Routine cardiovascular referral at the start of androgen deprivation lowered cholesterol but not events

Design

Multinational randomised clinical trial, 55 sites, median 5.8 years

Population

2,487 men with prostate cancer starting androgen deprivation therapy

Primary outcome

Hierarchical composite: CV death, MI, stroke, heart failure, suboptimal cholesterol and BP (win ratio)

Effect

Win ratio 1.60 (95% CI 1.42–1.81); hard CV events sHR 1.08 (0.79–1.49)

This international trial at 55 sites randomised 2,487 men (mean age 68) newly starting androgen deprivation therapy for prostate cancer to usual care or usual care plus referral to an internist or cardiologist. The specialists targeted systolic blood pressure of 130 mmHg or lower, started a statin regardless of cholesterol, and advised on smoking, diet and exercise.

Over a median 5.8 years, the hierarchical composite favoured referral (win ratio 1.60, 95% CI 1.42–1.81), but this was driven mostly by cholesterol, which was 12 mg/dL lower because of protocol statins. Blood pressure barely differed (131 vs 133 mmHg). Cardiovascular death, MI, stroke or heart failure did not differ (subdistribution HR 1.08, 0.79–1.49).

Men on androgen deprivation are often under-treated for cardiovascular risk, and a physician's attention changed the lipid numbers. It did not change clinical events. The lesson is less about referral and more about making sure these patients' risk factors are treated by whoever sees them.

• Check blood pressure, lipids, glucose and smoking in every man starting androgen deprivation therapy.
• Treat cardiovascular risk by standard guideline thresholds; a formal specialist referral added no reduction in events.
• Androgen deprivation worsens insulin resistance and weight — recheck HbA1c and weight within a year.
• Share the cardiovascular plan with the oncology or urology team so it is not lost between services.

Why it matters

It shows that improving risk-factor numbers in a trial does not automatically translate into fewer events over six years.

Don't overread it

The positive win ratio rests on cholesterol levels, a surrogate — it is not evidence that referral prevents cardiovascular events.

The statistics, in plain English

A win ratio compares every patient pair and ranks outcomes from most to least serious; a value of 1.60 means the intervention 'won' more pairs. But when most wins come from the least serious item — here cholesterol — the headline figure can look strong while hard outcomes are unchanged, as the HR of 1.08 shows.

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