Clopidogrel for High Atherothrombotic Risk, Ischemic Stabilisation, Management and Avoidance (CHARISMA) is based on the already established fact that the dual antiplatelet therapy (aspirin plus clopidogrel) is superior and the benefits outweigh the side-effects when considered in patients with ST elevation MI, Non-ST elevation MI or in revascularization with PCI. However, the dual antiplatelet therapy has not been put under trial in patients with high atherothrombotic risk. Therefore, the idea was to broaden the scope of study and include a group enrolling patients with multiple risk factors prone to cardiovascular events and another group with established vascular disease. The idea seems to be quite intriguing especially considering the fact that high risk patients (diabetes) are now labelled as coronary artery disease equivalents and are treated as aggressively as established coronary artery disease (CAD). Therefore, it seems appropriate to have challenged the efficacy of dual antiplatelet therapy in patients at risk of developing atherothrombotic events.

While we have talked about its background importance, it is now easy for us to understand its implication in a physician’s practice. Unquestionably, it is a physician in general, in the primary healthcare services, who encounters these subset of patients without established disease, but at increased risk of developing the disease due to the presence of risk factors. Therefore, the results have more practical implication in the setting of a primary healthcare provider.


CHARISMA trial was carried out to find out whether or not dual antiplatelet therapy can provide enhanced protection against vascular events, as compared to aspirin alone, in patients with high risk factors, established coronary artery disease and/or symptomatic peripheral arterial disease (PAD). Over 15,000 patients were included from 32 countries and were followed up for a period of 28 months. Therefore, making it one of the largest trials in the field of cardiovascular medicine.

There was statistically no significant difference between the two groups (dual antiplatelet therapy group vs. aspirin alone) in terms of reducing primary end point events which were; myocardial infarction. Stroke or death for cardiovascular causes.

However, this result should not confuse any physician of the established fact that the dual antiplatelet therapy is significantly advantageous in patients with established coronary artery disease and/or those who have undergone revascularization procedure with stenting. Nevertheless, the debate still remains at deciding the optimal duration for continuation of dual antiplatelet therapy in such patients. American Heart Association (AHA) and European Society of Cardiology (ESC) further warns that patients should not decide on their own when to quit the dual antiplatelet therapy but rather should be discussed with the treating physician.

Giving a closer look at the subset of patients divided in to two groups; one, based on the established CAD and the other, with multiple risk factors for cardiovascular events. The results reinforced the findings that the benefits of adding clopidogrel to aspirin in patients with CAD outweighs the adverse events. Conversely, the dual antiplatelet therapy did not show any advantage in the risk factor only group. Rather, there was more harm in terms of increased risk of (GUSTO) bleeding.

Therefore, adding clopidogrel to aspirin, in patients with multiple risk factors, do not provide any protection against cardiovascular events. Adopting such practice doesn’t only prove to be cost-effective but also saves the patient and doctor from the harm of bleeding and transfusion, respectively.