Study Title:

Blood Pressure Medication and Cancer Risk

Study Abstract

Background
Angiotensin-receptor blockers (ARBs) are a widely used drug class approved for treatment of hypertension, heart failure, diabetic nephropathy, and, recently, for cardiovascular risk reduction. Experimental studies implicate the renin-angiotensin system, particularly angiotensin II type-1 and type-2 receptors, in the regulation of cell proliferation, angiogenesis, and tumour progression. We assessed whether ARBs affect cancer occurrence with a meta-analysis of randomised controlled trials of these drugs.

Methods
We searched Medline, Scopus (including Embase), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the US Food and Drug Administration website for studies published before November, 2009, that included any of the seven currently available ARBs. Randomised controlled trials with an ARB given in at least one group, with a follow-up of at least 1 year, and that enrolled at least 100 patients were included. New-cancer data were available for 61 590 patients from five trials. Data on common types of solid organ cancers were available for 68 402 patients from five trials, and data on cancer deaths were available for 93 515 patients from eight trials.

Findings
Telmisartan was the study drug in 30 014 (85·7%) patients who received ARBs as part of the trials with new cancer data. Patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7·2% vs 6·0%, risk ratio [RR] 1·08, 95% CI 1·01—1·15; p=0·016). When analysis was limited to trials where cancer was a prespecified endpoint, the RR was 1·11 (95% CI 1·04—1·18, p=0·001). Among specific solid organ cancers examined, only new lung-cancer occurrence was significantly higher in patients randomly assigned to receive ARBs than in those assigned to receive control (0·9% vs 0·7%, RR 1·25, 1·05—1·49; p=0·01). No statistically significant difference in cancer deaths was observed (1·8% vs 1·6%, RR 1·07, 0·97—1·18; p=0·183).

Interpretation
This meta-analysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis. Given the limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each particular drug. These findings warrant further investigation.

From press release:

University Hospitals Case Medical Center cardiologists have uncovered new research showing an increased risk of cancer with a group of blood pressure medications known as angiotensin-receptor blockers (ARBs).

This class of drugs is used by millions of patients not only for high blood pressure but also for heart failure, cardiovascular risk reduction and diabetic kidney disease.

University Hospitals Harrington-McLaughlin Heart & Vascular Institute's Drs. Ilke Sipahi, Daniel I. Simon and James C. Fang recently completed a meta-analysis of over 60,000 patients randomly assigned to take either an ARB or a control medication. Their findings are published online in The Lancet Oncology.

The researchers found that patients randomized to ARBs has "significantly increased risk of new cancer" compared to control patients.

"We have found the risk of new cancers was increased with these medications by 8-11 percent," said Dr. Ilke Sipahi, associate director of heart failure and transplantation and assistant professor at Case Western Reserve University School of Medicine. "Most importantly, risk of lung cancer was increased by 25 percent."

However, the research did not establish any link between ARBs and other types of cancer such breast cancer.

"This is the first time an association between ARBs and cancer development is suggested," Dr. Sipahi continued. "While our findings are robust, they need to be replicated in other studies before they can be considered as definitive."

Before this study, there were no major safety concerns with ARBs except for their use in pregnancy and in patients with chronic kidney or blockages of kidney arteries. Interestingly, previous animal studies with ARBs have been negative for cancer development.

"In medicine, physicians must balance the benefits and risks of all drug and device therapies," said Dr. Daniel Simon, director of the Harrington-McLaughlin Heart & Vascular Institute at University Hospitals Case Medical Center and professor at Case Western Reserve University School of Medicine. "We recommend that patients discuss the findings of this study with their physicians since ARBs are effective agents in the treatment of high blood pressure and heart failure. Meta-analyses are a powerful tool to look at low frequency safety signals, but require confirmation with other approaches, such as large national health and managed care registries."

Study Information

1.Ilke Sipahi, Sara M Debanne, Douglas Y Rowland, Daniel I Simon, James C Fang
Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials
The Lancet Oncology
2010 July
University Hospitals Case Medical Center

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