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Venomous bites are medical emergencies that may result in life-threatening clinical effects. Cardiovascular complications are uncommon but they can be dangerous if not early detected and treated. Cerebral and myocardial infarction are described; myocarditis as consequence of viper envenomation in humans are very rare, almost anedoctal. We present the case of a 33-year-old man, working as keeper in a reptile zoo, who arrived after a viper bite of the Vipera aspis species, on the left wrist. The patient presented with clouded sensorium, edema of the lips and tongue, rapidly worsened with angioedema, and the need for oro-tracheal intubation; severe thrombocytopenia and anemia were treated with transfusions of platelet, plasma and red blood cells. The left hand and arm worsened, with compartment syndrome, treated with surgical fasciotomy. From a cardiological point of view, the patient presented a sudden drop in blood pressure, electrocardiographic anterior and infero-lateral ST depression, pericardial effusion and hypokinesia of the interventricular septum on echocardiography, and a significant increase in troponin T. Cardiac magnetic resonance imaging confirmed the myocarditis, with the presence of septal and anterior intramyocardial edema in T2 weighted sequences, with prolonged T2 time at T2 mapping analysis, without late gadolinium enhancement areas. Cardiological and general clinical conditions gradually improved only after the antivenom was administred. This is one of the rare cases of viper bite myocarditis with echocardiographic and magnetic resonance imaging documentation in Europe; it emphasizes the importance of identifying uncommon complications of venomous snake-bites and the prompt administration of antivenom, even though snake bites are less frequent at our latitudes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Immunological memory is critical for immune protection, particularly at epithelial sites, which are under constant risk of pathogen invasions. To counter invading pathogens, CD8 + memory T cells develop at the location of infection: tissue-resident memory T cells (T RM ). CD8 + T-cell responses are associated with type-1 infections and type-1 regulatory T cells (T REG ) are important for CD8 + T-cell development, however, if CD8 + T RM cells develop under other infection types and require immune type-specific T REG cells is unknown. We used three distinct lung infection models, to show that type-2 helminth infection does not establish CD8 + T RM cells. Intracellular (type-1) and extracellular (type-3) infections do and rely on the recruitment of response type-matching T REG population contributing transforming growth factor-β. Nevertheless, type-1 T REG cells remain the most important population for T RM cell development. Once established, T RM cells maintain their immune type profile. These results may have implications in the development of vaccines inducing CD8 + T RM cells., (© 2023. Springer Nature Limited.)

SARS-CoV-2 infection is associated with an increased risk of venous thromboembolism (VTE), which is common during active illness but unusual in milder cases and after healing. We describe a case of bilateral acute pulmonary embolism occurring 3 months after recovery from a paucisymptomatic SARS-CoV-2 infection. The only VTE risk factor demonstrable was a history of previous SARS-CoV-2 infection, with laboratory signs of residual low-grade inflammation. Clinicians should be aware of VTE as a potential cause of sudden dyspnoea after COVID-19 resolution, especially in the presence of persistent systemic inflammation., Learning Points: Venous thromboembolism may occur after COVID-19, even in milder SARS-CoV-2 infections and late after coronavirus clearance.Laboratory signs of systemic inflammation are clues for suspecting venous thromboembolism as a cause of sudden dyspnoea in patients with low risk scores for pulmonary embolism but with previous COVID-19 infection., Competing Interests: Conflicts of Interests: The authors declare there are no competing interests., (© EFIM 2021.)

Functional tuning of T cells based on their degree of self-reactivity is established during positive selection in the thymus, although how positive selection differs for thymocytes with relatively low versus high self-reactivity is unclear. In addition, preselection thymocytes are highly sensitive to low-affinity ligands, but the mechanism underlying their enhanced T cell receptor (TCR) sensitivity is not fully understood. Here we show that murine thymocytes with low self-reactivity experience briefer TCR signals and complete positive selection more slowly than those with high self-reactivity. Additionally, we provide evidence that cells with low self-reactivity retain a preselection gene expression signature as they mature, including genes previously implicated in modulating TCR sensitivity and a novel group of ion channel genes. Our results imply that thymocytes with low self-reactivity downregulate TCR sensitivity more slowly during positive selection, and associate membrane ion channel expression with thymocyte self-reactivity and progress through positive selection., Competing Interests: LL, ZS, LM, SP, JK, AH, SA, AS, NY, ER No competing interests declared, (© 2021, Lutes et al.)

SARS-CoV-2 has emerged as a human pathogen, causing clinical signs, from fever to pneumonia-COVID-19-but may remain mild or asymptomatic. To understand the continuing spread of the virus, to detect those who are and were infected, and to follow the immune response longitudinally, reliable and robust assays for SARS-CoV-2 detection and immunological monitoring are needed. We quantified IgM, IgG, and IgA antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) or the Spike (S) protein over a period of 6 months following COVID-19 onset. We report the detailed setup to monitor the humoral immune response from over 300 COVID-19 hospital patients and healthcare workers, 2500 University staff, and 198 post-COVID-19 volunteers. Anti-SARS-CoV-2 antibody responses follow a classic pattern with a rapid increase within the first three weeks after symptoms. Although titres reduce subsequently, the ability to detect anti-SARS-CoV-2 IgG antibodies remained robust with confirmed neutralization activity for up to 6 months in a large proportion of previously virus-positive screened subjects. Our work provides detailed information for the assays used, facilitating further and longitudinal analysis of protective immunity to SARS-CoV-2. Importantly, it highlights a continued level of circulating neutralising antibodies in most people with confirmed SARS-CoV-2., (© 2020 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Skin-resident T cells protect against invasive microorganisms. A new study reports that commensal-specific type-17 (but not type-1) T cells in the skin are poised to switch to a type-2 response upon tissue injury and contribute to wound repair., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: The study sought to assess whether treatment with ticagrelor, as compared with prasugrel and clopidogrel, improves endothelium-dependent dilation throughout the course of the treatment and other vascular biomarkers, including systemic adenosine plasma levels., Background: The in vivo off-target effects of ticagrelor in post-acute coronary syndrome (ACS) patients remain poorly characterized., Methods: Fifty-four stable post-ACS patients were sequentially exposed to each of the 3 oral P2Y 12 inhibitors following a 3-period balanced Latin square crossover design with 4 weeks per treatment in 5 European centers. The primary endpoint was the assessment of endothelial function with pulse amplitude tonometry and expressed as reactive hyperemia index at treatment steady state. Secondary endpoints included reactive hyperemia index after loading or before maintenance regimen, systemic adenosine plasma levels, a wide set of vascular biomarkers, and ticagrelor or AR-C124910XX plasma levels throughout each ticagrelor period. In 9 patients, the evaluation of endothelial function was performed simultaneously by pulse amplitude tonometry and flow-mediated dilation., Results: Reactive hyperemia index did not differ after ticagrelor (1.970 ± 0.535) as compared with prasugrel (2.007 ± 0.640; p = 0.557) or clopidogrel (2.072 ± 0.646; p = 0.685), nor did systemic adenosine plasma levels or vascular biomarkers at any time points. P2Y 12 platelet reactivity units were lower after ticagrelor as compared with clopidogrel at all time points and after maintenance dose as compared with prasugrel. Flow-mediated dilation did not differ after the maintenance dose of ticagrelor as compared with clopidogrel and prasugrel., Conclusions: Ticagrelor did not improve endothelial function or increased systemic adenosine plasma levels as compared with prasugrel and clopidogrel in stabilized patients who suffered from an ACS. (Hunting for the Off-Target Properties of Ticagrelor on Endothelial Function in Humans [HI-TECH]; NCT02587260)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The diuretic response has been shown to be a robust independent marker of cardiovascular outcomes in acute heart failure (ADHF) patients. The objectives of this clinical research, will aim are to: a) include diuresis in the formula for diuretic response (R-to-D); b) add to R-to-D the value of a pre-discharged determination of galectin-3 and BNP in predicting mid-term clinical outcome., Methods: Consecutive patients discharged alive after an ADHF were enrolled. All patients underwent BNP and galectin-3, a 6 min walk test and an echocardiogram together with diuresis and body weight during diuretic administration. Death by any cause, cardiac transplantation and worsening HF requiring readmission to the hospital were considered cardiovascular events., Results: 141 patients (98 males, age 73.8) were analysed (follow-up 17 months). During the follow-up 45 (31.9%) events were scheduled (19 cardiac deaths, 26 re-hospitalisation for HF). Patients who experienced CV-event had a worst renal function (p = 0.003), an higher BNP (p = 0.006) and galectin-3 (p = 0.008). At multivariate analysis, only R-to-D, galectin-3 and BNP showed a significant correlation with worst clinical prognosis (respectively p = 0.043; OR 6.01; p = 0.01; OR 8.9; p = 0.02 OR 10.38), independently of age and renal function. Kaplan-Meier curves depicted a powerful stratification using an R-to-D <1.2 kg/40 mg furosemide (log rank 10.96; p = 0.0009). Adding R-to-D<1.2 mg/40 mg furosemide to galectin-3>17.6 pg/mL and BNP>500 pg/mL the predictive value improved (log rank 23.59; p = 0.0001)., Conclusion: Adding R-to-D to Gal-3 and BNP, a single pre-discharge strategy testing seemed to obtain a satisfactorily predictive value in alive HF patients discharged after an ADHF episode., (Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.)

Aim: Contemporary data comparing early versus newer generation transcatheter heart valve (THV) devices in routine clinical practice are lacking. We sought to compare the safety and efficacy of early versus newer generation THVs in unselected patients undergoing transcatheter aortic valve implantation (TAVI)., Methods and Results: We performed a propensity score matched analysis of patients undergoing transfemoral TAVI at a single centre with early versus newer generation devices between 2007 and 2016. Patients were matched for balloon-expandable versus self-expandable valves and Society of Thoracic Surgeons score. The primary end point was the Valve Academic Research Consortium (VARC)-2 early safety composite end point at 30 days. Among the 391 matched pairs, no differences between early (21.2%) and newer generation (20.8%) THVs regarding the early safety composite end point (HR 0.98, 95% CI 0.72 to 1.33, P=0.88) were observed. The rates of valve embolisation (0.8% vs 4.2%, P=0.005), bleeding events (24.8% vs 32.0%, P=0.028) and moderate-to-severe paravalvular regurgitation (PVR) (3.1% vs 12.1%, P<0.001) were lower among patients receiving newer generation devices. Conversely, patients treated with early generation THVs less frequently experienced annulus rupture (0% vs 2.0%, P=0.008)., Conclusion: Newer compared with early generation THV devices were associated with a lower rate of valve embolisation, PVR and bleeding events., Competing Interests: Competing interests: None declared.

Objectives: This study sought to assess whether transradial access (TRA) compared with transfemoral access (TFA) is associated with consistent outcomes in male and female patients with acute coronary syndrome undergoing invasive management., Background: There are limited and contrasting data about sex disparities for the safety and efficacy of TRA versus TFA for coronary intervention., Methods: In the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) program, 8,404 patients were randomized to TRA or TFA. The 30-day coprimary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE), defined as death, myocardial infarction, or stroke, and net adverse clinical events (NACE), defined as MACCE or major bleeding., Results: Among 8,404 patients, 2,232 (26.6%) were women and 6,172 (73.4%) were men. MACCE and NACE were not significantly different between men and women after adjustment, but women had higher risk of access site bleeding (male vs. female rate ratio [RR]: 0.64; p = 0.0016), severe bleeding (RR: 0.17; p = 0.0012), and transfusion (RR: 0.56; p = 0.0089). When comparing radial versus femoral, there was no significant interaction for MACCE and NACE stratified by sex (p int  = 0.15 and 0.18, respectively), although for both coprimary endpoints the benefit with TRA was relatively greater in women (RR: 0.73; p = 0.019; and RR: 0.73; p = 0.012, respectively). Similarly, there was no significant interaction between male and female patients for the individual endpoints of all-cause death (p int  = 0.79), myocardial infarction (p int  = 0.25), stroke (p int  = 0.18), and Bleeding Academic Research Consortium type 3 or 5 (p int  = 0.45)., Conclusions: Women showed a higher risk of severe bleeding and access site complications, and radial access was an effective method to reduce these complications as well as composite ischemic and ischemic or bleeding endpoints., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess whether moderate-to-severe CKD is a treatment modifier for benefit or harm in patients randomly allocated to 24-month versus 6-month DAPT., Background: It is still unclear whether chronic kidney disease CKD should impact on the decision-making on optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI)., Methods and Results: PRODIGY trial randomized 1970 all-comer patients at 24-month versus 6-month DAPT after PCI. Patients with moderate-to-severe CKD (n = 604; 30.7%) were older, more likely to be women, to have hypertension, diabetes, prior MI or PCI, with higher severity of coronary artery disease (CAD), but were less frequently smokers or presenting with stable CAD. After adjustment, the 2-year rates of primary endpoint (composite of death, myocardial infarction and cerebrovascular accident), as well as bleeding and net adverse clinical events were higher in patients with moderate-to-severe CKD. DAPT prolongation at 24-month did not reduce the primary endpoint in both CKD (adj. HR: 0.957; 95% CI 0.652-1.407; P = 0.825) and no-CKD (adj. HR: 1.341; 95% CI 0.861-2.086; P = 0.194) groups (Pint = 0.249), but increased bleeding in both groups (CKD: adj. HR: 1.999; 95% CI 1.100-3.632; P = 0.023; no-CKD: adj. HR: 2.880; 95% CI 1.558-5.326; P = 0.001; Pint = 0.407)., Conclusions: Moderate-to-severe CKD did not modify the effect of a prolonged or shortened DAPT duration in largely unselected patients undergoing stent implantation. Our analysis suggests that CKD should not be a major driver in the decision-making on the duration of DAPT after stent implantation. This exploratory study is underpowered and should be considered hypothesis-generating only. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: The dual-antiplatelet therapy (DAPT) score was developed to identify patients more likely to derive harm (score <2) or benefit (score ≥2) from prolonged DAPT after percutaneous coronary intervention (PCI)., Objective: To evaluate the safety and efficacy of DAPT duration according to DAPT score., Design: Retrospective assessment of DAPT score-guided treatment duration in a randomized clinical trial. (ClinicalTrials.gov: NCT00611286)., Setting: PCI patients., Patients: 1970 patients undergoing PCI., Intervention: DAPT (aspirin and clopidogrel) for 24 versus 6 months., Measurements: Primary efficacy outcomes were death, myocardial infarction, or cerebrovascular accident. The primary safety outcome was type 3 or 5 bleeding according to the Bleeding Academic Research Consortium definition. Outcomes were assessed between 6 and 24 months., Results: 884 patients (44.9%) had a DAPT score of at least 2, and 1086 (55.1%) had a score less than 2. The reduction in the primary efficacy outcome with 24- versus 6-month DAPT was greater in patients with high scores (risk difference [RD] for score ≥2, -2.05 percentage points [95% CI, -5.04 to 0.95 percentage points]; RD for score <2, 2.91 percentage points [CI, -0.43 to 6.25 percentage points]; P = 0.030). However, the difference by score for the primary efficacy outcome varied by stent type; prolonged DAPT with high scores was effective only in patients receiving paclitaxel-eluting stents (RD, -7.55 percentage points [CI, -12.85 to -2.25 percentage points]). The increase in the primary safety outcome with 24- versus 6-month DAPT was greater in patients with low scores (RD for score ≥2, 0.20 percentage point [CI, -1.20 to 1.60 percentage points]; RD for score <2, 2.58 percentage points [CI, 0.71 to 4.46 percentage points]; P = 0.046)., Limitation: Retrospective calculation of the DAPT score., Conclusion: Prolonged DAPT resulted in harm in patients with low DAPT scores undergoing PCI but reduced risk for ischemic events in patients with high scores receiving paclitaxel-eluting stents. Whether prolonged DAPT benefits patients with high scores treated with contemporary drug-eluting stents requires further study., Primary Funding Source: None.

Background: Among the 3 approved oral P2Y 12 inhibitors for the treatment for patients with acute coronary syndrome (ACS), ticagrelor, but not prasugrel or clopidogrel, has been associated with off-target properties, such as improved endothelial-dependent vasomotion and increased adenosine plasma levels., Methods: The HI-TECH study (NCT02587260) is a multinational, randomized, open-label, crossover study with a Latin squares design, conducted at 5 European sites, in which patients free from recurrent ischemic or bleeding events ≥30 days after a qualifying ACS were allocated to sequentially receive a 30 ± 5-day treatment with prasugrel, clopidogrel, and ticagrelor in random order. The primary objective was to evaluate whether ticagrelor, at treatment steady state (ie, after 30 ± 5 days of drug administration), as compared with both clopidogrel and prasugrel, is associated with an improved endothelial function, assessed with peripheral arterial tonometry. Thirty-six patients undergoing evaluable endothelial function assessment for each of the assigned P2Y 12 inhibitor were needed to provide 90% power to detect a 10% relative change of the reactive hyperemia index in the ticagrelor group., Conclusion: The HI-TECH study is the first randomized, crossover study aiming to ascertain whether ticagrelor, when administered at approved regimen in post-ACS patients, improves endothelial function as compared with both clopidogrel and prasugrel., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to evaluate the efficacy and safety of 24-month vs. six-month dual antiplatelet therapy (DAPT) among elderly (≥75 years) and non-elderly patients (<75 years) undergoing percutaneous coronary intervention., Methods and Results: The primary efficacy endpoint of the PRODIGY trial was the composite of death, myocardial infarction, or cerebrovascular accident at 24-month follow-up. The key safety endpoint was type 2, 3 or 5 bleeding according to the BARC criteria. Of 1,970 participants, 587 (29.8%) were elderly and had a higher risk of adverse events compared with younger patients. The risk of the primary endpoint was not significantly reduced with 24-month compared to six-month DAPT among both elderly (HR 0.80, 95% CI: 0.55-1.16, p=0.24) and non-elderly patients (HR 1.48, 95% CI: 0.95-2.30, p=0.08), although interaction testing was significant (p=0.036). A 24-month versus six-month DAPT significantly increased the risk of BARC type 2, 3 or 5 bleeding in both older (HR 1.90, 95% CI: 1.06-3.38, p=0.03) and younger patients (HR 2.54, 95% CI: 1.43-4.53, p=0.002, p-interaction=0.48). However, measures of absolute risk difference indicated a less favourable safety profile of prolonged DAPT for older rather than younger patients., Conclusions: In the PRODIGY trial, prolonging clopidogrel-based DAPT beyond six months in elderly patients increased the risk of bleeding, without affording a significant prevention of ischaemic events.

Purpose of Review: This review aims to summarize and discuss safety and effectiveness of the long-term use of ticagrelor in patients with coronary artery disease (CAD)., Recent Findings: Ticagrelor is an orally administered, direct, and reversible inhibitor of the P2Y 12 -platelet receptor. Long-term use of ticagrelor in patients with previous myocardial infarction (MI) has been investigated in the PEGASUS-TIMI-54 trial. Overall, 21,162 patients with a spontaneous MI 1 to 3 years before randomization were randomly assigned to ticagrelor 90 mg bid, ticagrelor 60 mg bid, or placebo. Compared with placebo, both doses of ticagrelor showed that they were capable of significantly reducing the primary efficacy endpoint, although with a significant increase in TIMI major bleeding. Intracranial hemorrhage or fatal bleeding did not differ across groups. These findings establish clear benefit of DAPT extension with ticagrelor beyond 1 year of treatment, which comes with a tradeoff of clinically meaningful bleeding. Altogether, current evidence suggests that the duration of DAPT remains a patient-by-patient decision based on thrombotic and bleeding risk profiles.

Importance: Patients with concomitant peripheral arterial disease (PAD) experience worse cardiovascular outcomes after percutaneous coronary intervention (PCI)., Objective: To assess the efficacy and safety of prolonged (24 months) vs short (≤6 months) dual antiplatelet therapy (DAPT) in patients with PAD undergoing PCI., Design, Setting, and Participants: This subanalysis of the randomized Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study (PRODIGY) trial assessed unselected patients from tertiary care hospitals with stable coronary artery disease or acute coronary syndromes with or without concomitant PAD from December 2006 to December 2008. Data analysis was performed from January 7 to April 4, 2016., Interventions: Percutaneous coronary intervention., Main Outcomes and Measures: Rates of the primary efficacy end point, composite of death, myocardial infarction, or cerebrovascular accidents, and occurrence of the key safety end point, a composite of Bleeding Academic Research Consortium type 2, 3, or 5., Results: This analysis comprised 246 and 1724 patients with and without PAD, respectively. In the patients with PAD, mean (SD) age was 73.2 (9.2) in the prolonged group and 75.7 (8.7) years in the short DAPT group, and 97 (82.2%) were male in the prolonged group and 92 (71.9%) were male in the short DAPT group. In the patients without PAD, mean (SD) age was 67.1 (11.2) years in the prolonged group and 66.8 (11.3) years in the short DAPT group, and 667 (76.8%) were male in the prolonged group and 655 (76.6%) were male in the short DAPT group. Status of PAD was associated with a higher risk of death and ischemic events (hazard ratio [HR], 2.80; 95% CI, 2.05-3.83; P < .001). Prolonged vs short DAPT conveyed a lower risk of the primary efficacy end point in patients with PAD (19 [16.1%] vs 35 [27.3%]; HR, 0.54; 95% CI, 0.31-0.95; P = .03) but not in patients without PAD (81 [9.3%] vs 63 [7.4%]; HR, 1.28; 95% CI, 0.92-1.77; P = .15), with positive interaction (P = .01). The risk of definite or probable stent thrombosis was significantly lower in patients with PAD treated with prolonged compared with short DAPT (HR, 0.07; 95% CI, 0-1.21; P = .01). Bleeding Academic Research Consortium type 2, 3, or 5 bleeding occurred in 6 patients with PAD (5.2%) receiving prolonged DAPT relative to 8 (6.9%) of those receiving short DAPT (HR, 0.77; 95% CI, 0.27-2.21; P = .62), with a significant interaction (P = .04) compared with patients without PAD., Conclusions and Relevance: Peripheral artery disease confers a poor prognosis in patients undergoing PCI in the setting of stable coronary artery disease or acute coronary syndromes. Prolonged DAPT lowers the risk of ischemic events with no apparent bleeding liability in this high-risk group., Trial Registration: clinicaltrials.gov Identifier: NCT00611286.

Objectives: The aim of this study was to assess the impact of sex on 2-year outcomes after percutaneous coronary intervention (PCI) in patients randomly allocated to 24-month versus 6-month dual-antiplatelet therapy (DAPT)., Background: The optimal duration of DAPT after PCI is highly debated. Whether sex per se should drive decision making on DAPT duration remains unclear., Methods: The primary efficacy endpoint of PRODIGY (Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study) was the composite of death, myocardial infarction, or cerebrovascular accident at 24-month follow-up. The key safety endpoint was type 2, 3, or 5 bleeding according to the Bleeding Academic Research Consortium criteria., Results: Women (n = 459 [23.3%]) were older and more likely to have hypertension, lower creatinine clearance, and acute coronary syndrome but had a lower severity of coronary artery disease. After adjustment, prolonged DAPT, compared with 6-month treatment, did not reduce the primary endpoint in both men (adjusted hazard ratio: 1.080; 95% confidence interval: 0.766 to 1.522; p = 0.661) and women (adjusted hazard ratio: 1.013; 95% confidence interval: 0.588 to 1.748; p = 0.962) (interaction p = 0.785). No sex disparity was identified across multiple secondary ischemic endpoints, including overall or cardiovascular mortality, myocardial infarction, and stent thrombosis. There was also no clear sex-related effect on clinically relevant bleeding, including Bleeding Academic Research Consortium type 3 or 5, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) scales., Conclusions: The present findings suggest that men and women undergoing PCI have similar adjusted 2-year ischemic and bleeding outcomes, despite being characterized by different clinical presentation. Sex failed to emerge as a treatment modifier with respect to DAPT duration, suggesting that decision making on DAPT duration in female patients should weigh ischemic versus bleeding risks., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate whether the 2 tirofiban formulations tested in the early and late phases of the PRISM (Platelet Receptor Inhibitor in Ischemic Syndrome Management) trial might differ with respect to risk for thrombocytopenia and clinical outcomes compared with unfractionated heparin (UFH)., Background: Citrate-buffered tirofiban is currently marketed as brand-name drug. However, tirofiban has recently been promoted in some countries as a generic drug with different formulations, such as phosphate-buffered product., Methods: In the PRISM trial 3,232 patients were randomly assigned to receive tirofiban or UFH. In the early phase, 879 patients were allocated to phosphate-buffered tirofiban and 874 patients to UFH group. After a protocol amendment due to a study drug instability report, citrate-buffered tirofiban replaced the phosphate-buffered formulation. Therefore, in the late phase, 737 and 742 patients were treated with citrate-buffered tirofiban and UFH, respectively., Results: The relative risk for thrombocytopenia (nadir <90,000/mm(3) or <100,000/mm(3)) was increased in patients treated with phosphate-buffered tirofiban in the early phase (odds ratio [OR]: 3.51; 95% confidence interval [CI]: 1.15 to 10.73; p = 0.027; and OR: 2.83; 95% CI: 1.11 to 7.22; p = 0.029, respectively) but not in patients treated with citrate-buffered tirofiban in the late phase (OR: 1.01; 95% CI: 0.20 to 5.05; p = 0.987; and OR: 0.99; 95% CI: 0.26 to 3.45; p = 0.991, respectively). Using a combined definition of thrombocytopenia (nadir <150,000/mm(3) or a decrease ≥50%), the randomization period significantly modified the effect of the treatment (tirofiban vs. UFH) on platelet decrease (p for interaction = 0.024). Thrombocytopenia was associated with a 5- to 10-fold increased risk for TIMI (Thrombolysis In Myocardial Infarction) bleeding and a 2-fold increased risk for net adverse cardiovascular events., Conclusions: Phosphate-buffered tirofiban, currently marketed as a generic drug, is associated with a higher rate of thrombocytopenia with a potentially increased risk for adverse clinical outcomes compared with citrate-buffered tirofiban., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)