- Design
- Post hoc analysis of the STAMPEDE randomised trial with linked health records
- Population
- 6,292 men with high-risk localised or metastatic prostate cancer starting long-term androgen deprivation
- Primary outcome
- Major adverse cardiovascular events and SCORE2 performance
- Effect
- 5-year MACE 9% (M0) and 7% (M1) with ARPI intensification; abiraterone SDHR 1.15 (0.80 to 1.67) M0, 1.36 (0.87 to 2.10) M1
Androgen receptor pathway inhibitors improve cancer outcomes in prostate cancer but may add cardiovascular risk. This post hoc analysis of the STAMPEDE trial used linked English health records for 6,292 men allocated to abiraterone plus prednisolone, abiraterone plus enzalutamide, docetaxel, zoledronic acid or prostate radiotherapy, each added to standard androgen deprivation therapy.
Five-year cumulative major adverse cardiovascular events with these inhibitors were 9% in non-metastatic and 7% in metastatic disease, comparable to androgen deprivation alone. Subdistribution hazard ratios for abiraterone were 1.15 (95% CI 0.80 to 1.67) in non-metastatic and 1.36 (0.87 to 2.10) in metastatic disease; for abiraterone plus enzalutamide they were 1.34 (0.91 to 1.98) and 1.28 (0.85 to 1.94). None were statistically significant, but several point estimates exceed 1.3 and intervals extend to about 2, so a moderate increase is not excluded. A history of cardiovascular disease was the strongest predictor of events.
The SCORE2 risk tool discriminated poorly (10-year AUC 0.63 in non-metastatic and 0.61 in metastatic disease) and underestimated absolute risk. Men with severe cardiovascular comorbidity were under-represented. Existing cardiovascular risk assessment before and during hormone therapy should continue.
- No statistically significant MACE increase with abiraterone, enzalutamide, docetaxel, zoledronic acid or radiotherapy versus androgen deprivation alone.
- Intervals were wide (for example abiraterone metastatic SDHR 1.36, 95% CI 0.87 to 2.10), so a moderate rise is not excluded.
- Prior cardiovascular disease was the strongest predictor of events.
- SCORE2 underestimated risk in these men; do not treat a low score as reassurance.
- Assess and optimise cardiovascular risk factors before and during treatment.
Why it matters
It shows that the cardiovascular question for these drugs is not settled by a trial that was not designed to answer it.
Don't overread it
This is a post hoc analysis of a trial not powered for cardiovascular outcomes, and men with severe cardiovascular disease were under-represented.
The statistics, in plain English
A hazard ratio of 1.36 with an interval of 0.87 to 2.10 is not statistically significant, but it is also compatible with more than a doubling of risk. 'No significant increase' therefore means the analysis could not tell, not that there is no risk.
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