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3.
Neth Heart J ; 32(2): 84-90, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37768542

ABSTRACT

OBJECTIVE: We describe the current treatment of elderly patients with non-ST-elevation myocardial infarction (NSTEMI) enrolled in a national registry. METHODS: The POPular AGE registry is a prospective, multicentre study of patients ≥ 75 years of age presenting with NSTEMI, performed in the Netherlands. Management was at the discretion of the treating physician. Cardiovascular events consisted of cardiovascular death, myocardial infarction and ischaemic stroke. Bleeding was classified according to the Bleeding Academic Research Consortium (BARC) criteria. RESULTS: A total of 646 patients were enrolled between August 2016 and May 2018. Median age was 81 (IQR 77-84) years and 58% were male. Overall, 75% underwent coronary angiography, 40% percutaneous coronary intervention, and 11% coronary artery bypass grafting, while 49.8% received pharmacological therapy only. At discharge, dual antiplatelet therapy (aspirin and P2Y12 inhibitor) was prescribed to 56.7%, and 27.4% received oral anticoagulation plus at least one antiplatelet agent. At 1­year follow-up, cardiovascular death, myocardial infarction or stroke had occurred in 13.6% and major bleeding (BARC 3 and 5) in 3.9% of patients. The risk of both cardiovascular events and major bleeding was highest during the 1st month. However, cardiovascular risk was three times as high as bleeding risk in this elderly population, both after 1 month and after 1 year. CONCLUSIONS: In this national registry of elderly patients with NSTEMI, the majority are treated according to current European Society of Cardiology guidelines. Both the cardiovascular and bleeding risk are highest during the 1st month after NSTEMI. However, the cardiovascular risk was three times as high as the bleeding risk.

4.
J Am Heart Assoc ; 12(24): e031855, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38063187

ABSTRACT

Thrombocytopenia is a rare but serious complication of the intravenous glycoprotein IIb/IIIa (GPIIb/IIIa; integrin αIIbß3) receptor inhibitors (GPIs), abciximab, eptifibatide, and tirofiban. The thrombocytopenia ranges from mild (50 000-100 000 platelets/µL), to severe (20 000 to <50 000/µL), to profound (<20 000/µL). Profound thrombocytopenia appears to occur in <1% of patients receiving their first course of therapy. Thrombocytopenia can be either acute (<24 hours) or delayed (up to ~14 days). Both hemorrhagic and thrombotic complications have been reported in association with thrombocytopenia. Diagnosis requires exclusion of pseudothrombocytopenia and heparin-induced thrombocytopenia. Therapy based on the severity of thrombocytopenia and symptoms may include drug withdrawals and treatment with steroids, intravenous IgG, and platelet transfusions. Abciximab-associated thrombocytopenia is most common and due to either preformed antibodies or antibodies induced in response to abciximab (delayed). Readministration of abciximab is associated with increased risk of thrombocytopenia. Evidence also supports an immune basis for thrombocytopenia associated with the 2 small molecule GPIs. The latter bind αIIbß3 like the natural ligands and thus induce the receptor to undergo major conformational changes that potentially create neoepitopes. Thrombocytopenia associated with these drugs is also immune-mediated, with antibodies recognizing the αIIbß3 receptor only in the presence of the drug. It is unclear whether the antibody binding depends on the conformational change and whether the drug contributes directly to the epitope. Zalunfiban, a second-generation subcutaneous small molecule GPI, does not induce the conformational changes; therefore, data from studies of zalunfiban will provide information on the contribution of the conformational changes to the development of GPI-associated thrombocytopenia.


Subject(s)
Platelet Aggregation Inhibitors , Thrombocytopenia , Humans , Abciximab/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Platelet Glycoprotein GPIIb-IIIa Complex , Antibodies, Monoclonal/therapeutic use , Immunoglobulin Fab Fragments/adverse effects , Tyrosine , Thrombocytopenia/chemically induced
5.
Heart ; 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-37996242

ABSTRACT

OBJECTIVES: The use of cerebral embolic protection (CEP) during transcatheter aortic valve implantation (TAVI) has been studied in several randomised trials. We aimed to perform a systematic review and Bayesian meta-analysis of randomised CEP trials, focusing on a clinically relevant reduction in disabling stroke. METHODS: A systematic search was applied to three electronic databases, including trials that randomised TAVI patients to CEP versus standard treatment. The primary outcome was the risk of disabling stroke. Outcomes were presented as relative risk (RR), absolute risk differences (ARDs), numbers needed to treat (NNTs) and the 95% credible intervals (CrIs). The minimal clinically important difference was determined at 1.1% ARD, per expert consensus (NNT 91). The principal Bayesian meta-analysis was performed under a vague prior, and secondary analyses were performed under two informed literature-based priors. RESULTS: Seven randomised studies were included for meta-analysis (n=3996: CEP n=2126, control n=1870). Under a vague prior, the estimated median RR of CEP use for disabling stroke was 0.56 (95% CrI 0.28 to 1.19, derived ARD 0.56% and NNT 179, I2=0%). Although the estimated posterior probability of any benefit was 94.4%, the probability of a clinically relevant effect was 0-0.1% under the vague and informed literature-based priors. Results were robust across multiple sensitivity analyses. CONCLUSION: There is a high probability of a beneficial CEP treatment effect, but this is unlikely to be clinically relevant. These findings suggest that future trials should focus on identifying TAVI patients with an increased baseline risk of stroke, and on the development of new generation devices. PROSPERO REGISTRATION NUMBER: CRD42023407006.

6.
Future Cardiol ; 19(13): 639-647, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37916603

ABSTRACT

The management of patients with suspected acute coronary syndrome, especially in prehospital settings, is challenging. This Special Report focuses on studies in emergency medical services concerning chest pain patients' triage and risk stratification. In addition, it emphasizes advancements in point-of-care cardiac troponin testing. These developments are compared with in-hospital guidelines, proposing an initial framework for a new acute care pathway. This pathway integrates a risk stratification tool with high-sensitivity cardiac troponin testing, aiming to deliver optimal care and collaboration within the acute care chain. It has the potential to contribute to a significant reduction in hospital referrals, reduce observation time and overcrowding at emergency departments and hospital admissions.


Subject(s)
Acute Coronary Syndrome , Emergency Medical Services , Humans , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/therapy , Triage , Emergency Service, Hospital , Troponin , Electrocardiography
7.
Eur Heart J Acute Cardiovasc Care ; 12(11): 782-791, 2023 Nov 16.
Article in English | MEDLINE | ID: mdl-37812760

ABSTRACT

AIMS: The role of coronary calcification on clinical outcomes among different revascularization strategies in patients presenting with acute coronary syndromes (ACSs) has been rarely investigated. The aim of this investigation is to evaluate the role of coronary calcification, detected by coronary angiography, in the whole spectrum of patients presenting with acute ACS. METHODS AND RESULTS: The present study was a post hoc analysis of the MATRIX programme. The primary endpoint was major adverse cardiovascular events (MACE), defined as the composite of all-cause mortality, myocardial infarction (MI), or stroke up to 365 days. Among the 8404 patients randomized in the MATRIX trial, data about coronary calcification were available in 7446 (88.6%) and therefore were included in this post hoc analysis. Overall, 875 patients (11.7%) presented with severe coronary calcification, while 6571 patients (88.3%) did not present severe coronary calcification on coronary angiography. Fewer patients with severe coronary calcification underwent percutaneous coronary intervention whereas coronary artery bypass grafting or medical therapy-only was more frequent compared with patients without severe calcification. At 1-year follow-up, MACE occurred in 237 (27.1%) patients with severe calcified coronary lesions and 985 (15%) patients without severe coronary calcified lesions [hazard ratio (HR) 1.91; 95% confidence interval (CI) 1.66-2.20, P < 0.001]. All-cause mortality was 8.6% in patients presenting with and 3.7% in those without severe coronary calcification (HR 2.38, 1.84-3.09, P < 0.001). Patients with severe coronary calcification incurred higher rate of MI (20.1% vs. 11.5%, HR 1.81; 95% CI 1.53-2.1, P < 0.001) and similar rate of stroke (0.8% vs. 0.6%, HR 1.35; 95% CI 0.61-3.02, P = 0.46). CONCLUSION: Patients with ACS and severe coronary calcification, as compared to those without, are associated with worse clinical outcomes irrespective of the management strategy.


Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Humans , Acute Coronary Syndrome/complications , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/epidemiology , Coronary Artery Bypass , Coronary Artery Disease/complications , Coronary Artery Disease/diagnosis , Coronary Artery Disease/surgery , Myocardial Infarction/complications , Percutaneous Coronary Intervention/methods , Randomized Controlled Trials as Topic , Risk Factors , Stroke/etiology , Treatment Outcome
8.
J Clin Med ; 12(17)2023 Aug 22.
Article in English | MEDLINE | ID: mdl-37685517

ABSTRACT

This registry assessed the impact of conservative and invasive strategies on major adverse clinical events (MACE) in elderly patients with non-ST-elevation myocardial infarction (NSTEMI). Patients aged ≥75 years with NSTEMI were prospectively registered from European centers and followed up for one year. Outcomes were compared between conservative and invasive groups in the overall population and a propensity score-matched (PSM) cohort. MACE included cardiovascular death, acute coronary syndrome, and stroke. The study included 1190 patients (median age 80 years, 43% female). CAG was performed in 67% (N = 798), with two-thirds undergoing revascularization. Conservatively treated patients had higher baseline risk. After propensity score matching, 319 patient pairs were successfully matched. MACE occurred more frequently in the conservative group (total population 20% vs. 12%, adjHR 0.53, 95% CI 0.37-0.77, p = 0.001), remaining significant in the PSM cohort (18% vs. 12%, adjHR 0.50, 95% CI 0.31-0.81, p = 0.004). In conclusion, an early invasive strategy was associated with benefits over conservative management in elderly patients with NSTEMI. Risk factors associated with ischemia and bleeding should guide strategy selection rather than solely relying on age.

9.
J Clin Med ; 12(18)2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37763014

ABSTRACT

The key role played by platelets in the atherosclerosis physiopathology, especially in the acute setting, is ascertained: they are the main actors during thrombus formation and, thus, one of the major investigated elements related to atherothrombotic process involving coronary arteries. Platelets have been studied from different points of view, according with the technology advances and the improvement in the hemostasis knowledge achieved in the last years. Morphology and reactivity constitute the first aspects investigated related to platelets with a significant body of evidence published linking a number of their values and markers to coronary artery disease and cardiovascular events. Recently, the impact of genetics on platelet activation has been explored with promising findings as additional instrument for patient risk stratification; however, this deserves further confirmations. Moreover, the interplay between immune system and platelets has been partially elucidated in the last years, providing intriguing elements that will be basic components for future research to better understand platelet regulation and improve cardiovascular outcome of patients.

10.
Neth Heart J ; 31(11): 426-433, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37713051

ABSTRACT

BACKGROUND: The safety of administration of tirofiban, a platelet glycoprotein IIb/IIIa inhibitor, followed by a clopidogrel loading dose in clopidogrel-naïve patients undergoing ad-hoc percutaneous coronary intervention (PCI) is not yet clear. METHODS: In a retrospective observational cohort analysis, clopidogrel-naïve patients undergoing ad-hoc PCI who received a high-dose bolus of tirofiban (25 µg/kg) followed by a 600-mg clopidogrel loading dose (group 1) were compared with patients undergoing elective PCI who were pretreated with clopidogrel (group 2), between September 2014 and October 2021. The primary outcome was major adverse cardiovascular events (MACE) defined as the composite of death, myocardial infarction, stroke, target-lesion revascularisation and bleeding at 30 days. Secondary outcomes were MACE at 7 days and individual components of the primary outcome at 7 and 30 days. RESULTS: A total of 1404 patients were included: 432 (31%) in group 1 and 972 (69%) in group 2. Median age was 69 years, and 28% were female. At 7­day follow-up, MACE occurred in 1.4% in group 1 versus 3.0% in group 2 (p = 0.08). 30-day MACE were observed in 1.9% in group 1 and 4.2% in group 2 (p = 0.03). Secondary outcomes were comparable between the groups. Cox regression analysis, corrected for baseline differences, revealed no significant difference in the primary outcome (hazard ratio: 1.8; 95% confidence interval: 0.8-3.9). CONCLUSION: Ad-hoc PCI in clopidogrel-naïve patients who were treated with high-dose bolus of tirofiban followed by a clopidogrel loading dose immediately after the procedure appeared to be safe.

11.
Front Cardiovasc Med ; 10: 1219589, 2023.
Article in English | MEDLINE | ID: mdl-37727302

ABSTRACT

Background: Inefficient ventilation is an established prognostic marker in patients with heart failure. It is not known whether inefficient ventilation is also linked to poor prognosis in patients with left ventricular dysfunction (LVD) but without overt heart failure. Objectives: To investigate whether inefficient ventilation in elderly patients with LVD is more common than in patients without LVD, whether it improves with exercise-based cardiac rehabilitation (exCR), and whether it is associated with major adverse cardiovascular events (MACE). Methods: In this large multicentre observational longitudinal study, patients aged ≥65 years with acute or chronic coronary syndromes (ACS, CCS) without cardiac surgery who participated in a study on the effectiveness of exCR in seven European countries were included. Cardiopulmonary exercise testing (CPET) was performed before, at the termination of exCR, and at 12 months follow-up. Ventilation (VE), breathing frequency (BF), tidal volume (VT), and end-expiratory carbon dioxide pressure (PETCO2) were measured at rest, at the first ventilatory threshold, and at peak exercise. Ventilatory parameters were compared between patients with and without LVD (based on cardio-echography) and related to MACE at 12 month follow-up. Results: In 818 patients, age was 72.5 ± 5.4 years, 21.9% were women, 79.8% had ACS, and 151 (18%) had LVD. Compared to noLVD, in LVD resting VE was increased by 8%, resting BF by 6%, peak VE, peak VT, and peak PETCO2 reduced by 6%, 8%, and 5%, respectively, and VE/VCO2 slope increased by 11%. From before to after exCR, resting VE decreased and peak PETCO2 increased significantly more in patients with compared to without LVD. In LVD, higher resting BF, higher nadir VE/VCO2, and lower peak PETCO2 at baseline were associated with MACE. Conclusions: Similarly to patients with HF, in elderly patients with ischemic LVD, inefficient resting and exercise ventilation was associated with worse outcomes, and ExCR alleviated abnormal breathing patterns and gas exchange parameters.

12.
Future Cardiol ; 19(10): 497-504, 2023 08.
Article in English | MEDLINE | ID: mdl-37702223

ABSTRACT

Aim: This study aims to enhance prehospital risk assessment for suspected non-ST-elevation acute coronary syndrome (NSTE-ACS) patients using the HEART-score. By incorporating novel point-of-care high-sensitivity cardiac troponin devices, a modified HEART-score was developed and compared with the conventional approach. Patients & methods: Troponin points within the modified HEART-score are based on values below the limit of quantitation (LoQ), between the LoQ and 99th percentile and above the 99th percentile of the used device. A total HEART-score of three or lower is considered low-risk for major adverse cardiac events. Results & conclusion: The number of low-risk patients decreased based on the modified HEART-score. The sensitivity and negative predictive value increased which suggests increasing safety in ruling out patients with suspected NSTE-ACS.


Subject(s)
Acute Coronary Syndrome , Humans , Acute Coronary Syndrome/diagnosis , Troponin , Risk Assessment/methods , Predictive Value of Tests , Biomarkers
13.
J Thromb Thrombolysis ; 56(4): 499-510, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37563502

ABSTRACT

Understanding the pharmacodynamic effects of platelet inhibitors is standard for developing more effective antithrombotic therapies. An example is the antithrombotic treatment of acute coronary syndrome (ACS), in particular ST-elevated myocardial infarction (STEMI) patients who are in need for rapid acting strong antithrombotic therapy despite the use of aspirin and oral P2Y12-inhibitors. In this study, we evaluated two injectable platelet inhibitors under clinical development (the P2Y12 antagonist selatogrel and the GPIIb-IIIa antagonist zalunfiban) that may be amenable to pre-hospital treatment of STEMI patients. Platelet reactivity was assessed at inhibitor concentrations that represent clinically relevant levels of platelet inhibition (IC20-50%, 1/2Cmax, and Cmax). Light transmission aggregometry (LTA), was used to evaluate the initial rate of aggregation (primary slope, PS) and maximal aggregation (MA). Both adenosine diphosphate (ADP) and thrombin receptor agonist peptide (TRAP) were used as agonists. Zalunfiban demonstrated similar inhibition of platelet aggregation when blood was collected in PPACK or TSC, whereas selatogrel demonstrated greater inhibition in PPACK. In this study, using PPACK anticoagulant, selatogrel and zalunfiban affected PS in response to ADP equivalently at all drug concentrations tested. In contrast, zalunfiban had significantly greater potency at its Cmax concentration compared to selatogrel using TRAP as agonist. Upon evaluation of MA responses at lower doses, selatogrel had greater inhibition of MA in response to ADP than zalunfiban; however, at concentrations that represent Cmax, the drugs were equivalent. Zalunfiban also had greater inhibition of MA in response to TRAP at the Cmax dose. These data suggest that zalunfiban may provide greater protection in reducing thrombus formation than selatogrel, especially since thrombin is an early, key primary agonist in the pathophysiology of thrombotic events.

14.
Article in English | MEDLINE | ID: mdl-37567588

ABSTRACT

OBJECTIVES: Multidisciplinary approach is well established in various disciplines, with evidence highlighting improved patient outcomes. The objective of this survey was to determine the real-world practice of heart teams across Europe. METHODS: The survey was drafted after a consensus opinion from the authors. The survey was sent to cardiac surgeons and cardiologists identified through electronic search. The survey link and the information sheet were sent through email followed by survey completion reminders. The survey responses were cumulated and analysed. RESULTS: Among 2188 invited clinicians, 220 clinicians from 26 countries took part in the survey (response rate 10%). The completion rate for the survey questions was 85%. A total of 140 (64%) were cardiac surgeons and 80 (36%) were cardiologists. The heart team meeting frequency was weekly according to 104 (55%) respondents. This was conducted face to face according to 139 (73%) of the responses. Eighty-seven (56%) of the respondents reported 10-20% of patients undergoing percutaneous coronary intervention were discussed at the heart team meeting. Seventy-nine (47%) respondents had ad hoc percutaneous coronary intervention institutional guidelines. Fifty-four (32%) respondents reported an audit process for the heart team decisions. CONCLUSIONS: This survey suggests that there is marked variability in the infra-structure and execution of heart teams in different institutions. The results of the survey suggest a need to formulate guidelines on the composition and execution of heart teams which may result in an increase in transparency of decision-making within different institutions in reporting and comparing outcomes.

15.
EuroIntervention ; 19(9): 766-771, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37605804

ABSTRACT

About one-third of patients undergoing transcatheter aortic valve implantation (TAVI) use oral anticoagulants (OAC), mainly due to atrial fibrillation. General guidelines advise interrupting OAC in patients with a high risk of bleeding undergoing interventions. However, preliminary observational data suggest that the continuation of OAC during TAVI is safe and may reduce the risk of periprocedural thromboembolic events. The Periprocedural Continuation Versus Interruption of Oral Anticoagulant Drugs During Transcatheter Aortic Valve Implantation (POPular PAUSE TAVI) is a multicentre, randomised clinical trial with open-label treatment and blinded endpoint assessment. Patients are randomised 1:1 to periprocedural continuation versus interruption of OAC and are stratified for vitamin K antagonist or direct oral anticoagulant use. The primary endpoint is a composite of cardiovascular mortality, all stroke, myocardial infarction, major vascular complications and type 2-4 bleeding within 30 days after TAVI, according to the Valve Academic Research Consortium-3 criteria. Secondary endpoints include separate individual and composite outcomes, quality of life and cost-effectiveness. Since continuation of OAC is associated with the ancillary benefit that it simplifies periprocedural management, the primary outcome is first analysed for non-inferiority; if non-inferiority is proven, superiority will be tested. Recruitment started in November 2020, and the trial will continue until a total of 858 patients have been included and followed for 90 days. In summary, POPular PAUSE TAVI is the first randomised clinical trial to assess the safety and efficacy of periprocedural continuation versus interruption of OAC in patients undergoing TAVI.


Subject(s)
Aortic Valve Stenosis , Transcatheter Aortic Valve Replacement , Humans , Quality of Life , Anticoagulants/therapeutic use , Hemorrhage , Treatment Outcome , Aortic Valve/surgery , Risk Factors
16.
Am Heart J ; 265: 114-120, 2023 11.
Article in English | MEDLINE | ID: mdl-37517430

ABSTRACT

BACKGROUND: Early aspirin withdrawal, also known as P2Y12-inhibitor monotherapy, following percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can reduce bleeding without a trade-off in efficacy. Still the average daily bleeding risk is highest during the first months and it remains unclear if aspirin can be omitted immediately following PCI. METHODS: The LEGACY study is an open-label, multicenter randomized controlled trial evaluating the safety and efficacy of immediate P2Y12-inhibitor monotherapy versus dual antiplatelet therapy (DAPT) for 12 months in 3,090 patients. Patients are randomized immediately following successful PCI for NSTE-ACS to 75-100 mg aspirin once daily versus no aspirin. The primary hypothesis is that immediately omitting aspirin is superior to DAPT with respect to major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, while maintaining noninferiority for the composite of all-cause mortality, myocardial infarction and stroke compared to DAPT. CONCLUSIONS: The LEGACY study is the first randomized study that is specifically designed to evaluate the impact of immediately omitting aspirin, and thus treating patients with P2Y12-inhibitor monotherapy, as compared to DAPT for 12 months on bleeding and ischemic events within 12 months following PCI for NSTE-ACS.


Subject(s)
Acute Coronary Syndrome , Percutaneous Coronary Intervention , Humans , Aspirin , Platelet Aggregation Inhibitors/adverse effects , Acute Coronary Syndrome/drug therapy , Acute Coronary Syndrome/surgery , Percutaneous Coronary Intervention/methods , Drug Therapy, Combination , Hemorrhage/chemically induced , Treatment Outcome
17.
Article in English | MEDLINE | ID: mdl-37486278

ABSTRACT

OBJECTIVES: Prehabilitation through a digital platform could preoperatively improve the physical and mental fitness of patients undergoing cardiothoracic surgery, thereby improving treatment outcomes. This study aimed to describe the reasons and predictors of non-participation in a personalized digital prehabilitation care trial (Digital Cardiac Counseling randomized controlled trial) for patients undergoing elective cardiothoracic surgery. METHODS: Adult patients scheduled for elective cardiothoracic surgery at the Maastricht University Medical Center+ were approached to participate in a digital prehabilitation care trial, in which patients were informed about their care pathway, monitored for symptom progression and screened for preoperative modifiable risk factors. Baseline characteristics of all eligible patients and reasons of non-participation were registered prospectively. Predictors of non-participation were determined using logistic regression. RESULTS: Between May 2020 and August 2022, 815 patients were eligible for participation; 421 (52%) did not participate in the personalized digital prehabilitation care trial. Reasons for non-participation were 'lack of internet access or insufficient digital skills' (32%), 'wishing no participation' (39%) and 'other reasons' (30%; e.g. vision or hearing impairments, analphabetism, language barriers). Independent predictors of non-participation were age [odds ratio (OR) 1.024 (1.003-1.046), P = 0.024], socioeconomic status [OR 0.267 (0.133-0.536), P < 0.001], current smoker [OR 1.823 (1.124-2.954), P = 0.015] and EuroSCORE II [OR 1.160 (1.042-1.292), P = 0.007]. CONCLUSIONS: Half of the eligible patients did not participate in a personalized digital prehabilitation care trial. Non-participants were vulnerable patients, with a more unfavourable risk profile and more modifiable risk factors, who could potentially benefit the most from prehabilitation.

19.
Am Heart J ; 262: 75-82, 2023 08.
Article in English | MEDLINE | ID: mdl-37088164

ABSTRACT

BACKGROUND: Zalunfiban (RUC-4) is a novel, subcutaneously administered glycoprotein IIb/IIIa inhibitor (GPI) designed for prehospital treatment to initiate reperfusion in the infarct-related artery (IRA) before primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction (STEMI). Since GPIs have been reported to rapidly reperfuse IRAs, we assessed whether there was a dose-dependent relationship between zalunfiban treatment and angiographic reperfusion indices and thrombus grade of the IRA at initial angiogram in patients with STEMI. METHODS: This was a post hoc analysis from the open-label Phase IIa study that investigated the pharmacodynamics, pharmacokinetics, and tolerability of three doses of zalunfiban - 0.075, 0.090 and 0.110 mg/kg - in STEMI patients. This analysis explored dose-dependent associations between zalunfiban and three angiographic indices of the IRA, namely coronary and myocardial blood flow and thrombus burden. Zalunfiban was administered in the cardiac catheterization laboratory prior to vascular access, ∼10 to 15 minutes before the initial angiogram. All angiographic data were analyzed by a blinded, independent, core laboratory. RESULTS: Twentyfour out of 27 STEMI patients were evaluable for angiographic analysis (0.075 mg/kg [n=7], 0.090 mg/kg [n=9], and 0.110 mg/kg [n=8]). TIMI flow grade 2 or 3 was seen in 1/7 patients receiving zalunfiban at 0.075 mg/kg, in 6/9 patients receiving 0.090 mg/kg, and in 7/8 patients receiving 0.110 mg/kg (ptrend = 0.004). A similar trend was observed based on TIMI flow grade 3. Myocardial perfusion was also related to zalunfiban dose (ptrend = 0.005) as reflected by more frequent TIMI myocardial perfusion grade 3. Consistent with the dose-dependent trends in greater coronary and myocardial perfusion, TIMI thrombus ≥4 grade was inversely related to zalunfiban dose (ptrend = 0.02). CONCLUSION: This post hoc analysis found that higher doses of zalunfiban administered in the cardiac catheterization lab prior to vascular access were associated with greater coronary and myocardial perfusion, and lower thrombus burden at initial angiogram in patients with STEMI undergoing primary percutaneous coronary intervention.


Subject(s)
Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/drug therapy , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/drug therapy , Coronary Angiography , Heart , Treatment Outcome
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