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According to the results of an observational study published earlier this week in BmjAngiotensin-converting enzyme (ACE) inhibitors were associated with an increased risk of lung cancer, compared to a similar, but distinct, type of antihypertensive drug called receptor antagonist. Angiotensin (ARA).
Lisinopril, molecular model. Drug class angiotensin converting enzyme inhibitors (ACE) used to treat hypertension, congestive heart failure and heart attacks. Atoms are represented as spheres and are color-coded: carbon (gray), hydrogen (white), nitrogen (blue) and oxygen (red). (Courtesy of Getty Images)
The researchers evaluated patients from a primary care database in the UK and identified more than 900,000 adults who had started treatment with any type of antihypertensive drug between 1995 and 2015 They excluded patients with a history of cancer.
More than 335,000 patients were treated with ACE inhibitors, 29,000 with ARBs and 101,000 with an ACE inhibitor and ARBs. Ramipril (26%) was the most commonly observed ACE in the study, with lisinopril (12%) and perindopril (7%).
Over a 6-year follow-up period, lung cancer was diagnosed in 0.8% (7,952) of this cohort of 900,000 people. After taking into account smoking and other potential confounding factors, the use of ACE inhibitors was associated with a 14% higher risk of lung cancer compared with the use of BRA (1.6 vs. 1.2 per 1,000 person-years). In a secondary analysis, the use of an ACE inhibitor for less than 5 years was not associated with a high risk of lung cancer.
However, the study noted that the high risk did not manifest until the patient had been taking an ACE inhibitor for 5 years but increased with more than 10 years of use (31% increase in risk).
In their study, the researchers explained that the use of ACE inhibitors causes an accumulation of bradykinin in the lungs , "which has been reported to stimulate the growth of lung cancer." The use of ACE inhibitors can also result in elevated levels of a compound called substance P, produced in lung cancer cells and related to the growth of the tumor and its tumors. associated blood vessels.
In light of this data, it is important for the public to understand that this is only an observational study – not a randomized, double-blind, placebo-controlled study – thereby reducing the absolute risk to patients . However, the data indicate that ACE inhibitors account for nearly one-third of all hypertension medications prescribed in the UK, making the results potentially of concern for a large number of patients.
Although ACE inhibitors are very effective drugs used in the short term to treat high blood pressure, concerns have been expressed about the safety of their long-term use, particularly with regard to high risk of lung cancer.
In addition, observational studies have yielded mixed results (related to the actual risk of lung cancer versus overall cancer risk), with no clear consensus to date, and meta-analyzes of randomized controlled trials Have not demonstrated high cancer risk, due to: the small sample size and the length of the follow-up (median 3.5 years) compromising the validity of the results.
Important limitations of the study to mention include the lack of information on socioeconomic status, diet, exposure to asbestos or radon, as well as family history of lung cancer in patients included in the study. the study. The authors also did not have detailed information on the number of years of conditioning, a significant risk factor for the incidence of lung cancer.
That said, There is biochemical evidence demonstrating a possible association between the use of ACE inhibitors and lung cancer risk with high levels of bradykinin and substance P that could facilitate the growth of lung cancer.
It is certain that in any patient at risk for lung cancer, one must weigh the benefits associated with taking an ACE inhibitor to reduce blood pressure and cardiac risk, compared to the risk of lung cancer.
This view is echoed by an expert who has expressed concern about the risks associated with ACE inhibitors.
"This high-quality study shows that ACE inhibitors are a risk factor for lung cancer," said Klaus Lessnau, MD, specialist in pulmonology and critical care at Lenox Hill Hospital in New York.
"The most important factor remains smoking, but implies that ACE inhibitors should be contraindicated in smokers and ex-smokers, while they were armed with a revealing study." a significant statistical association and a biological plausibility, "proposed Lessnau. "One may wonder if they should be prosecuted non-smokers," he added.
Therefore, it is important to highlight this study because of the large number of patients currently taking long-term ACE inhibitors and the inherent concern that they may have for a high cancer risk – and the need to change treatment – depending on the results. of this study.
Again, it is important to emphasize that this is an observational study and that the overall risk to patients is relatively low. Patients should discuss with their health care provider the risks and benefits of staying on an ACE inhibitor. One option might be to switch to an ARB if there is constant concern, no risk of lung cancer having been observed so far with this class of antihypertensives. ARAs can actually reduce the risk of lung cancer with a protective effect, according to recent studies.
In an accompanying editorial of BMJDeirdre Cronin-Fenton, Associate Professor in the Department of Clinical Epidemiology, University of Aarhus, Denmark, attributes the validity to the results, but recommends the need to continue current and future studies for validate the results of this prospective cohort study.
Cronin-Fenton writes that the study "highlights the value of registry data and a" Big Data "approach to evaluating long-term outcomes, which can be difficult to study in clinical trials Although a 14% relative increase in the incidence of lung cancer does not translate to a high absolute risk, the results are important given the considerable use of CIRA worldwide. whole ".
Cronin-Fenton continues: "Nevertheless, in an individual patient, concerns about the long-term risk of lung cancer need to be weighed against the life expectancy gains associated with the use of ACEIs. [the authors] It should be noted that new studies with long-term follow-up are now needed to strengthen the scientific evidence on the long-term safety of these drugs. "
ACE inhibitors have certainly been beneficial in the control of blood pressure in a clinical setting. Although this study highlights an existing biochemical mechanism, the data are still observational in nature and will require further study in order to make a definitive decision as to the decision to discontinue and replace it in favor of the disease. a new class of management drugs. blood pressure.
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According to the results of an observational study published earlier this week in BmjAngiotensin-converting enzyme (ACE) inhibitors were associated with an increased risk of lung cancer, compared to a similar, but distinct, type of antihypertensive drug called receptor antagonist. Angiotensin (ARA).
Lisinopril, molecular model. Drug class angiotensin converting enzyme inhibitors (ACE) used to treat hypertension, congestive heart failure and heart attacks. Atoms are represented as spheres and are color-coded: carbon (gray), hydrogen (white), nitrogen (blue) and oxygen (red). (Courtesy of Getty Images)
The researchers evaluated patients from a primary care database in the UK and identified more than 900,000 adults who had started treatment with any type of antihypertensive drug between 1995 and 2015 They excluded patients with a history of cancer.
More than 335,000 patients were treated with ACE inhibitors, 29,000 with ARBs and 101,000 with an ACE inhibitor and ARBs. Ramipril (26%) was the most commonly observed ACE in the study, with lisinopril (12%) and perindopril (7%).
Over a 6-year follow-up period, lung cancer was diagnosed in 0.8% (7,952) of this cohort of 900,000 people. After taking into account smoking and other potential confounding factors, the use of ACE inhibitors was associated with a 14% higher risk of lung cancer compared with the use of BRA (1.6 vs. 1.2 per 1,000 person-years). In a secondary analysis, the use of an ACE inhibitor for less than 5 years was not associated with a high risk of lung cancer.
However, the study noted that the high risk did not manifest until the patient had been taking an ACE inhibitor for 5 years but increased with more than 10 years of use (31% increase in risk).
In their study, the researchers explained that the use of ACE inhibitors causes an accumulation of bradykinin in the lungs , "which has been reported to stimulate the growth of lung cancer." The use of ACE inhibitors can also result in elevated levels of a compound called substance P, produced in lung cancer cells and related to the growth of the tumor and its tumors. associated blood vessels.
In light of this data, it is important for the public to understand that this is only an observational study – not a randomized, double-blind, placebo-controlled study – thereby reducing the absolute risk to patients . However, the data indicate that ACE inhibitors account for nearly one-third of all hypertension medications prescribed in the UK, making the results potentially of concern for a large number of patients.
Although ACE inhibitors are very effective drugs used in the short term to treat high blood pressure, concerns have been expressed about the safety of their long-term use, particularly with regard to high risk of lung cancer.
In addition, observational studies have yielded mixed results (related to the actual risk of lung cancer versus overall cancer risk), with no clear consensus to date, and meta-analyzes of randomized controlled trials Have not demonstrated high cancer risk, due to: the small sample size and the length of the follow-up (median 3.5 years) compromising the validity of the results.
Important limitations of the study to mention include the lack of information on socioeconomic status, diet, exposure to asbestos or radon, as well as family history of lung cancer in patients included in the study. the study. The authors also did not have detailed information on the number of years of conditioning, a significant risk factor for the incidence of lung cancer.
That said, There is biochemical evidence demonstrating a possible association between the use of ACE inhibitors and lung cancer risk with high levels of bradykinin and substance P that could facilitate the growth of lung cancer.
It is certain that in any patient at risk for lung cancer, one must weigh the benefits associated with taking an ACE inhibitor to reduce blood pressure and cardiac risk, compared to the risk of lung cancer.
This view is echoed by an expert who has expressed concern about the risks associated with ACE inhibitors.
"This high-quality study shows that ACE inhibitors are a risk factor for lung cancer," said Klaus Lessnau, MD, specialist in pulmonology and critical care at Lenox Hill Hospital in New York.
"The most important factor remains smoking, but implies that ACE inhibitors should be contraindicated in smokers and ex-smokers, while they were armed with a revealing study." a significant statistical association and a biological plausibility, "proposed Lessnau. "One may wonder if they should be prosecuted non-smokers," he added.
Therefore, it is important to highlight this study because of the large number of patients currently taking long-term ACE inhibitors and the inherent concern that they may have for a high cancer risk – and the need to change treatment – depending on the results. of this study.
Again, it is important to emphasize that this is an observational study and that the overall risk to patients is relatively low. Patients should discuss with their health care provider the risks and benefits of staying on an ACE inhibitor. One option might be to switch to an ARB if there is constant concern, no risk of lung cancer having been observed so far with this class of antihypertensives. ARAs can actually reduce the risk of lung cancer with a protective effect, according to recent studies.
In an accompanying editorial of BMJDeirdre Cronin-Fenton, Associate Professor in the Department of Clinical Epidemiology, University of Aarhus, Denmark, attributes the validity to the results, but recommends the need to continue current and future studies for validate the results of this prospective cohort study.
Cronin-Fenton writes that the study "highlights the value of registry data and a" Big Data "approach to evaluating long-term outcomes, which can be difficult to study in clinical trials Although a 14% relative increase in the incidence of lung cancer does not translate to a high absolute risk, the results are important given the considerable use of CIRA worldwide. whole ".
Cronin-Fenton continues: "Nevertheless, in an individual patient, concerns about the long-term risk of lung cancer need to be weighed against the life expectancy gains associated with the use of ACEIs. [the authors] It should be noted that new studies with long-term follow-up are now needed to strengthen the scientific evidence on the long-term safety of these drugs. "
ACE inhibitors have certainly been beneficial in the control of blood pressure in a clinical setting. Although this study highlights an existing biochemical mechanism, the data are still observational in nature and will require further study in order to make a definitive decision as to the decision to discontinue and replace it in favor of the disease. a new class of management drugs. blood pressure.
