Angiotensin-converting-enzyme (ACE) inhibitors are associated with increased lung cancer risk compared with angiotensin-receptor blockers (ARBs), an observational study in The BMJ suggests.
Using a U.K. primary care database, researchers identified over 900,000 adults who began treatment with a new antihypertensive drug class from 1995 through 2015. Those with histories of cancer were excluded.
During a mean 6 years' follow-up, lung cancer was diagnosed in 0.8% of the cohort. After adjustment for smoking and other confounders, ACE inhibitor use was associated with significantly increased lung cancer risk relative to ARB use (1.6 vs. 1.2 per 1000 person-years). The increased risk didn't appear until after 5 years of ACE inhibitor use, and then increased with increasing duration of use.
The authors note that ACE inhibitors lead to accumulation of bradykinin in the lungs, which "may directly stimulate growth of lung cancer." An editorialist, meanwhile, concludes, "In an individual patient, concerns about the long term risk of lung cancer should be balanced against gains in life expectancy associated with use of [ACE inhibitors]."
ACE inhibitors are one of the three antihypertensive medications I mentioned in last Friday’s blog. Remember that I also mentioned that these drugs cause fluid retention in the lungs and legs (congestive heart failure). Bradykinin is a peptide produced in the kidneys that causes vasodilatation thus lowering blood pressure. When the body is in homeostasis, bradykinin is short lived. However, ACE inhibitors cause this peptide to build up in the lungs, along with the edema, where it acts as a carcinogen.
This action of ACE (angiotensin converting enzyme) inhibitors is secondary to the major effect of reducing angiotensin II, also produced in the kidneys. In the normal metabolic state, when excess fluid is present in the kidneys, they produce angiotensin II. Angiotensin II raises blood pressure, reducing the fluid in the kidneys, lungs and lower extremities. That is why the typical side effects of ACE inhibitors are edema in the legs, kidneys and lungs.
If you are on an ACE inhibitor for hypertension, talk to your prescribing doctor about long term use and the risks of lung cancer. If you note swelling of the ankles and/or a dry cough, please mention these symptoms as well.
For those not yet on hypertensive medications, please redouble your efforts to improve your lifestyle through diet, weight control and regular exercise. At the age of 66, my friends, relatives and physicians are always shocked when they learn that I don’t take any prescription drugs. When I was 50 and consulting with a urologist, he told me he’d “never met anyone like me” when reviewing my medical history. I replied “that’s because I’m healthy, and not sick like all your other patients.”
Source: October 25, 2018 New England Journal of Medicine
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