Prasugrel (trade name Effient in the US and India, and Efient in the EU) is a drug used to prevent the formation of blood clots. It is a platelet inhibitor and an irreversible anatagonist of P2Y12 ADP receptors and is of the thienopyridine drug class. It was developed by Daiichi Sankyo Co. and produced by Ube and currently marketed in the United States in cooperation with Eli Lilly and Company.
Prasugrel was approved for use in Europe in February 2009, and in the US in July 2009, for the reduction of thrombotic cardiovascular events (including stent thrombosis) in people with acute coronary syndrome (ACS) who are to be managed with a percutaneous coronary intervention (PCI).
Key points about prasugrel:
Mechanism of Action: Prasugrel blocks the P2Y12 receptor on platelets, which is responsible for platelet activation and aggregation. By inhibiting this receptor, prasugrel reduces the likelihood of blood clot formation, thereby helping to prevent heart attacks and other cardiovascular events.
Indications: Prasugrel is primarily used in combination with aspirin to prevent thrombotic events in patients with acute coronary syndrome (ACS) undergoing PCI, which includes angioplasty and stent placement. It may also be prescribed for patients with unstable angina.
Dosage: The dosage of prasugrel varies depending on the individual's health condition and medical history. It is typically administered as an oral tablet.
Onset and Duration of Action: Prasugrel exhibits a quicker onset of action compared to another commonly used antiplatelet drug, clopidogrel. It achieves its maximal effect within a few hours after administration and remains active in the body for a few days.
Precautions and Side Effects: Like other antiplatelet medications, prasugrel can increase the risk of bleeding. Patients taking prasugrel should be cautious and report any signs of bleeding or unusual bruising to their healthcare provider. It is important to inform the healthcare provider about any other medications being taken, as certain drugs can interact with prasugrel and affect its effectiveness or increase the risk of bleeding.
Contraindications: Prasugrel is not recommended for patients with a history of stroke or transient ischemic attack (TIA) due to an increased risk of bleeding. It is also contraindicated in patients with active pathological bleeding and those with a known hypersensitivity to the drug.
Prophylactic prasugrel for endovascular treatment of intracranial aneurysms has been introduced and increased, but HTPR (high on-treatment platelet reactivity) or LTPR (low on-treatment platelet reactivity) of prasugrel is not uncommon in clinical circumstances. To investigate the predisposing factors of HTPR and LTPR on prasugrel premedication in the neurointerventional field and to determine its clinical implications.
Between February 2016 and December 2020, 191 patients treated with coil embolization using prophylactic prasugrel in 234 intracranial aneurysms were the final candidates for this study. Patient and aneurysm characteristics, clinical status, and laboratory study values were carefully reviewed retrospectively. We performed risk factor analyses for HTPR and LTPR on prasugrel.
Ultimately, 20 patients (10.5%) had HTPR, and 74 patients (38.7%) were categorized as having LTPR. In multivariable analyses, the factors related to HTPR were BMI (adjusted OR 1.21, 95% CI 1.04-1.41, p = 0.01), history of antithrombotics (adjusted OR 3.79, 95% CI 1.39-10.34, p = 0.01), and hematocrit (adjusted OR 0.91, 95% CI 0.84-0.99, p = 0.03). Low BMI was the only risk factor for LTPR (adjusted OR 0.84, 95% CI 0.76-0.94, p = 0.001).
In the neurointerventional field, high BMI and prior use of antithrombotic agents were related to HTPR, and low BMI was associated with LTPR on prophylactic prasugrel. High hematocrit levels decreased the risk of HTPR. When preparing endovascular treatment for intracranial aneurysms, attention to patients with these clinical features is required to address the possibility of ischemic or bleeding complications 1).
In a cohort of patients treated with PEDs, prasugrel (10 mg/day) was a safe alternative to clopidogrel-resistant or clopidogrel-allergic patients, or nonresponders 2).
Data suggest that many patients exhibit clopidogrel resistance. Prasugrel a thienopyridine lowers the rate of cardiac stent thromboses in clopidogrel non-responders.
A study examined the safety and efficacy of prasugrel in the management of clopidogrel-resistant patients treated for cerebral aneurysms.
Four hundred thirty-seven consecutive patients were identified between January 2011 and May 2016. Patients allergic, or having less than 30% platelet inhibition, to a daily 75-mg dose of clopidogrel received 10 mg of prasugrel daily (n = 20) or 90 mg of ticagrelor twice daily (n = 2). The mean (± SD) follow-up duration was 15.8 ± 12.4 months. The primary outcome was the modified Rankin Scale (mRS) score registered before discharge and at each follow-up visit. To control confounding, multivariable mixed-effects logistic regression and propensity score conditioning were used. RESULTS Twenty-six (5.9%) of 437 patients presented with a subarachnoid hemorrhage (SAH). The mean patient age was 56.3 years, and 62 were women (14.2%). One of the 7 patients lost to follow-up received prasugrel. One patient was allergic to clopidogrel and prasugrel simultaneously. All patients receiving prasugrel or ticagrelor (n = 22) had an mRS score ≤ 2 on their latest follow-up visit (mean score 0.67 ± 1.15). In a multivariate analysis, clopidogrel did not affect the mRS score on last follow-up (p = 0.14). Multivariable logistic regression showed that clopidogrel was not associated with an increased long-term recurrence rate (OR 0.17, 95% CI 0.01-2.70, p = 0.21), an increased thromboembolic complication rate (OR 0.46, 95% CI 0.12-1.67, p = 0.24), or an increased hemorrhagic event rate (OR 0.39, 95% CI 0.91-1.64, p = 0.20). None of the patients receiving prasugrel or ticagrelor died or suffered a long-term recurrence or a hemorrhagic event; only 1 patient suffered from mild aphasia subsequent to a thromboembolic event. Three patients taking clopidogrel died during the study: 2 from acute SAH and 1 from intraparenchymal hemorrhage. Clopidogrel was not associated with an increased mortality rate (OR 2.18, 95% CI 0.11-43.27, p = 0.61). The same associations were present in propensity score-adjusted models.
In a cohort of patients treated with PEDs, prasugrel (10 mg/day) was a safe alternative to clopidogrel-resistant or clopidogrel-allergic patients, or nonresponders 3).
Significant heterogeneity in dual antiplatelet therapy regimens following Pipeline Embolization Device (PED) placement and associated costs, exists at major academic neurovascular centers. The most commonly used first line dual antiplatelet regimen consists of aspirin and clopidogrel. Two major alternate protocols involving ticagrelor and prasugrel, are administered to clopidogrel hypo-responders. The optimal dual antiplatelet regimen for patients with cerebrovascular conditions has not been established, given limited prospective data within the neurointerventional literature 4).
Results suggest that DAPT with aspirin/prasugrel may predispose to a higher risk of hemorrhage during neurointerventional surgery compared with DAPT with aspirin/clopidogrel 5).
In a pilot trial, treatment of distal unruptured intracranial aneurysms with an FD under monotherapy with prasugrel, followed by monotherapy with aspirin, appeared to be safe and effective. Randomized studies with long term follow-up are needed to confirm these results 6)