Aspirin is still the standard of care (SoC) in the US for patients with non-cardioembolic acute ischemic stroke (AIS) and transient ischemic attack (TIA) to reduce the risk of recurrence. Another antiplatelet drug, clopidogrel, which is sold by Sanofi under the brand name Plavix, is routinely prescribed in combination with aspirin in China. This combination is based on data from the CHANCE trial, which demonstrated a lower risk of stroke recurrence among Chinese patients who were assigned to the dual therapy. The administration of aspirin + clopidogrel has not been recommended by the American Heart Association (AHA)/American Stroke Association (ASA) guidelines, which were updated in January 2018, due to the restricted ethnic population and patterns of care in the CHANCE trial. Results of the Phase III POINT trial, which aimed to establish the generalised intervention of the drug combination in non-Asian populations, were published on May 16, 2018. Based on these results, GlobalData believes that clopidogrel prescriptions could increase in the US and EU for secondary stroke prevention; however, careful patient selection for the dual therapy will still be required.
The POINT trial enrolled 4881 patients with minor stroke or high-risk TIA at 269 international sites. Patients with a minor stroke had a score of ≥3 on the National Institutes of Health Stroke Scale (NIHSS), representing mild symptoms. High-risk TIA patients were defined by a score of ≥4 on the ABCD2 scale, which estimates the risk of recurrent stroke after a TIA on the basis of age, blood pressure, clinical features, duration of symptoms, and presence of diabetes. Although minor AIS and TIA do not cause disabling symptoms, they often precede a more severe stroke, signifying the importance of secondary stroke prevention to prevent debilitating and life-threatening events in these patients.
Antiplatelet treatment is recommended for patients with non-cardioembolic AIS or TIA to prevent another stroke or cardiovascular event, rather than anticoagulation treatment. Trials have unquestionably demonstrated that aspirin can reduce the risk of recurrent stroke by approximately 20%, but the same cannot be said for clopidogrel. As such, the drug has not been recommended a SoC by the US and EU guidelines, except for the UK, where clopidogrel monotherapy is recommended by the National Institute for Health and Care Excellence (NICE) as an option to prevent occlusive vascular events for patients who have had an AIS event.
Aspirin and clopidogrel are both platelet inhibitors, which act synergistically with aspirin in platelet-aggregation assays according to the POINT study authors. The aspirin + clopidogrel combination has been used for many years by cardiologists in patients with acute coronary syndrome (ACS) to reduce the risk of ischemic events. However, clopidogrel is prescribed sparingly for secondary stroke prevention, mainly in patients who are allergic to aspirin or who had a recent heart attack or coronary artery stenting.
The efficacy results of the POINT trial are encouraging since the trial showed a significantly lower risk of major ischemic events occurring in patients with minor AIS or high-risk TIA who received clopidogrel + aspirin (5.0%), compared to those who received aspirin alone (6.5%). However, unlike the CHANCE trial, the POINT trial also reported a higher risk of major hemorrhage at 90 days in patients receiving the combination compared to those who received aspirin monotherapy.
The major safety hurdle of all antithrombotic therapies is the associated increased risk of bleeding. Adding aspirin to clopidogrel in high-risk patients with recent AIS and TIA was previously associated with a higher risk of life-threatening bleeding in the randomised, double-blind MATCH trial. However, this trial did not show a significant improvement in stroke prevention when compared to SoC aspirin monotherapy.
Whether or not the recommendations by the AHA/ASA and EU guidelines about the use of clopidogrel + aspirin will be reconsidered based on the POINT trial results remains to be seen. Nevertheless, GlobalData expects that the encouraging efficacy data demonstrated by the POINT trial will increase the use of the dual therapy in AIS and TIA; however, physicians will still have to carefully select which patients should be prescribed the combination.
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