Analyses Suggest Prasugrel Causes No Excess Bleeding in Stable CAD Patients
LONDON, England—Prasugrel can be taken just as safely by patients with stable CAD as by those with ACS, according to subanalysis of the BASKET-PROVE II trial presented August 31, 2015, at the European Society of Cardiology Congress. Moreover, in a comparison with historical controls, prasugrel and clopidogrel were similarly safe at 2 years in a stable CAD population.
Prasugrel (Effient; Eli Lilly/Daiichi Sankyo) is approved for use in PCI patients with ACS, but there has not yet been a sufficiently large trial to support the drug’s approval in stable CAD, pointed out Raban V. Jeger, MD, of University Hospital (Basel, Switzerland).
Dr. Jeger and colleagues used 2 approaches to assess the safety of prasugrel after stent placement:
- Prespecified subgroup analysis of stable CAD (n = 845) vs ACS patients (n = 1,436) who received prasugrel in BASKET-PROVE II
- Comparison between the aforementioned patients with stable CAD who received prasugrel in BASKET-PROVE II and those with the same presentation who received clopidogrel in the original BASKET-PROVE trial (n = 822)
In the subgroup analysis, those with ACS were younger and less likely to have had a previous MI than those with stable CAD.
After adjustment for baseline differences, 2-year risk of non-CABG-related major bleeding (BARC 3 and 5) occurred with similar frequency whether prasugrel-treated patients had ACS or stable CAD (P = 0.167). However, within the first 30 days of treatment, there was a trend toward fewer events with stable CAD vs ACS presentation (P = .058).
Even when patients who were older or had a lower body weight were given a reduced 5-mg dose of prasugrel, they still had higher likelihood of bleeding than their lower-risk peers on the standard 10-mg dose. Looked at separately, patients aged 75 years and older had increased bleeding risk compared with those younger than 65 years. In contrast, there was no uptick in risk for patients with body weight less than 60 kg (table 1).
The bleeding difference between the 5- and 10-mg prasugrel doses was seen only within the first 12 months (P = .021).
Compared with historical controls, stable CAD patients receiving prasugrel were more likely to have diabetes and arterial hypertension than those taking clopidogrel.
Major non-CABG-related bleeding was similarly likely between the prasugrel and clopidogrel groups, although there was a trend toward higher bleeding risk among prasugrel-treated patients within the first 12 months of therapy (P = .052).
Additionally, the combined ischemic endpoint (cardiac death, MI, definite/probable stent thrombosis) did not differ at 2 years in either the comparison between CAD and ACS patients on prasugrel or in that between prasugrel- and clopidogrel-treated stable CAD patients.
Reluctance to Use 5-mg Prasugrel Dose
Dr. Jeger readily acknowledged the limitations of the study design but said its results may have clinical implications. Given that high-risk patients continued to have more bleeding even when on the lower prasugrel dose, “corresponding label prescriptions of 5 mg for high bleeding-risk patients have to be questioned,”he noted.
Session chair Patrick O’Gara, MD, of Brigham and Women’s Hospital (Boston, MA), asked, “Is there a patient subgroup for whom you would ever recommend the 5-mg dose of prasugrel?”
The current labeling regarding age and weight is not based on randomized data, so it is hard to know what to make of it, Dr. Jeger replied, reporting that he still prescribes prasugrel at 5 mg in high-risk patients but “without a good feeling.”
One explanation for the added bleeding risk in older, lower-weight
patients is use of the femoral approach, he said. “I think
that the picture will probably be a little bit different [in a place like
France] where everybody does the radial approach…. We are
changing to the radial approach and hope the outcomes are better.”
Jeger R. Bleeding risk of prasugrel-based dual antiplatelet therapy after stent implantation in stable coronary artery disease. Presented at: European Society of Cardiology Congress; August 31, 2015; London, England.
- Dr. Jeger reports no relevant conflicts of interest.