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Centre for Evidence-
Based Medicine

Hypertension - Calcium-channel blockers may cause cancer

Clinical Bottom Line

  1. Until this gets sorted out properly, if your patient's problem could be treated as well by some alternative drug (e.g., hypertension), it would be prudent to avoid using calcium-channel agents.
  2. If this result is true, the NNH to cause one additional cancer from taking CCBs for 3.7 years is 116.

Citation

Pahor M et al: Calcium-channel blockade and incidence of cancer in aged populations. Lancet 1996;348:493-7. (also see 487-9 and 541-2)

Clinical Question

In patients taking calcium antagonists for hypertension, are they at increased risk of cancer?

Search Terms

From the newspaper headline or from MEDLINE using "calcium antagonists" and "cancer"

The Study

Total or stratified random samples (>80% response rate) of 65+ y/o men and women in 3 sites in the USA. Showed their meds, were interviewed 90 minutes, and had their blood pressure, height and weight measured. Anyone with cancer in previous 3 years or on any cancer Rx was excluded and 94% of the remainder were followed for an average of 3.7 years by follow-up interview, hospital discharge info and the national death registry for the occurrence of new cancers.

The Evidence

Later Cancer Totals
Present Absent
Exposed to Calcium Channel Blockers Yes (Cohort)

3.03%

a

b

a + b

No (Cohort)

2.17%

c

d

c + d

Totals

a + c

b + d

a + b + c + d

Relative Risk (RR) = 3.03%/2.17%
= 1.4 (P = 0.032)

(and when adjusted for several baseline differences, RR ROSE (!) to 1.7 (P = 0.0005)).

Comments

  1. Individuals on CCBs had more cardiovascular disease, diabetes, disability, and hospitalisations but lower diastolic blood pressure. But when they adjusted for all these baseline differences, the RR rose rather than fell, suggesting that bias from confounding (of cancer risk and CCB use) of these characteristics could not explain these results.
  2. There was a dose-response gradient.
  3. The difference in risk by type of CCB was impressive but not stat sig (RR 2 for verapamil; 1.5 for nifedipine; 0.94 for diltiazem).
  4. Only 47 events in CCB takers, and spread over all sorts of different cancers.
  5. The proposed mechanism (interference with the apoptotic destruction of cancer cells) pooh-poohed by commentators.
  6. Other studies of CCBs and mortality go both ways (they're bad or have no effect), and some authors of the former have received anonymous death threats.

Appraised By

Sackett 1996, Reviewed 1998

Expiry Date

2000