CALCIUM CHANNEL BLOCKERS

*--Available in combination with ACE Inhibitors as of 1999

I. Ca-blockers and mortality

1. Short-acting nifedipine, dilt, or verapamil used for HTN ass'd with RR of 1.5 for MI c/w other antihypertensives in a case-control study (JAMA 274:620, 1995)
2. Short-acting nifedipine ass'd with RR 1.16 for death in pts with CAD in a meta-analysis (Circ 92:1326, 1995)
3. Other studies have shown no increase in mort/morbidity with short-acting Ca-channel blockers.
4. 888 Pts randomized to isradipine vs. HCTZ & f/u'd for 3y had nonsig. higher incidence of MI, CVA, CHF, or sudden death with isradipine (5.65 vs. 3.17, p = 0.07; JAMA 276:785, 1996)
5. Long-acting Ca-blockers were not ass'd w/increased risk for a major CV event (OR 0.76) but short-acting agents were (OR 3.88) in a case-control study of 189 pts with a first cardiovascular event and 189 controls matched for age, sex, and length of f/u. (Lancet 349:594, 1997-JW)
6. 470 pts with NIDDM randomized to enalapril vs. nisoldipine with equivalent BP control in both groups; at 5y, sig. greater # of MI's in nisoldipine group (25 vs. 5)--RR of MI was 7.0 for nisoldipine after adjustment for risk factors (NEJM 338:645, 1998--JW)
7. Among 14,000 women 30-55yo with HTN in the Nurses' Health Study followed x 6y, Ca-blockers ass'd with RR 1.64 for MI c/w tx with diuretics alone, after controlling for other risk factors for MI; summary also alludes to "increased risk for total mortality among Ca-channel blocker uses." Note that the study period ran from 1988-94 so may not have included much use of long-acting Ca-channel blockers (Circ 97:1540, 1998--JW)
8. Amlodipine use (for avg. 5-16wks) and long-acting nifedipine use were not ass'd with sig. diff. incidence of CV events c/w placebo, in a review of clinical trial databases of Pfizer (Am. J. Cardiol. 81:163, 1998)

(Source: Med. Letter 39:14, 1997 & others as cited-they conclude that pending randomized controlled trials, "short acting Ca-channel blockers, particularly nifedipine, should not be used for treatment of HTN...pts taking a short-acting Ca-blocker for HTN should probably switch to a long-acting formulation" Also recc. beta-blockers or nitrates over Ca-blockers for angina)

II. Risk of Cancer:

1. Breast: the Cardiovascular Health Study looked at a cohort of 3200 women > 65yo who were given annual questionnaires re: health status and medication use. Use of Ca-channel blockers was ass'd w/a hazard ratio of 2.57 (sig.) of hospitalization for breast Ca c/w non-users. The association persisted in comparison w/other antihypertensives. No associations found between use of other antihypertensives and breast Ca. The authors hypothesize that the mechanism is interference w/apoptosis (programmed cell death) due to interference of Ca-dependent endonuclease (Cancer 80:1438, 1997-read abstract and part of the paper)
2. However, a case-control study comparing 9500 pts 40-69yo admitted to a hosp. with Ca and 6500 control admitted for other causes; no difference in overall risk of Ca or any of 23 individual Ca's, except for renal Ca (but similar increased risk w/use of beta-blockers or ACEI's; JAMA 279:1000, 1998--abst)
3. Also, another prospective trial of 11,500 pts with CAD followed for avg. 2.8y, no assn w/use of a Ca-channel blocker and risk of developing Ca; also no assn' between use of Ca-channel blocker and risk of death

III. Ca-blockers associated with sig. increased risk of GI hemorrhage compared with beta-blockers and ACEIs; unclear mechanism; perhaps platelet inhibition (Lancet 347:1061, 1996-JW)