Expert Review: Acute Coronary Syndrome

High on-thienopyridine platelet reactivity in elderly coronary patients: the SENIOR-PLATELET study

The authors of this study investigated whether there is a difference between younger and older patients in the ability of thienopyridine antiplatelet drugs to inhibit platelet responsiveness. They found that, in a population of patients chronically treated with aspirin plus clopidogrel 75 mg daily for coronary disease, those aged 75 years exhibited high platelet reactivity more commonly than those < 75 years; in those treated with aspirin plus either clopidogrel 150 mg daily or prasugrel 10 mg daily, there was also a trend for higher platelet reactivity in the older group, but this was not significant. This suggests that age may impact on the ability of thienopyridines to adequately suppress platelet function.

Background 

Dual antiplatelet therapy with aspirin and a thienopyridine (clopidogrel or prasugrel) is now routinely used in patients following acute coronary syndromes (ACS) as well as following percutaneous coronary intervention (PCI), and is also occasionally used in other patient groups where intensive antiplatelet therapy is needed for other clinical reasons. The platelet response to such therapy correlates closely with the corresponding clinical outcomes, both benefit (prevention of recurrent ischemic events) and risk (predominantly rate of bleeding). To date, however, very few data exist on its efficacy in the elderly.

Knowledge Gap

The evidence base regarding the efficacy of clopidogrel and prasugrel in the elderly is poorly defined, as compared with younger patients. This is important, since an increasing number of elderly patients are being treated with these drugs, usually in combination with aspirin.

Aim of the Study 

The present study examined platelet reactivity in older (≥ 75 years old) versus younger (< 75 years old) patients with coronary disease treated chronically with aspirin plus either clopidogrel (at either 75 or 150 mg daily) or prasugrel (10 mg daily).

Methods

The investigators studied 1331 coronary patients chronically (>14 days) treated with aspirin and a thienopyridine (clopidogrel 75 mg, n= 1027; clopidogrel 150 mg, n= 139;
or prasugrel 10 mg, n= 165). Platelet response to clopidogrel and prasugrel was assessed by two independent methods: the VerifyNow assay and light transmission aggregrometry.

Results

On-treatment platelet reactivity with clopidogrel 75 mg, 150 mg or prasugrel 10 mg was higher in elderly patients (n= 205) than in younger patients (n= 1126), regardless of the test used. The difference was greatest in magnitude, and highly significant, in patients treated with clopidogrel 75 mg (P< 0.0001). For those treated with clopidogrel 150 mg or prasugrel 10 mg daily, the differences between the two age groups were smaller in magnitude and did not reach significance. Elderly patients treated with clopidogrel 75 mg were more likely to have high on-treatment platelet reactivity than younger patients, even after adjustment for potential confounders (adjusted OR: 1.83, 95% CI: 1.16–2.87; P= 0.009).

Conclusion 

This study showed that patients aged ≥ 75 years are likely to respond less well to clopidogrel 75 mg daily than patients < 75 years. There may be a similar effect in those treated with either clopidogrel 150 mg daily or prasugrel 10 mg daily, but it is less obvious and, at least in this study, was found to be non-significant and in any case lesser in magnitude.

Perspective-Clinical Impact 

The results of this study suggest that, in patients ≥75 years who require dual antiplatelet therapy, higher-dose clopidogrel, or alternatively prasugrel, may be indicated; or instead there may be a place in the elderly patient population for the newer non-thienopyidine P2Y12 antagonist ticagrelor.

Further studies are needed to investigate the optimal dual antiplatelet therapy in this age group. Also, the reasons underlying reduced response in those ≥75 years remain to be defined. Possibilities include decreased medication adherence, higher baseline platelet reactivity (even prior to starting therapy), increased platelet turnover, or more frequent co-morbidities which may influence platelet function. These possibilities also merit investigation in future studies.

Corresponding author from original paper

Gilles Montalescot, 1Bureau 236, Institut de Cardiologie, INSERM UMRS937, Pitie-Salpetrie`re Hospital (AP-HP), Universite Paris 6, 47-83 bld de l’Hopital, 75013 Paris, France. E-mail: gilles.montalescot@psl.aphp.fr 

Citation: Eur Heart J (2012) 33 (10): 1241-1249

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