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

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

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. 2010 Apr; 25(4): 326–333.

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. 2010 Mar; 8(1): 41. Clin J Am Soc Nephol. 2014 Feb 7; 9(2): 295–301.

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 http://content.nejm.org/cgi/content/abstract/351/6/543 Arch Intern Med 2000;685–693. JAMA 2003;289:1652-1658. NEJM 2004;351:543-551.

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. 2010 Mar; 8(1): 41

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

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

Patient Safety Reports

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

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

Patient Safety Culture and Safe Medication Practices

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

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… http://academicdepartments.musc.edu/PPRNet/Research/PPRNet_Medication_Safety_Toolkithttp://academicdepartments.musc.edu/PPRNet/Research/PPRNet_Medication_Safety_Toolkit

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); 238-243

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

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.

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

For more information: Wilson Pace, MD DARTNet Institute, CMO Wilson.Pace@DARTNet.info Andrea Wessell, PharmD DARTNet Institute, PSO Director Wessell@musc.edu