Statin therapy is associated with reduced restenosis rates after coronary stent implantation in carriers of the PlA2allele of the platelet glycoprotein IIIa gene

Abstract

Aims Platelets play a central role in the restenosis process by inducing neointimal proliferation after coronary interventions. Glycoprotein IIb/IIIa Pl(A2)polymorphism has been associated with the occurrence of acute coronary syndromes and increased restenosis rates. Statins have been shown to exert potent antiproliferative, antiinflammatory and antithrombotic properties, thereby potentially interfering with the major processes of in-stent restenosis. Therefore, we sought to find out whether statin therapy interferes with restenosis and clinical outcome at 6 months following successful coronary stent implantation in the presence or absence of the Pl(A2)allele. Methods and Results Six hundred and fifty consecutive patients were followed for 6 months after coronary stent insertion. Carriers of the Pl(A2)allele demonstrated a significantly increased restenosis rate, which was abrogated by statin therapy (50.9% vs 28.6%, P=0.01). Moreover, statin therapy was associated with a significant reduction (28.2% vs 49.3%, P<0.01) in the occurrence of major adverse coronary events (myocardial infarction, cardiac death, target vessel revascularization) in the 6 months after the intervention in patients with the Pl(A2)allele. Conclusion Statin therapy reduces increased stent restenosis rates and improves clinical outcome following coronary stent implantation in patients bearing the Pl(A2)allele, suggesting that statins interfere with the functional consequence of a genetically determined platelet-mediated risk factor associated with Pl(A2)polymorphism.

Smoking and the Platelet Fibrinogen Receptor Glycoprotein IIb/IIIA Pl A1/A2 Polymorphism Interact in the Risk of Lacunar Stroke and Midterm Survival

“…Statin therapy also significantly reduced the risk of coronary events in carriers of the Pl A2 allele. 29 There are no studies concerning the possible effect of statin therapy on survival among Pl A2 allele-carrying stroke patients.…”

Clinical implications of pharmacogenomics of statin treatment

“…[94][95][96] The IGTB3 gene encodes the platelet-specific fibrinogen receptor and variation in this gene has been associated under basal conditions with elevated risk of coronary disease. 94,97 This increase in risk was reported to be abolished by statin treatment. 94,97 The TLR4 gene encodes for toll-like receptor 4, which is involved in innate immunity.…”

“…94,97 This increase in risk was reported to be abolished by statin treatment. 94,97 The TLR4 gene encodes for toll-like receptor 4, which is involved in innate immunity. Carriers of a non-synonymous TLR4 variant (D299G) demonstrated reduced risk of post-treatment coronary events.…”

Restenosis

“…Both of these drugs improve endothelial function, but their role in the prevention of restenosis is still controversial. The beneficial effect of these drugs on both endothelial function and restenosis may be dependent on the genotype of the patients 17,18 as well as on the inflammatory and oxidative stress status, which was not addressed in the present article.…”