HDCN Article Review/Hyperlink

Jick H, Jick S, Derby LE, Vasilakis C, Myers MW, Meier CR

Calcium-channel blockers and the risk of cancer

Lancet (Feb) 349:525-528 1997

This study was prompted by a previous report by Pahor et al. which suggested that Ca-channel blockers (CCB) increase the risk of all types of cancer compared B-blockers in hypertensive patients (RR=2.02,.95% CI 1.16-3.54). This study sought to clarify this issue.

Study Design: All cases of cancer (446) were identified from patients using CCB, angiotensin-converting enzyme inhibitors (ACE), and B-blockers in 1995 from the General Practice Research Database in the UK. 1750 controls were identified and were matched on age, sex, practitioner. The index date on which the cancer patient was diagnoses was also used as the index date for the matched controls. Controls had to have been using only one of the study drugs in the year before the index date. Cases and controls had to have at least 4 years of recorded medical history. The particular drug which the person was on in the year before the cancer was identified as the exposure drug.

The relative risk of developing all cancers combined in patients taking CCB compared to those taking B-blockers was 1.27 (0.98-1.63) controlling for smoking, body-mass index, duration of hypertension, change of medication and use of diuretics. Risk estimates were similar with duration of CCB use. Adjusted relative risk estimates for specific cancers in users of CCBs were not increased compared to users of B-blockers.

Hypertensive patients who are taking CCBs are not at increased risk of cancer compared to those taking B-blockers

Comment: We have several problems with this study, centering around the selection of the control group. Because of similarities in the way in which physicians treat patients, matching on physician results in cases and controls appearing more similar potentially decreasing the magnitude of the effect found. Secondly, exposure status (i.e. type of drug therapy) was determined in the year before the cancer was diagnosed. This is likely too short a period of time for the CCBs to cause cancer. In addition, a third of the patients changed their hypertensive treatment in the years prior to the identification of exposure. It is therefore difficult to determine if patients in the B-blocker group had actually been treated with CCBs for substantial periods of time. If that were the case, any increased risk of cancer in the CBB group would be diminished. It may have made more sense to define drug exposure as a certain number of months of exposure to CCB more than a year before the time of diagnosis of cancer or to exclude the patients who used more than one drug. Finally, it would have been interesting to further explore the risk of particular types of cancer in those taking CBB compared to B-blockers. This study however had little power to do this. The study addresses an important question. However, several flaws in the study design make it difficult to draw firm conclusions from the study. (Catherine Stehman-Breen, MD MS for the Nephrology Research Training Group at the University of Washington)

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