Can angiotensin receptor antagonists prevent restenosis after stent placement?

Restenosis rates after coronary stent implantation in complex lesions are between 30 and 50%. Neointimal hyperplasia promoted by complex interaction between cellular and acellular elements, such as cytokines and growth factors, is thought to be the primary process responsible for restenosis. The risk of in-stent restenosis is increased in patients with a history of restenosis after percutaneous transluminal coronary angioplasty, in long lesions, in total occlusions, in patients with diabetes mellitus, in small vessels, in the proximal parts of the left anterior descending coronary artery and in cases of stent oversizing. In-stent restenosis represents a serious economic burden on society because treatment strategies include expensive approaches such as cutting-balloon angioplasty, rotational atherectomy and brachytherapy. A number of pharmacological agents, including ACE inhibitors, have been unsuccessful in preventing restenosis. Alternative procedures such as brachytherapy, radioactive stents and drug-eluting stents are under evaluation. Although sirolimus- or paclitaxel-eluting stents have been associated with very low restenosis rates over durations of 6 to 12 months, the long-term efficacy and tolerability of this approach is currently being investigated. Although ACE inhibitors have failed in reducing restenosis rates, the selective angiotensin II type 1 (AT1) receptor antagonist valsartan has shown encouraging results in the single-center Valsartan for Prevention of Restenosis after Stenting of Type B2/C lesions trial (ValPREST). The ValPREST trial is the first randomized, placebo-controlled study to have evaluated the effect of an angiotensin receptor antagonist on in-stent restenosis in a moderate number of patients. Compared with ACE inhibitors, angiotensin receptor blockers exert additional effects on the pathophysiological processes which lead to restenosis. Angiotensin receptor antagonists may affect several mechanisms involved in neointimal hyperplasia such as decreasing circulating cytokine and growth factor levels and reducing neutrophil activation, especially after stenting in acute coronary syndromes, but the results need to be confirmed in a large multicenter trial. The question whether long-term therapy, with an oral angiotensin receptor antagonist, is cost-effective and whether angiotensin receptor antagonists should be used as an add-on therapy to drug-eluting stents, requires clarification.