Rivaroxaban + aspirin combo halves stroke risk in COMPASS
Combining the anticoagulant rivaroxaban with aspirin reduces the risk of ischaemic stroke by almost half without a significant increase in the risk of intracerebral haemorrhage (ICH) or haemorrhagic transformation compared with aspirin alone in patients with stable coronary artery disease (CAD), according to new data from the COMPASS* study presented at ISC 2018.
The multinational double-blind study enrolled 27,395 patients predominantly with stable CAD (91 percent) or peripheral artery disease (PAD), including those who had carotid stenosis or revascularization (27 percent) or both (18 percent). They were randomized to either rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin alone. Patients with atrial fibrillation (AF) were excluded from the study.
Primary results of the study had been published simultaneously with data presentation during the European Society of Cardiology 2017 meeting, which showed a reduction in the risk of the primary composite endpoint of cardiovascular-related death, stroke, or myocardial infarction with combination therapy vs aspirin alone (hazard ratio [HR], 0.76; p<0.0001) but an increased risk of major bleeds (HR, 1.70; p<0.001).
Initially scheduled to run up to 4 years, the study was terminated early at 23 months due to “overwhelming efficacy” of the combined therapy in an interim analysis, according to Dr Mike Sharma of McMaster University in Hamilton, Canada, who presented the study.
New stroke data – reduced stroke risk without haemorrhagic conversion
The current data presented at the ISC 2018 Meeting were specifically on stroke outcomes, which revealed a significantly lower risk of the combined ischaemic and haemorrhagic stroke outcome with combination therapy vs aspirin alone (HR, 0.58; p<0.0001). The HR for the rivaroxaban-alone arm was 0.82 compared with aspirin alone (p=0.12). [ISC 2018, LB7]
In particular, the risk for ischaemic stroke was 49 percent lower (HR, 0.51, 95 percent confidence interval, 0.38–0.69) with combination therapy vs aspirin alone, with the benefits seen early in the course of therapy as indicated by the “robust early separation of the curves”, said Sharma.
A lower rate of haemorrhagic transformation ─ bleeding into areas of infarct ─ was also seen with combination therapy than with aspirin alone (HR, 0.35; p=0.04).
“Any time you affect blood coagulation, you’re going to get some bleeding,” said Sharma. “In this trial … we saw a slight increase in bleeding outside the brain [with combination therapy] but happily no real increase inside the brain.”
Although haemorrhagic stroke events were more common in the combination therapy vs the aspirin arms (15 vs 10), the difference was not statistically significant (rate, 0.09 vs 0.06 percent per year, HR, 1.49; p=0.33).
Mortality rate at 30 days was also not significantly different between the two groups (HR, 0.84; p=0.68).
Compared with aspirin alone, the risk of disability from stroke was significantly reduced with combination therapy, as indicated by the modified Rankin Scale score of 3 to 6 at 7 days or at hospital discharge (rate, 0.3 vs 0.2 percent/year, HR, 0.58; p=0.01).
In a subgroup of patients with prior stroke, the rate of stroke fell from 3.4 percent per year with aspirin alone to 0.7 percent per year with combination therapy (HR, 0.42; p=0.03). This translates to an absolute risk reduction of stroke of 2.7 percentage points per year in secondary prevention, with a number needed to treat of 37.
“This is a significant advance in stroke prevention for those with CAD/PAD without AF,” said Sharma.
Nonetheless, he also cautioned that combination therapy is not for every patient. “If you’ve got CAD, had a previous heart attack, or have PAD or carotid stenosis, then this is absolutely a combination to consider; but if you don’t have those, we’re not sure it will have the same benefit,” he said, adding that the same applies for aspirin alone.