Abiraterone or enzalutamide intensification: no significant rise in cardiovascular events, but standard risk tools underestimate risk

Design

Post hoc analysis of a multi-arm randomised trial with linked health records

Population

6292 men in England starting long-term hormone therapy for high-risk localised or metastatic prostate cancer

Primary outcome

Major adverse cardiovascular events; SCORE2 performance

Effect

5-year MACE 7–9% with ARPI intensification; SDHR 1.15–1.36 (all CIs cross 1); SCORE2 AUC 0.61–0.63

This post hoc analysis of STAMPEDE linked trial data for 6292 men in England to hospital records to identify major adverse cardiovascular events after starting long-term androgen deprivation, with or without intensification by abiraterone plus prednisolone, abiraterone plus enzalutamide, docetaxel, zoledronic acid or prostate radiotherapy.

Five-year event incidence with androgen receptor pathway inhibitor intensification was 9% in non-metastatic and 7% in metastatic disease, similar to androgen deprivation alone. Subdistribution hazard ratios ranged from 1.15 to 1.36, with all intervals crossing 1. A history of cardiovascular disease was the strongest predictor of events. The SCORE2 risk tool discriminated only modestly (AUC 0.63 and 0.61) and underestimated absolute risk.

The hazard ratios leave room for a modest increase, and men with severe cardiovascular disease were under-represented. The practical message is twofold: cardiovascular concern should not by itself withhold life-prolonging intensification, and a standard risk calculator will make these men look safer than they are.

• Do not withhold abiraterone or enzalutamide intensification on cardiovascular grounds alone; this analysis found no significant excess in events.
• Take a cardiovascular history at the start of hormone therapy; prior disease was the strongest predictor of events.
• Treat SCORE2 estimates as an underestimate in men on androgen deprivation.
• Check blood pressure, glucose, lipids and potassium regularly, especially on abiraterone with prednisolone.
• Involve the GP or cardiologist in risk factor management from the start of treatment.

Why it matters

It answers a frequent reason for hesitating over intensification, while exposing a gap in standard risk tools.

Don't overread it

A post hoc analysis with intervals that allow a modest increase; men with severe cardiovascular disease were under-represented.

The statistics, in plain English

A subdistribution hazard ratio of 1.36 with an interval from 0.87 to 2.10 means the data fit anything from a small decrease to a doubling of risk, so 'not significant' is not proof of no effect. An AUC of about 0.6 means SCORE2 ranked risk only slightly better than chance in these men.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.