Everything You Need to Know About ACE Inhibitors

Editor’s note (08/06/20): Because COVID-19 is thought to attach itself to ACE-2 enzymes as a way to gain entry to the human body, some people believe that taking ACE inhibitors may increase one’s chances of contracting the virus. This isn’t proven.

One in two Americans has hypertension, aka high blood pressure, and about 87 million of them are prescribed a medication. Of the drugs liberally doled out to Americans, Angiotensin-converting enzyme (ACE) inhibitors are the most common. Like any drug, ACE inhibitors can cause serious side effects, and it’s essential to understand all the facts about this medication, as well as alternatives to it, before taking it. Otherwise, you can’t be empowered to make the best decision for you.

Common Names

Monopril (fosinopril), Vasotec (enalapril), Capoten (captopril), Lotensin (benazepril), Accupril (quinapril), Zestril (lisinopril), Univasc (moexipril), Aceon  (perindopril), Altace (ramipril), Mavik (trandolapril)

How They Work (Method of Action)

ACE inhibitors block the angiotensin-converting enzyme, which relaxes blood vessels to lower blood pressure and increases the amount of blood your heart pumps so that it doesn’t have to work as hard. In addition to being used to treat hypertension and heart disease, ACE Inhibitors also aid in treating scleroderma, migraines, diabetes, kidney disease, and even post-traumatic stress disorder (PTSD).

Side Effects and What to Do About Them

Common Side Effects

According to the U.S. National Library of Medicine, most side effects of ACE Inhibitors are uncommon but some can be severe and possibly fatal. Common side effects include dizziness, headaches, dry cough, rash, fatigue, nausea, and loss of taste. These symptoms may go away once you get used to the medication. Otherwise, your doctor may lower your dose or switch you to another drug.

Severe Side Effects

More severe side effects can include fever, sore throat, swelling of the lower extremities, sores in the mouth, bruising, chest pain, and irregular or rapid heartbeat. Let your doctor know if you experience any side effects.

High Potassium

High potassium levels are another possible outcome of taking ACE inhibitors, so you will need regular blood tests to monitor your potassium level. Signs of too much potassium in your blood include weakness and fatigue, irregular heartbeat, nausea, confusion, leg weakness, numbness in the hands, lips or feet, breathing difficulties, and nervousness. This condition can be potentially life-threatening, so contact your doctor right away if you develop any of these symptoms.

Angioedema

Another uncommon but severe side effect of ACE inhibitors is angioedema — swelling of the throat, face, lips, tongue, hands, and feet caused by an allergic reaction. A rare type of angioedema linked to ACE inhibitors is intestinal angioedema, which causes abdominal pain, cramping, diarrhea, vomiting, and anorexia. In severe cases, angioedema can lead to life-threatening obstruction of the throat or intestine. Contact your doctor immediately if you develop any symptoms of angioedema.

Lung Cancer

ACE inhibitors may slightly increase the risk of developing lung cancer. In a study in the BMJ, researchers looked at nearly one million people that were prescribed blood pressure-lowering drugs in the United Kingdom. Once prescribed, they were followed for an average of 6.4 years. Some people received an ACE inhibitor, some received another class of drugs, angiotensin receptor blockers (ARBs), and others received both groups of drugs. 

The patients that took an ACE inhibitor had a 14% increased risk of lung cancer compared to those on an ARB. The risk also increased the longer a patient was on an ACE inhibitor. After ten years, the increased risk rose to 31% compared to ARBs. 

The researchers surmise that the increased lung cancer risk may be the result of ACE inhibitors promoting the production of protein-like chemicals known as bradykinin and substance P, which can stimulate lung cancer growth. An editorial accompanying the study said that the long-term risk of lung cancer associated with ACE inhibitors should be “balanced against gains in life expectancy associated with use.”

Neutropenia

Among those taking the specific ACE inhibitor, Lotensin, there have been reports of neutropenia, a rare but potentially lethal condition in which a person’s white blood cell count is severely diminished. In one case study discussed in the American Journal of Case Reports, a 61-year-old man went to the emergency room with severe throat pain and difficulty swallowing that lasted over a week. The man was being treated for hypertension with Norvasc (amlodipine) and Lotensin (benazepril).

At the hospital, the patient was diagnosed with neutropenia. Given that he had started Lotensin two months before symptoms began, and neutropenia is rarely seen with Norvasc, doctors suspected Lotensin to be the cause of his drug-induced condition. After he was taken off Lotensin, the patient achieved a quick recovery in white blood cell count. And after three weeks, the patient’s white blood cell count remained in the normal range.

User Experiences

Judy Olson, 64, has been on lisinopril for the past 20 years for her hypertension. She says the medication keeps her blood pressure controlled, though she does experience a cough that she describes as “tolerable.”

Several years ago, Michelle Haselhorst, 36, was on a low dose of lisinopril for two years to prevent kidney damage from her diabetes. She experienced dizziness and nausea if she stood up too fast or took a warm bath, so her doctor cut her dosage in half. Though decreasing her dose helped with those symptoms, she was still constantly losing her voice, a less common side effect. Her doctor decided to take her off lisinopril, and her voice has been much better ever since.

Drug Interactions

Talk to your doctor before taking any nonsteroidal anti-inflammatory medications (NSAIDs), such as Advil (ibuprofen), Aleve (naproxen), or aspirin, as these can decrease the effectiveness of your ACE inhibitor. ACE inhibitors can interfere with certain diabetes medications. As with any prescription medication, let your doctor know about any other prescription or over-the-counter medications, supplements, or herbs you are taking.

Effectiveness and Considerations

There are no significant differences in the effectiveness of each drug, according to a Cochrane review of 92 ACE inhibitor trials. Additionally, the review found that 60-70% of the effect of lowering a patient’s blood pressure is found in the lowest recommended dose. This means that you may be able to use the least expensive ACE inhibitor at a starting dose to minimize potential side effects while still getting the majority of the blood pressure-lowering effect.

In a study in the journal Medicine which compared the safety and effectiveness of ACE inhibitors in patients with heart failure, researchers determined that enalapril was the most effective at improving the volume of blood pumped with each heartbeat, arterial pressure, and other factors. But enalapril produced the highest incidence of cough, gastrointestinal discomfort, and kidney problems. Trandolapril was best at reducing blood pressure, and ramipril was associated with the lowest risk of death from any cause. Lisinopril was the worst at lowering blood pressure and increased the risk of death more than any others.

Pregnant women should not take ACE inhibitors as they can cause life-threatening conditions for the mother, increased risk of miscarriage, and congenital disabilities in the baby. Also, because ACE inhibitors can pass through breast milk, mothers should either not breastfeed while taking them or find another medication.

ACE Inhibitors and COVID-19

There have been questions about the potential increased risk of COVID-19 infection in people taking ACE inhibitors, and the likelihood of more severe illness. In a June 2020 study reported in JAMA Network, researchers examined the association between the use of ACE inhibitors or ARBs versus other antihypertensive drugs and the risk of COVID infection in patients with hypertension. Approximately 4,500 patients with COVID were included in the study. The researchers determined that prior use of ACE inhibitors or ARBS did not increase the risk of contracting COVID in hypertensive patients, nor did it increase the risk of death or severe disease among those with COVID. 

A May 2020 report from the World Health Organization notes that, based on a review of 11 studies, a history of ACE inhibitor use was not found to be associated with severe COVID. An early study from researchers at Yale found that patients taking ACE inhibitors may have a reduced risk of hospitalization. 

In a joint statement from the American Heart Association, the Heart Failure Society of America, and the American College of Cardiology, experts recommend that people who are taking ACE inhibitors and contract COVID-19 should not stop taking this medication. The experts note that in experimental studies, ACE inhibitors can reduce lung injuries in some viral cases of pneumonia, and may be beneficial in COVID-19. Much more research is needed to clarify concerns about cardiovascular disease and COVID-19.

Alternatives to ACE Inhibitors

There are natural ACE inhibitors and alternatives to blood pressure medications that you can add to your diet, such as pomegranate juice, flaxseed, beet juice, apple juice, prunes, dark chocolate, kiwis and blueberries. Pomegranates are also high in antioxidants, which can improve blood flow, help keep arteries flexible, and reduce the risk of blood clots. Foods high in flavonoids, such as grapes, berries, citrus fruit, beans, onions, broccoli, kale, and Brussels sprouts, as well as foods containing vitamin E, like nuts, sunflower seeds, and avocados, are also beneficial for your heart and blood vessels.

Keep in mind that foods are not as effective as medication for acute cases of high blood pressure, though they may be useful in helping to prevent hypertension in the first place. If you take an ACE inhibitor, check with your doctor before eating or drinking anything that can lower your blood pressure naturally. The combination could cause low blood pressure.

The DASH (Dietary Approaches to Stop Hypertension) diet is another alternative to combat high blood pressure by committing to a lifetime of eating a healthy, balanced diet that’s low in sodium and rich in nutrients. This diet may also help you lose weight and prevent osteoporosis, heart disease, stroke, cancer, and diabetes. If you’re already on an ACE inhibitor, implementing the DASH diet can supplement the medication’s effects, especially if you take a low dose. Check with your doctor before making a change in your diet.

Lifestyle changes like regular exercise, weight loss, reducing your stress, cutting back on alcohol and/or caffeine, and quitting smoking are other drug-free ways to reduce your blood pressure. (See MedShadow’s Ways to Lower High Blood Pressure Without Relying on Drugs)

Never decrease or discontinue your ACE inhibitor without medical supervision and always discuss any alternative treatment plan with your doctor before you start, even if it’s supplemental.