What is the clinical evidence from this study?

Study design: Cohort. Population: Prostate cancer (n=229147). Intervention: Gonadotropin-releasing hormone (GnRH) agonists vs. Age-matched, prostate cancer-free comparison cohort. Primary outcome: Incident cardiovascular disease (HR 1.21, 95% CI 1.18-1.25).

What does this research mean for the field?

Gonadotropin-releasing hormone agonists increase the risk of incident cardiovascular disease by 21% compared to a prostate cancer-free cohort, with the highest risk occurring during the first 6 months of therapy, particularly in men with a prior history of cardiovascular events. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

March 3, 2015Open Access

Risk and Timing of Cardiovascular Disease After Androgen-Deprivation Therapy in Men With Prostate Cancer

Key Result

Gonadotropin-releasing hormone agonists increased the risk of incident cardiovascular disease by 21% (HR 1.21) compared to a prostate cancer-free cohort, with the highest risk during the first 6 months of therapy.

Study Design

Type

Cohort (n=229,147)

Structured PICO

Does androgen-deprivation therapy increase the risk of incident and fatal cardiovascular disease in men with prostate cancer compared to a prostate cancer-free cohort?

Population

41,362 men with prostate cancer (PCa) on androgen-deprivation therapy (ADT), mean age 75.7, from Swedish national health care registers.

Intervention

Androgen-deprivation therapy (ADT), including antiandrogens (AA), gonadotropin-releasing hormone (GnRH) agonists, or surgical orchiectomy.

Comparator

Age-matched, prostate cancer-free comparison cohort (n = 187,785).

Outcome

Incident and fatal overall cardiovascular disease (CVD) (ICD-10: I00 through I99).hard clinical

GnRH agonists and surgical orchiectomy for prostate cancer are associated with an increased risk of cardiovascular disease, especially during the first 6 months of therapy in men with a prior history of CVD.

Main Result

Effect estimate: HR 1.21 (95% CI 1.18-1.25)

Absolute Event Rate: 24.9% vs 23.5%

Limitations

Lack of information about lifestyle factors
Potential residual confounders, such as confounding by indication of treatment, which could not be accounted for

Abstract

PURPOSE: Findings on the association between risk of cardiovascular disease (CVD) and the duration and type of androgen-deprivation therapy (ADT) in men with prostate cancer (PCa) are inconsistent. METHODS: By using data on filled drug prescriptions in Swedish national health care registers, we investigated the risk of CVD in a cohort of 41,362 men with PCa on ADT compared with an age-matched, PCa-free comparison cohort (n = 187,785) by use of multivariable Cox proportional hazards regression models. RESULTS: From 2006 to 2012, 10,656 men were on antiandrogens (AA), 26,959 were on gonadotropin-releasing hormone (GnRH) agonists, and 3,747 underwent surgical orchiectomy. CVD risk was increased in men on GnRH agonists compared with the comparison cohort (hazard ratio HR of incident CVD, 1.21; 95% CI, 1.18 to 1.25; and orchiectomy: HR, 1.16; 95% CI, 1.08 to 1.25). Men with PCa on AA were at decreased risk (HR of incident CVD, 0.87; 95% CI, 0.82 to 0.91). CVD risk was highest during the first 6 months of ADT in men who experienced two or more cardiovascular events before therapy, with an HR of CVD during the first 6 months of GnRH agonist therapy of 1.91 (95% CI, 1.66 to 2.20), an HR of CVD with AA of 1.60 (95% CI, 1.24 to 2.06), and an HR of CVD with orchiectomy of 1.79 (95% CI, 1.16 to 2.76) versus the comparison cohort. CONCLUSION: Our results support that there should be a solid indication for ADT in men with PCa so that benefit outweighs potential harm; this is of particular importance among men with a recent history of CVD.

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