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To investigate the potential effect of intracoronary administration of the glycoprotein IIb/IIIa inhibitor tirofiban on the microvascular obstruction (MVO) assessed by cardiac magnetic resonance (CMR) imaging compared to the intravenous route in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI). Two hundred eight patients were randomized into two groups (tirofiban i.v. and tirofiban i.c.). CMR was completed within 3-7 days after ST-segment-elevation myocardial infarction. One hundred thirty-two patients had a follow-up CMR at 6 months after discharge. The primary end point was the CMR measurements including myocardium strain, myocardial perfusion index, final infarct size, prevalence and extent of MVO, and the change of left ventricular end-diastolic volume (LVEDV) at six months follow-up. The second endpoint was major adverse cardiovascular events (composite of all-cause death, nonfatal reinfarction and congestive heart failure) in one year. The MVO prevalence and extent [56% versus 36%, p = 0.004; 2.08 (IQR: 1.18-5.07) g versus 1.68 (IQR: 0.30-3.28) g, p = 0.041] showed a significant difference between the intravenous and intracoronary groups. Global left ventricular peak longitudinal strain was significantly different in intracoronary groups compared to intravenous groups, - 12.5 [IQR: - 13.4 to - 10.9] versus - 12.3 [IQR: - 13.4 to - 10.4], respectively (P = 0.042). Infarcted myocardial perfusion index was significantly different in intracoronary groups compared to intravenous groups, 0.11 [IQR: 0.08 to 0.15] versus 0.09 [IQR: 0.07 to 0.14], respectively (P = 0.026). Intracoronary tirofiban was associated with a higher change in LVEDV compared with intravenous group (- 10.2% [IQR: - 13.7% to - 2.6%] versus 1.3% [IQR: - 5.6% to 6.1%], p < 0.001). Intracoronary tirofiban application showed no benefit on the occurrence of major adverse cardiovascular events during follow-up compared to intravenous administration. This CMR study in ST-segment-elevation myocardial infarction patients showed a benefit in MVO and left ventricular remodeling for intracoronary tirofiban administration compared to intravenous administration in patients undergoing PCI.

Background: For patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), the efficacy and safety of novel P2Y 12 antagonists, including prasugrel or ticagrelor, has not been established relative to that of the clopidogrel-based triple-antiplatelet treatments (TAPTs; in combination with glycoprotein IIb/IIIa inhibitor). The present meta-analysis evaluated the efficacy and safety of prasugrel- or ticagrelor-based TAPTs relative to that of clopidogrel TAPTs in patients with STEMI undergoing PCI., Methods: The databases PubMed, Embase, and Cochrane's Library were systematically searched for relevant randomized controlled trials concerning prasugrel or ticagrelor (test) relative to clopidogrel (control). Depending on heterogeneity, studies were pooled with a random effects or a fixed effects model. Outcomes of blood flow after PCI were evaluated, including TIMI (thrombolysis in myocardial infarction), bleeding events, and major adverse cardiovascular events (MACEs)., Results: Seven studies comprising 11,874 patients conformed to the inclusion criteria. The pooled results with the fixed effects model indicated that after PCI patients in the prasugrel or ticagrelor groups were as likely as those treated with clopidogrel to achieve TIMI grade 3 flow or experience bleeding events. However, compared with the control, the test groups had significantly less risk of MACE (OR: 0.81, 95% CI: 0.70-0.94, P = 0.004), especially at the 1-year follow-up (OR: 0.79, 95% CI: 0.66-0.95, P = 0.01)., Conclusions: A prasugrel- or ticagrelor-based TAPT may reduce the rate of MACEs, without increasing bleeding in STEMI patients undergoing PCI. However, due to the limited RCT studies and variations in study weight, results of this meta-analysis should be confirmed in a large RCT with adequate sample size and follow-up duration.

Background: We conducted a randomized controlled trial to investigate whether an additional platelet inhibition with tirofiban would reduce the extent of myocardial damage and prevent periprocedural myonecrosis in patients with Non-ST-elevation acute coronary syndrome (NSTE-ACS) with a high residual platelet activity (HPR)., Methods: Patients with an HPR, defined as P 2 Y 12 reaction unit (PRU) > 230, were randomly assigned to group A (tirofiban treatment, n = 30) or C1 (n = 30) and patients without an HPR to C2 (n = 78). Periprocedural myocardial damage was assessed using the area under the curve (AUC) of serial cardiac enzyme levels from the time of the procedure to post-36 h. Periprocedural myonecrosis incidence was evaluated., Results: The troponin I AUC was not different between the groups (197.2 [41.5395.7], 37.9 [8.9313.9], 121.3 [43.7481.8] h∙ng/mL; p = 0.088). The results did not change when the baseline levels were adjusted (365.3 [279.5, 451.1], 293.0 [207.1, 379.0], and 298.0 [244.7, 351.3] h∙ng/mL; p = 0.487). The rate of periprocedural myonecrosis was also not different between the groups (53.0% vs. 50.0% vs. 33.3%, p = 0.092). The CK-MB isoenzyme analysis showed similar results. No difference in complications was noted., Conclusion: Additional tirofiban administration was not beneficial to patients with NSTE-ACS even with an HPR., Trial Registration: Clinical trial no. NCT03114995 , registered 11 April, 2017, retrospectively.

In seeking to improve care in coronary artery disease patients, further platelet inhibition has been occasionally applied beyond that provided by aspirin and a P2Y 12 receptor antagonist. This review aims to offer insights about the rationale, the efficacy and safety of combination antiplatelet therapy, involving three or more agents. Overall, the use of glycoprotein (GP) IIb/IIIa inhibitors did not significantly modify the treatment effect of different antiplatelet strategies, including double vs standard clopidogrel, prasugrel vs clopidogrel, ticagrelor vs clopidogrel, cangrelor vs clopidogrel, and vorapaxar vs placebo. With the caveat that the use of GP IIb/IIIa inhibitor was not randomized, adding such an agent to aspirin and a P2Y 12 receptor antagonist appears to carry a significantly increased bleeding potential. Moreover, adding vorapaxar to aspirin- and clopidogrel-treated patients is associated with more bleeding events, while the bleeding potential is further exacerbated in cases of quadruplicate antiplatelet treatment including aspirin, clopidogrel, vorapaxar, and a GP IIb/IIIa inhibitor. In ST-segment elevation, myocardial infarction patients' administration of an intravenous antiplatelet agent (GP IIb/IIIa inhibitor or cangrelor), in addition to aspirin and a P2Y 12 receptor antagonist, efficiently bridges the pharmacodynamic gap of oral agents. Cilostazol on top of aspirin and clopidogrel appears to be safe, although of questionable clinical benefit. In conclusion, combination antiplatelet therapy should be reserved only for selected cases and following thoughtful consideration of the associated risk/benefit ratio.

The risk and benefit of GP-IIb/IIIa Inhibition (GPI) in combination with recent antiplatelet regimens in acute coronary syndromes (ACS) remain unassessed. The advent of fast-acting highly active oral P2Y 12 inhibitors questions the additional value and risk of their association with GPI. We studied the effect of GPI in combination with prasugrel and ticagrelor, compared to clopidogrel on major bleeding in pivotal randomized controlled trials in the setting of ACS, using a meta-analytic approach. A similar analysis, further including the comparison of a double versus standard dose clopidogrel regimen, was performed for the risk of the primary efficacy endpoint. The combination of GPI and recent P2Y 12 inhibitors was associated with a similar risk of bleeding as compared with GPI and the standard clopidogrel regimen (RR 0.92 [0.74; 1.13]). The benefit of recent regimens, including double dose clopidogrel, in reducing the primary ischemic endpoint (RR 0.86 [0.78; 0.94]) persisted in those treated with GPI. Although GPI use was associated with a consistent increase in the risk of bleeding in both recent (RR 1.27 [1.05-1.55]) and standard regimens (RR 2.01 [1.64-2.47]), the relative magnitude of such an increase was lower in association with prasugrel or ticagrelor as compared with clopidogrel. The risk of bleeding using a combination of GPI and oral antiplatelet regimens is mainly related to the use of GPI and not the oral antiplatelet regimen. Considering the absence of increased risk of bleeding and the persistence of the benefit of recent P2Y 12 regimens in combination with GPI as compared with the standard clopidogrel regimen, the use of such a combination within the guidelines is supported by our findings.

Our aim was to compare the efficacy and safety of bivalirudin (Biv) versus heparin (Hep) with or without similar usage rate of glycoprotein IIb/IIIa inhibitors (GPIs) during percutaneous coronary intervention (PCI). The PubMed and EMbase were searched. Randomized trials comparing Biv versus Hep were eligible for inclusion. With imbalanced GPI use, Biv had significantly lower major bleeding (pooled risk ratio [RR], 0.67; 95% confidence interval [CI], 0.54-0.83) without difference in mortality (pooled RR, 0.95; 95% CI, 0.80-1.14). With comparable GPI use, no significant difference was observed in major bleeding (pooled RR, 0.95; 95% CI, 0.82-1.10) and mortality (pooled RR, 1.13; 95% CI, 0.85-1.50). With no GPI use, Biv was associated with numerically higher mortality (pooled RR, 1.17; 95% CI, 0.83-1.65) without significant difference in major bleeding (pooled RR, 0.81; 95% CI, 0.64-1.02). In conclusion, when comparing different anticoagulants during PCI, the effect of GPIs should not be underestimated. Heparin as such was found noninferior to Biv., (© The Author(s) 2015.)

Objective: Despite major trials showing the opposite, one of three small randomized trials conducted outside the US has raised questions about whether heparin alone is a viable antithrombotic strategy for primary percutaneous coronary interventions (PPCI). We determined the frequency and in-hospital outcomes of anticoagulation strategies in patients undergoing PPCI., Methods: We analyzed records from 2008 through 2013 in the Premier Research Database of patients hospitalized with ST-segment elevation myocardial infarction (STEMI) undergoing PPCI. Patients were categorized into one of four anticoagulation strategies: bivalirudin alone, bivalirudin plus glycoprotein IIb/IIIa inhibitors (GPI), unfractionated or low-molecular-weight heparin alone or heparin plus GPI. In-hospital clinical outcomes were compared between treatment groups after propensity score matching., Results: Among 114,134 eligible STEMI patients, heparin alone was the least frequent anticoagulation strategy, used in 14.4% to 18.1% of cases per year. Bivalirudin alone nearly tripled during the study period, from 12.7% to 37.8% and surpassed that of heparin plus GPI by 2013. Bivalirudin alone performed better than heparin alone for mortality (4.7% vs 5.3%, p = 0.010), clinically apparent bleeding (5.7% vs 6.7%, p < 0.001), transfusion rates (4.1% vs 4.8%, p = 0.003) and mean length of stay (4.1 vs 4.2 days, p < 0.001). The in-hospital death rate was lower with heparin plus GPI than with heparin alone (4.9% vs 5.9%, p < 0.001), but clinically apparent bleeding was higher in heparin plus GPI than in heparin alone (9.4% vs 7.1%, p < 0.001)., Conclusion: In patients hospitalized for STEMI undergoing PPCI, heparin alone is not commonly used and is inferior to bivalirudin for mortality, bleeding and length of stay outcomes. Heparin is also inferior to heparin plus GPI for ischemic protection but associated with less bleeding.

Continuous-flow left ventricular assist devices reduce short-term mortality and improve quality of life in patients with end-stage heart failure. Unfortunately, device-related complications remain common, with many patients experiencing adverse events within the first year. New literature suggests that rates of device-related thrombosis may be increasing since 2011, which is particularly troublesome given that this pathology can result in a disabling stroke, organ damage, and death. In 2013, a group of practitioners in the field of mechanical circulatory support published a treatment algorithm based on their expert opinion. However, a comprehensive review of the pharmacotherapy of this condition is lacking. A search of the literature revealed 20 separate publications of case reports or case series describing outcomes associated with the use of drug therapy for suspected pump thrombosis. Each of these experiences was limited by small sample size, nonrandomized treatment allocation, and nonstandardized medication dosing. Data describing the outcomes of surgical versus medical management of device thrombosis are also sparse, with only three published reports identified. Based on the review of this limited literature, surgical management appears to be the preferred treatment modality, especially in those with organ hypoperfusion or hemodynamic instability. In patients ineligible for surgery, pharmacotherapy options remain limited. Use of all drug classes described in the literature for the HeartMate II device-fibrinolytics, glycoprotein IIb/IIIa inhibitors, and direct thrombin inhibitors-was hindered by either marginal efficacy or bleeding. Based on historical experience with unfractionated heparin in patients under HeartMate II support, we recommend this agent as a possible option for those with suspected pump thrombosis in lieu of surgical device exchange. For the HeartWare HVAD, limited data suggest that direct intraventricular administration of alteplase may be an acceptable treatment alternative. Additional research is clearly needed to further delineate the role of pharmacotherapy and to identify the optimal agent for managing this potentially life-threatening condition., (© 2014 Pharmacotherapy Publications, Inc.)

Background: Elderly patients with acute coronary syndromes (ACS) are at high risk for death and recurrent thrombotic events. We evaluated the efficacy and safety of intensive treatment with glycoprotein IIb/IIIa inhibitors in an elderly population, and the relationships between age, timing of administration, and clinical outcomes., Methods: We used data from high-risk non-ST-segment elevation ACS patients randomized to early eptifibatide vs. delayed provisional use at percutaneous coronary intervention. In multivariable models, we included age×treatment interaction terms to assess whether treatment effect varied by age after adjusting for confounders., Results: Of 9406 patients, 13.9% were aged <55 years; 27.6%, 55-64 years; 33.2%, 65-74 years; and 25.3%, ≥ 75 years. For each 10-year age increase, the adjusted odds ratio (OR) (95% confidence interval [CI]) for 96-hour death, myocardial infarction (MI), recurrent ischemia requiring urgent revascularization, or thrombotic bailout was 1.13 (1.04-1.23) and for 30-day death or MI was 1.13 (1.04-1.22). Increasing age was also associated with greater 1-year mortality (adjusted hazard ratio per 10 years: 1.44, 95% CI 1.30-1.60). There was no interaction between age and treatment (p interaction=0.99, 0.54, and 0.87, respectively). Increasing age was associated with more non-coronary artery bypass grafting-related TIMI major bleeding (adjusted OR and 95% CI per 10 years: 1.54 [1.24-1.92]), GUSTO moderate/severe bleeding (1.52 [1.33-1.75]), and transfusion (1.25 [1.07-1.45]). The amount by which TIMI major bleeding was increased with early vs. delayed provisional eptifibatide use was significantly greater with increasing age (p interaction=0.02), but the age×treatment interactions were not significant for GUSTO moderate/severe bleeding or transfusion (p interaction=0.33 and 0.54, respectively)., Conclusion: Increasing age was associated with greater risk for ischemic events and more bleeding. Despite higher baseline ischemic risk in older patients, there was no preferential benefit of early vs. delayed provisional eptifibatide use for ischemic outcomes as age increased, but the incremental bleeding risk was amplified., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background and Objectives: Eptifibatide is indicated during percutaneous coronary intervention (PCI) with continuation for 18-24 hours post procedure but is associated with bleeding. We examined the efficacy and safety of shorter post-PCI eptifibatide infusions in high-risk non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients., Methods: EARLY ACS patients treated with PCI and eptifibatide were grouped by post-procedure infusion duration: <10, 10-13, 13-17, and 17-25 (per protocol) hours. Adjusted estimated event rates for 96-hour death/myocardial infarction (MI)/recurrent ischaemia requiring urgent revascularization (RIUR), 30-day death/MI, post-PCI packed red blood cell (PRBC) transfusion, and GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) moderate/severe bleeding were obtained using inverse-propensity weighting to account for informative censoring of infusions., Results: Among 3271 eptifibatide-treated PCI patients, there were 66 96-hour death/MI/RIUR events, 94 30-day death/MI events, 127 PRBC transfusions, and 115 GUSTO moderate/severe bleeds. Compared with per protocol, patients receiving post-PCI infusions <10 hours had similar adjusted estimated rates of 96-hour death/MI/RIUR (absolute difference 0.021 higher; 0.040 vs. 0.019, 95% CI -0.023 to 0.064; p=0.35) and 30-day death/MI (0.020 higher; 0.046 vs. 0.026, 95% CI -0.021 to 0.062; p=0.34). There were also no differences in ischaemic outcomes between infusions of 10-17 hours and per-protocol infusions. Adjusted estimated rates of PRBC transfusion were higher for the <10-hour infusion group compared with per protocol (0.048 higher; 0.079 vs. 0.031, 95% CI 0.005 to 0.091, p=0.03) but were similar for other groups. Adjusted GUSTO moderate/severe bleeding rates were similar to per-protocol rates for all groups., Conclusions: In high-risk NSTE ACS patients, post-PCI eptifibatide infusions <18 hours were not associated with worse ischaemic outcomes. Shorter eptifibatide infusions in this population may be feasible.

Despite implementation of new interventional techniques and therapeutic advances, elderly patients with acute coronary syndrome (ACS) continue to be susceptible to in-hospital bleeding compared with younger ones. Thus, we investigated the incidence of in-hospital bleeding events and associated risk factors in elderly (≥ 75°years) ACS patients. We also wanted to define the bleeding sites, characteristics, and associated mortality. Bleeding Academic Research Consortium (BARC) classification type 2, 3, or 5 was used to define bleeding events. Overall, 539 patients were included in the study (mean age: 82.5 ± 4.8°years; 282 (52.3%) females). Of these patients, 69 (12.8%) developed in-hospital bleeding. Factors that were independently related with in-hospital bleeding were age (odds ratio (OR): 1.08; 95% confidence interval (CI): 1.011.14, P =.01), acute kidney injury (OR: 3.66; 95% CI: 2.016.69; P <.01), tirofiban (OR: 4.43; 95% CI: 1.7810.99; P <.01), and ticagrelor (OR: 1.93; 95% CI: 1.013.73; P =.04) administration. The urinary tract was the most frequent bleeding site, followed by femoral arteries. In conclusion, ticagrelor and tirofiban should be used with caution in elderly ACS patients. [ABSTRACT FROM AUTHOR]

Progressive ischemic stroke (PIS) is a therapeutic challenge in clinical practice. The present retrospective study aimed to investigate the safety and effectiveness of eptifibatide in the treatment of PIS. The present study enrolled patients with PIS admitted to Xiangtan Central Hospital (Xiangtan, China) between March 2020 and March 2021 with National Institutes of Health Stroke Scale (NIHSS) progression scores of ≥2 points during the initial 72 h. Patients were then divided into two groups according to their different anti-platelet treatment regimens. The control group was administered anti-platelet aggregation with aspirin 100 mg/day, or aspirin 100 mg/day in combination with clopidogrel 75 mg/day, whilst eptifibatide was administered in the eptifibatide group in addition to the treatment regimen used in the control group. Changes in NIHSS scores at the time of progression and 7 days after treatment (∆NIHSS) were used to assess early neurological recovery, and there were no significant differences in ∆NIHSS and adverse reactions between the groups (P>0.05). Subgroup analysis was subsequently performed according to the type of blood vessel that was involved [large artery atherosclerosis (LAA) or small artery occlusion (SAO)]. For the SAO subgroup, the ∆NIHSS in the eptifibatide group was significantly superior to that of the control group (P=0.008), while for the LAA subgroup, there were no significant differences in ∆NIHSS between groups (P=0.334). The present retrospective study found that patients with PIS tolerated eptifibatide treatment well. Eptifibatide exerted different effects on patients with acute PIS involving different types of blood vessels compared with oral antiplatelet drugs. In addition, application of eptifibatide may lead to faster and earlier recovery in patients with SAO, but not in those with LAA. Low-dose eptifibatide is a safe and effective treatment option for patients with PIS caused by SAO. [ABSTRACT FROM AUTHOR]

Antiplatelet therapy is integral to the acute and long-term management of acute coronary syndromes (ACSs) and for minimizing the thrombotic complications of percutaneous coronary intervention (PCI). This article reviews the most commonly used antiplatelet agents in ACS therapy—aspirin, adenosine diphosphate (ADP)-receptor blockers, and glycoprotein IIb/IIIa inhibitors. More recent data are also reviewed on novel ADP-receptor blockers and thrombin inhibitors before addressing issues of adherence to antiplatelet regimens. [ABSTRACT FROM PUBLISHER]