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European Heart Journal 2001 22(15):1343-1352; doi:10.1053/euhj.2001.2729
Copyright © 2001 by the European Society of Cardiology.
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Antihypertensive therapy and the risk of malignancies

E Grossmana, F.H Messerlib,f1 and U Goldbourtc,d

a Internal Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer, Israel
b Department of Internal Medicine, Section on Hypertensive Diseases, Ochsner Clinic and Alton Ochsner Medical Foundation, New Orleans, LA, U.S.A.
c The Neufeld Cardiac Institute, The Chaim Sheba Medical Center, Tel-Hashomer, Israel
d Division of Epidemiology and Preventive Medicine, Sackler School of Medicine, Tel-Aviv University, Israel

revised April 3, 2001; accepted April 4, 2001

Abstract

Aims To assess the relationship between antihypertensive therapy and malignancy.

Methods and Results A MEDLINE search for English-language articles published between January 1966 and August 1999 identified 29 prospective studies that reported cancer incidence or mortality and 28 case-control studies that reported specific drug use in cancer patients and controls. The association between rauwolfia derivatives and breast cancer was analysed in 5852 cases and 9776 controls, yielding an odds ratio (OR) of 1·25 (95% CI, 1·09–1·44). The association between diuretics and renal cell carcinoma was analysed in 4389 cases and 6566 controls, yielding a pooled OR of 1·54 (95% CI, 1·41–1·68). The association between atenolol and cancer death was analysed pooling three randomized controlled studies, including 1879 treated patients and 3078 non-treated patients, yielding a pooled OR of 1·36 (95% CI, 1·02–1·82); however, data from non-randomized studies did not confirm the latter. The association between calcium antagonists and malignancy was analysed pooling five randomized controlled studies, including 5451 treated patients and 5207 untreated ones, yielding a pooled OR of 0·78 (CI, 0·60–1·00). A meta-analysis of an additional five longitudinal studies, including 9087 treated patients and 15559 non-treated patients, yielded a pooled OR of 1·04 (CI, 0·91–1·19). The association between ACE inhibitors and malignancy was analysed pooling two randomized controlled trials involving 1585 treated patients and 1567 non-treated patients, yielding a pooled OR of 1·57 (95% CI, 0·97–2·57); however, non-randomized studies showed no association or a decreased risk for malignancy with ACE inhibitors.

Conclusions With the exception of diuretics and renal cell carcinoma, the association between antihypertensive drugs and malignancy was either low grade (rauwolfia), uncertain (atenolol), absent (ACE inhibitors), or absent with a yet to be investigated inverse association (calcium antagonists). Ongoing long-term prospective studies with cardiovascular drugs should carefully monitor the risk of malignancy.

Key Words: Antihypertensive therapy and malignancy, diuretics, renal cell carcinoma, calcium antagonists, ACE inhibitors

f1 Correspondence: Franz H. Messerli, MD, Ochsner Clinic, 1514 Jefferson Highway, New Orleans, LA 70121, U.S.A.

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