While a new study published in Plos One reveals that the long-term intake of drugs against hypertension called “ARA2” would increase the risk of developing lung cancer, Professor Jean-Jacques Mourad, head of the internal medicine department at the Saint-Joseph Hospital, sheds light on the ins and outs of this scientific controversy.
– Why doctor: Can you explain to us what ARA2 are and what they are used for?
Jean Jacques Mourad ARBs (angiotensin II receptor antagonists) are drugs that block the action of a particular angiotensin II receptor. They were put on the market in the 90s and are widely used today to treat high blood pressure, because they are really well tolerated by patients.
– How many French people take these drugs?
A lot. It is estimated that one third of the 12 million French patients with arterial hypertension are treated with ARBs2.
– Why do some people fear that there is a link between the development of cancer and the taking of ARA2?
This questioning has punctuated the lives of all classes of hypertensors for decades. But in 2010, Dr. Ilke Sipahi published a paper in the prestigious journal The Lancet Oncology which indicated that ARA2 increased the risk of cancer. This study had triggered an investigation by the FDA at the time, which had finally extinguished the alarm signal.
– Where did this cancer risk come from, according to Dr. Ilke Sipahi?
This researcher has tried to make a link between the excess risk of cancer and the impurities contained in ARA2 molecules since they are manufactured in India or China.
– Dr. Ilke Sipah has just completed a new study on the same subject, published this time in Plos One. What is she saying ?
This new research establishes very questionable links between the duration of exposure to ARA2 and the occurrence of cancers, mainly lung cancers.
– Can there actually be a link?
Yes, especially because the lung is an organ where the renin-angiotensin system is extremely present, and the ARA2s act on this.
By increasing angiotensin II levels in the body, ARA2 could also influence many other receptors, potentially inducing carcinogenic effects. Therefore, the hypothesis that these drugs could accelerate (and not cause) the development of pre-existing tumors when they are taken deserves to be analysed.
What are the limits of the new study published in Plos One?
When I personally met Dr. Ilke Sipahi at a conference following the publication of his first study, it seemed to me that he had a lot of bitterness towards the American authorities. I think this researcher is clearly biased, because he seems to have made ARA2 a personal and self-love story, which is not healthy.
Moreover, he signs his new study alone unlike the first, which means that other scientists did not want to join him to endorse his results. I also remind you that the review Plos One is of very average quality, since you have to pay to be published there.
On the merits, the author himself emphasizes the limits of his work: he did not have access to individual patient data. Without knowing the confounding and explanatory factors of the cancers diagnosed, he was therefore unable to adjust his analyses. Then, concerning the potential carcinogenic impurities of the molecules linked to the relocation of their production, all the studies on which it is based were carried out while these drugs were still being designed in Switzerland. So the temporal link does not hold water.
Finally, there are many recent studies which, using largely the same data as Dr. Ilke Sipahi, find no carcinogenic signal linked to taking ARBs, or a very slight signal whose causes have not been yet been explored.
– Does this research still revive the controversy?
In terms of statistics and public health, the quantity of carcinogenic signals linked to ARA2 really does not seem to me to be sufficient to make it a state affair. At this stage, we cannot say that the ARA2 cause cancer.
– Concretely, what should be done in practice with the ARA2?
Caregivers and patients should not be panicked, and no direct consequences should be drawn from the new Plos One paper by stopping ARA2s.
For physicians, this trial is nevertheless an opportunity to recall that this therapeutic class is not essential, thanks in particular to ACE inhibitors (angiotensin-converting enzyme). And in the case of uncontrolled hypertension, I think it is better to combine different classes of drugs rather than pushing monotherapies to their highest dosage.