Antiplatelet drug resistance and newer antiplatelet agents

Antiplatelet drug resistance and newer antiplatelet agents

Antiplatelet drug resistance and newer antiplatelet agents:

Aspirin resistance

Aspirin resistance identified in 1978, initially in patients undergoing cardiac catheterisation and later in stroke patients. Prior aspirin use has been identified as a risk factor in those presenting with acute coronary syndrome. This means that they have aspirin resistance.
Bleeding time, flow cytometry, light transmittance aggregometry are some of the measures to assess aspirin resistance. Light transmittance aggregometry is the most useful method. This depends on whether platelet plugs are formed or not. If platelet plugs are formed, they settle down and allow light transmission. This indicates residual platelet function and hence aspirin resistance. The various assays vary between them and with clinical correlation. Hence the clinical utility of assays still remain doubtful.
Eliminating the interfering substances like ibuprofen may decrease the resistance. Non-enteric coated preparations are better than enteric coated ones, though the more commonly used one is the later. Combining with other antiplatelet agents is useful in overcoming aspirin resistance.

Clopidogrel resistance

There is a wide variation in individual responsiveness to clopidogrel. There are non-responders and semi-responders. Females, those with metabolic syndrome and high triglyceride levels are known to have higher clopidogrel resistance. Atorvastatin – clopidogrel interaction has also to be considered, though the clinical significance of the interaction has not been established.

Newer antiplatelet agents

Prasugrel, Cangrelor and Ticagrelor are the newer agents. Prasugrel and Ticagrelor are oral agents while Cangrelor is a parenteral agent. TRITON TIMI 38 trial compared prasugrel with clopidogrel found prasugrel to be more effective, but with a slightly higher bleeding risk. Stent thrombosis was significantly lower with prasugrel. Platelet inhibition is much superior with prasugrel, compared with clopidogrel. PLATO (NEJM, September 2009) compared Ticagrelor vs Clopidogrel and showed the former to be more effective with no significant increase in bleeding. Prasugrel has been approved by FDA, with a warning on the label regarding the potential small risk of fatal bleeding noted in some studies.

Clinical role of assessment of aspirin resistance in the setting of PCI
Increased risk of stent thrombosis occurs with resistance and detection by pre procedure testing may indicate use of additional glycoprotein IIb/IIIa receptor blockers in the setting of PCI.