In clinical trials hormone treatment does not increase cardiovascular deaths

[JimJimJimJim]

JAMA. 2011 Dec 7;306(21):2359-66.

Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials.

Nguyen PL, Je Y, Schutz FA, Hoffman KE, Hu JC, Parekh A, Beckman JA, Choueiri TK.

Source

Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA. pnguyen@LROC.harvard.edu

Abstract

CONTEXT:

Whether androgen deprivation therapy (ADT) causes excess cardiovascular deaths in men with prostate cancer is highly controversial and was the subject of a joint statement by multiple medical societies and a US Food and Drug Administration safety warning.

OBJECTIVE:

To perform a systematic review and meta-analysis of randomized trials to determine whether ADT is associated with cardiovascular mortality, prostate cancer-specific mortality (PCSM), and all-cause mortality in men with unfavorable-risk, nonmetastatic prostate cancer.

DATA SOURCES:

A search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases for relevant randomized controlled trials in English between January 1, 1966, and April 11, 2011.

STUDY SELECTION:

Inclusion required nonmetastatic disease, intervention group with gonadotropin-releasing hormone agonist-based ADT, control group with no immediate ADT, complete information on cardiovascular deaths, and median follow-up of more than 1 year.

DATA EXTRACTION:

Extraction was by 2 independent reviewers. Summary incidence, relative risk (RR), and CIs were calculated using random-effects or fixed-effects models.

RESULTS:

Among 4141 patients from 8 randomized trials, cardiovascular death in patients receiving ADT vs control was not significantly different (255/2200 vs 252/1941 events; incidence, 11.0%; 95% CI, 8.3%-14.5%; vs 11.2%; 95% CI, 8.3%-15.0%; RR, 0.93; 95% CI, 0.79-1.10; P = .41). ADT was not associated with excess cardiovascular death in trials of at least 3 years (long duration) of ADT (11.5%; 95% CI, 8.1%-16.0%; vs 11.5%; 95% CI, 7.5%-17.3%; RR, 0.91; 95% CI, 0.75-1.10; P = .34) or in trials of 6 months or less (short duration) of ADT (10.5%; 95% CI, 6.3%-17.0%; vs 10.3%; 95% CI, 8.2%-13.0%; RR, 1.00; 95% CI, 0.73-1.37; P = .99). Among 4805 patients from 11 trials with overall death data, ADT was associated with lower PCSM (443/2527 vs 552/2278 events; 13.5%; 95% CI, 8.8%-20.3%; vs 22.1%; 95% CI, 15.1%-31.1%; RR, 0.69; 95% CI, 0.56-0.84; P < .001) and lower all-cause mortality (1140/2527 vs 1213/2278 events; 37.7%; 95% CI, 27.3%-49.4%; vs 44.4%; 95% CI, 32.5%-57.0%; RR, 0.86; 95% CI, 0.80-0.93; P < .001).

CONCLUSION:

In a pooled analysis of randomized trials in unfavorable-risk prostate cancer, ADT use was not associated with an increased risk of cardiovascular death but was associated with a lower risk of PCSM and all-cause mortality.

Comment in

JAMA. 2011 Dec 7;306(21):2382-3.

PMID: 22147380

This extract can be found on http://PubMed.com, and is in the public domain.On PubMed.com there will be a link to the full paper (often $30, sometimes free).Any highlighting (except the title) is not by the author, but by Jim Marshall.Jim is not a doctor.

In men in the trials:

• deaths from heart problems were the same whether you had hormone therapy (ADT) or not.
  
• short term ADT (less than 6 months) or long term ADT (greater than 3 years) did not make a difference.
  
• deaths from prostate cancer were lower in men on ADT (13.5% for ADT treated men, 22.1% for non-ADT treated men).
  
• deaths from any cause were lower in men on ADT (32.7% for ADT treated men, 44.4% for non-ADT treated men).
  

As trials often exclude men with more complicated health issues, if you already have heart problems or other serious health issues this research result will probably be less useful to you and your doctors.

It appears that when men and their doctors choose how long to be on, or off, ADT, they may be changing the odds of death by prostate cancer vs some other cause.

In my discussions with my doctors, this is a factor in my decision making.