to Safe and Effective Treatment for Early Reperfusion) Multicenter Registry.

Objectives To investigate the safety and clinical efficacy of tirofiban during primary percutaneous coronary interventions (pPCI). Background Gp IIb/IIIa inhibitors (GPI) use during pPCI has declined over years, mainly for the increased hemorrhagic risk associated to their use and for the availability of potent, fast-acting oral antiplatelet drugs. However, several pharmacodynamic studies showed suboptimal platelet inhibition with P2Y12-blockers, such as prasugrel or ticagrelor. Methods Patients with ST-segment elevation myocardial infarction (STEMI) undergoing pPCI were prospectively enrolled in a multicenter registry conducted in high-volume centers in Italy. All patients received intraprocedural tirofiban. The primary safety endpoint was the occurrence of in-hospital bleedings according to the Bleeding Academic Research Consortium definition. In-hospital major adverse coronary events (MACE, defined as death, reinfarction, stent thrombosis, and target vessel revascularization), final TIMI flow, myocardial blush grade, and ST-segment resolution were also evaluated. Results A total of 472 patients (mean age 61 ± 11 years, 83% males) were enrolled in 16 Italian centers from October 2015 to June 2018. Mean basal thrombus grade score was 3.47 ± 1.25. PCI was performed by transradial approach in 88% of patients. We observed a very low rate of 30 days BARC bleedings (2.1%) and MACE (0.8%). Complete (>70%) ST-segment resolution was observed in 67% of patients. Conclusions In the FASTER registry, the use of tirofiban during primary PCI, performed with a transradial approach in most cases, in patients with high thrombus burden was associated with high rates of complete ST-segment resolution and low rates of in-hospital bleeding and MACE.

Exercise May Ameliorate the Detrimental Side Effects of High Vitamin D Supplementation on Muscle Function in Mice.

ABSTRACTVitamin D is commonly prescribed to normalize deficiencies and to treat osteoporosis. However, the effect vitamin D supplements have on skeletal muscle health is equivocal. Although vitamin D is known to play a role in the various processes that maintain muscle integrity and function, recent studies utilizing high bolus dose vitamin D supplementation has demonstrated an increased risk of falls. Thus, the aim of this study was to investigate the effects of high vitamin D supplementation on skeletal muscle function with and without exercise enrichment. Four‐week old C57BL/10 mice (n = 48) were separated into either normal vitamin D (1500 IU/kg diet; unsupplemented) or high vitamin D (20,000 IU/kg diet; supplemented) treatment groups. Each dietary group was further separated into interventional subgroups where mice either remained sedentary or received exercise‐enrichment for 8 weeks in the form of voluntary running. Following the intervention period, whole body in vivo and ex vivo contractile analysis were performed. High vitamin D supplementation decreased force production in the slow‐twitch soleus muscles of sedentary mice (p < .01); however, exercise normalized this effect. Eight weeks of exercise did not improve fatigue resistance of the extensor digitorum longus (EDL) or soleus muscles in unsupplemented mice, likely due to low levels of activation in these muscles. In contrast, fatigability was improved in the EDL (p < .01) and even more so in the soleus (p < .001) in the supplemented exercise‐enriched group. Our data highlights that increasing vitamin D levels above normal reduces postural muscle force as seen in the soleus. Thus, unnecessary vitamin D supplementation may contribute to the increased risk of falls observed in some studies. Interestingly, when vitamin D supplementation was combined with exercise, force production was effectively restored, and fatigue resistance improved, even in muscles lowly activated. Regular exercise may modulate the effects of vitamin D on skeletal muscle, and be recommended for individuals receiving vitamin D supplements. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Effect of Upstream High Bolus Dose of Tirofiban in Primary PCI for the Patients With STEMI on Short Term Outcome

Effect of Upstream High Bolus Dose of Tirofiban in Primary PCI for the Patients With STEMI on Short Term Outcome

Cyp2b-Knockdown Mice Poorly Metabolize Corn Oil and Are Age-Dependent Obese.

We previously made a RNAi-based cytochrome P450 2b (Cyp2b)-knockdown (Cyp2b-KD) mouse to determine the in vivo role of the Cyp2b subfamily in xenobiotic detoxification. Further studies reported here indicate a role for Cyp2b in unsaturated fatty-acid (UFA) metabolism and in turn obesity. Mice were treated intraperitoneally (i.p.) with 100 μL corn oil as a carrier or the potent Cyp2b-inducer 3,3',5,5'-Tetrachloro-1,4-bis(pyridyloxy)benzene (TCPOBOP (TC)) dissolved in corn oil. Surprisingly, female Cyp2b-KD mice but not male mice showed increased liver lipid accumulation. Male Cyp2b-KD mice had higher serum triacylglycerols, cholesterol, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) than wildtype (WT) mice; females had higher cholesterol, LDL, and HDL. Thus, Cyp2b-KD mice are unable to clear a high bolus dose of corn oil, potentially because the Cyp2b-KD mice were unable to metabolize the UFA in the corn oil. Therefore, WT and Cyp2b-KD mice were housed for 35 weeks and necropsies performed to test whether Cyp2b-KD mice develop age onset obesity. Cyp2b-KD mice exhibited a significant increase in body weight caused by an increase in white adipose tissue deposition relative to WT mice. Serum cholesterol, triacylglycerol, LDL, and VLDL were significantly greater in 35-week-old Cyp2b-KD males compared to WT males; only serum triacylglycerol and LDL were higher in females. In conclusion, changes in Cyp2b expression led to perturbation in lipid metabolism and depuration in Cyp2b-KD mice. This suggests that Cyp2b is more than a detoxification enzyme, but also involved in the metabolism of UFA, as Cyp2b-KD mice have increased the body weight, fat deposition, and serum lipids.

O-38 The influence of body composi-tion on paediatric drug dosing

Background Body size is an important patient covariate in scaling drug doses. While total body weight has been the most commonly used size descriptor, fat free mass (FFM) has been advocated as an alternative size descrip-tor to scale drug doses in adults and children. FFM de-scribes the non-fat component of the body thus having a better correlation with the metabolic rate and drug clear-ance (CL). The aim of this work was to evaluate FFM as a covariate in a PK model of unfractionated heparin (UFH) developed in a paediatric population. Methods Data from 64 infants and children who re-ceived 75–100 IU/kg of UFH during cardiac angiography were analysed. Four plasma samples were collected at baseline and at 15, 30, 45, and 120 min post-dose. UFH concentration (231 measurements) was quantified using a protamine titration assay. UFH effect (164 mea-surements) was quantified using activated partial throm-boplastin time (aPTT). A PKPD model was fitted to the data using the non-linear mixed effects modelling (in NONMEM v7.2). Various patient covariates such as age, weight (Wt), body surface area, and FFM were tested. The final model was evaluated using the likelihood ratio test and visual predictive checks (VPCs). Results A one-compartment model with linear elimina-tion provided the best fit for the dose-concentration data. Wt and FFM had substantial influence on model fit; FFM was preferred statistically. A linear model provided the best fit for the concentration-effect data using the PPP and D sequential estimation method. Censored PD data (above the upper limit of quantification) were accounted for us-ing likelihood estimation. The PKPD model performed well using visual predictive checks. Conclusion A PKPD model to describe the time-course of UFH effect was developed in a paediatric population which received a high single bolus dose. FFM was shown to describe drug disposition well and can potentially be used in dose calculation after appropriate evaluation.

Optimizing the Dose of Erythropoietin Required to Prevent Acute Ventilation-Induced Cerebral White Matter Injury in Preterm Lambs

Erythropoietin (EPO) is being trialed in preterm neonates for neuroprotection. We have recently demonstrated that a single high bolus dose (5,000 IU/kg) of recombinant human EPO amplified preterm lung and brain ventilation-induced injury. We aimed to determine the optimal dose of EPO to reduce ventilation-induced cerebral white matter inflammation and injury in preterm lambs. Lambs (0.85 gestation) were ventilated with an injurious strategy for 15 min followed by conventional ventilation for 105 min. Lambs were randomized to no treatment (VENT; n = 8) or received a bolus dose of EPO (EPREX®): 300 IU/kg (EPO 300; n = 5), 1,000 IU/kg (EPO 1,000; n = 5), or 3,000 IU/kg (EPO 3,000; n = 5). Physiological parameters were measured throughout the study. After 2 h, brains were collected for analysis; real-time quantitative polymerase chain reaction and immunohistochemistry were used to assess inflammation, cell death, and vascular leakage in the periventricular and subcortical white matter (PVWM; SCWM). Molecular and histological inflammatory indices in the PVWM were not different between groups. EPO 300 lambs had higher IL-6 (p = 0.006) and caspase-3 (p = 0.025) mRNA expression in the SCWM than VENT lambs. Blood-brain barrier (BBB) occludin mRNA levels were higher in EPO 3,000 lambs in the PVWM and SCWM than VENT lambs. The number of blood vessels with protein extravasation in the SCWM was lower in EPO 1,000 (p = 0.010) and EPO 3,000 (p = 0.025) lambs compared to VENT controls but not different between groups in the PVWM. Early administration of EPO at lower doses neither reduced nor exacerbated cerebral white matter inflammation or injury. 3,000 IU/kg EPO may provide neuroprotection by improving BBB integrity.

Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories

Inhalation is the main pathway of ZnO exposure in the occupational environment but only few studies have addressed toxic effects after pulmonary exposure to ZnO nanoparticles (NP). Here we present results from three studies of pulmonary exposure and toxicity of ZnO NP in mice. The studies were prematurely terminated because interim results unexpectedly showed severe pulmonary toxicity. High bolus doses of ZnO NP (25 up to 100 μg; ≥1.4 mg/kg) were clearly associated with a dose dependent mortality in the mice. Lower doses (≥6 μg; ≥0.3 mg/kg) elicited acute toxicity in terms of reduced weight gain, desquamation of epithelial cells with concomitantly increased barrier permeability of the alveolar/blood as well as DNA damage. Oxidative stress was shown via a strong increase in lipid peroxidation and reduced glutathione in the pulmonary tissue. Two months post-exposure revealed no obvious toxicity for 12.5 and 25 μg on a range of parameters. However, mice that survived a high dose (50 μg; 2.7 mg/kg) had an increased pulmonary collagen accumulation (fibrosis) at a similar level as a high bolus dose of crystalline silica. The recovery from these toxicological effects appeared dose-dependent. The results indicate that alveolar deposition of ZnO NP may cause significant adverse health effects.

English

It was always been a matter of great-controversy regarding the dosage protocol of anti- snake venom (ASV) in the management of snake envenomation. The only definitive treatment of poisonous snake bite is ASV administration. MATERIAL AND METHODS: This study was carried out for a period of two years. All patients of neuroparaplytic snake bite who presented to the emergency department were included in this prospectively study. RESULTS: Fifty eight patients of neurotoxic snake bite became eligible for the study over a period of 2 yrs. By using chi-square test, the outcomes in low and high bolus dose group were statistically non-significant (P>0.05). Statistical analysis showed no significant difference in both groups. From this study it can be firmly concluded that low dose ASV is as effective as high dose in treatment of neurotoxic snake bite.

Impact of upstream high bolus dose tirofiban on left ventricular systolic function in patients with acute anterior myocardial infarction treated by primary coronary intervention

Background: Glycoprotein IIb/IIIa inhibitor therapy during primary percutaneous coronary intervention (PCI) decreases the incidence of major adverse cardiac events. Aim: To study the impact of high bolus dose tirofiban on left ventricular ejection fraction in patients with acute anterior ST segment elevation MI treated with primary PCI. Patients and methods: Forty patients presenting to Ain Shams University, and specialized hospitals with the diagnosis of acute anterior STEMI were treated with primary PCI. Twenty patients were given conventional intravenous bolus dose tirofiban (10 lg/kg) upstream prior to primary angio- plasty and twenty patients were given intravenous high bolus dose tirofiban (25 lg/kg) upstream prior to PCI. In-hospital follow up was done including echocardiography, and serial cardiac enzymes in addition to clinical follow up for MACE and bleeding complications. Results: Successful primary angioplasty was attained in all patients. The LV systolic function was significantly better in the high bolus dose group in comparison to the conventional bolus dose groups (48% vs 41%, P 0.05). Both regimens were safe and the bleeding complications were minimal and did not differ between the study groups. Conclusion: In patients presenting with acute anterior STEMI and treated with primary PCI, the high bolus dose tirofiban given intravenously upstream prior to PCI seems to be a safe and effective regimen to achieve a better left ventricular ejection fraction in comparison to the conventional bolus dose regimen, without increasing the risk of bleeding. a 2014 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology.

The effect of high doses of remifentanil in brain near-infrared spectroscopy and in electroencephalographic parameters in pigs

ObjectiveTo study the effects of a high remifentanil bolus dose on pig’s electroencephalographic indices and on brain regional and global oxygenation. Study designProspective experimental study. AnimalsTwelve healthy Large-White male pigs, age 3 months and weight 26.2 ± 3.6 kg. MethodsAnaesthesia was induced with intravenous propofol 4 mg kg−1, then maintained with constant rate infusions of propofol (15 mg kg−1 hour−1) and remifentanil (0.3 μg kg−1 minute−1). Following instrumentation, all pigs received a 5 μg kg−1 remifentanil bolus. The responses of jugular venous oxygen saturation, cardiac output and cerebral oxygen saturation to the remifentanil bolus were studied. The Bispectral index, spectral edge frequency 95%, total power, approximate entropy and permutation entropy were also studied. Repeated measures anova and Pearson correlation were used to analyze the effect of remifentanil bolus on these variables until 5 minutes after the bolus. ResultsCardiac output and cerebral oxygen saturation decreased significantly after the remifentanil bolus from 4.6 ± 0.9 to 3.8 ± 1.0 L minute−1 and from 65 ± 6 to 62 ± 1% (p < 0.05), respectively. No significant changes were observed in the jugular venous oxygen saturation (p > 0.05) nor in any of the electroencephalogram derived indices (p > 0.05). Correlation analysis revealed strong positive significant correlations between cerebral oxygen saturation and cardiac output (r = 0.82, p < 0.001) and between cerebral oxygen saturation and approximate entropy (r = 0.65, p < 0.001). Conclusions and Clinical RelevanceThe effect caused by the remifentanil bolus on the brain oxygenation seems to be better reflected by the cerebral oxygen saturation than the jugular venous oxygen saturation. The effect of remifentanil on the electroencephalogram may not be reflected in indices derived from the electroencephalogram, but the potential of the approximate entropy in reflecting changes caused by opioids on the electroencephalogram should be further investigated.

Four-Factor Prothrombin Complex Concentrate (4-PCC) Effectively Reverses Edoxaban Induced Bleeding In a Rabbit Model Of Acute Injury

This study was designed to determine whether the four-factor Prothrombin Complex Concentrate (4-PCC) Beriplex® P/N (Kcentra™) can effectively reverse bleeding following edoxaban administration in a rabbit kidney injury model.The oral direct and selective factor Xa inhibitor edoxaban (Daiichi Sankyo) is currently available in Japan for the prophylaxis of venous thromboembolism (VTE) in patients undergoing major orthopedic surgery and is undergoing investigation in phase III trials for the prevention of stroke in patients with atrial fibrillation and the treatment and secondary prevetion of VTE. The primary complication of any available anticoagulant therapy is the risk of bleeding. Rapid reversal of anticoagulation may be necessary in patients requiring emergency treatment due to uncontrolled bleeding. PCCs are frequently used to reverse the effect of vitamin K antagonists such as warfarin and have also been suggested to be potentially effective in reversing the effects of the new oral anticoagulants.The present study was therefore designed to further investigate the ability of 4-PCC to reverse the anticoagulant action of edoxaban using an in vivo rabbit model of acute bleeding.Animals were treated with a high intravenous bolus dose of edoxaban (1200 µg/kg) leading to increased and prolonged bleeding following standardized kidney injury compared to vehicle administration. Parallel monitoring of biomarkers of haemostasis showed that edoxaban treatment resulted in the prolongation of prothrombin time (PT), activated partial thromboplastin time, and whole blood clotting time (WBCT), and affected the thrombin generation parameters thrombin peak, endogenous thrombin potential (ETP), lagtime and time to peak. Subsequent administration of the 4-PCC (25-75 IU/kg) resulted in a dose-dependent reversal of edoxaban induced bleeding as indicated by reduced time to haemostasis and total blood loss. Both parameters achieved statistical significance compared to placebo at the 4-PCC dose of 50 IU/kg under fully blinded study conditions. The biomarkers correlating best with 4-PCC mediated edoxaban anticoagulation reversal included PT, WBCT and ETP.In summary, 4-PCC treatment effectively decreased edoxaban induced hemorrhage in an animal model of acute bleeding at clinically relevant dose levels. Disclosures:Herzog:CSL Behring GmbH: Employment. Kaspereit:CSL Behring GmbH: Employment. Krege:CSL Behring GmbH: Employment. Pragst:CSL Behring GmbH: Employment. Morishima:Daiichi Sankyo: Employment. Schulte:CSL Behring GmbH: Employment. Dickneite:CSL Behring GmbH: Employment.

Effects of Tirofiban Maintenance Duration on Myocardial Perfusion Defect Severity in Anterior Myocardial Infarction

Percutaneous coronary intervention (PCI) does not often produce optimal results, despite restoration of coronary blood flow at myocardial recovery, because of impaired microvascular perfusion. This study aimed to investigate and evaluate with (99m)Tc-sestamibi scan whether the results of PCI can be changed by maintenance infusion of tirofiban for 24 or 48 h in patients presenting with anterior ST-elevation myocardial infarction (STEMI). The study included 84 patients with anterior STEMI who were candidates for primary PCI and whose occlusion was in the proximal or mid-left anterior descending artery. Patients were given 25 μg/kg/3 min tirofiban and randomized to receive maintenance infusion at 0.15 μg/kg/min for 24 or 48 h. A resting (99m)Tc sestamibi scan was performed on the 5th day post-procedure before discharge. The primary efficacy endpoint was a patient's score on a 5-point scoring system for perfusion defect severity. Major adverse cardiac events (MACE) were defined as death from any cause, re-infarction, and clinically driven target-vessel revascularization within the first 6 months. Baseline characteristics of the patients were similar in the two infusion groups (n = 42 per group). There was no significant difference in the symptom onset-to-presentation time or door-to-balloon time between the two groups. With the exception of basal anteroseptal and basal anterior segments, significant reductions were obtained on the 5-point scoring system for perfusion defect severity in segments and in the summed rest scores. No significant differences were observed between the two groups in the incidence of MACE at 6 months. The safety profile did not differ between 24 and 48 h infusions of tirofiban. The use of tirofiban, when administered at a high bolus dose and maintained for 48 h, was safe and significantly reduced perfusion defect severity in patients with anterior STEMI presenting early after symptom onset and undergoing primary PCI.

Short‐term Effect of Upstream Administration in Comparison to Deferred Injection of Tirofiban on Patients with Acute ST‐Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

High bolus dose tirofiban has been demonstrated to provide greater inhibition of platelet aggregation, but the most appropriate timing of its administration remains unknown. To evaluate the efficacy of upstream vs. deferred administration of tirofiban in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI) on clinical outcomes. The 660 patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention were divided into upstream (n=330, administration of tirofiban to all patients in emergency room) and deferred groups (n=330, treatment of patients with large thrombus burden or no-reflow phenomenon in cardiac catheterization laboratory during PCI). The primary end-points were death, nonfatal myocardial infarction (MI), stent thrombosis (ST), revascularization of targeted vessels (TVR) or major adverse cardiac events (MACE) at 1 month and 6 months following PCI, with safety end-point at 7 days. Compared with that of the deferred group, there was a significant increase of left ventricular ejection fraction (LVEF) in the upstream group within 7 days (55.5 ± 6.6% vs. 54.6 ± 7.9%, P=0.011). The rates of 7-day and 1-month MACE in the upstream group were lower than those in the deferred group (1.5% vs. 4.2%, 3.3% vs. 7.0%, P=0.037 and 0.034, respectively). However, there were higher tendencies for major and minor bleedings in the upstream group (1.8% vs. 0.9%, 2.7% vs. 1.5%, P=0.315 and 0.280, respectively). To the Chinese patients with acute myocardial infarction undergoing primary PCI, upstream administration of tirofiban was slightly superior to deferred injection for short-term clinical outcomes.

Platelet aggregation inhibition by Eptifibatide versus high dose Tirofiban during primary percutaneous interventions

Abstract Background Platelet aggregation occurs as a central role in acute coronary syndrome (ACS), and glycoprotein GP IIb/IIIa inhibitors may enhance the benefits expected from early recanalisation. Aim To compare the degree of platelet aggregation inhibition achieved by Eptifibatide versus high dose Tirofiban, and its clinical effects regarding myocardial reperfusion parameters: myocardial blush grade (MBG) and ST-segment resolution (STR) >70%, and regarding peri procedural complications, bleeding and major adverse cardiac events (MACE). Methods Between the period of June 2010–January 2012, 46 patients with acute myocardial infarction whose symptom onset is within 12 h of presentation and ECG showing ST-segment elevation 1 mm in two contiguous limb leads or 2 mm in two contiguous precordial leads or acute left bundle branch block were included. Exclusion criteria were active bleeding, thrombocytopenia, bleeding diathesis, anticoagulation or thrombolitics, recent major surgery or stroke, cardiogenic shock, and pregnancy. Patients were randomized alternatively (1:1) into two groups before primary percutaneous cardiac intervention (PCI) to receive the specific glycoprotin IIb/IIIa inhibitor as follows: (I) Tirofiban group: intravenous high bolus dose of 25 mcg/kg over 3 min followed by maintenance infusion of 0.15 mcg/kg/min. (II) Eptifibatide group: intravenous two boluses 10 min apart (each one is 180 mcg/kg) followed by maintenance of 2 mcg/kg/min. Platelet aggregation inhibition was measured by light transmission aggregometer, angiographic assessment was done before and after final interventions for TIMI flow and myocardial blush grade before and after the procedure. Electrocardiographic assessment standard 12-lead ECG on admission, immediately after PCI. Resolution of ST segment elevation was expressed as a percentage of the initial ST segment elevation. Resolution of ⩾70% was defined as complete resolution. Clinical safety assessment was done in terms of the incidence of: bleeding complications and major adverse cardiac events (MACE): death, non-fatal myocardial infarction (MI), and target vessel revascularization (TVR). Results The total patients in our study included 46 patients, 40 males (87%) and six females (13%) with a mean age of 55 ± 10, Tirofiban group: included 23 patients, 19 males (82.5%) and four females (17.4%) with a mean age of 57 ± 9.65. Eptifibatide group: included 23 patients, 21 males (87%) and two females (8.7%) with a mean age of 53.48 ± 8.6. Platelet aggregation inhibition during PCI was significantly correlated with STR (p 0.013, r 0.71). The cut-off point for platelet aggregation inhibition as a predictor of STR >70% was 89.5% (sensitivity 92.3%, specificity 69.2%, PPV 75% and NPV 10%, AUC 0.87). Platelet aggregation inhibition during PCI was positively correlated with MBG (p 0.045, r 0.453). The cut-off point for platelet aggregation inhibition as a predictor of MBG 2–3 was 87.5% (sensitivity 73.6%, specificity 66.7%, PPV 93.9% and NPV 76.9%, AUC 0.81). Platelet aggregation inhibition 60 min after bolus was (93.57 ± 2.07% versus 87.62 ± 3.2%, p 70% (56.22% versus 39.13%, p 0.005) in Eptifibatide versus Tirofiban group, respectively. There was no significant statistical difference regarding thrombocytopenia (46.73 ± 41.48 versus 39.04 ± 34.41, p 0.37), minor bleeding (17.4% versus 21.7%, p 0.5), major bleeding (0% versus 4.3%, p 0.5), post procedural infarction (0% versus 17.4%, p 0.12), TVR (0% versus 8.7%, p 0.24), MACE and 30 days mortality (4.3% versus 13%, p 0.34) in Eptifibatide versus Tirofiban group, respectively. Conclusions • Platelet aggregation inhibition during PCI was significantly correlated with STR and MBG. Platelet aggregation inhibition cut-off point as a predictor of STR >70% was 89.5%, and as a predictor of MBG 2–3 was 87.5%. • Eptifibatide achieves better platelet aggregation inhibition 60 min after bolus and 6 h after PCI than high dose Tirofiban. • Eptifibatide is associated with better myocardial perfusion as indicated by post procedural mean MBG and STR >70% than high dose Tirofiban. • There was no significant differences between Eptifibatide and high dose Tirofiban regarding thrombocytopenia, major or minor bleeding, MACE and 30 days mortality.

JDSA Journal Abstracts

JDSA Journal Abstracts

High Bolus Tirofiban vs Abciximab in Acute STEMI Patients Undergoing Primary PCI - The Tamip Study.

Background:Primary percutaneous coronary intervention (PCI) has been shown to be an effective therapy for patients with acute myocardial infarction (MI). Glycoprotein (GP) IIb/IIIa receptor blockers reduce thrombotic complications in patients undergoing PCI. Most available data relate to Reopro, which has been registered for this indication. GP IIb/IIIa reduce unfavorable outcome in U/A and non ST-elevation myocardial infarction (STEMI) patients. Only few studies focused on high dose Aggrastat for STEMI patients in the emergency department (ED) before PCI. The aim is to increase the patency during the time awaiting coronary angioplasty in patients with acute MI.Objectives:To study the effect of upfront high bolus dose (HDR) of tirofiban on the extent of residual ST segment deviation 1 hour after primary PCI and the incidence of TIMI 3 flow of the infarct-related artery (IRA).Materials and Methods:A randomized, open label, single center study in the ED. A total of 90 patients with acute ST-elevation MI, diagnosed clinically by ECG criteria (ST segment elevation of >2 mm in two adjacent ECG leads), and with an expectation that a patient will undergo primary PCI. Patients were aged 21-85 years and all received heparin 5000 u, aspirin 160 mg, and Plavix 600 mg. Patients were divided in two groups (group I: triofiban high bolus vs group II: Reopro) with 45 patients in each group. In group I, high bolus triofiban 25 mcg/kg over 3 min was started in the ED with maintenance infusion of 0.15 mcg/ kg/min continued for 12 hours and transferred to cath lab for PCI. Patients in group II were transferred to cath lab, where a standard dose of Reopro was given with a bolus of 0.25 mcg/kg and maintenance infusion of 0.125 mcg/kg/min over 12 hours.Results:ST segment resolution and TIMI flow were evaluated in both groups before and after PCI. Thirty-five patients (78%) enrolled in group I and 29 patients (64%) in group II had resolution of ST segment (P-value 0.24). Twenty-one patients (47% group I) vs 23 patients (51% group II) with P-value 0.83 achieved TIMI 0 flow. Twenty-four patients (53% group I) compared with 22 patients (49% group II) with P-value 0.83 had TIMI 1 to 3 flow before PCI. TIMI 3 flow was achieved in 40 patients (89% group I) compared with 38 patients (84% group II) with P-value 0.76.Conclusion:In this study there was a trend toward better ST segment resolution and patency of IRA (i.e., improved TIMI flow) in patients given high bolus dose Aggrastat in the ED. Larger studies are needed to confirm this finding.

The effect of pre‐hospital glycoprotein IIb–IIIa inhibitors on angiographic outcome in STEMI patients who are candidates for primary PCI

Aim of this study was to assess the effect of early initiation of high bolus dose tirofiban on top of dual antiplatelet therapy on angiographic outcome before and after primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infraction patients. Glycoprotein IIb/IIIa inhibitors are effective inhibitors of platelet aggregation, and have shown to reduce thrombotic complications in patients undergoing PCI. This is a pre-specified angiographic analysis of the On-TIME 2 trial (N = 984) and its open label run-in phase (N = 414). All angiographic parameters, including quantitative coronary angiography (QCA) were performed in an independent angiographic core lab. Of the 1,398 patients, 709 patients (50.7%) were randomized to pre-hospital tirofiban. An open infarct related vessel (TIMI 2 or 3 flow) at initial angiography was more often present in the tirofiban group as compared to the no tirofiban group (58.3% vs. 49.7%, P = 0.002). Tirofiban also reduced initial thrombus burden (P for trend = 0.035) as well as thrombus grade 5 (46.9% vs. 54.3%, P = 0.016) and showed a trend toward a reduction in large thrombus burden (LTB) (69.4% vs. 74.5%, P = 0.055). After PCI, a trend towards a lower corrected TIMI frame count (cTFC) in the tirofiban group was found. A significant interaction was found with time of initiation of study drug, with highest efficacy of tirofiban when given within 76 min after symptom onset, with a significantly lower cTFC after PCI (21.9 ± 17.6 vs. 23.9 ± 18.5, P = 0.008, P for interaction P = 0.006). In patients undergoing primary PCI, pre-hospital administration of tirofiban reduces initial thrombus burden and improves initial patency of the infarct related vessel before PCI. Initiation of tirofiban seems to be most effective when given very early after the onset of symptoms; however, this finding needs confirmation in other studies. The On-TIME 2 trial is registered, at http://isrctn.org, number ISRCTN06195297.

The Impact of Age on Effects of Pre-hospital Initiation of High Bolus Dose of Tirofiban Before Primary Angioplasty for ST-Elevation Myocardial Infarction

Glycoprotein IIb/IIIa inhibitors are favourable in ST-elevation myocardial infarction (STEMI) patients, and the additional value of early pre-hospital high bolus dose tirofiban has recently been established. The aim of this study was to determine the impact of age on myocardial reperfusion and clinical outcomes of pre-hospital administration of high bolus dose tirofiban. This is a pre-specified sub-analysis of the multicentre, double-blind, placebo-controlled, randomised On-TIME 2 trial and it's open label phase. The primary endpoint was mean residual ST segment deviation 1h after primary PCI and was evaluated in three age groups. Of the 466 patients in the highest tertile (≥68years), median age was 74.4years (IQR 71.3-78.6years) and 231 (50%) were randomised to tirofiban. Mean residual ST segment deviation 1 h after PCI was significantly lower in elderly patients pre-treated with tirofiban compared to elderly patients without tirofiban pre-treatment (4.2 ± 5.2mm vs 6.4 ± 7.5mm, p = 0.001). Furthermore, elderly patients pre-treated with tirofiban had a non-significantly higher rate of 30-day major or minor bleeding compared to elderly patients without tirofiban pre-treatment (14.2% vs 9.0%, p = 0.088). 30-day net adverse clinical events in elderly patients with- or without tirofiban was not significantly different (11.9% vs 15.2%, p = 0.300). The effect of pre-hospital initiation of high bolus dose tirofiban on myocardial reperfusion, as determined by ST-segment resolution is highest in the elderly patients. However, this was associated with a trend towards more bleeding complications, resulting in a balanced clinical effect after 30-day follow-up. Future studies should evaluate whether the elderly STEMI patient may benefit from highly effective and safer antiplatelet therapy.

Comparison between the effect of intracoronary bolus of tirofiban versus eptifibatide as adjunctive antiplatelet therapy on the outcome of primary coronary intervention in patients with acute anterior ST segment elevation myocardial infarction

Primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) has been shown to be the preferred reperfusion strategy. Adjunctive GP IIb/IIIa inhibitors improve the outcome in patients with ST-elevation myocardial infarction undergoing primary percutaneous intervention (PCI). Intracoronary (IC) GP IIb/IIIa bolus application results in high local drug concentrations and may be more effective than a standard intravenous bolus. It remains unclear which of the two available GP IIb/IIIa inhibitors in Egypt eptifibatide and tirofiban would be of great benefit when used as IC bolus. Sixty patients with anterior STEMI undergoing primary PCI in Ain Shams University Hospitals were randomized to either intracoronary eptifibatide (Integrilin®) double bolus dose (n = 30) or IC tirofiban (Aggrastat®) high bolus dose (n = 30) with subsequent 12–24 h intravenous infusion of the same GP IIb/IIIa inhibitors. The primary end point was achievement of TIMI III flow and at least MBG II or III. The secondary end points were in hospital occurrence of major adverse cardiac events (MACE) including death, recurrent ischemia and target vessel revascularization, successful ST segment resolution and preservation of systolic function. The safety endpoint was in hospital occurrence of any major or minor bleeding according to TIMI classification. All baseline characteristics including demographics, risk factors, clinical data, time of chest pain, basic ECG data and angiographic data were statistically nonsignificant among both study groups. Regarding primary endpoint: No statistically significant difference in achievement of TIMI III flow, but achievement of MBG II and III indicating successful perfusion was much higher in eptifibatide group (76.6%) than tirofiban group (36.6%) p = 0.005. Regarding secondary end points: No statistically significant difference in rate of in-hospital MACE among both groups with one death (3.3%) in each group, but less recurrent ischemia in eptifibatide group (0%) than tirofiban group (16.7%) p = 0.026., also successful ST segment resolution as indirect sign of successful reperfusion (70.9 ± 11.3 versus 59.7 ± 9) and systolic function preservation (EF of 46.6 ± 5.5 versus 39.9 ± 6) were significantly better in eptifibatide group p < 0.001. Regarding safety end points: There was no difference in TIMI major bleeding among both groups but TIMI minor bleeding had occurred in tirofiban group (33.3%) more than eptifibatide group (0%) p < 0.001. In patient with anterior STEMI treated by primary PCI IC eptifibatide was superior to IC tirofiban in terms of successful perfusion, less recurrent ischemia, more ST segment resolution, and systolic function preservation with less TIMI minor bleeding.