Experts Debate If ARBs Are Linked to Cancer

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 - Debate

Evidence published earlier this year found that angiotensin-receptor blockers (ARBs), a drug class commonly prescribed to treat hypertension and sometimes cardiovascular events, may have the potential to increase the rates of new cancers by 8 to 11 percent. Here, the experts face off, arguing about whether ARBs are an effective drug class or whether this excess risk of cancer should cause concern.

Participants:

  •  Sverre E. Kjeldsen  MD, PhD, Chief Physician at the Ullevaal University Hospital in Oslo, and Adjunct Professor of Medicine at the Division of Cardiovascular Medicine at the University of Michigan, Ann Arbor
  •  FDA Representative  Mary Ross Southworth, PharmD, Deputy Director for Safety, FDA’s Division of Cardiovascular and Renal Drugs
  •  Ilke Sipahi  MD, Assistant Professor of Cardiovascular Medicine at University Hospitals Case Medical Center in Cleveland, and lead author of the Lancet Oncology meta-analysis

The meta-analysis, published in Lancet Oncology, pooled data from nine randomized controlled trials on ARBs and focused mostly on three of the seven FDA-approved ARBs: telmisartan (Micardis; Boehringer Ingelheim), losartan (Cozaar; Merck) and candesartan (Atacand; AstraZeneca). While these data portray ARBs in a rather negative light, a meta-analysis launched by the FDA in response to this Lancet Oncology analysis found no association between cancer and ARBs. Previously, ARBs have been shown to reduce hospital admissions and may be superior to ACE inhibitors to prevent stroke. However, the potential risk of cancer would obviously be problematic. While many backers say the cancer risk is unfounded and stand behind the drugs as a first-rate option to help reduce hypertension and cardiovascular disease, Sipahi and colleagues argue that safer, more effective drugs are out there that work just as well, or better than ARBs. Is this still an ongoing debate or did the FDA's meta-analysis silence the issue?

Q: ARBs are commonly prescribed to lower blood pressure, but what have the data shown about their benefits?

 Sipahi  TRANSCEND, a placebo-controlled trial, which sought to determine whether telmisartan reduced cardiovascular events, showed no statistically significant reduction in cardiovascular events. There was no reduction in MIs and the primary endpoint was not met. I would disagree with the claim that ARBs reduce cardiovascular events in patients at a high-risk of cardiovascular disease. While ARBs have the ability to reduce heart failure mortality, they have never been shown to reduce MIs, arguably the most important cardiovascular event. Despite these facts, the FDA has approved telmisartan for the reduction of cardiovascular risk. Additionally, ARBs are not superior to ACE inhibitors for the prevention of stroke like some have previously thought. While ARBs may be equivalent to ACE inhibitors for reducing stroke, they have absolutely no effect on MIs.

Annual Medicaid Claims & Expenditures for
ACE Inhibitors & ARBs: 1991-2008

Year Expenditures ARB/
Spending %
ARB/
Claim $
1991 $179,228,516 0.0%
1992 $236,948,154 0.0%
1993 $270,943,988 0.0%
1994 $281,378,322 0.0%
1995 $312,848,726 0.4% $38.24
1996 $296,581,719 2.0% $41.10
1997 $312,588,794 8.7% $43.72
1998 $365,062,415 15.3% $46.00
1999 $438,141,415 20.4% $48.37
2000 $530,752,819 25.5% $50.73
2001 $678,945,950 28.7% $53.18
2002 $804,525,700 33.7% $55.59
2003 $898,430,207 41.6% $58.78
2004 $1,001,525,549 46.6% $62.18
2005 $1,000,142,045 51.5% $65.51
2006 $390,270,946 46.0% $61.36
2007 $368,784,282 57.7% $84.33
2008 $309,842,354 65.1% $81.98
Source: J Manag Care Pharm 2010;16[9]:671-679.

 Kjeldsen  ARBs were the first drugs to treat hypertension. The previously published VALUE trial, which tested the efficacy of valsartan to reduce cardiac morbidity and mortality in hypertension patients at a high cardiovascular risk, showed that ARBs were just as effective as amlodipine (Norvasc, Pfizer) (Hypertension 2006;48:385-391). Previous meta-analyses all have concluded that ARBs are as equally effective as other drugs (calcium-channel blockers [CCBs], ACE inhibitors and beta-blockers). Additionally, ARBs have a better tolerability and are preferred by both physicians and patients.

Q: Explain the 8 to 11 percent increased risk of new cancers found in the Lancet Oncology meta-analysis.

 Sipahi  Two hundred million people are administered ARBs globally. Our