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Antihypertensive drugs associated with reduced risk of colorectal cancer


Treatment High blood pressure With angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), Colorectal cancer, According to findings from a large retrospective study.

However, another Investigation Reports over a year ago suggest that ACE inhibitors, but not ARB, are associated with an increased risk of lung cancer.

Experts approached for comment emphasized that both studies were observable and therefore they only showed an association and could not infer a causal relationship.

In this latest study, Published online Today’s journal High blood pressure, ACE inhibitor/ARB use was associated with a 22% lower risk of colorectal cancer occurring within 3 years after negative baseline Colonoscopy..

The authors note that this is the largest study to date using a cohort of more than 185,000 patients, suggesting a significant protective effect against these two common antihypertensive agents.

The risk of developing colorectal cancer decreased with longer duration ACE inhibitor/ Use of ARB. Adjusted hazard ratio risk is reduced by 5% for each year of use.

However, this effect was limited to patients who had a negative colonoscopy within 3 years and did not extend beyond that time.

Wai K. Leung, MD, a clinical professor of medicine at the University of Hong Kong, explained that he does not encourage patients to take ACE inhibitors just to prevent cancer. “Wrong aspirin Statins, the potential chemopreventive role of ACE inhibitors against cancer, have not been established,” he said. Medscape Medical News. “The findings may support the use of ACE inhibitors to treat high blood pressure in some patients, rather than many other antihypertensive drugs, to prevent colorectal cancer.”

Increased or decreased risk?

The authors say that there is considerable debate about the potential carcinogenic effects of ACE inhibitors and ARB, “the relationship between various solid organ cancer risks is unresolved.” Studies have shown contradictory results associated with these agents, with no overall cancer risk and a slightly increased overall cancer risk.

Recent Investigation ACE inhibitors reported a 14% increased risk of lung cancer compared to ARB. The risk of lung cancer was increased by 22% in patients using ACE inhibitors for 5 years and peaked in 31% of patients taking ACE inhibitors for more than 10 years.

The lead author of the lung cancer study, PhD, Laurent Azoulay of McGill University in Montreal, Canada, is currently reporting some of the potentially inconsistent data that indicate a reduced risk of colorectal cancer. Provided an idea.

“In a nutshell, this study has important methodological issues that can explain the findings it has observed,” he said. Medscape Medical News.

Azoulay noted that the use of ACE inhibitors/ARBs in a univariate model was associated with a 26% increased risk of colorectal cancer. “It was only after adjusting for propensity scores that the effect estimates reversed in the direction of protection,” he noted. “But the variables included in the propensity score model were measured in the same time frame as exposure, which can lead to over-adjustment bias and give erroneous results.”

Another problem is that the study period did not begin at the time of exposure, but at a distant point after the start of treatment, in this case screening for colorectal cancer. “So the authors excluded patients who had been diagnosed with colorectal cancer before that time point, which could include patients exposed to the ACE inhibitor/ARB,” he said. Said. “This approach could lead to inclusion of “survivors” who have a lower risk of developing colorectal cancer. “

“But certainly Azoulay added, “This possible link should be investigated using a methodologically sound approach.”

Takeaway message to doctor

Another expert highlighted the observational nature of both studies. Raymond Townsend, MD, Ph.D., director of hypertension programs at the University of Pennsylvania Philadelphia Hospital, said: “First and foremost, these are observational studies and we can’t reason about causal relationships. We can only show associations.” He pointed out that there may be biases and confounding that cannot be controlled physically. Nevertheless, the size of this latest study is positive and has a reasonable follow-up period.

“Take out [message] For practitioners, it may be beneficial to maintain the likelihood of developing colorectal cancer in older people with ACE inhibitors if the last colonoscopies were negative.” There was no Townsend said. Medscape Medical News.

But there are some open questions about the characteristics of the cohort, Townsend pointed out. “Who had the colonoscopy in the first place? The risk to the group was high. Why did some people use ACE inhibitors/ARBs and others did not?” ?”

There are other conclusions clinicians can gather from now on. “Choose a treatment for your patient based on the best estimates for lowering blood pressure and preventing organ damage from high blood pressure,” said Townsend, a volunteer expert at the American Heart Association. “Patients hear about these studies and read unreviewed blogs on the web, so keep in mind that you have questions.”

He emphasized that it always comes back to two things. “One is that every treatment decision is essentially a risk-benefit scenario,” he said. “Second, most patients are adults, and if we choose not to be treated for hypertension despite our best advice and reasoning, give up control, let it progress as desired, and , When to renegotiate. If they reconsider.”

Research details

In the latest study, Leung and colleagues conducted a retrospective cohort study using data from the Hong Kong hospital authorities’ electronic medical database. A total of 187,897 people over the age of 40 underwent colonoscopies between 2005 and 2013 with negative results and were included in the analysis.

The main outcome of this study was colorectal cancer diagnosed between 6 and 36 months after undergoing colonoscopy, with a median age at colonoscopy of 60.6 years. Within this population 30,856 (16.4%) used the ACE inhibitor/ARB.

Between 6 months and 3 years after having a colonoscopy, 854 cases of colorectal cancer were diagnosed, with an incidence of 15.2 per 10,000 person-years. The median time from colonoscopy to diagnosis was 1.2 years.

Users of the ACE inhibitor/ARB had a median duration of 3.3 years in the 5 years prior to colonoscopy with 169 cases (0.55%) of colorectal cancers within this group. In the univariate analysis, the crude hazard ratio (HR) of colorectal cancer and ACE inhibitor/ARB was 1.26 (P = .008), the adjusted HR was 0.78 after regression adjustment of the propensity score.

The absolute reduction in risk propensity score for users was 3.2 per 10,000 person-years compared to non-users, and stratification by subsite showed an HR of 0.77 for distal cancer and 0.83 for proximal cancer. it was done.

In a subgroup analysis, the benefits of ACE inhibitors and ARB were found in patients age 55 and older (adjusted HR, 0.79) and in patients with a history Colonic polyp (Adjusted HR, 0.71).

The authors also evaluated whether there was an association between these medications and other types of cancer. In univariate analysis, use was associated with increased lung risk, Prostate cancer, But lower risk breast cancer.. However, after regression adjustment of the propensity score, the association disappeared.

This study was funded by the Healthcare Research Fund of the Hong Kong SAR Government. Leung was honored for attending the advisory committees of AbbVie, Takeda, and Abbott Laboratories. Co-author Estelle W. Chan is funded by Pfizer, Bristol-Myers Squibb, Bayer, Takeda and Janssen (a division of Johnson & Johnson). Hong Kong Research Grants Council; Security Bureau Drug Division; China National Natural Science Foundation, all for work unrelated to current research. Other authors do not disclose the financial relationships involved.

Azoulay does not disclose related financial relationships. Townsend is employed by Penn Medical.

High blood pressure.. Published July 6, 2020 Online. Overview

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