Highlights: - Angiotensin-converting enzyme inhibitors (ACEI) are
a class of drugs used in the treatment of blood pressure. A similar class
of drugs are the angiotensin receptor blockers
(ARB), which can also lower blood pressure
- ACEIs and ARBs were compared to see which is linked
to lung cancer. ACEIs were found to be strongly linked to the risk of
developing lung cancer
- The association between ACEIs and lung cancer risk
depends on the duration of use of ACEIs. The risk of lung cancer was
evident after 5 years, peaking after more than 10 years
A commonly used
medication belonging to the class angiotensin converting enzyme inhibitors
(ACEI), which is used for controlling high blood pressure (hypertension) has
been linked to increased risk of lung cancer, compared to another similar class
of drugs known as angiotensin receptor blockers (ARB), according to a new study
published in the
British Medical
Journal (BMJ). The study was led by Dr. Laurent Azoulay, Associate Professor,
Department of Epidemiology, Biostatistics, and Occupational Health, McGill
University, Montreal, Quebec, Canada.
What are Angiotensin Converting Enzyme
Inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB)?
- ACEI:
These are drugs that prevent the angiotensin-converting enzyme (ACE) from
catalyzing the reaction that converts the hormone angiotensin I to
angiotensin II, which causes the blood vessels to narrow
(vasoconstriction) causing the blood pressure to rise. Thus, ACEIs are
used to treat
hypertension by lowering the blood pressure.
- ARB:
These are drugs that block angiotensin II from binding to its receptors on
the blood vessel walls, thereby preventing vasoconstriction. Thus, ARBs
relax the blood vessels, causing them to dilate (vasodilation), thereby
reducing the blood pressure. Thus, like ACEIs, ARBs are also used to treat
hypertension, but with a different mechanism of action.
Background of the Study
ACEIs and ARBs are
not only used for the treatment of hypertension, but also other conditions,
such as heart disease, renal insufficiency, and
chronic kidney disease. ACEIs decrease the production of
angiotensin II, whereas ARBs selectively blocks it from binding to the
angiotensin receptors. These drugs target the renin-angiotensin aldosterone
system (RAAS), which has been suspected to play a role in the development of
cancer.
Objective of the Study
The main objective
of the study was to compare the use of ACEIs with ARBs to see which of these
drugs cause an increased risk of
lung cancer.
Study Design
This was a
population-based cohort study that utilized data from the UK Clinical Practice
Research Datalink (CPRD). The patients were at least 18 years of age and had no
history of cancer. The cohort consisted of 992,061 newly diagnosed high blood
pressure patients who were prescribed
antihypertensive drugs between January 1, 1995 and December 31,
2015. The main outcome that was measured was the incidence of lung cancer
associated with the duration of use of ACEIs compared to ARBs.
Study Findings
The study cohort
was followed for a period of 6.4 years. During this period, a total of 7,952
cases of lung cancer were detected, with an incidence rate of 1.3 per 1000
person-years. Factors that could potentially influence the findings, such
as age, sex, body mass index (BMI), smoking status, alcohol use (or abuse), and
history of lung diseases were taken into consideration.
After
accounting for all these factors, it was found that the overall use of ACEIs
were associated with an increased risk of lung cancer compared to ARBs, with an
incidence rate of 1.6 vs 1.2 per 1000 person-years, respectively. The risk of
lung cancer increased with longer duration of use of ACEIs, with an association
becoming evident after 5 years of use and peaking after more than 10 years of
use.
‘A class of drugs called angiotensin-converting enzyme inhibitors (ACEI), which are used for treating high blood pressure, have been found to be linked to lung cancer. This association between ACEIs and the risk of lung cancer depends on the duration of use of ACEIs. The risk increases after 5 years and peaks after more than 10 years of use.’
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Although the magnitude of the observed
association was modest at the individual level, however, since ACEIs are one of
the most widely prescribed classes of antihypertensive drugs, "so these
small relative effects could translate into large absolute numbers of patients
at risk," the researchers pointed out. In this regard, Dr. Deirdre
Cronin-Fenton, Associate Professor, Department of Clinical Epidemiology, Aarhus
University, Aarhus, Denmark, in her editorial states:
"Nonetheless, in
an individual patient, concerns about the long-term risk of lung cancer should
be balanced against gains in life expectancy associated with the use of
ACEIs."
Conclusion
This
population-based cohort study revealed that ACEIs were associated with an increased
risk of lung cancer. The association of ACEI use and lung cancer became
particularly pronounced after 5 years of use of ACEIs. The researchers propose
that the underlying mechanism for the association is due to the accumulation of
bradykinin and substance P in the lungs, which have been implicated in lung
cancer.
Strengths of the Study
- With over 990,000 patients, this was the largest
cohort ever used to establish the association between ACEI use and risk of
lung cancer
- The use of prospectively registered,
population-based CPRD data completely removed recall bias and minimized
selection bias
- The cancer registration data from CPRD is highly
reliable
- The CPRD allowed retrieval of data on several
potential confounders, including smoking status
Limitations of the Study
- The study
lacked information on confounders like socioeconomic status, diet, exposure to radon or
asbestos and family history of lung cancer
- The CPRD
prescriptions are by general practitioners, so there is a chance of
misclassification of exposure if the patients did not adhere to the
treatment regimen
- There is a
possibility of misclassification of the outcome
- Since
patients on ACEIs experience a persistent cough, chest x-rays for evaluation of the lung condition is very common,
which increases the likelihood of detecting lung cancer, if present. This
could lead to detection bias
Future Plans
The researchers
indicate that the findings "should be replicated in other settings,
particularly among patients exposed for longer durations." So, they plan to
carry out further studies with long-term follow-up to closely monitor the role
of ACEIs on the incidence of lung cancer. This will help to enhance the
scientific evidence on the long-term safety of these drugs.
Funding Details
The study was
funded by a Foundation Scheme grant from the Canadian Institutes of Health
Research.
Reference : - Angiotensin converting enzyme inhibitors and risk of lung cancer: population based cohort study - (https://www.bmj.com/content/363/bmj.k4209)
Source: Medindia
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