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Platelet aggregation inhibitors reduce the risk of complications during and after acute coronary syndromes and after a TIA or stroke. Acetylsalicylic acid plays a major role in secondary prevention; the combination of acetylsalicylic acid and a platelet ADP receptor antagonist, such as clopidogrel, may have added value. In percutaneous coronary intervention, dual platelet inhibition appears to be effective in the prevention of stent thrombosis. Long-term (> 1 year) use of dual platelet inhibition has an unfavourable risk-benefit profile, partly due to an increase in the number of bleeding events, particularly in the stomach. The use of the combination of acetylsalicylic acid and clopidogrel may be helpful after a TIA or minor stroke, but further research is needed to identify the group of patients for whom this combination would be applicable. This article provides an overview of the modern cardiological and neurological indications for platelet inhibition as well as the risk factors for severe bleeding events when using dual antiplatelet therapy.

Cerebral infarction is the most serious complication of atrial fibrillation. Coumarin derivatives (vitamin K antagonists) counteract systemic thromboembolism and reduce the risk of stroke by more than 60%, but carry a risk of serious bleeding. Antiplatelet therapy and subcutaneous low-molecular-weight heparin are as yet not sufficiently effective and are associated with a bleeding risk similar to vitamin K antagonists. Vitamin K antagonists require intensive INR monitoring to ensure efficacy and safety. In the past decade, oral agents have been developed that directly inhibit the activity of thrombin (factor IIa) and of activated factor X (Xa), which is the first compound in the final common pathway of the coagulation cascade. These do require INR monitoring and have rapid onset and offset of action. The first results with thrombin blockers, such as dabigatran, look promising in efficacy and safety and Xa inhibitors are currently under investigation in atrial fibrillation in 3 large clinical trials. Long-term safety of the new agents in patients with atrial fibrillation has not yet been determined.

The drug interaction between proton pump inhibitors and clopidogrel has been the subject of much study in recent years. Contradictory results regarding the effect of proton pump inhibitors on platelet reactivity and on clinical outcome in clopidogrel-treated patients have been reported in literature. Concomitant use of omeprazole and clopidogrel was found to decrease the exposure (AUC) to clopidogrel's active metabolite by 50% and to sharply increase platelet reactivity, as a result of inhibition by omeprazole of CYP2C19, a cytochrome P450 (CYP) enzyme. Pantoprazole has a much weaker effect on clopidogrel's pharmacokinetics and on platelet reactivity during concomitant use. The influence of the other proton pump inhibitors when used simultaneously with clopidogrel has not yet been investigated in adequately randomized studies. Regulatory agencies state that the combination of clopidogrel and the CYP2C19 inhibitors omeprazole and esomeprazole should be avoided. To date, there is no conclusive evidence of a clinically-relevant interaction between any of the proton pump inhibitors and clopidogrel.

In a 55-year-old woman and a 51-year-old man with an ST segment elevation myocardial infarction confirmed by ECG, the infarction could still be aborted by percutaneous coronary intervention with stenting. An aborted myocardial infarction can be described as an acute myocardial infarction in which rapid reperfusion therapy allows normalization of ECG abnormalities with no meaningful cardiac enzyme abnormalities found in the blood. Scientific evidence shows fibrinolysis to be effective in aborting myocardial infarction, but for percutaneous coronary intervention this has not been proven. Nevertheless, the results of the 2 cases discussed in our article are promising.