News · Longevity & Aging
Sending prostate cancer patients to a heart specialist won the trial on cholesterol, not on heart attacks
Hormone therapy for prostate cancer raises cardiovascular risk that nobody owns. A 2,487-patient trial across 8 countries referred half of them to a cardiologist and met its primary endpoint, almost entirely through statin prescribing.
- Referring men on prostate hormone therapy to a heart specialist met the trial's main goal.
- Almost all of that win came from one thing: more of them were put on a statin.
- Cholesterol came down in the referred group, and that was the whole of the benefit.
- Heart attacks, strokes, heart failure and cardiovascular deaths were no different.
- 2,487 men at 55 sites in eight countries, followed nearly six years, so the null counts.
Prostate cancer is one of the most common types of cancer, and it often grows very slowly. That is the good news and also the problem: men live long enough with it that something else gets them, and the something else is usually the heart.
Hormone treatment makes that worse. Patients with prostate cancer have a high burden of cardiovascular risk factors, often suboptimally controlled. The hormone drugs push cholesterol, weight and blood sugar the wrong way. Meanwhile the cancer team, quite reasonably, is watching the cancer.
Writing in JAMA Internal Medicine, researchers ran the obvious experiment across 55 sites in 8 countries: refer half of these men to a cardiologist or internist and see what happens.
The trial met its primary endpoint convincingly. It did not prevent a single extra heart attack.
What the referral involved
This was not a consultation and a leaflet.
Patients were allocated to usual care alone or usual care plus routine referral to an internist or cardiologist, and the specialists worked to a protocol: a target of systolic blood pressure of 130 mm Hg or lower and a statin medication, irrespective of the patient’s cholesterol levels, plus smoking cessation support and advice on diet and exercise.
That statin instruction is the important one. It applied even if not usual or guideline-driven practice, meaning men were started on cholesterol-lowering drugs they would not otherwise have been offered.
Reading a win ratio honestly
The primary endpoint was a hierarchical composite analyzed by win ratio, and the result was decisive: 1.60, with an interval from 1.42 to 1.81.
A win ratio ranks outcomes by how bad they are. It then compares patients pair by pair. Death counts first, then heart attack, then stroke, then heart failure. Only if two men tie on all of those does the comparison drop to the next item. Here the next items were cholesterol and blood pressure.
The trial reports where its win came from without being asked twice: mostly attributable to lower cholesterol in the intervention group, a mean difference of 12 mg/dL, as a consequence of greater protocol-mandated statin use.
In other words, most pairs of men tied on all the serious outcomes, and the comparison was settled on a laboratory value.
What did not move
There was no difference in time to cardiovascular death, myocardial infarction, stroke, or heart failure between groups.
Five years of specialist heart care, in men picked for their high risk, changed none of the events that care exists to prevent. The blood pressure result is just as flat. Mean close-out systolic values were 131.1 mm Hg in the intervention group and 132.9 mm Hg in the control group.
Under two millimeters of mercury. In a trial where the specialists were working to an explicit target of 130 or below.
Why this is worth reporting rather than dismissing
It would be easy to file this as a failure, and that is not quite right either.
Cholesterol did fall, and it fell a long way. It fell because men were put on statins they should arguably have been taking already. Heart disease is the leading cause of death in the United States, but there are ways to prevent and manage many types of heart disease. Lowering cholesterol in a high-risk group is one of the surest. A 12 mg/dL gap held for decades is not nothing. It is simply not something a five-year trial of 2,487 men can pick up as events.
The honest summary is the authors’ own: routine referral led to improved outcomes, specifically through better cholesterol control, however it is uncertain whether this reduced clinical cardiovascular events.
The finding underneath the finding
The most useful thing here may be what the control arm reveals rather than what the intervention achieved.
Men in usual care, all of them starting a treatment known to raise cardiovascular risk, mostly did not get a statin. The intervention worked by mandating one. That is less a discovery about cardiology referral than a measurement of a gap: when a cancer team manages a man’s hormone therapy, nobody is reliably managing what that therapy does to his arteries.
Fixing that does not obviously require a cardiologist. It requires somebody to own the question, and the trial’s most transferable lesson is that in current practice, often nobody does.
People also ask
What did the trial find?
During a median follow-up of 5.8 years, the win ratio in favor of the intervention was 1.60 (95% CI 1.42-1.81), mostly attributable to lower cholesterol in the intervention group (mean difference 12 mg/dL, 9-15) as a consequence of greater protocol-mandated statin use. There was no difference in time to cardiovascular death, myocardial infarction, stroke, or heart failure between groups (subdistribution hazard ratio 1.08, 0.79-1.49).
Why do prostate cancer patients need a cardiologist?
Because androgen deprivation therapy, the standard hormone treatment, worsens cholesterol, body composition and insulin sensitivity. Patients with prostate cancer have a high burden of cardiovascular risk factors, often suboptimally controlled, and adverse cardiovascular outcomes.
What is a win ratio?
A way of comparing two groups on a ranked list of outcomes, most serious first. Each patient in one arm is compared with each in the other, and whoever did better on the highest-ranked outcome where they differ wins. A ratio above 1 favors the intervention.
So did the trial succeed or not?
It met its prespecified primary endpoint clearly. It did not reduce the hard clinical events inside that endpoint. Both statements are true, and the authors say it is uncertain whether the intervention reduced clinical cardiovascular events.
Why did the composite move if the events did not?
Because the composite included suboptimal cholesterol and suboptimal blood pressure alongside death, heart attack, stroke and heart failure. Those risk-factor components are far more common than events, so they dominate the comparison.
Was blood pressure controlled better too?
Barely. Close-out systolic blood pressure was 131.1 mm Hg in the intervention group and 132.9 in the control group. Under 2 mm Hg apart after five years of specialist input is close to nothing.
What should a man starting hormone therapy do?
Ask who is managing his cardiovascular risk, because on this evidence the answer is often nobody. Whether that requires a cardiologist or a statin from the family doctor is exactly what the trial leaves open. This is general information rather than medical advice.