STAMPEDE: intensified hormone therapy was not linked to more cardiac events, but SCORE2 underestimated risk

Design

Post hoc analysis of a randomised platform trial (STAMPEDE) with linked health records

Population

6,292 men with high-risk localised or metastatic prostate cancer starting long-term hormone therapy

Primary outcome

Major adverse cardiovascular events; SCORE2 performance

Effect

5-year MACE 9% (M0) and 7% (M1) on ARPIs; abiraterone M0 SDHR 1.15 (0.80–1.67); SCORE2 AUC 0.61–0.63

This post hoc analysis of the STAMPEDE platform trial linked 6,292 men with high-risk localised or metastatic prostate cancer to English hospital records to look for major adverse cardiovascular events after adding abiraterone, abiraterone with enzalutamide, docetaxel, zoledronic acid or prostate radiotherapy to androgen deprivation.

Five-year cardiovascular event rates with androgen receptor pathway inhibitors were about 9% in non-metastatic and 7% in metastatic disease, similar to androgen deprivation alone. None of the intensification strategies showed a statistically significant increase, although the point estimates for abiraterone-based regimens sat above 1 and the intervals were wide. A history of cardiovascular disease was the strongest predictor.

The widely used SCORE2 tool discriminated poorly in these men, with an AUC of about 0.6, and underestimated absolute risk.

For practice, this supports offering intensified treatment without withholding it for cardiovascular fear alone, while taking a careful cardiac history and recognising that standard risk calculators will understate risk. Men with severe cardiac disease were underrepresented, so caution remains for them.

• Do not withhold abiraterone-based intensification solely for cardiovascular concern in typical patients.
• Take a full cardiovascular history; prior disease was the strongest predictor of events.
• Do not rely on SCORE2 to estimate cardiovascular risk in men on hormone therapy.
• Monitor blood pressure and potassium on abiraterone, as per its label.
• Involve cardiology for men with established severe cardiac disease.

Why it matters

It reassures on a common reason for hesitating over intensification, while showing the usual risk tool does not fit this population.

Don't overread it

A post hoc analysis with wide intervals; a modest increase in cardiovascular risk has not been excluded.

The statistics, in plain English

Subdistribution hazard ratios of 1.15 to 1.36 with intervals crossing 1.0 mean no significant increase was shown, but a modest rise cannot be ruled out. An AUC of 0.61–0.63 means SCORE2 ranked risk only slightly better than chance in these men.

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