Clinical Brief – August 28
In a trial published yesterday, a blood thinner, rivaroxaban (Xarelto), failed to outperform aspirin at preventing cardiovascular death, a stroke, or a heart attack for patients who had hardened arteries. However, the drug came with a significantly higher risk of uncontrolled bleeding vs aspirin.
The combo of rivaroxaban + aspirin was significantly more protective than aspirin alone, but also came with a higher bleed risk.
Rivaroxaban is a blood thinner designed to prevent blood clots from forming where they shouldn’t. It’s currently used to treat and prevent deep vein clots and prevent stroke or clots for some patients with A-fib.
It belongs to the factor Xa inhibitor class, along with apixaban (Eliquis), betrixaban (Bevyxxa), edoxaban (Savaysa), and fondaparinux (Arixtra).
Previous trials in patients with other conditions have shown that rivaroxaban may help prevent cardiovascular death, stroke, or heart attack. So, the maker, Bayer, did a trial to see if it’ll work for patients with hardened arteries.
The COMPASS trial
In a large global trial involving over 600 hospitals in 33 countries, more than 27k patients were randomized to receive either rivaroxaban 2.5 mg + aspirin 100 mg, rivaroxaban alone 5 mg, or aspirin 100 mg.
Their main goal was to see if any of these three treatments can prevent cardiovascular death, a stroke, or a heart attack.
Rivaroxaban vs aspirin
They found that rivaroxaban was no more protective than aspirin, but came with an 84% higher risk of major bleeding.
For context, 2.8% of patients on rivaroxaban had a major bleed vs 1.9% on aspirin.
Rivaroxaban + aspirin vs aspirin
When taken together, rivaroxaban + aspirin was 24% more protective than aspirin alone, but also came with a 70% higher risk of major bleeds. The bleeding was significantly faster with the combo therapy and was mostly in the gut.
Researchers also looked at a “composite net-clinical-benefit” endpoint. Basically, “How many patients had cardiovascular death, a stroke, a heart attack, fatal bleeding, or symptomatic bleeding into a critical organ?”
The idea is to see how good the treatment is when we factor in both efficacy and safety. And if we count it this way, rivaroxaban + aspirin was only 20% better than aspirin.
For context, 4.1% of patients on combo therapy had cardiovascular death, a stroke, or a heart attack; vs 5.4% on aspirin. Match this with 3.1% of patients on combo therapy who had a major bleed; vs 1.9% on aspirin. For the net-clinical-benefit endpoint, it was 4.7% for combo therapy vs 5.9% for aspirin.
Rivaroxaban isn’t any better than aspirin for protection against cardiovascular death, stroke, or heart attack. So, it’s only coming in with side effects.
Lower dose rivaroxaban + aspirin may help a bit but comes with the predictable bleeding risk as well.
Also of note, rivaroxaban likely costs around $400 a month vs aspirin, which is likely $30 a month tops. So that skinny 20% improvement comes at a 10x hike in treatment cost.