Meeting New Challenges with Antiplatelet Therapy in Primary Care

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Medical Education Library

Meeting New Challenges with Antiplatelet Therapy in Primary Care

June 2012 · Vol. 61, No. 06 Suppl: S22-S28

References

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I’ve heard a lot about testing platelet aggregability. Should I be considering that for my patients?

Not at the present time. One prospective study evaluated the capability of platelet function tests to predict clinical outcome in patients taking clopidogrel undergoing elective stent implantation.³³ On-treatment platelet reactivity was measured using: light transmittance aggregometry, VerifyNow P2Y12, Plateletworks, and the IMPACT-R and the platelet function analysis system (PFA-100) (with the Dade PFA collagen/ADP cartridge and Innovance PFA P2Y). After 1 year of follow-up, only the light transmittance aggregometry, VerifyNow, Plateletworks, and Innovance PFA P2Y tests were significantly associated with patient outcome, but had only modest predictive accuracy. Also, none of the tests studied provided accurate prognostic information to identify patients at higher risk of bleeding following stent implantation.

How concerning are the findings on ticagrelor and dyspnea?

The occurrence of dyspnea associated with ticagrelor was observed during its clinical development. While the mechanism is not known, dyspnea is a transient phenomenon, and there is no suggestion that ticagrelor is associated with an increased incidence of heart failure.

The incidence and characterization of dyspnea has been investigated in subanalyses of 2 large clinical trials of ticagrelor. Prospective analysis of the ONSET/OFFSET study (N = 123) showed that dyspnea was experienced by more patients treated with ticagrelor than clopidogrel or placebo over 6 weeks (38.6% vs 9.3% vs 8.3%, respectively; P < .001).³⁴ Episodes of dyspnea were generally mild, lasted <24 hours, and easily tolerated. Moderate dyspnea that led to study discontinuation occurred in 3 patients (5.3%) treated with ticagrelor. Dyspnea occurred within the first 24 hours in 8 of 22 patients (36.4%) and within the first week in 17 of 22 patients (77.3%) of the ticagrelor-treated patients who experienced dyspnea. Dyspnea persisted through the study follow-up (10 days after the 6 week study) in 3 of 22 patients (13.6%) treated with ticagrelor. Dyspnea was not associated with any significant adverse change in cardiac or pulmonary function tests.³⁴

In a subanalysis of the PLATO study to investigate the occurrence of dyspnea (N = 18,421), dyspnea occurred in 14.5% of patients treated with ticagrelor and 8.7% of patients treated with clopidogrel.³⁵ Severe dyspnea occurred in 0.4% and 0.3% of patients, respectively. Dyspnea had no impact on the composite end point after excluding dyspnea that occurred after the secondary end point of MI. The mechanism whereby ticagrelor induces dyspnea is not certain, but may be mediated via an adenosine-related mechanism.³⁶

Conclusion

Aspirin and clopidogrel have been the predominant antiplatelet agents used in the management of patients with ACS, yet their use can be challenging. Differences in the clinical pharmacology of prasugrel and ticagrelor provide the opportunity to address some of these challenges and better enable antiplatelet therapy to be individualized.