Side Effects of Blood Pressure Drugs Often Unmonitored, Unaddressed

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are effective for treating high blood pressure, heart failure and kidney disease. They also are very widely used, with an estimated 164 million ACE inhibitor prescriptions and 86 million ARB prescriptions dispensed in the U.S. in 2011.[1]

Yet they also come with the potential for serious side effects. The drugs have long been known to impair kidney function and dangerously elevate blood potassium levels in certain patients. Therefore, guidelines and the labeling for some of these products recommend monitoring patients’ kidney function and potassium levels before and after starting or increasing the dosage of ACE inhibitor or ARB therapy and periodically thereafter.[2]

Two new studies published this year confirmed that ACE inhibitors and ARBs can potentially harm the kidneys and increase potassium levels. The studies also indicated that many doctors are not heeding recommendations to look out for these side effects and, if necessary, adjust therapy for patients being treated with ACE inhibitors or ARBs.

About the drugs

ACE inhibitors and ARBs act on a biological pathway that is central to regulating blood pressure and the body’s salt and water balance; this pathway is known as the renin-angiotensin-aldosterone system. When used individually, these drugs are of great benefit in treating high blood pressure, with some also slowing the progression of congestive heart failure, cardiovascular disease and chronic kidney disease.

ACE inhibitor- and ARB-induced kidney damage

One study, published in The BMJ, analyzed the medical records of more than 120,000 patients living in the U.K. in a large electronic database for evidence of sudden declines in kidney function soon after starting ACE inhibitors or ARBs and associated long-term health outcomes.[3] The authors looked at a substance in the blood known as creatinine, which is routinely measured in patients to estimate kidney function, with an increase in creatinine indicating a reduction in kidney function. Nearly 2 percent of patients had a substantial reduction in kidney function, as defined by a creatinine increase of 30 percent or more, within two months of starting an ACE inhibitor or ARB. These patients, over a follow-up period of up to 10 years, had significantly higher rates of end-stage kidney disease (for which the patient requires dialysis or a kidney transplant to survive), heart attack, heart failure and death than patients with an increase in creatinine of less than 30 percent.

It had long been thought that increases in creatinine of less than 30 percent that occur after a patient starts an ACE inhibitor or ARB were not harmful. But this study found that increases in creatinine between 10 and 30 percent within two months of starting an ACE inhibitor or ARB — which occurred in nearly 15 percent of the patients — also were associated with an increased risk of end-stage kidney disease, heart attack, heart failure and death, with the risk increasing with higher creatinine increases.

Many patients not monitored and managed safely

The other study, published in BMJ Open, set out to determine the extent to which primary health care providers in the U.K. were monitoring kidney function and blood potassium levels after initiation of ACE inhibitor or ARB therapy.[4] The authors analyzed the medical records of more than 220,000 patients who were started on ACE inhibitors or ARBs from 2004 through March 2014.

The study found that only 10 percent of these patients had, as is recommended by the guidelines, creatinine levels measured within one month before starting therapy and follow-up measurements within two weeks after starting to take the medication. More than one half of all patients had missed either a baseline creatinine test within a year before or two months after starting the medications.

Especially concerning was the fact that even when patients’ kidney function and potassium levels were monitored, guideline recommendations were almost never followed when concerning measurements were found. Of the patients who had a creatinine increase of 30 percent or more, or a dangerously high potassium level, after starting an ACE inhibitor or an ARB, 80 percent were continued on the medications for longer than 30 days and 60 to 65 percent were continued for longer than 90 days after these concerning findings were discovered.

What the studies say

Together, these two new studies confirm that ACE inhibitors and ARBs can be dangerous for certain patients, with the potential for long-term damage, and that health care providers are frequently neglectful in monitoring and protecting patients from these harms. Even slight decreases in kidney function soon after starting ACE inhibitors or ARBs are associated with increased long-term risks of life-threatening heart and kidney disease, making it critically important to administer or prescribe the drugs only to patients who can tolerate them safely.

What You Can Do

For high blood pressure, a thiazide diuretic such as hydrochlorothiazide (MICROZIDE) should be the initial drug of choice.

For most patients with high blood pressure not adequately controlled with a diuretic, heart failure or kidney disease, ACE inhibitors and ARBs are effective drugs.

Your health care provider should monitor you very carefully, assessing your kidney function and potassium levels, both before and soon after starting you on either of these drugs or after increasing the dosage.

Although ACE inhibitors and ARBs can harm the kidneys and raise blood potassium to dangerous levels if taken alone, they are much more likely to do so if taken in combination. For this reason, we have previously warned Worst Pills, Best Pills News readers never to take ACE inhibitors and ARBs in combination.[5]

ACE Inhibitors and ARBs on the U.S. Market (Combination Drugs Excluded)

All drugs in the table are designated as Limited Use, except for azilsartan, which is designated as Do Not Use for Seven Years (until at least March 2018).
* FDA-approved for the treatment of heart failure, cardiovascular disease or kidney disease in addition to high blood pressure.

References

[1] IMS Institute for Healthcare Informatics. The use of medicines in the United States: Review of 2011.https://www.imshealth.com/files/web/IMSH%20Institute/Reports/The%20Use%20of%20Medicines%20in%20the %20United%20States%202011/IHII_Medicines_in_U.S_Report_2011.pdf Accessed April 2, 2017.
[2] McDowell SE, Thomas SK, Coleman JJ, et al. A practical guide to monitoring for adverse drug reactions during antihypertensive drug therapy. J R Soc Med. 2013;106(3):87-95.
[3] Schmidt M, Mansfield KE, Bhaskaran K, et al. Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study. BMJ. 2017;356:j791.
[4] Schmidt M, Mansfield KE, Bhaskaran K, et al. Adherence to guidelines for creatinine and potassium monitoring and discontinuation following renin-angiotensin system blockade: a UK general practice-based cohort study. BMJ Open. 2017;7(1):e012818.
[5] Worst Pills Best Pills News. Further Evidence Confirms Danger Of Blood Pressure Drugs Used Together. April 2015. /newsletters/view/955. Accessed April 2, 2017.