Under Pressure Episode #8: An overview of ARBs and ACE inhibitors

---

ONLINEABIM MOC Part 2ACPEAMAANCCIPCEMOCPodcastsUnder Pressure

Instructions

Monday, November 28, 2022, 12:00 PM - Friday, November 28, 2025, 12:00 PM

Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are often lumped together because they both work on the RAAS cascade just at different points. ACE-I work by preventing the conversion of angiotensin 1 to angiotensin 2 thus leading to natriuresis and reducing preload and afterload among other things. Unfortunately, there is still the possibility of ACE escape at low levels through other pathways and that is where ARBs come in. They are able to block the effect of angiotensin at the final point thus getting around the ACE escape. The other advantage of ARBs is that they don’t lead to the by-product of bradykinin unlike ACE-I. Bradykinin is what is responsible for one of the major side effects of ACE-I, cough. In fact, cough occurs at such a high rate that it is a common reason for discontinuation and adherence issues from a patient perspective. It can happen at with a higher incidence in some demographics.1-2 This effect is usually seen at initiation or dose increase unlike the other major side effect concern with ACE-I, angioedema. Angioedema is an allergy reaction and can occur at any time but particularly if patients are smokers, taking NSAIDs, are of certain ethnic backgrounds3-4, elderly or are women. It tends to occur more frequently at initiation.  ARBs avoid both of these side effects. There initially was a thought that ARBs were associated with angioedema but more recent studies have disproven that theory. Now the recommendation is waiting 4-6 weeks after angioedema with an ACE-I then starting an ARB if indicated.

What about the warning or concern with ARBs and angioedema?

There initially was a thought that ARBs were associated with angioedema but more recent studies have disproven that theory. Now the recommendation is waiting 4-6 weeks after angioedema with an ACE-I then starting an ARB if indicated.

When do you think about ACE-I and ARBs?

I usually use ARBs given their minimal side effect profile especially in the setting of the multinational cohort study last year that showed they are safer in pretty much every way compared with ACE-I.7

Most common indications for this group is: CKD, CAD, HF, h/o stroke. Notably a couple of the ARBs have specific scenarios where they have carved out a niche. Losartan in patients with gout or hyperuricemia and can decrease uric acid by up to 25% depending on how high baseline uric acid is.11 The drawback is it is short-acting and needs bid dosing. Candesartan is an option for patients with migraines according to the Canadian Headache Society and AAN. It is a level C and often needs bid dosing since it is short-acting. I also like valsartan because it comes combined with amlodipine and is generic or irbesartan for its renoprotective effect and ease of access on some pharmacies’ cash programs. Olmesartan is sometimes used, but its blood pressure lowering effect is similar to valsartan and has the unusual risk of sprue-like enteropathy. The incidence is very low but given there are other agents that have the same benefits without the risk I err towards using those.  

I think their use is optimal for patients with low potassium who don’t have hyperaldosteronism. Usually you would repeat a chem-6  2-4 weeks after starting these agents or making a dose change. You can expect an acute bump in SCr but if >20-30% then you would reduce the dose or repeat the chem-6 1-2 weeks later to see if it improves.5

Are there situations where ACE-I is favored over ARBs?

If you have a woman who is breastfeeding and has proteinuria or needs an ACE/ARB then you would think of enalapril or captopril as they have the most safety data.6 The relative infant dose (or RID) is 1.1%. This is a measure of how much of the drug is in breast milk. The accepted threshold is 10% so this is well below it.

Further reading/works cited:

1. BMJ 2006:332:1177-81
2. Am J Med 2010;123:183.e11-5
3. Otolaryngol Head Neck Surg. 2008;139:105–108
4. Clin Pharmacol Ther. 1996;60:8–13
5. https://www.nice.org.uk/guidance/cg127#choosing-antihypertensive-drug-treatment-2
6. https://www.sps.nhs.uk/articles/safety-in-lactation-drugs-for-hypertension/
7. Hypertension. 2021;78:00-00
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947116/
9. https://pubmed.ncbi.nlm.nih.gov/17391291/
10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587798/pdf/CDR-36-na.pdf
11. Choi, H. K., Soriano, L. C., Zhang, Y., & Rodríguez, L. A. (2012). Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study. BMJ (Clinical research ed.), 344, d8190. https://doi.org/10.1136/bmj.d8190

1. Discuss the concern with ARBs and angioedema.
2. Discuss ARBs and ACE inhibitors.

There is no registration fee to participate.  Learners must listen to the entire podcast, review resource materials, score at least 100% on the post-test, and complete an activity evaluation in order to receive credit.
 
The Under Pressure faculty report no relevant financial disclosures.

In support of improving patient care, this activity has been planned and implemented by Under Pressure and VCU Health Continuing Education. VCU Health Continuing Education is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

 

 

VCU Health Continuing Education designates this enduring activity for a maximum of 1.0 AMA PRA Category 1 Credits^TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

 

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1 medical knowledge MOC point in the American Board of Internal Medicine (ABIM) Maintenance of Certification (MOC) program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

VCU Health Continuing Education designates this activity for a maximum of 1.0 ANCC contact hour. Nurses should claim only the credit commensurate with the extent of their participation in the activity.


VCU Health Continuing Education has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 1.0 AAPA Category 1 CME credits. Approval is valid until the activity end date. PAs should only claim credit commensurate with the extent of their participation.

 

This activity provides 1.0 contact hours (0.1 CEUs) of continuing education credit. ACPE Universal Activity Number (UAN): JA4008237-9999-22-203-H01-P.

NOTE FOR PHARMACISTS: VCU Health Continuing Education will upload the pharmacy-related continuing education information to CPE Monitor within 60 days of activity completion. Per ACPE rules, VCU Health Continuing Education does not have access nor the ability to upload credits requested more than 60 days after activity completion. It is the responsibility of the pharmacist or pharmacy technician to provide the correct information [NABP ePID and DOB (in MMDD format)] in order to receive credit for participating in a continuing education activity.

Accommodation

All participants have the right to participate in this continuing education activity without discrimination due to age, race, ethnicity, religion, culture, language, physical or mental disability, socioeconomic status, sex (sexual orientation, gender identity or expression and pregnancy), protected veteran status, marital status, genetic information, or any other protected characteristics under applicable federal, state, or local law. If you need accommodations to participate in this activity, please contact us at [email protected] for more information. Requests for accommodations must be received 21 days prior to activity start date.

Complaint Policy and Resolution Process
All complaints must be made in writing to [email protected].

All complaints will be logged into the complaint log. The Director, Continuing Education will attempt to resolve the complaint within the first contact, when possible, and will respond to the client and customer's concerns within 5 business days of the initial complaint. At the time of the first contact, Director, Continuing Education will inform the complainant if more time will be needed to research the complaint.

If the complaint is still unresolved after communication with the Director, Continuing Education, or if the initial complaint is not addressed in a timely manner, the complainant may contact the President & CEO, UHS-PEP. The President & CEO will then contact the complainant and endeavor to resolve the complaint within 10 business days after being contacted.

The complaint log will be regularly reviewed to identify areas of operations and service that may require improvement. The Director, Continuing Education will research reoccurring complaint matters and recommend process and procedure changes, when appropriate. These changes will be noted on the Complaint Resolution Log, and any necessary policy and/or procedure updates will be made within 15 business days thereafter.

Disclaimers
Minimum and maximum numbers for attendance at this event have been established, and we reserve the right to substitute speakers/topics, adjust credit hours, or cancel if necessary.

By attending this event you grant VCU Health Continuing Education the right at the event to record, film, photograph, or capture your likeness in any media and to distribute, broadcast, use, or otherwise disseminate, in perpetuity, such media without any further approval from or any payment to you.

AMA PRA Category 1 Credits™ (1.00 hours), ABIM MOC Part 2 (1.00 hours), ACPE - Accreditation Council for Pharmacy Education (1.00 hours), ANCC - American Nurses Credentialing Center (1.00 hours), IPCE - Interprofessional Continuing Education Credit (1.00 hours), Non-Physician Attendance (1.00 hours)

Mitigation of Relevant Financial Relationships

VCU Health Continuing Education adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of a CE activity, including faculty, planners, reviewers or others are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant conflicts of interest have been mitigated prior to the commencement of the activity.