Do you like managing bleeding on aspirin? How about aspirin plus clopidogrel? What would you say to aspirin + clopidogrel + vorapaxar?
Vorapaxar, a selective antagonist for protease-activated receptor 1, is the next proposed layer of anti-thrombotic prevention for high-risk cardiovascular patients. Just this week, back from the dead, it received a favorable review from an FDA panel tasked with examining its application for approval.
The subject of both TRACER and TRA 2°P-TIMI 50, vorapaxar may soon bless your Emergency Department with a roughly 60% increase (2% vs. 3.5%) the risk of GUSTO moderate or severe bleeding. What’s most fascinating about this drug is, technically, both trials were negative for the primary endpoint, and TRACER was stopped early after interim safety review. However, a pre-specified and pre-allocated subgroup from TRA 2°P-TIMI 50 for patients with recent MI – and no history of stroke – showed benefit.
Of course, as is standard for these sorts of cardiovascular trials, it showed benefit primarily in the questionable combined endpoints – and, likewise, was only safe in the narrowest slicing and dicing of favorable endpoints and bleeding outcomes.
It should be of no surprise to anyone most authors are being substantially enriched by multiple drug companies. I’m certain whatever foot-in-the-door Merck receives will be enough to extract the necessary healthcare dollars from the system for minimal benefit – a net NNT for mortality of ~450.
Oh, and as the great Tom Deloughery (@bloodman) writes:
“Hmmm – a competitive platelet inhibitor with a T1/2 of ~300hrs! So, sounds like it will inhibit any platelets you give for the next 12 days … I guess Dr. Radecki will be holding direct pressure for a long time!”
“Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: a prespecified subgroup analysis of the TRA 2°P-TIMI 50 trial”
http://www.ncbi.nlm.nih.gov/pubmed/22932716
Good morning,
But is the " net NNT for mortality of ~1000" for the whole group or the subgroup-?
This is for the previous MI subgroup of TRA 2°P-TIMI 50.
There was a net reduction in all-cause mortality of 20 patients (273 deaths vs. 293 deaths) in the 8898 in the vorapaxar group – but I see now I used the wrong numerator for my maths, and the correct net NNT is ~450.