Is Pre-Hospital Administration the Future for Antiplatelet Therapies?
Primary Percutaneous Coronary Intervention (PCI), the insertion of a stent to widen blood vessels around the heart, is the preferred treatment for patients suffering an Acute Myocardial Infarction (AMI), and to address atherosclerosis. Patients undergoing PCI are commonly administered an adjuvant antiplatelet therapy to reduce the risk of clots forming on the stent and to improve blood flow. Currently available options include aspirin, P2Y12 inhibitors, glycoprotein IIb/IIIa inhibitors and heparins. However, with multiple novel antiplatelet therapies entering late-stage development in 2021, the future treatment algorithm for PCI-adjunctive therapies may be set to change.
There is a drive for earlier antiplatelet administration in AMI, and emerging PCI-adjunctive antiplatelet therapies are being developed for use in pre-hospital settings. A key factor in enabling this is route of administration (RoA), as established intravenous therapies, such as Chiesi’s Kengreal and Medicure’s Aggrastat, are reserved for in-hospital settings. In contrast, PCI-adjunctive therapies in development are characterised by convenient RoAs that facilitate administration and potentially lead to a more rapid onset of effect. For example, AstraZeneca’s Brilinta OTD dissolves in the mouth, improving absorption, and has been evaluated in comparison to standard of care as a PCI-adjunctive. Subcutaneous (SC) administration is also being explored for Indorsia’s Selatogrel, a P2Y12 inhibitor, and Celecor’s Zalunfiban, a glycoprotein IIb/IIIa inhibitor. In particular, the latter two companies are leveraging the SC RoA of their products to position them as suitable for early administration to MI patients in pre-hospital settings.
Pre-hospital settings being explored include self-administration, with Indorsia’s ongoing Ph3 SOS-AMI trial investigating the efficacy of Selatogrel when self-administered by acute coronary syndrome patients who suspect they are having an AMI. To facilitate self-administration, Selatogrel is delivered via an easy-to-use autoinjector, and the company provides training on recognition of the symptoms of AMI and on use of the autoinjector. Additionally, administration of antiplatelet therapies in ambulances is being explored; the efficacy of Celecor’s Zalunfiban when given to AMI patients by paramedics in the ambulance, pre-PCI, is currently being investigated in the pivotal Ph2b CELEBRATE trial.
Safety is also important consideration for use of antiplatelet therapies in pre-hospital settings. Several established PCI-adjunctive therapies feature black box warnings due to the risk of severe bleeding, and administration outside a controlled hospital setting could be expected to increase this risk. To address this, Advance Cor are developing a novel glycoprotein IV antagonist, Revacept, which blocks thrombi formation without increasing the risk of bleeding and could also be suitable for use in outpatient settings. Indorsia’s Selatogrel also boasts a short duration of action, reducing the risk of bleeding.
Multiple novel antiplatelet therapies have entered registrational trials in the first half of 2021 and a wave of potential approvals is anticipated in 2024-25. Early antiplatelet treatment leads to better outcomes for AMI patients and emerging therapies are being positioned as suitable for near-immediate administration in pre-hospital settings. These products could significantly change the treatment algorithm for PCI-adjunctive therapies, and the future of AMI treatment may begin with a self- or paramedic-administered antiplatelet therapy, analogous to the use of an EpiPen for severe allergies.