Risk and timing of cardiovascular disease after androgen-deprivation therapy in men with prostate cancer.
OBJECTIVE
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.


CONCLUSIONS
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.
Sean O'Farrell, Hans Garmo, Lars Holmberg, and Mieke Van Hemelrijck, King's College London, School of Medicine; Sean O'Farrell, Guy's and St Thomas' National Health Service Foundation Trust and King's College London's Comprehensive Biomedical Research Centre, London, United Kingdom; Hans Garmo and Lars Holmberg, Regional Cancer Centre, Uppsala Örebro; Lars Holmberg, Uppsala University, Uppsala; Jan Adolfsson and Mieke Van Hemelrijck, Karolinska Institutet, Stockholm; and Pär Stattin, Umeå University, Umeå, Sweden. sean.o'farrell@kcl.ac.uk.
Sean
S
O'Farrell
Sean O'Farrell, Hans Garmo, Lars Holmberg, and Mieke Van Hemelrijck, King's College London, School of Medicine; Sean O'Farrell, Guy's and St Thomas' National Health Service Foundation Trust and King's College London's Comprehensive Biomedical Research Centre, London, United Kingdom; Hans Garmo and Lars Holmberg, Regional Cancer Centre, Uppsala Örebro; Lars Holmberg, Uppsala University, Uppsala; Jan Adolfsson and Mieke Van Hemelrijck, Karolinska Institutet, Stockholm; and Pär Stattin, Umeå University, Umeå, Sweden.
Hans
H
Garmo
Sean O'Farrell, Hans Garmo, Lars Holmberg, and Mieke Van Hemelrijck, King's College London, School of Medicine; Sean O'Farrell, Guy's and St Thomas' National Health Service Foundation Trust and King's College London's Comprehensive Biomedical Research Centre, London, United Kingdom; Hans Garmo and Lars Holmberg, Regional Cancer Centre, Uppsala Örebro; Lars Holmberg, Uppsala University, Uppsala; Jan Adolfsson and Mieke Van Hemelrijck, Karolinska Institutet, Stockholm; and Pär Stattin, Umeå University, Umeå, Sweden.
Lars
L
Holmberg
Sean O'Farrell, Hans Garmo, Lars Holmberg, and Mieke Van Hemelrijck, King's College London, School of Medicine; Sean O'Farrell, Guy's and St Thomas' National Health Service Foundation Trust and King's College London's Comprehensive Biomedical Research Centre, London, United Kingdom; Hans Garmo and Lars Holmberg, Regional Cancer Centre, Uppsala Örebro; Lars Holmberg, Uppsala University, Uppsala; Jan Adolfsson and Mieke Van Hemelrijck, Karolinska Institutet, Stockholm; and Pär Stattin, Umeå University, Umeå, Sweden.
Jan
J
Adolfsson
Sean O'Farrell, Hans Garmo, Lars Holmberg, and Mieke Van Hemelrijck, King's College London, School of Medicine; Sean O'Farrell, Guy's and St Thomas' National Health Service Foundation Trust and King's College London's Comprehensive Biomedical Research Centre, London, United Kingdom; Hans Garmo and Lars Holmberg, Regional Cancer Centre, Uppsala Örebro; Lars Holmberg, Uppsala University, Uppsala; Jan Adolfsson and Mieke Van Hemelrijck, Karolinska Institutet, Stockholm; and Pär Stattin, Umeå University, Umeå, Sweden.
Pär
P
Stattin
Sean O'Farrell, Hans Garmo, Lars Holmberg, and Mieke Van Hemelrijck, King's College London, School of Medicine; Sean O'Farrell, Guy's and St Thomas' National Health Service Foundation Trust and King's College London's Comprehensive Biomedical Research Centre, London, United Kingdom; Hans Garmo and Lars Holmberg, Regional Cancer Centre, Uppsala Örebro; Lars Holmberg, Uppsala University, Uppsala; Jan Adolfsson and Mieke Van Hemelrijck, Karolinska Institutet, Stockholm; and Pär Stattin, Umeå University, Umeå, Sweden.
Mieke
M
Van Hemelrijck
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology*; D016022:Case-Control Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009919:Orchiectomy / Q000009:adverse effects*; D018579:Patient Selection; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000628:therapy*; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal