Effects of Antihypertensive Drugs on Outcomes of Breast Reconstruction



Angiotensin receptor blocker (ARB), a commonly used antihypertensive drug, is reported to affect wound healing and flap survival in animal models. However, this has not been elucidated in a clinical series. This study aimed to investigate the impact that perioperative use of ARB has on outcomes after breast reconstruction.


Patients who underwent immediate breast reconstruction using a tissue expander or a deep inferior epigastric perforator (DIEP) flap were reviewed. The patients were categorized according to the types of antihypertensive medications as follows: the ARB group consisted of hypertensive patients treated with ARB alone or a combination of ARB and other drugs; the non-ARB group included those receiving drugs other than ARB; and the control group did not receive any medication. The effects of antihypertensive drugs on the development of complications were evaluated.


The study analyzed 1390 cases including 999 cases of tissue-expander insertion and 391 cases of DIEP flap reconstruction. With regard to tissue-expander reconstruction, the rates of seroma, reoperation, reconstruction failure, and overall complications were significantly higher in the ARB group than in the other two groups. Compared with no medication, ARB use was an independent risk factor for these complications. With regard to DIEP flap reconstruction, the ARB group showed a significantly higher rate of fat necrosis and significantly greater odds for the development of overall perfusion-related complications and fat necrosis than the control group after adjustment for other variables.


Perioperative administration of ARB might be associated with adverse outcomes after breast reconstruction.

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  1. 1.

    Heneghan HM, Prichard RS, Lyons R, et al. Quality of life after immediate breast reconstruction and skin-sparing mastectomy: a comparison with patients undergoing breast conserving surgery. Eur J Surg Oncol. 2011;37:937–43.

    Article  CAS  PubMed  Google Scholar 

  2. 2.

    Tran BNN, Fadayomi A, Lin SJ, et al. Cost analysis of postmastectomy reconstruction: a comparison of two-staged implant reconstruction using tissue expander and acellular dermal matrix with abdominal based perforator free flaps. J Surg Oncol. 2017;116:448–9.

    Article  PubMed  Google Scholar 

  3. 3.

    Chang DW. Breast reconstruction with microvascular MS-TRAM and DIEP flaps. Arch Plast Surg. 2012;39:3–10.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Mills KT, Bundy JD, Kelly TN, et al. Global disparities of hypertension prevalence and control: a systematic analysis of population-based studies from 90 countries. Circulation. 2016;134:441–50.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    James PA, Oparil S, Carter BL, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507–20.

    Article  CAS  Google Scholar 

  6. 6.

    Pazoki-Toroudi H, Ajami M, Habibey R, Hajiaboli E, Firooz A. The effect of enalapril on skin flap viability is independent of angiotensin II AT1 receptors. Ann Plast Surg. 2009;62:699–702.

    Article  CAS  PubMed  Google Scholar 

  7. 7.

    Criss CN, Gao Y, De Silva G, et al. The effects of losartan on abdominal wall fascial healing. Hernia. 2015;19:645–50.

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    Park JW, Mun GH. Comparative analysis of the effect of antihypertensive drugs on the survival of perforator flaps in a rat model. Microsurgery. 2018;38:310–17.

    Article  PubMed  Google Scholar 

  9. 9.

    Gu Q, Burt VL, Dillon CF, Yoon S. Trends in antihypertensive medication use and blood pressure control among United States adults with hypertension: the National Health And Nutrition Examination Survey, 2001 to 2010. Circulation. 2012;126:2105–14.

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Fleisher LA, Fleischmann KE, Auerbach AD, et al. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Developed in collaboration with the American College of Surgeons, American Society of Anesthesiologists, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Anesthesiologists, and Society of Vascular Medicine Endorsed by the Society of Hospital Medicine. J Nucl Cardiol. 2015;22:162–215.

  11. 11.

    Duceppe E, Parlow J, MacDonald P, et al. Canadian Cardiovascular Society guidelines on perioperative cardiac risk assessment and management for patients who undergo noncardiac surgery. Can J Cardiol. 2017;33:17–32.

    Article  PubMed  Google Scholar 

  12. 12.

    Schmieder RE. Mechanisms for the clinical benefits of angiotensin II receptor blockers. Am J Hypertens. 2005;18:720–30.

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Shibasaki Y, Matsubara H, Nozawa Y, et al. Angiotensin II type 2 receptor inhibits epidermal growth factor receptor transactivation by increasing association of SHP-1 tyrosine phosphatase. Hypertension. 2001;38:367–72.

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Murasawa S, Mori Y, Nozawa Y, et al. Angiotensin II type 1 receptor-induced extracellular signal-regulated protein kinase activation is mediated by Ca2 +/calmodulin-dependent transactivation of epidermal growth factor receptor. Circ Res. 1998;82:1338–48.

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Eguchi S, Numaguchi K, Iwasaki H, et al. Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. J Biol Chem. 1998;273:8890–6.

    Article  CAS  PubMed  Google Scholar 

  16. 16.

    Rodgers K, Abiko M, Girgis W, St Amand K, Campeau J, diZerega G. Acceleration of dermal tissue repair by angiotensin II. Wound Repair Regen. 1997;5:175–83.

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    Rodgers K, Xiong S, Felix J, et al. Development of angiotensin (1–7) as an agent to accelerate dermal repair. Wound Repair Regen. 2001;9:238–47.

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Takeda H, Katagata Y, Hozumi Y, Kondo S. Effects of angiotensin II receptor signaling during skin wound healing. Am J Pathol. 2004;165:1653–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Fernandez LA, Twickler J, Mead A. Neovascularization produced by angiotensin II. J Lab Clin Med. 1985;105:141–5.

    CAS  PubMed  Google Scholar 

  20. 20.

    Biondo-Simoes Mde L, Zazula AD, Gomes AB, Poncio C, Torres LF, Borsato KS. Influence of arterial hypertension treated with losartan on skin healing in rats. Acta Cir Bras. 2006;21:144–50.

    Article  PubMed  Google Scholar 

  21. 21.

    Fischer JP, Nelson JA, Serletti JM, Wu LC. Perioperative risk factors associated with early tissue expander (TE) loss following immediate breast reconstruction (IBR): a review of 9305 patients from the 2005–2010 ACS-NSQIP datasets. J Plast Reconstr Aesthet Surg. 2013;66:1504–12.

    Article  PubMed  Google Scholar 

  22. 22.

    Gill PS, Hunt JP, Guerra AB, et al. A 10-year retrospective review of 758 DIEP flaps for breast reconstruction. Plast Reconstr Surg. 2004;113:1153–60.

    Article  PubMed  Google Scholar 

  23. 23.

    Santanelli F, Longo B, Sorotos M, Farcomeni A, Paolini G. Flap survival of skin-sparing mastectomy type IV: a retrospective cohort study of 75 consecutive cases. Ann Surg Oncol. 2013;20:981–9.

    Article  PubMed  Google Scholar 

  24. 24.

    Lee KT, Eom Y, Jeon BJ, Mun GH. Vertical spacing of perforators in deep inferior epigastric perforator flap breast reconstruction can affect the outcomes. Plast Reconstr Surg. 2018;142:319–29.

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    Santanelli F, Longo B, Cagli B, Pugliese P, Sorotos M, Paolini G. Predictive and protective factors for partial necrosis in DIEP flap breast reconstruction: does nulliparity bias flap viability? Ann Plast Surg. 2015;74:47–51.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Goo-Hyun Mun MD, PhD.

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Park, J., Lee, K., Jeon, B. et al. Effects of Antihypertensive Drugs on Outcomes of Breast Reconstruction. Ann Surg Oncol 26, 1712–1719 (2019). https://doi.org/10.1245/s10434-019-07293-z

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