1. DARTNet Patient Safety Organization – Risks Associated with ACE/ ARB Use
Based on work of the PPRNet
Andrea Wessell, PharmD, Clinical Director DARTNet PSO

2. ACE/ARB Safety Angiotensin Converting Enzyme Inhibitors (ACE)
Angiotensin Receptor Blockers (ARB)
One of the most common drug classes in use in the USA
Beneficial for HTN, Heart Failure and to delay kidney injury
Concerning potentially preventable adverse events include: Hyperkalemia and Acute Kidney Injury

3. ACE/ARB Adverse Drug Events
Patients at higher risk for hyperkalemia and elevations in serum creatinine can be predicted
Treatment with an ACE/ARB may still be warranted with attention to monitoring
Monitoring decreases bad outcomes
Alternative treatment options may be appropriate for some patients
J Gen Int Med Apr; 25(4): 326–333.

4. ACE/ARB Patients at Risk
Initiation of ACE/ARB plus a potassium sparing diuretic
Initiation of ACE/ARB with high baseline potassium (5.5 mg/dl or higher)
Initiation of ACE/ARB with significant underlying chronic kidney disease (eGFR <45 or Stage IIIb kidney disease)
Ther Clin Risk Manag. 2009; 5: 547–552.
Clin Med Res Mar; 8(1): 41.
Clin J Am Soc Nephol Feb 7; 9(2): 295–301.

5. ACE/ARB + K+-sparing diuretic
Hyperkalemia and renal injury are common adverse reactions
Admissions for and mortality from hyperkalemia significantly increased when spironolactone was added to ACE in heart failure patients
Older patients admitted to the hospital for hyperkalemia on an ACEI were 20 times more likely to have received a K-sparing diuretic in the past week
Heart failure patients hyperkalemia admissions increased 11 fold after combination therapy was noted to improve outcomes
1994 vs 2001, post RALES
Hospitalizations – 2.4 to 11
Mortality – 0.3 to 2.0
Arch Intern Med 2000;685–693. JAMA 2003;289: NEJM 2004;351:

6. ACE/ARB and Hyperkalemia
Various conditions can cause baseline hyperkalemia (e.g. Type IV Renal Tubular Acidosis)
Adding ACE/ARB may induce extreme hyperkalemia
If the baseline Potassium >=5.5 use with caution
Thiazide or loop diuretics decrease the risk
Clin Med Res Mar; 8(1): 41

7. ACE/ARB & Acute Renal Injury
Initiation of an ACE/ARB – with or without a potassium sparing diuretic – patients with significant renal injury can induce further decreases in glomerular filtration
Patients with eGFRs below 45 ml/min (Stage IIIb renal disease) should be monitored when starting an ACE/ARB
refs

8. General Recommendation
In high risk patients when initiating ACE/ARB or potassium sparing diuretic plus ACE/ARB recheck potassium within 2 to 4 weeks (hospitalizations occurred within one week)
In high risk patients recheck serum creatinine within 2 to 4 weeks
Monitor K+ serum Cr every 6 months

9. Patient Safety Reports

10. ACE/ARB Safety Reports
Initiation of dual ACE/ARB and potassium sparing diuretic – Potassium check at 14 and 30 days
Initiation of ACE/ARB with baseline K+
>= 5.5 check K+ in 2 to 4 weeks
Initiation of ACE/ARB with Stage IIIb or higher kidney injury recheck serum Cr in 2 to 4 weeks
If no baseline K+ or Cr draw at initiation

11. PSO Reports Linkages
Patient Safety reports can be linked back to a Patient ID that is available to the practice

12. Patient Safety Culture and Safe Medication Practices

13. Medication Safety Approaches From Practice Partners Research Network
Practice strategies:
Develop practice culture of medication safety
Assure the accuracy of each patient’s med list
Integrate EHR decision support features
Implement a practice protocol for med refills
Design and execute case management for patients who meet criteria for preventable med errors

14. Develop Med. Safety Culture
Deliver medication safety reminders consistently across practice
Ask patients to bring medications to all visits
Provide patients with a medication list at end of appointment
Perform medication reconciliation at all visits
Many practices revised their approach to reminding patients to bring meds to appts…

15. EHR Decision Support (CDS)
Adjust ACE/ARB reminder messages to account for high potassium and low eGFR
Provide ability to turn off reminders for these patients related to ACE/ARB if not used
Create reminders for monitoring in EHR and Population Registry
Allergy and interaction alert functionality were familiar to participants.
Ex from Cookeville – INR template and Kelly Omalia – HTN/NSAIDs.
 Journal of Patient Safety, 2010, 6(4);

16. Schedule Lab Follow-up
At the time an ACE/ARB or potassium sparing diuretic initiated in higher risk patient schedule the lab follow-up in EHR
Track missing F/U appointments as part of registry function
Draw labs if no baseline available
If high baseline potassium or stage IIIb renal disease noted make positive contact with patient for follow-up lab tests

17. Medication Refills Add CDS for medication refill staff
Educate staff to understand and use the CDS and how to deal with patient concerns
Consider scheduling refill requirements based on monitoring requirements
Consider monitoring selected refills in Registry and sending reminders for Refills and not just testing or visit requirements
..that prioritizes safe med use and appropriate monitoring.

18. Patient Registry and Safety
Develop patient focused, not disease focused, registries
Consider medication monitoring as key component of recall “messaging”
Develop consistent approach to patient outreach
Track outreach activities
Assure CDS in EHR tracks with registry outreach
Make time for this
MS-TRIP quarterly reports
-start w/measures <median
-use registry to identify patients – adapted according to practice needs

19. For more information: Wilson Pace, MD DARTNet Institute, CMO
Andrea Wessell, PharmD
DARTNet Institute, PSO Director