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.
Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EIT Health education grant. Background Cardiac telerehabilitation (CTR) is a continuously developing cardiac rehabilitation (CR) format that might offer a solution to some of the challenges centre-based CR programs face. CR centres continue to face suboptimal participation in their provided CR program. The COVID-19 pandemic encouraged CR centres to implement their own CTR program to tackle practical challenges and to improve participation in CR. Multiple centres have since then developed a CTR program in accordance to (inter)national guidelines. CTR aims to improve the quality of life of patients, therefore analyses of quality of life is essential. Purpose Our study aims to analyse quality of life changes over a period of three months after program initiation for patients choosing to participate in either centre-based CR or CTR. Methods Our study included (N)STEMI patients eligible for CR between November 2021 and November 2022. Patients were invited by the cardiac rehabilitation nurse during intake to participate in CR. Patients were offered the choice between centre-based CR and CTR. The centre-based CR exercise program typically lasted for 6-8 weeks and the CTR program for a total of 48 weeks. CTR offers remote-access, digital platform for patients to interact with their healthcare professionals. The digital platform monitors physical activity and progress, which can be access by both patients and coaches. Coaches provide remote-access feedback. The SF-36 questionnaire was send out right after the CR intake procedure (T0) and three months after the CR intake procedure (T1). We only analysed data from participants who completed both T0 and T1 questionnaires, using the paired sample T-test for both CTR and centre-based CR. Results Until now, 173 patients have been included in the study of which 42 patients (24%) participated in CTR. 143 patients reached T1. 84 (59%) participants completed both T0 and T1 questionnaires, of which 24 (29%) participate in CTR (92% male, mean age 60) and 60 (71%) participate in centre-based CR (80% male, mean age 64). Participants from the centre-based CR program improved on both physical (score: +11,12; p < 0,001) and emotional (score: +9,30; p = 0,028) role functioning over a three month period. Participants in the CTR program improved on physical role functioning (score: +18,75; p = 0,002) and social functioning (score: + 13,54; p = 0,019). Conclusion Our preliminary show that patients were able to improve quality of life in both CTR and centre-based CR. Therefore, CTR can be used as an alternative to centre-based CR as standard care. Future research should focus on long term effects on quality of life.
Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EIT Health Campus Rationale Cardiac rehabilitation (CR) programmes are successful in educating patients and lowering their cardiovascular (CV) risk. However attendance before COVID was between 8 and 50%. Because of short duration of CR programmes sustainability in behaviour change is often suboptimal. The COVID pandemic has shown us the need for high quality remote CR. Mobile guided CR (mCR) has proven to be equally effective as centre-based CR and has the potential to increase participation rates. It also provides possibilities to extend the CR programme. Extending CR programmes with ehealth solutions have shown mixed results on sustainable behaviour change. It is still unknown what type of patients prefer mCR above regular CR when offered as standard care. REHAB+ Rehab+ is a mobile CR program, offered for one year to patients after myocardial infarction as an alternative to the regular CR program. It offers an optimised digital platform and regular interaction with the healthcare team. Patients are able to measure and register physical activity, heart frequency and intensity (BORG scale) and can monitor progress. A care professional (coach) also has access to a portal to monitor progress of different patients, advice on rehabilitation approach and stimulate compliance. Rehab+ is co-created with patients and rehab centres. In 2022, it will conclude its pilot and evaluation in 4 centres (Spain and the Netherlands), and scaled to more in the EU. Objectives 1. To assess whether mCR programmes result in better sustained effects, as compared to the regular CR programme. 2. To explore what type of patients prefer mCR above a regular CR programme. Study population 900 Post myocardial infarction patients (300 mCR, 600 regular CR) who are indicated for CR. (See figure 1) Patients not able or willing to participate will be registered in an exclusion log. mCR patients will be coached for 12 months with decreasing amounts of touchpoints. Regular CR patients receive no coaching after the end of the regular CR program. Study design Prospective, matched control observational trial Follow-up Patients will be monitored at (see table 1): - T0: baseline characteristics, exercise test, laboratory tests, Fägerstrom test, IPAQ questionnaire, SF-36 questionnaire - T1 (3 months): Physical exam, medication, ECG, laboratory tests, adherence and compliance (mCR only),Fägerstrom test, IPAQ questionnaire, SF-36 questionnaire, eHIQ questionnaire - T2 (12 months): Physical exam, medication, ECG, laboratory tests, exercise test, adherence and compliance (mCR only),Fägerstrom test, IPAQ questionnaire, SF-36 questionnaire, eHIQ questionnaire Conclusion Inclusion will start in November 2021. The results of this study will give insight in what type of patients choose to participate in mCR. With this information mCR programmes can be further optimised and adjusted. It may help to further increase participation rates in CR.
Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Celecor Therapeutics Background/Introduction Thrombocytopenia is a rare but severe complication (0.5%-2.0%) of all currently available glycoprotein IIb/IIIa inhibitors (GPI). As thrombocytopenia is inherently linked to bleeding, careful consideration is mandated in ST-elevation myocardial infarction (STEMI) patients as they require multiple antithrombotic medications. Moreover, thrombocytopenia is associated with poor clinical outcomes in comparison to patients without thrombocytopenia. Thus, there is a need for safer GPIs that are not associated with drug-induced thrombocytopenia. Zalunfiban is a novel, second-generation GPI primarily designed for the pre-hospital phase to initiate target vessel reperfusion. In addition, Zalunfiban has a unique mechanism of action that locks the receptor into an inactive conformation, potentially decreasing the likelihood of developing thrombocytopenia. In healthy individuals and in patients with stable coronary artery disease treated with Zalunfiban, no thrombocytopenia was seen. Purpose To assess the occurrence of thrombocytopenia of Zalunfiban in STEMI patients. Methods This was a prospective, single centre, open-label, phase 2a study designed to assess the pharmacodynamics, pharmacokinetics, and tolerability of Zalunfiban in patients with STEMI undergoing primary percutaneous coronary intervention. The primary endpoint in this sub-analysis was the occurrence of thrombocytopenia, defined as a platelet count less than 150 × 10^9/L, as measured at 4 time points up to 72 hours after drug administration. Secondary analyses were laboratory assessments including haemoglobin, creatinine and liver function tests. Results A total of 27 patients received a weight-adjusted subcutaneous injection of Zalunfiban in escalating doses (0.075 mg/kg [n=8], 0.090 mg/kg [n=9], or 0.110 mg/kg [n=10]). No thrombocytopenia (0.0%) was observed within the first 72 hours post dose. Also, haemoglobin, creatinine and liver function tests were stable during hospitalisation. Conclusion In this sub-analysis Zalunfiban did not cause thrombocytopenia in the 27 patients enrolled in the study, which is in accord with the lack of thrombocytopenia in the 44 patients receiving Zalunfiban in the Phase 1 studies in healthy volunteers and stable angina patients. The ongoing CELEBRATE study, in which Zalunfiban is administered in the ambulance, is scheduled to enrol 1667 STEMI patients and thus will provide important additional information on Zalunfiban safety and efficacy.
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