A new course for cardiovascular outcomes in ACS

Cardiovascular diseases continue to be a leading cause of death globally, with an estimated 17.9 million deaths annually due to these conditions. In the Philippines, the situation is no different. Statistics covering January to April of 2025 show that ischemic heart diseases were the leading cause of death in the country, accounting for 20% of all deaths during this period.^1,2

This data shows the importance of optimizing approaches to cardiovascular care, especially when it comes to conditions like acute coronary syndrome (ACS) or stroke. In these conditions, secondary prevention of recurring events is essential as recurrence is likely for patients who have experienced these events, putting them at great risk of mortality.³

Antiplatelet agents like clopidogrel are essential for the secondary prevention for stroke and myocardial infarction (MI), making them an important aspect of managing ACS. Clopidogrel is an antiplatelet medication that inhibits the P2Y12 adenosine diphosphate receptor, which is key to platelet function, making it a potent antithrombotic agent.^4,5

CAPRIE study: Clopidogrel vs. aspirin

The CAPRIE study was one of the first major clinical trials to show the efficacy of clopidogrel for secondary prevention of thrombotic events. The trial included over 19,000 patients who had suffered from stroke, MI or atherosclerotic peripheral arterial disease who were given either clopidogrel or aspirin, another mainstay of antithrombotic treatment.⁶

The study followed patients for up to three years, with ischemic stroke, MI, primary intracranial hemorrhage and leg amputation as non-fatal outcome events. It also tracked deaths due to stroke, MI, hemorrhage, or non-vascular causes. The study found that patients taking clopidogrel had an 8.7% relative risk reduction for ischemic stroke, MI, and vascular death compared to patients taking aspirin (see Figure).

 Figure. Cumulative risk reduction in ischemic stroke, myocardial infarction or vascular death in patients taking either aspirin or clopidogrel in the CAPRIE trial.⁶

Clopidogrel in DAPT regimen: Efficacy and risks

While clopidogrel has proven to be an effective antithrombotic in its own right, dual antiplatelet therapy (DAPT) has become a central strategy for the prevention of MI and stroke. This approach usually combines aspirin and a P2Y12 inhibitor, reducing the risk of a recurrent event more effectively compared to either treatment alone.⁷

In addition to its efficacy as a monotherapy, clopidogrel has also found a home as part of a DAPT regimen. The CURE study looked at over 12,000 patients recovering from non-ST-elevation MI taking aspirin in combination with clopidogrel or placebo, with a primary composite outcome of cardiovascular death, or nonfatal MI or stroke.⁵

The primary outcome occurred in 9.3% of clopidogrel patients, compared to 11.4% of placebo patients, for a relative risk reduction of 20%, illustrating the efficacy of DAPT, as well as the effectiveness of pairing clopidogrel with aspirin.⁵

However, patients in the DAPT group also experienced a higher rate of major bleeding at 3.7%, compared to only 2.7%. So, while DAPT with clopidogrel is more effective at preventing recurrence of thrombotic events, physicians should weigh the risk of bleeding with the benefit of MI and stroke prevention for every patient individually.⁵

DAPT with clopidogrel has also been found to be effective in the secondary prevention of stroke. A meta-analysis of over 29,000 ischemic stroke patients compared the use of aspirin alone to aspirin and clopidogrel. Patients on DAPT had a 28% relative risk reduction in major adverse cardiovascular events, a 24% relative risk reduction for any ischemic or hemorrhagic stroke, and a 28% relative risk reduction for any ischemic stroke.⁷

Backed by a combination of clinical and real-world evidence, clopidogrel—with its potent antiplatelet activity and efficacy at preventing recurrent thrombotic events—continues to be an essential component of the management of ACS and stroke patients.