This document summarizes the STOP ACEi trial, which investigated whether continuing or discontinuing renin-angiotensin system (RAS) inhibitors impacted kidney function decline in patients with advanced chronic kidney disease (CKD). The trial randomized 411 patients with CKD stages 4-5 to either continue or discontinue their RAS inhibitor treatment. The primary outcome was estimated glomerular filtration rate (eGFR) after 3 years, with secondary outcomes including time to end-stage kidney disease and hospitalization rates. The results showed no improvement in kidney function for those who discontinued RAS inhibitors. The authors concluded that stopping RAS inhibitors in advanced CKD does not provide benefit and may be harmful.

1. Presenter: Mohamed Hufane (R1/1M)
Moderator: Abdul-Aziz, MD (consultant internist)
THE STOP ACEI TRIAL
RENIN–ANGIOTENSIN
SYSTEM INHIBITION IN
ADVANCED CHRONIC
KIDNEY DISEASE

3. PREVIOUS TRIALS
Lewis et al
2001
• The angiotensin-II-
receptor blocker
irbesartan is effective in
protecting against the
progression of
nephropathy due to type
2 diabetes. This
protection is independent
of the reduction in blood
pressure it causes.
Lancet
1997
• In chronic nephropathies
with proteinuria of 3 g or
more per 24 h, ramipril
safely reduces
proteinuria and the rate
of GFR decline to an
extent that seems to
exceed the reduction
expected for the degree
of blood-pressure
lowering.
Jafar et al
2001
• The beneficial effect of
ACE inhibitors is
mediated by factors in
addition to decreasing
blood pressure and
urinary protein excretion
and is greater in patients
with proteinuria.
• Bateman E et al. NEJM. 2018;378(20):1877-1887.

4. CLINICAL QUESTION
• To continue or not to continue RAAS inhibitio in advanced CKD.

5. TRIAL DESIGN
• STOP ACEi was a multi-center, randomized, open-label trial that
examined the impact of continuation of RAS inhibitors on the
eGFR in advanced CKD.
• Patients were enrolled at 39 centers in the United Kingdom.
• RAS inhibitors were defined as ACEi or ARB
• 17,290 patients screened between July 11, 2014, and June 19,
2018. Of these, 1,210 patients were invited to participate, and
411 patients (from 37 centers) were randomized.

6. POPULATION
Inclusion Criteria
• Adults >18 years old
• CKD Stage 4-5 (eGFR < 30 ml/min/1.73m2)
• Decrease in eGFR >2 ml/min/1.73m2 per year in the previous 2 years
• Receiving treatment with an ACEi, ARB or both for > 6 months

7. Exclusion Criteria
• Receiving dialysis
• Having had a kidney transplant
• Uncontrolled hypertension (BP > 160/90 mmHg)
• Immune mediated kidney disease requiring specific
therapy
• MI or stroke within the previous 3 months

11. INTERVENTIONS
• Randomized in a 1:1
• RAS continue group
• No RAS continue group
• Both groups were allowed to have any guideline-
recommended antihypertensive added to their regimens to
meet the study blood pressure target of <140/85 mmHg,
including MRAs (which also inhibit RAS via
mineralocorticoid receptor antagonism).
• Patients in the discontinuation group were not to resume
ACEi or ARB unless all other options were ineffective or
associated with intolerable side effects.
• Participants were followed every 3 months after
randomization for a total period of 3 years.

12. OUTCOMES
Primary endoints
• The eGFR at 3-years follow-up calculated using the 4-variable
MDRD175 equation was the primary end-point.
• They also repeated the primary analysis using the CKD-EPI
2009 equation and the MDRD186 equation

15. Secondary endpoints
• Time to development of ESKD (defined by the local investigator,
with criteria including palliative care and RRT)
• Composite including decrease in eGFR > 50%, development of
ESKD and initiation of KRT
• Any cause hospitalization
• Blood pressure measures
• Quality of life (Kidney Disease Quality of Life 36-Item Short Form
Survey, version 1.3)
• Exercise capacity (6-minute walk test)
• CVD events
• Death
• Hemoglobin
• Urinary Protein-to-creatinine Ratio (uPCR)

18. STRENGHTS
• Good trial design
• Good monitoring and follow up.
• Even representation of different
etiologies of CKD
• Authors did not include dosing
information for the RAS inhibitors
• The open-label nature of this
study may have contributed to
bias, particularly with respect to
subjective endpoints (e.g. quality-
of-life).
WEAKNESSES
CRITICISM

19. IMPLICATIONS
• ACE inhibitors are cost effective and widely available.

20. AUTHOR’S
CONCLUSIONS
• The results of this trial confirm that
discontinuation of ACEi or ARB in
patients with advanced CKD does
not provide meaningful
improvement of kidney function.
• A knee jerk response of stopping
RAS inhibitors in advanced CKD at
an arbitrary GFR threshold is
incorrect.
Beasley RD et al. NEJM. 2019; 380(21):2020-
2030.

21. SUMMARY

22. THANK YOU