The TGA has extended the indications for rivaroxaban to include patients with severe renal impairment.
The change comes as a relief to some cardiologists and GPs who have long suspected that the NOAC was an appropriate medication to prevent thrombosis and strokes in patients with severe renal impairment, but haven’t been able to prescribe it for this group.
Following the TGA’s decision, rivaroxaban is now the only NOAC in Australia approved for use in patients with creatinine clearance down to 15mL/minute.
The TGA approval of rivaroxaban for patients with renal impairment follows a similar decision by the FDA and the European Medicines Agency.
In the past, prescribers had either had to withdraw rivaroxaban treatment once patients fell below the specified threshold for renal function of 30 mL/minute (and risk cardiovascular issues) or put these patients on warfarin and risk bleeding complications, said Dr Chris Hammett, a cardiologist at Royal Brisbane and Women’s Hospital.
Patients with declining kidney function were contraindicated for rivaroxaban on the product information sheet not because there was evidence that the drug was particularly harmful in this group, but because the original RCTs happened to exclude this patient population.
“We always understood that [the exclusion of patients with severe renal impairment] was a slightly artificial concept that came about because of the trial design,” Dr Hammett said.
“Whenever you are designing a trial, you don’t really know whether the drugs work and you don’t really know how safe they are, and you have to put thresholds around which patients you are going to enrol.”
For the landmark ROCKET AF trial, the study architects chose not to enrol patients with renal function below 30 mL/minute.
But post hoc analyses of the study data showed patients with some renal impairment who were included in the trial actually had an even greater benefit from rivaroxaban (compared with warfarin) than the patients with normal renal function, Dr Hammett said.
“So, as you drift down below 30 mL/minute renal function, the benefit of rivaroxaban increases over warfarin. So, all of that indirectly says to us, it’s going to be safe in that lower group.”
There had been no RCTs specifically comparing warfarin and rivaroxaban in patients with renal function down to 15 mL/minute, but there were “lots of lines of more indirect evidence” that had led to the TGA and overseas regulators to lift the restriction on prescribing in this group, Dr Hammett said.
“As we’ve got used to [rivaroxaban], we’ve realised they are really safe in renal impairment.
“They’ve analysed the trials in more depth for people with renal impairment and they’ve found that, as your renal function gets worse, the benefit for rivaroxaban over warfarin gets greater,” he said.
“And the people that we thought were the ones that might be at risk – the people who have quite rapidly changing renal function – are actually the ones that are even safer on NOACs.”