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Suppressive effect of pitavastatin on aortic arch dilatation in acute stanford type B aortic dissection: analysis of STANP trial

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Abstract

Objectives

Medical therapy for patients with uncomplicated acute type B aortic dissection (ABAD) is essentially accepted for its excellent early outcome; however, long-term outcomes have not been satisfactory due to aorta-related complications. This trial was performed to investigate the efficacy of a statin as an additive that may enhance the effectiveness of conventional medical treatment in patients with ABAD.

Methods

This was a multi-center, prospective, and randomized comparative investigation of patients with uncomplicated ABAD. Fifty patients with ABAD compatible with inclusion criteria were randomly assigned to two groups and then received administration of pitavastatin (group P) or not (group C). We followed up the patients for 1 year from study onset.

Results

Two patients demised during the follow-up period (both were in group C). In addition, aorta-related interventions were performed in two patients (entry closure for aortic dissection by endovascular repair in one patient in each group). Aortic arch diameters at 1 year in group P tended to be smaller than in group C (P = 0.17), and the rate of change of the aortic arch diameters from onset to 1 year was significantly lower in group P (P = 0.046). Multivariate analysis identified patency of the false lumen was detected as a risk factor for aortic arch dilatation (P = 0.02), and pitavastatin intake was a negative risk factor (P = 0.03).

Conclusions

Pitavastatin treatment, in addition to the standard antihypertensive therapy, may have a suppressive effect on aortic arch dilatation in patients with ABAD.

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References

  1. Suzuki T, Isselbacher EM, Nienaber CA, Pyeritz RE, Eagle KA, Tsai TT, et al. Type-selective benefits of medications in treatment of acute aortic dissection (from the International Registry of Acute Aortic Dissection [IRAD]). Am J Cardiol. 2012;109:122–7.

    Article  PubMed  CAS  Google Scholar 

  2. Durham CA, Cambria RP, Wang LJ, Ergul EA, Aranson NJ, Patel VI, et al. The natural history of medically managed acute type B aortic dissection. J Vasc Surg. 2015;61:1192–8.

    Article  PubMed  Google Scholar 

  3. Akutsu K, Nejima J, Kiuchi K, Sasaki K, Ochi M, Tanaka K, et al. Effects of the patent false lumen on the long-term outcome of type B acute aortic dissection. Eur J Cardiothorac Surg. 2004;26:359–66.

    Article  PubMed  Google Scholar 

  4. Suzuki T, Mehta RH, Ince H, Nagai R, Sakomura Y, Weber F, et al. Clinical profiles and outcomes of acute type B aortic dissection in the current era: lessons from the International Registry of Aortic Dissection (IRAD). Circulation. 2003;108(Suppl 1):Ii312–7.

    PubMed  Google Scholar 

  5. Charilaou P, Ziganshin BA, Peterss S, Rajbanshi BG, Rajakaruna C, Zaza KJ, et al. Current experience with acute type B aortic dissection: validity of the complication-specific approach in the present era. Ann Thorac Surg. 2016;101:936–43.

    Article  PubMed  Google Scholar 

  6. Genoni M, Paul M, Jenni R, Graves K, Seifert B, Turina M. Chronic beta-blocker therapy improves outcome and reduces treatment costs in chronic type B aortic dissection. Eur J Cardiothorac Surg. 2001;19:606–10.

    Article  PubMed  CAS  Google Scholar 

  7. Takagi H, Matsui M, Umemoto T. A meta-analysis of clinical studies of statins for prevention of abdominal aortic aneurysm expansion. J Vasc Surg. 2010;52:1675–81.

    Article  PubMed  Google Scholar 

  8. Raux M, Cochennec F, Becquemin JP. Statin therapy is associated with aneurysm sac regression after endovascular aortic repair. J Vasc Surg. 2012;55:1587–92.

    Article  PubMed  Google Scholar 

  9. Sukhija R, Aronow WS, Sandhu R, Kakar P, Babu S. Mortality and size of abdominal aortic aneurysm at long-term follow-up of patients not treated surgically and treated with and without statins. Am J Cardiol. 2006;97:279–80.

    Article  PubMed  Google Scholar 

  10. Kalyanasundaram A, Elmore JR, Manazer JR, Golden A, Franklin DP, Galt SW, et al. Simvastatin suppresses experimental aortic aneurysm expansion. J Vasc Surg. 2006;43:117–24.

    Article  PubMed  Google Scholar 

  11. Steinmetz EF, Buckley C, Shames ML, Ennis TL, Vanvickle-Chavez SJ, Mao D, et al. Treatment with simvastatin suppresses the development of experimental abdominal aortic aneurysms in normal and hypercholesterolemic mice. Ann Surg. 2005;241:92–101.

    PubMed  PubMed Central  Google Scholar 

  12. Schneiderman J, Bordin GM, Adar R, Smolinsky A, Seiffert D, Engelberg I, et al. Patterns of expression of fibrinolytic genes and matrix metalloproteinase-9 in dissecting aortic aneurysms. Am J Pathol. 1998;152:703–10.

    PubMed  PubMed Central  CAS  Google Scholar 

  13. Zhang X, Shen YH, LeMaire SA. Thoracic aortic dissection: are matrix metalloproteinases involved? Vascular. 2009;17:147–57.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Akiyama M, Ohtani H, Sato E, Nagura H, Tabayashi K. Up-regulation of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase were coupled with that of type I procollagen in granulation tissue response after the onset of aortic dissection. Virchows Arch. 2006;448:811–21.

    Article  PubMed  CAS  Google Scholar 

  15. Yoshida O, Kondo T, Kureishi-Bando Y, Sugiura T, Maeda K, Okumura K, et al. Pitavastatin, an HMG-CoA reductase inhibitor, ameliorates endothelial function in chronic smokers. Circ J. 2010;74:195–202.

    Article  PubMed  CAS  Google Scholar 

  16. Jia LX, Zhang WM, Li TT, Liu Y, Piao CM, Ma YC, et al. ER stress dependent microparticles derived from smooth muscle cells promote endothelial dysfunction during thoracic aortic aneurysm and dissection. Clin Sci (Lond). 2017;131:1287–99.

    Article  CAS  Google Scholar 

  17. Kamman AV, Brunkwall J, Verhoeven EL, Heijmen RH, Trimarchi S. Predictors of aortic growth in uncomplicated type B aortic dissection from the acute dissection stent grafting or best medical treatment (ADSORB) database. J Vasc Surg. 2017;65:964–71.e3.

    Article  PubMed  Google Scholar 

  18. Grubb BP, Sirio C, Zelis R. Intravenous labetalol in acute aortic dissection. JAMA. 1987;258:78–9.

    Article  PubMed  CAS  Google Scholar 

  19. Shores J, Berger KR, Murphy EA, Pyeritz RE. Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan’s syndrome. N Engl J Med. 1994;330:1335–41.

    Article  PubMed  CAS  Google Scholar 

  20. Kodama K, Nishigami K, Sakamoto T, Sawamura T, Hirayama T, Misumi H, et al. Tight heart rate control reduces secondary adverse events in patients with type B acute aortic dissection. Circulation. 2008;118:S167–70.

    Article  PubMed  Google Scholar 

  21. Takeshita S, Sakamoto S, Kitada S, Akutsu K, Hashimoto H. Angiotensin-converting enzyme inhibitors reduce long-term aortic events in patients with acute type B aortic dissection. Circ J. 2008;72:1758–61.

    Article  PubMed  Google Scholar 

  22. Hackam DG, Thiruchelvam D, Redelmeier DA. Angiotensin-converting enzyme inhibitors and aortic rupture: a population-based case-control study. Lancet. 2006;368:659–65.

    Article  PubMed  CAS  Google Scholar 

  23. Nienaber CA, Kische S, Rousseau H, Eggebrecht H, Rehders TC, Kundt G, et al. Endovascular repair of type B aortic dissection: long-term results of the randomized investigation of stent grafts in aortic dissection trial. Circ Cardiovasc Interv. 2013;6:407–16.

    Article  PubMed  CAS  Google Scholar 

  24. Nienaber CA, Rousseau H, Eggebrecht H, Kische S, Fattori R, Rehders TC, et al. Randomized comparison of strategies for type B aortic dissection: the investigation of stent grafts in aortic dissection (INSTEAD) trial. Circulation. 2009;120:2519–28.

    Article  PubMed  Google Scholar 

  25. Brunkwall J, Lammer J, Verhoeven E, Taylor P. ADSORB: a study on the efficacy of endovascular grafting in uncomplicated acute dissection of the descending aorta. Eur J Vasc Endovasc Surg. 2012;44:31–6.

    Article  PubMed  CAS  Google Scholar 

  26. Hughes GC. Management of acute type B aortic dissection; ADSORB trial. J Thorac Cardiovasc Surg. 2015;149:S158-162.

    Article  Google Scholar 

  27. Coselli JS, Spiliotopoulos K, Preventza O, de la Cruz KI, Amarasekara H, Green SY. Open aortic surgery after thoracic endovascular aortic repair. Gen Thorac Cardiovasc Surg. 2016;64:441–9.

    Article  PubMed  Google Scholar 

  28. van Bogerijen GH, Tolenaar JL, Rampoldi V, Moll FL, van Herwaarden JA, Jonker FH, et al. Predictors of aortic growth in uncomplicated type B aortic dissection. J Vasc Surg. 2014;59:1134–43.

    Article  PubMed  Google Scholar 

  29. Jonker FH, Trimarchi S, Rampoldi V, Patel HJ, O’Gara P, Peterson MD, et al. Aortic expansion after acute type B aortic dissection. Ann Thorac Surg. 2012;94:1223–9.

    Article  PubMed  Google Scholar 

  30. Matsuda H. Treatment of uncomplicated type B aortic dissection. Gen Thorac Cardiovasc Surg. 2017;65:74–9.

    Article  PubMed  Google Scholar 

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Acknowledgements

List of all contributors to the STANP trial. Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine: Yumi Sugawara, PhD; Department of Radiology, Tohoku University Graduate School of Medicine: Hidenobu Takagi, MD, PhD, Satoshi Higuchi, MD, Hideki Ota, MD, PhD, Kei Takase, MD, PhD; Department of Thoracic and Cardiovascular Surgery, Hirosaki University Graduate School of Medicine: Kazuyuki Daitoku, MD, PhD, Ikuo Fukuda, MD, PhD; Department of Cardiovascular Surgery, Hirosaki Central Hospital: Hiroyuki Itaya, MD, PhD; Department of Cardiovascular Surgery, Tohoku Medical and Pharmaceutical University Hospital: Suguru Watanabe, MD, PhD; Department of Cardiovascular Surgery, Sendai Open Hospital: Seijiro Yoshida, MD, PhD; Department of Cardiovascular Surgery, Sendai Kousei Hospital: Masaki Hata, MD; Department of Cardiology, Sendai Kousei Hospital: Norio Tada, MD, PhD; Department of Cardiovascular Surgery, Aomori Prefectural Central Hospital: Koichi Nagaya, MD, PhD; Department of Cardiovascular Surgery, Iwate Prefectural Central Hospital: Katsuhiko Oda, MD, PhD; Department of Cardiovascular Surgery, Mito Medical Center: Kei Sakuma, MD, PhD; Department of Cardiovascular Surgery, Sendai City Hospital: Tetsuo Watanabe, MD, PhD.

Funding

None.

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Author notes

  1. Naoki Masaki and Kiichiro Kumagai contributed equally and should be considered co-first authors.

Authors and Affiliations

  1. Division of Cardiovascular Surgery, Tohoku University Graduate School of Medicine, Seiryocho, Aoba-ku, Sendai, 980-8574, Japan

    Naoki Masaki, Konosuke Sasaki, Satoshi Matsuo, Naotaka Motoyoshi, Osamu Adachi, Masatoshi Akiyama, Shunsuke Kawamoto, Koichi Tabayashi & Yoshikatsu Saiki

  2. Research Division of Sciences for Aortic Disease, Tohoku University Graduate School of Medicine, Sendai, Japan

    Kiichiro Kumagai

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  1. Naoki Masaki
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Consortia

For the STANP trial investigators

  • Yumi Sugawara
  • , Hidenobu Takagi
  • , Satoshi Higuchi
  • , Hideki Ota
  • , Kei Takase
  • , Kazuyuki Daitoku
  • , Ikuo Fukuda
  • , Hiroyuki Itaya
  • , Suguru Watanabe
  • , Seijiro Yoshida
  • , Masaki Hata
  • , Norio Tada
  • , Koichi Nagaya
  • , Katsuhiko Oda
  • , Kei Sakuma
  •  & Tetsuo Watanabe

Corresponding author

Correspondence to Yoshikatsu Saiki.

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Conflict of interest

The authors have no potential conflicts of interest.

Additional information

STANP trial investigators are listed in “Acknowledgements”.

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Masaki, N., Kumagai, K., Sasaki, K. et al. Suppressive effect of pitavastatin on aortic arch dilatation in acute stanford type B aortic dissection: analysis of STANP trial. Gen Thorac Cardiovasc Surg 66, 334–343 (2018). https://doi.org/10.1007/s11748-018-0916-z

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  • DOI: https://doi.org/10.1007/s11748-018-0916-z

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