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ACE Inhibitors and Lung Cancer | Should You Be Concerned?

Millions of people take blood pressure pills like lisinopril every day. They work well, but is there an association between ACE inhibitors and lung cancer?

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 ACEi 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.

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.

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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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
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