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Neointimal Hyperplasia Inhibition Effect of Angiotensin II Type 1 Receptor Blockers in Patients after Coronary Stent Implantation

A Meta-Analysis

  • Original Research Article
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American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Background and Objective

It remains unclear whether angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) can inhibit neointimal hyperplasia after stent implantation in patients with coronary artery disease. The aim of this meta-analysis was therefore to evaluate the benefits of ARBs in patients after coronary stent implantation based on the currently available randomized controlled trials.

Methods

We conducted a pooled analysis of randomized controlled trials to compare outcomes after stent implantation in patients administered ARBs with those not administered ARBs. We searched Ovid/MEDLINE, EMBASE, and the ISI web of knowledge using the terms ‘angiotensin receptor blocker,’ ‘renin angiotensin system inhibitor,’ ‘angiotensin receptor antagonist,’ ‘stent,’ ‘angiograph,’ ‘percutaneous coronary intervention (PCI),’ and ‘coronary artery disease.’ Published meta-analyses, review articles, and editorials were reviewed for potential studies of interest. The inclusion criteria were randomized controlled trials published in English, with a follow-up period of 6 months, comparing the outcomes after coronary stent implantation with and without the administration of any kind of ARB, reporting at least one outcome of interest (restenosis rate and late lumen loss). Data abstraction included study design, patient characteristics, follow-up period, type of ARB, type of stent, restenosis rate, and late lumen loss. Fixed-effects models were used to calculate the pooled relative risk for the restenosis rate and the standardized mean difference for late lumen loss.

Results

Five studies were included, with a total number of 624 patients. Seventy-five of 314 patients in the ARB group were diagnosed with in-stent restenosis at the 6-month follow-up, compared with 87 of 310 patients in the control group (relative risk 0.85; 95% CI 0.65, 1.11; p = 0.23). Consistent with this, there was no significant difference in late lumen loss between the two groups (0.04 mm; 95% CI −0.15, 0.23; p = 0.66).

Conclusion

There is no evident benefit with the use of an ARB in terms of inhibition of neointimal hyperplasia in patients after coronary stent implantation.

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References

  1. Yamada T, Kondo T, Numaguchi Y, et al. Angiotensin II receptor blocker inhibits neointimal hyperplasia through regulation of smooth muscle-like progenitor cells. Arterioscler Thromb Vasc Biol 2007; 27: 2363–9.

    Article  PubMed  CAS  Google Scholar 

  2. Ohtani K, Egashira K, Ihara Y, et al. Angiotensin II type 1 receptor blockade attenuates in-stent restenosis by inhibiting inflammation and progenitor cells. Hypertension 2006; 48: 664–70.

    Article  PubMed  CAS  Google Scholar 

  3. Alexander RW. Theodore Cooper Memorial Lecture. Hypertension and the pathogenesis of atherosclerosis: oxidative stress and the mediation of arterial inflammatory response: a new perspective. Hypertension 1995; 25: 155–61.

    Article  PubMed  CAS  Google Scholar 

  4. Wilensky RL. Angiotensin-receptor blockers: revival of the systemic prevention of restenosis? Cardiovasc Drug Ther 2003; 17: 63–73.

    Article  CAS  Google Scholar 

  5. Iwata A, Miura SI, Imaizumi S, et al. Do valsartan and losartan have the same effects in the treatment of coronary artery disease? Circ J 2007; 71: 32–8.

    Article  PubMed  CAS  Google Scholar 

  6. Peters S. Comparison of efficacy of low- (80mg/day) and high- (160–320mg/day) dose valsartan in the prevention of in-stent restenosis after implantation of bare-metal stents in type B2/C coronary artery lesions. Am J Cardiovasc Drugs 2008; 8: 83–7.

    Article  PubMed  Google Scholar 

  7. Hong SJ, Shim WJ, Choi J, et al. Comparison of effects of telmisartan and valsartan on late lumen loss and inflammatory markers after sirolimus-eluting stent implantation in hypertensive patients. Am J Cardiol 2007; 100: 1625–9.

    Article  PubMed  CAS  Google Scholar 

  8. Sugihara M, Miura S, Takamiya Y, et al. Safety and efficacy of anti-hypertensive therapy with add-on angiotensin II type 1 receptor blocker after successful coronary stent implantation. Hypertens Res 2009; 32: 625–30.

    Article  PubMed  CAS  Google Scholar 

  9. Waseda K, Ozaki Y, Takashima H, et al. Impact of angiotensin II receptor blockers on the progression and regression of coronary atherosclerosis: an intravascular ultrasound study. Circ J 2006; 70: 1111–5.

    Article  PubMed  CAS  Google Scholar 

  10. Fujita M, Yarnazaki T, Hayashi D, et al. Comparison of cardiovascular events in patients with angiographically documented coronary narrowing with combined renin-angiotensin system inhibitor plus statin versus renin-angio-tensin system inhibitor alone versus statin alone (from the Japanese Coronary Artery Disease Study). Am J Cardiol 2007; 100: 1750–3.

    Article  PubMed  CAS  Google Scholar 

  11. Jorgensen E, Kelbaek H, Helqvist S, et al. Predictors of coronary in-stent restenosis: importance of angiotensin-converting enzyme gene polymorphism and treatment with angiotensin-converting enzyme inhibitors. J Am Coll Cardiol 2001; 38: 1434–9.

    Article  PubMed  CAS  Google Scholar 

  12. Yoshida O, Hirayama H, Nanasato M, et al. The angiotensin II receptor blocker candesartan cilexetil reduces neointima proliferation after coronary stent implantation: a prospective randomized study under intravascular ultrasound guidance. Am Heart J 2005; 149: e2.

    Article  PubMed  Google Scholar 

  13. Nagasawa H, Mutoh M, Nogimura T, et al. A prospective randomized study of the use of an oral angiotensin II receptor blocker to prevent restenosis after percutaneous coronary intervention. Jikeikai Med J 2005; 52: 15–20.

    CAS  Google Scholar 

  14. Yoshikawa M, Nakamura K, Nagase S, et al. Effects of combined treatment with angiotensin II type 1 receptor blocker and statin on stent restenosis. J Cardiovasc Pharmacol 2009; 53: 179–86.

    Article  PubMed  CAS  Google Scholar 

  15. Nishikawa H, Miura S, Shimomura H, et al. Combined treatment with statin and angiotensin-receptor blocker after stenting as a useful strategy for prevention of coronary restenosis. J Cardiol 2005; 45: 107–13.

    PubMed  Google Scholar 

  16. Peters S, Trummel M, Meyners W, et al. Valsartan versus ACE inhibition after bare metal stent implantation: results of the VALVACE trial. Int J Cardiol 2005; 98: 331–5.

    Article  PubMed  Google Scholar 

  17. Yokoyama J, Higuma T, Tomita H, et al. Impact of telmisartan on coronary stenting in patients with acute myocardial infarction compared with enalapril. Int J Cardiol 2009; 132: 114–20.

    Article  PubMed  Google Scholar 

  18. Kramer J, Ruf RG, Schmidt S, et al. The CAIRP (CAndesartan for In-stent Restenosis Prevention) trial: a multicenter study of AT1-receptor blocker therapy in coronary stenting. J Invasive Cardiol 2008; 20: 205–10.

    PubMed  Google Scholar 

  19. Radke PW, Figulla HR, Drexler H, et al. A double-blind, randomized, placebo-controlled multicenter clinical trial to evaluate the effects of the angiotensin II receptor blocker candesartan cilexetil on intimal hyperplasia after coronary stent implantation. Am Heart J 2006; 152: 761. e1–6.

    PubMed  Google Scholar 

  20. Ujiie Y, Hirosaka A, Mitsugi M, et al. Effects of angiotensin-converting enzyme inhibitors or an angiotensin receptor blocker in combination with aspirin and cilostazol on in-stent restenosis. Int Heart J 2006; 47: 173–84.

    Article  PubMed  CAS  Google Scholar 

  21. Wakeyama T, Ogawa H, Iida H, et al. Effects of candesartan and probucol on restenosis after coronary stenting: results of Insight of Stent Intimal Hyperplasia Inhibition by New Angiotensin II Receptor Antagonist (ISHIN) trial. Circ J 2003; 67: 519–24.

    Article  PubMed  CAS  Google Scholar 

  22. Peters S, Gotting B, Trummel M, et al. Valsartan for prevention of restenosis after stenting of type B2/C lesions: the VAL-PREST trial. J Invasive Cardiol 2001; 13: 93–7.

    PubMed  CAS  Google Scholar 

  23. Clozel JP, Hess P, Michael C, et al. Inhibition of converting enzyme and neointimal formation after vascular injury in rabbits and guinea pigs. Hypertension 1991; 18 (4 Suppl.): II55–9.

    Article  PubMed  CAS  Google Scholar 

  24. Candipan RC, Hsiun PT, Pratt R, et al. Vascular injury augments adrenergic neurotransmission. Circulation 1994; 89: 777–84.

    Article  PubMed  CAS  Google Scholar 

  25. Multicenter European Research Trial with Cilazapril after Angioplasty to Prevent Transluminal Coronary Obstruction and Restenosis (MERCATOR) Study Group. Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary angioplasty? Results of the MERCATOR study: a multicenter, randomized, double-blind placebo-controlled trial. Circulation 1992; 86: 100–1.

    Article  Google Scholar 

  26. Ribichini F, Wins W, Ferrero V, et al. Effect of angiotensin-converting enzyme inhibition on restenosis after coronary stenting. Am J Cardiol 2003; 91: 154–8.

    Article  PubMed  CAS  Google Scholar 

  27. H. Vernon A, Janice M, Fred JC, et al. Platelet inhibition reduces cyclic flow variations and neointimal proliferation in normal and hypercholesterolemic-atherosclerotic canine coronary arteries. Circulation 2001; 104: 2331–7.

    Article  Google Scholar 

  28. Bysani C, Srinivas M, Lenin M, et al. Interleukin-18-induced human coronary artery smooth muscle cell migration is dependent on NF-κ B- and AP-1-mediated matrix metalloproteinase-9 expression and is inhibited by atorvas-tatin. J Biol Chem 2006; 281: 15099–109.

    Article  Google Scholar 

  29. Takayuki Y, Katsumi M, Takeshi K, et al. Inhibitory efficacy of pitavastatin on the early inflammatory response and neointimal thickening in a porcine coronary after stenting. Atherosclerosis 2004; 174: 253–9.

    Article  Google Scholar 

  30. Birgit J, Cornelia M, Stefan M, et al. Local statin therapy differentially interferes with smooth muscle and endothelial cell proliferation and reduces neointima on a drug-eluting stent platform. Cardiovasc Res 2005; 68: 483–92.

    Article  Google Scholar 

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Correspondence to Li Yong.

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Kun, X., Yong, L., Bo, J. et al. Neointimal Hyperplasia Inhibition Effect of Angiotensin II Type 1 Receptor Blockers in Patients after Coronary Stent Implantation. Am J Cardiovasc Drugs 11, 209–213 (2011). https://doi.org/10.2165/11591780-000000000-00000

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  • DOI: https://doi.org/10.2165/11591780-000000000-00000

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