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Popular blood pressure medications called ACE inhibitors have been associated with an increased risk of lung cancer. Angiotensin converting enzyme (ACE) inhibitors are taken daily by more than 30 million people (MEPS or Medical Expenditure Panel Survey). That translates into 166 million prescriptions each year. These are the most commonly prescribed medications for hypertension. Is there any reason to be concerned about a link between ACE inhibitors and lung cancer?

Lisinopril (Prinivil, Zestril) and Company:

Lisinopril is the most prescribed drug in the United States. Over 130 million prescriptions for this ACEi are dispensed annually. That doesn’t take into account other ACE inhibitors such as benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), ramipril (Altace) and quinapril (Accupril). If your medicine has “pril” at the end of the name, you are probably taking an ACE inhibitor.

What Is ACE and Why Is It Important?

Angiotensin Converting Enzyme (ACE) is critical for regulating the amount of fluids circulating in your body. Without going too deep into the weeds here, you should know that your body has an intricate system for managing fluids and blood pressure.

If you suddenly lost a lot of blood, your blood pressure would drop precipitously. That’s not compatible with life, so your body has a cool system for raising blood pressure. The kidneys release a substance called renin in response to blood loss or a number of other conditions (heart failure, cirrhosis of the liver, low sodium levels, etc.).

Renin helps the body make angiotensin I. ACE (angiotensin converting enzyme) converts angiotensin I to angiotensin II. It is angiotensin II that raises blood pressure back towards normal by constricting blood vessels. Blocking the conversion with an ACE inhibitor reduces the amount of angiotensin II circulating in the body, leads to vasodilation and lowers blood pressure.

ACE Inhibitors: An Amazing Drug Development!

We have always found the story of ACE inhibitors incredibly interesting. It all evolved from a discovery in the Amazon jungles of Brazil. A researcher there paid attention to what happened when people were bitten by the deadly jararaca snake. One of the first complications was a precipitous drop in blood pressure.

Scientists studied the venom-derived compounds. These substances blocked the conversion of angiotensin I to the powerful vasoconstrictor angiotensin II. By figuring out the mechanism and harnessing the power of these compounds, investigators were able to create ACE inhibitors. The first drug in this class was captopril (Capoten). It revolutionized the treatment of hypertension.

ACE Inhibitors and Lung Cancer?

This class of medications is very effective at lowering blood pressure. That is why over 30 million people swallow an ACIi every day. But a study raises questions about the safety of long-term use (BMJ, Oct. 24, 2018).

The investigators collected data on nearly one million hypertensive patients in the UK between 1988 and 2015. Taking an ACE inhibitor was associated with a 14% increased risk of lung cancer. This only became detectable after five years of use. The longer people took such drugs, the greater the risk. After 10 years the risk increased to 31%.

ACE Inhibitors and Lung Cancer: How Big is the Risk?

The absolute risk of lung cancer wasn’t very high: people not on medication had a rate of lung cancer of 1.2 people per 1000 person-years, while those taking an ACE inhibitor had a rate of 1.6 people per 1000 person-years. Many people would conclude that a 0.4 per 1,000 person year risk is hardly worth worrying about.

The authors point out that although the ACE inhibitors and lung cancer risk is small, so many people are taking these medications that the absolute number of patients affected could be quite large.

Remember, over 30 million people are taking this category of blood pressure drugs. If “only” 0.4 people out of 1000 might develop lung cancer in a year, that could conceivably amount to as many as 12,000 extra cases of lung cancer. That’s not trivial.

Is There an Explanation for a Link Between ACE Inhibitors and Lung Cancer?

Clinicians, researchers and people in general like explanations for unusual findings. Is there a mechanism that might explain the connection between ACE inhibitors and lung cancer?

The authors of the study point out that:

“The use of ACEIs causes an accumulation of bradykinin in the lung, which has been reported to stimulate growth of lung cancer. ACEI use also results in accumulation of substance P, which is expressed in lung cancer tissue and has been associated with tumor proliferation and angiogenesis.”

They used a lot of big medical terms in offering a biological explanation for the association of ACE inhibitors and lung cancer. The bottom line is that bradykinin and substance P can cause mischief in the lungs. Many people complain of an ACEi-induced cough. This uncontrollable cough is probably provoked by accumulation of kinins and substance P in the lungs. (Drug Safety, July, 1996).

If you would like to learn more about other, less serious but more common ACE inhibitor side effects, you will want to read this article.

Lisinopril Side Effects Can Be Lethal

The Bottom Line:

ACE inhibitors are very good drugs for controlling hypertension. They are also helpful against congestive heart failure and some other serious conditions.

That said, the association between ACE inhibitors and lung cancer is too serious to ignore. The FDA has had a very hard time dealing with drug-induced cancer risks. Most physicians and patients have no way to determine what to do with this information. Here is a link to an article on this controversial topic.

FDA Stance on Drugs & Cancer Is Confusing

What to Do About ACE Inhibitors and Cancer?

We agree with the researchers who conducted the large study in the BMJ: “these findings need to be replicated in other settings.”

In the meantime, if you are taking an ACE inhbitor like lisinopril it is worth printing the article and giving it to your physician. Let her help you decide if you should continue taking it or seek an alternative medication. Do not stop taking an ACE inhibitor on your own!

The authors did not find an association with ARBs (angiotensin receptor blockers like losartan or valsartan and lung cancer. Such drugs are somewhat similar to ACE inhibitors.

The BMJ, online Oct. 24, 2018

Please share your own thoughts about ACE inhibitors below in the comment section.

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  1. Barbara
    NY
    Reply

    Is the cancer connection truly with the ACE inhibitor or is it with the ‘filler’ used in the medication?

    I read that most generic meds are purchased from China and India. However, the Chinese-purchased medicine contained some kind of chemical not usually added to medicine. That batch was a small batch used in America and has since been recalled.

    So does this recent ‘scare’ encompass the entire classification of ACE Inhibitors or just the batch purchased from China? And was the harmful medication put into the ACE Inhibitors all of the time until recently?

    I was on Lisinopril for a short while a couple of years ago and my doctor switched me to Losartan because of the cough caused by Lisinopril. I’ve had no problems with Losartan.

    Please clarify. Thanks.

  2. John
    Baltimore
    Reply

    ARBs are about as effective as ACE inhibitors, the main difference is that ARBs don’t cause people to cough. I switched many years ago from Lisinopril to Candesartan and am happy with the result. I don’t understand why people who have cough problems with an ACE inhibitor stubbornly stay with it instead of trying an ARB.

  3. Cheryl
    Texas
    Reply

    My mother took lisinopril for years. She regularly went back to her physician complaining of a chronic cough. He kept telling her it was allergies and would prescribe Zyrtec. After a year of going back to him with no change he told her she must have GERD and sent her to a gastroenterologist. He found nothing. Not once did anyone prescribe a chest X-ray. After she started exhibiting weight loss and extreme fatigue I insisted on a chest xray and advanced lung cancer was discovered. She died 6 months later.

  4. Brenda
    Colorado
    Reply

    I too read back in 2010 that ARBs were associated with a higher risk of lung cancer. I was on Losartan for two months and that is why I went off of it. Now they are saying that it is the ACE associated with the risk instead. In my opinion I think all chemical sustances have the potential to cause cancer. I think I’ll switch back to Losartan adter reading this.

  5. Marty
    Lynnwood, WA
    Reply

    I was on Lisinopril and had the left side of my tongue swell up – ambulance to the emergency room. My doctor moved to Losartan which caused me three issues: kidney, UTI, and cough. Now, I just take Metoprolol and have not had any issues at all.

  6. Lou
    Texas
    Reply

    Every time I read your articles, I get depressed about the drugs I take. Every one of them, from Tylenol to prescription drugs, has something alarming about it. When I discuss it with my doctor, he asks me who I trust with my treatment – you or him. He went to medical school and has years of experience in his field and he knows my history. He says he’ll put me on something else if I’m worried, but don’t be surprised if PP demonizes it as well. I’ve been on lisinopril for 10 years with no cough. But he switched me to a new med, and now I have side effects I’ve never had before. I’m going to listen to him from now on.

    • Joe Graedon
      Reply

      Lou,

      It is always important to listen to your doctor. We also encourage patients and their health providers to read the research that we cite. That is why we provide links. We are not demonizing any drugs. Rather, we are trying to put medications into context and provide readers with resources so they can read the original source of our reporting. That way they can weigh benefits against harms.

      We made it very clear in this article that the risks of ACE inhibitors are very small. But when 30 million people are taking a class of medicines even a small risk can amount to a large number of people. That is not our point. That is the point of the researchers who wrote this article.

      We would hope that your physician would be open-minded enough and curious enough to want to read the article from front to back to see for himself what was studied and what the actual conclusions were.

    • Terry Graedon
      Reply

      We definitely encourage you to listen to your doctor! The information we provide is general, not specific to your situation.

  7. Roberta
    IL
    Reply

    What about atenolol?

  8. Maggie
    Virginia
    Reply

    I found your article interesting but was disturbed by the paragraph stating:
    “The authors did not find an association with ARBs (angiotensin receptor blockers like losartan or valsartan and lung cancer. Such drugs are somewhat similar to ACE inhibitors.”

    I have saved many articles that People’s Pharmacy have send out on ARBs and lung cancer, especially Valsartan (Diovan) . This really narrows down the list of blood pressure meds if one is concerned about getting lung cancer after taking them.

    Maggie

    • Joe Graedon
      Reply

      Science is a constantly moving target. Research a few years ago suggested a possible link between ARBs and lung cancer, but this new study suggests that is probably not the case. We have to adjust to changing data.

  9. Elizabeth
    Southern Maine
    Reply

    I was put on lisiniprol because I have both type 2 diabetes and hbp, and ACE inhibitors have a protective effect for kidneys. After a very bad cold I had a cough I could not get rid of. My doctor immediately took me off the lisiniprol he had originally prescribed. The cough went away immediately. He switched me to felodipine and later added losartan. Losing weight and exercising is still the best option, but is difficult for me long-term. But I’ll keep trying.

  10. John
    Sun City Fl.
    Reply

    Could hibiscus tea taken daily for mild BP reduction (which acts mimics an “ACE”) have the same potential risk of lung cancer ?

      • Clark
        VA
        Reply

        But, an interesting question is whether natural ACE inhibitors, like pomegranate juice and hibiscus tea, cause an accumulation of bradykinin and/or substance P in the lungs. That research has probably not yet been done, but would be very important information.

        One hint would be whether anyone reports a chronic cough from these substances. I don’t.

  11. Steve
    Chicago, IL
    Reply

    Always have loved your show and articles. Thanks!!
    I take very small dose (5mg) per night Lisinopril as a kidney protectant since I am diabetic. Otherwise my BP is good. In the lung cancer/Lisinopril study, was smoking and being around second hand smoke absolutely ruled out as contributor to the 1.4% “normal” risk of lung cancer to the increase to 1.6%? I’m just trying to verify if the increased risk is completely due to Lisinopril, even in non-smokers. Thank you.

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