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Recently, the international authoritative medical journal BMJ published a highly subversive heavyweight paper, which caused great sensation in the medical field.

A large cohort study based on nearly a million people showed that the use of ACEI-type antihypertensive drugs increased the overall risk of lung cancer by 14% compared with the use of ARBs. And as the time taken for ACEI drugs increases, the risk of lung cancer increases. For patients who have been taking ACEI for 5 years, the risk of lung cancer can be increased by 22%, and the risk of lung cancer is 31% when the drug is used for 10 years or more.

The researchers warned that because ACEI drugs are widely used to treat high blood pressure, this association may lead to the risk of lung cancer in the vast majority of patients.



Million people cohort study: lung cancer risk increased by up to 31%

In the UK, more than 70 million antihypertensive drugs are prescribed each year, of which about 32% are ACEI drugs. With such a broad audience, researchers can’t help but sprout the idea of ​​a long-term assessment. In addition, according to research author Azoulay and colleagues, although early observational studies reported an assessment of the risk of cancer using ACEI drugs, none of them were specifically designed to assess lung cancer.

To validate the relationship between ACEI drugs and lung cancer, the researchers used data from the Clinical Practice Research Datalink to identify 992,061 patients treated with antihypertensive drugs between January 1995 and December 2015. Follow-up was performed and the patients were all over 18 years of age.

Of these, 335,135 patients were treated with ACEI, 29,008 were treated with ARB, and 101,637 were treated with both ACE and ARBs. The three most common types of ACEI drugs are piraris’s ramipril (used in 26% of patients), lisinopril (used in 12% of patients), and perindopril (7%). Used by patients).

A total of 7,952 lung cancer patients (1.3/1000 person-years) were diagnosed during a median follow-up of 6.4 years.

After adjusting for risk factors including age, gender, weight (BMI), smoking status, alcohol-related disease, and lung history, the researchers found that patients taking ACEI (Pulsin) antihypertensive drugs had a higher cancer-causing rate than taking ARB (Shatan) antihypertensive drugs are up to a full 14%.

Previously, the antihypertensive drug valsartan contained the carcinogen “N-nitrosodimethylamine” and was rejected by the FDA. The cancer-causing rate of ACEI antihypertensive drugs was even higher than that of the sultan drugs. 14%, which makes the sartan drugs “slightly embarrassing.”

In addition, the most shocking thing is that compared with the use of ARB drugs (HR: 1.14), the risk of lung cancer increased by 22% (HR: 1.22) for patients who used ACEI for 5 years. For patients who took ACEI drugs for 10 years or longer, the risk of lung cancer increased to 31% (HR: 1.31).

The researchers further analyzed and found that the use of ACEI drugs for less than 5 years was not associated with an increased risk of lung cancer (HR 1.1).


Antihypertensive “God Medicine”: ACEI drugs


The sensation of this paper is that the ACEI drug is a very classic antihypertensive drug. There are three main antihypertensive drugs commonly used in hypertensive patients: angiotensin-converting enzyme inhibitors (ACEIs, Prils) antihypertensive drugs, angiotensin receptor blockers (ARBs, sartans), calcium ions. Antagonists (CCBs, horizons).

ACEI drugs are an angiotensin converting enzyme inhibitors commonly used in the treatment of hypertension and congestive heart failure. Angiotensin-converting enzyme catalyzes the production of angiotensin II by angiotensin I, which causes intense vasoconstriction and release of adrenal corticoaldosterone, resulting in elevated blood pressure. ACEI drugs control high blood pressure by inhibiting the biosynthesis of angiotensin II.

The clinical use of ACEI drugs has a long history. The first non-thiol-containing ACEI drug, Capotex (captopril), was approved by the US FDA in 1981. It has been nearly 37 years since its inception, and it still has its presence in the clinic. According to the database of the Rubik’s Cube, 19 ACEI drugs have been approved for marketing.

Compared with other breeds, ACEI has more indications and advantages. It prevents left ventricular remodeling after heart attack, treats cardiac insufficiency, reduces proteinuria, delays cerebral arteriosclerosis and stroke, delays diabetic nephropathy, and renal insufficiency. Diabetes complicated with cardiovascular disease has a definite effect.



Be cautious about the use of ACEI drugs

Although this result shocked the medical community, research author Azoulay said that doctors should be fully aware of this association.

However, Azoulay also pointed out that “considering that ACE is now widely used in clinical practice, it is still too early to stop this treatment for patients with known benefits. In addition, further research is needed to confirm the results of this study. ”

In a subsequent editorial, Dr. Deirdre Cronin Fenton, associate professor of clinical epidemiology at Aarhus University in Denmark, said that long-term studies are needed to verify the safety of ACEI drugs.

Like Azoulay, Fenton warns that patients should not be allowed to use ACEI drugs. “For individual patients, concerns about the long-term risk of lung cancer should be balanced against life expectancy growth associated with ACEI.”

In addition, Fenton also reminded that although the study used a rigorous analytical approach, the results may be affected by residual confounding factors. For example, in 1995, ACEI drugs were already on the market, but ARB drugs did not enter the market before 2010. During this period, socio-economic changes may affect prescription patterns. In addition, environmental exposures of alfalfa or asbestos may also affect lung cancer. Risk has an impact.

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