Chronic Angiotensin Converting Enzyme Inhibitors in Intermediate Risk Surgery

NCT01669434 | Completed Phase 4 Results DMC

• 1 other identifier: 0369-12-FB
• Study Type: interventional
• Target: 291
• Locations: 1 country
• Sites: 1

Brief Summary

Primary research hypothesis: Patients who continue their chronic ACEI therapy up to and including the morning of a non-cardiac, non-vascular surgery will experience more intraoperative hypotension than those who transiently hold their chronic ACEI preoperatively. Secondary research hypothesis #1: Patients who continue their chronic ACEI up to and including the morning of a non-cardiac, non-vascular surgery will experience better postoperative control of hypertension than those who transiently hold their chronic ACEI preoperatively. Secondary research hypothesis #2: Patients who continue their chronic ACEI up to and including the morning of a non-cardiac, non-vascular surgery will experience less acute renal failure than those who transiently hold their chronic ACEI preoperatively. Secondary research hypothesis #3: In the subgroup of patients with a preoperative systolic blood pressure less than 110 mmHg, those who continue their chronic ACEI therapy up to and including the morning of a non-cardiac, non-vascular surgery will experience more intraoperative hypotension than those who transiently hold their chronic ACEI preoperatively. Secondary research hypothesis #4: In the subgroup of patients above the age of 64, those who continue their chronic ACEI therapy up to and including the morning of a non-cardiac, non-vascular surgery will experience more intraoperative hypotension than those who transiently hold their chronic ACEI preoperatively.

Conditions

Hypotension on Induction

Keywords

Perioperative Period

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Interoperative Hypotension

  Number of Participants with Interoperative Hypotension (systolic blood pressure under 80 mmHg)

  During anesthesia, an expected average of 3 hours.

Secondary Outcomes (5)

• Acute Renal Failure

  Arrival in post-anesthesia care unit (PACU) to hospital discharge, an expected average of 4 days.

• Low Blood Pressure Subgroup

  During anesthesia, an expected average of 3 hours.

• Older Age Subgroup

  During anesthesia, an expected average of 3 hours.

• Postoperative Hypertension

  Arrival in PACU to hospital discharge, an expected average of 4 days.

• Postoperative Hypotension

  Arrival in PACU to hospital discharge, an expected average of 4 days.

Study Arms (2)

ACEI continuation

EXPERIMENTAL

Patients in this arm will be randomized to continue their chronic angiotensin converting enzyme inhibitor without interruption preoperatively

Drug: ACEI continuation

ACEI omission

EXPERIMENTAL

Patients randomized to this arm will be told to omit their final preoperative chronic angiotensin converting enzyme inhibitor dose.

Drug: ACEI omission

Interventions

ACEI continuation DRUG

These chronic medications will be taken without interruption preoperatively.

Also known as: quinapril, Accupril, perindopril, Aceon, ramipril, Altace, benazepril, Lotensin, captopril, Capoten, enalapril, Vasotec, fosinopril, Monopril, lisinopril, Prinivil, Zestril, trandolapril, Mavik, moexipril, Univasc

ACEI continuation

ACEI omission DRUG

Although taken chronically by patients in this intervention, the final preoperative dose of these medications will be omitted, whether it was scheduled for the morning of surgery or the day prior.

Also known as: quinapril, Accupril, perindopril, Aceon, ramipril, Altace, benazepril, Lotensin, captopril, Capoten, enalapril, Vasotec, fosinopril, Monopril, lisinopril, Prinivil, Zestril, trandolapril, Mavik, moexipril, Univasc

ACEI omission

Eligibility Criteria

• Age: 19 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Referred to the University of Nebraska Medical Center Pre-Anesthesia Screening Clinic for preoperative evaluation.
• Above referral must be in anticipation of a non-cardiac, non-vascular surgery.
• Must have been on ACE-Inhibitor therapy for at least six weeks.

You may not qualify if:

• Hypotension (systolic blood pressure \< 90 or diastolic blood pressure \<60) at the time of preoperative evaluation
• Uncontrolled Hypertension (systolic blood pressure \> 150 or diastolic blood pressure \> 95) at the time of preoperative evaluation
• Surgery during which vasopressor use is anticipated (carotid endarterectomy, major abdominal operations, orthopedic oncology)
• Surgery for pathology related to vasoactive substances (carcinoid, pheochromocytoma)
• Left Ventricular ejection fraction less than 40%
• Clinical evidence of decompensated heart failure at the time of preoperative evaluation
• End-stage renal disease
• Organ transplant surgeries

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Related Publications (21)

• McConachie I, Healy TE. ACE inhibitors and anaesthesia. Postgrad Med J. 1989 May;65(763):273-4. doi: 10.1136/pgmj.65.763.273. No abstract available.

  PMID: 2692007 BACKGROUND

• Coriat P, Richer C, Douraki T, Gomez C, Hendricks K, Giudicelli JF, Viars P. Influence of chronic angiotensin-converting enzyme inhibition on anesthetic induction. Anesthesiology. 1994 Aug;81(2):299-307. doi: 10.1097/00000542-199408000-00006.

  PMID: 8053578 BACKGROUND

• Comfere T, Sprung J, Kumar MM, Draper M, Wilson DP, Williams BA, Danielson DR, Liedl L, Warner DO. Angiotensin system inhibitors in a general surgical population. Anesth Analg. 2005 Mar;100(3):636-644. doi: 10.1213/01.ANE.0000146521.68059.A1.

  PMID: 15728043 BACKGROUND

• Pigott DW, Nagle C, Allman K, Westaby S, Evans RD. Effect of omitting regular ACE inhibitor medication before cardiac surgery on haemodynamic variables and vasoactive drug requirements. Br J Anaesth. 1999 Nov;83(5):715-20. doi: 10.1093/bja/83.5.715.

  PMID: 10690132 BACKGROUND

• Steiner CA, Karaca Z, Moore BJ, Imshaug MC, Pickens G. Surgeries in Hospital-Based Ambulatory Surgery and Hospital Inpatient Settings, 2014. 2017 May [updated 2020 Jul 20]. In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006 Feb-. Statistical Brief #223. Available from http://www.ncbi.nlm.nih.gov/books/NBK442035/

  PMID: 28722845 BACKGROUND

• Rate of all-listed procedures for discharges from short-stay hospitals, by procedure category and age: United States, 2010. 2010.

  BACKGROUND

• Turan A, You J, Shiba A, Kurz A, Saager L, Sessler DI. Angiotensin converting enzyme inhibitors are not associated with respiratory complications or mortality after noncardiac surgery. Anesth Analg. 2012 Mar;114(3):552-60. doi: 10.1213/ANE.0b013e318241f6af. Epub 2012 Jan 17.

  PMID: 22253266 BACKGROUND

• Mascha EJ, Yang D, Weiss S, Sessler DI. Intraoperative Mean Arterial Pressure Variability and 30-day Mortality in Patients Having Noncardiac Surgery. Anesthesiology. 2015 Jul;123(1):79-91. doi: 10.1097/ALN.0000000000000686.

  PMID: 25929547 BACKGROUND

• Walsh M, Devereaux PJ, Garg AX, Kurz A, Turan A, Rodseth RN, Cywinski J, Thabane L, Sessler DI. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology. 2013 Sep;119(3):507-15. doi: 10.1097/ALN.0b013e3182a10e26.

  PMID: 23835589 BACKGROUND

• Bertrand M, Godet G, Meersschaert K, Brun L, Salcedo E, Coriat P. Should the angiotensin II antagonists be discontinued before surgery? Anesth Analg. 2001 Jan;92(1):26-30. doi: 10.1097/00000539-200101000-00006.

  PMID: 11133595 BACKGROUND

• Roshanov PS, Rochwerg B, Patel A, Salehian O, Duceppe E, Belley-Cote EP, Guyatt GH, Sessler DI, Le Manach Y, Borges FK, Tandon V, Worster A, Thompson A, Koshy M, Devereaux B, Spencer FA, Sanders RD, Sloan EN, Morley EE, Paul J, Raymer KE, Punthakee Z, Devereaux PJ. Withholding versus Continuing Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers before Noncardiac Surgery: An Analysis of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN Prospective Cohort. Anesthesiology. 2017 Jan;126(1):16-27. doi: 10.1097/ALN.0000000000001404.

  PMID: 27775997 BACKGROUND

• Fleisher LA, Fleischmann KE, Auerbach AD, Barnason SA, Beckman JA, Bozkurt B, Davila-Roman VG, Gerhard-Herman MD, Holly TA, Kane GC, Marine JE, Nelson MT, Spencer CC, Thompson A, Ting HH, Uretsky BF, Wijeysundera DN; American College of Cardiology; American Heart Association. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2014 Dec 9;64(22):e77-137. doi: 10.1016/j.jacc.2014.07.944. Epub 2014 Aug 1. No abstract available.

  PMID: 25091544 BACKGROUND

• Kristensen SD, Knuuti J, Saraste A, Anker S, Botker HE, Hert SD, Ford I, Gonzalez-Juanatey JR, Gorenek B, Heyndrickx GR, Hoeft A, Huber K, Iung B, Kjeldsen KP, Longrois D, Luscher TF, Pierard L, Pocock S, Price S, Roffi M, Sirnes PA, Sousa-Uva M, Voudris V, Funck-Brentano C; Authors/Task Force Members. 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur Heart J. 2014 Sep 14;35(35):2383-431. doi: 10.1093/eurheartj/ehu282. Epub 2014 Aug 1. No abstract available.

  PMID: 25086026 BACKGROUND

• Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A; Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31. doi: 10.1186/cc5713.

  PMID: 17331245 BACKGROUND

• Monk TG, Bronsert MR, Henderson WG, Mangione MP, Sum-Ping ST, Bentt DR, Nguyen JD, Richman JS, Meguid RA, Hammermeister KE. Association between Intraoperative Hypotension and Hypertension and 30-day Postoperative Mortality in Noncardiac Surgery. Anesthesiology. 2015 Aug;123(2):307-19. doi: 10.1097/ALN.0000000000000756.

  PMID: 26083768 BACKGROUND

• Kheterpal S, Khodaparast O, Shanks A, O'Reilly M, Tremper KK. Chronic angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy combined with diuretic therapy is associated with increased episodes of hypotension in noncardiac surgery. J Cardiothorac Vasc Anesth. 2008 Apr;22(2):180-6. doi: 10.1053/j.jvca.2007.12.020.

  PMID: 18375317 BACKGROUND

• Twersky RS, Goel V, Narayan P, Weedon J. The risk of hypertension after preoperative discontinuation of angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists in ambulatory and same-day admission patients. Anesth Analg. 2014 May;118(5):938-44. doi: 10.1213/ANE.0000000000000076.

  PMID: 24681657 BACKGROUND

• Tan TW, Eslami MH, Kalish JA, Eberhardt RT, Doros G, Goodney PP, Cronenwett JL, Farber A; Vascular Study Group of New England. The need for treatment of hemodynamic instability following carotid endarterectomy is associated with increased perioperative and 1-year morbidity and mortality. J Vasc Surg. 2014 Jan;59(1):16-24.e1-2. doi: 10.1016/j.jvs.2013.07.025. Epub 2013 Aug 30.

  PMID: 23994095 BACKGROUND

• Lee SM, Takemoto S, Wallace AW. Association between Withholding Angiotensin Receptor Blockers in the Early Postoperative Period and 30-day Mortality: A Cohort Study of the Veterans Affairs Healthcare System. Anesthesiology. 2015 Aug;123(2):288-306. doi: 10.1097/ALN.0000000000000739.

  PMID: 26200181 BACKGROUND

• Drenger B, Fontes ML, Miao Y, Mathew JP, Gozal Y, Aronson S, Dietzel C, Mangano DT; Investigators of the Ischemia Research and Education Foundation; Multicenter Study of Perioperative Ischemia Research Group. Patterns of use of perioperative angiotensin-converting enzyme inhibitors in coronary artery bypass graft surgery with cardiopulmonary bypass: effects on in-hospital morbidity and mortality. Circulation. 2012 Jul 17;126(3):261-9. doi: 10.1161/CIRCULATIONAHA.111.059527. Epub 2012 Jun 19.

  PMID: 22715473 BACKGROUND

• Shiffermiller JF, Monson BJ, Vokoun CW, Beachy MW, Smith MP, Sullivan JN, Vasey AJ, Guda P, Lyden ER, Ellis SJ, Pang H, Thompson RE. Prospective Randomized Evaluation of Preoperative Angiotensin-Converting Enzyme Inhibition (PREOP-ACEI). J Hosp Med. 2018 Sep;13(10):661-667. doi: 10.12788/jhm.3036. Epub 2018 Jul 25.

  PMID: 30261084 DERIVED

MeSH Terms

Interventions

Quinapril; Perindopril; Ramipril; benazepril; Captopril; Enalapril; Enalaprilat; Fosinopril; Lisinopril; trandolapril; moexipril

Intervention Hierarchy (Ancestors)

Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Indoles; Proline; Imino Acids; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Dipeptides; Oligopeptides; Peptides; Phosphinic Acids; Organophosphorus Compounds; Organic Chemicals

Limitations and Caveats

Management decisions were made by the treatment which was not blinded to allocation; Intraoperative hypotension is an intermediate measure but one that has known associations with adverse outcomes, including mortality.

Results Point of Contact

• Title: Dr. Jason Shiffermiller
• Organization: University of Nebraska Medical Center

jshiffermiller@unmc.edu

402-559-7299

Study Officials

• Jason F Shiffermiller, MD, MPH

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2012
• First Posted: August 21, 2012
• Study Start: June 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2016
• Last Updated: September 25, 2023
• Results First Posted: December 11, 2017

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)