CKD Patients Undergoing PCI Much Less Likely to Receive Potent P2Y12 Inhibition

Patients with chronic kidney disease (CKD) undergoing PCI for acute coronary syndromes are at an increased risk of major adverse cardiac events, including MI and bleeding, at 90 days and 1 year when compared with patients with normal renal function, a new analysis shows.

The post-PCI use of prasugrel (Effient, Eli Lilly) in these higher-risk CKD patients was associated with a lower unadjusted risk of thrombotic and bleeding events compared with clopidogrel, but the differences were no longer statistically significant in the propensity-matched analysis.

Interestingly, just 11% of CKD patients received prasugrel following PCI—24% of patients without CKD received the potent antiplatelet agent—which suggests that clinicians are wary of the bleeding risks in patients with impaired renal function, according to the researchers.

“There might be opportunities to better calibrate our decision-making,” lead investigator Usman Baber, MD (Icahn School of Medicine at Mount Sinai, New York), told TCTMD. “Certainly, we recognize and understand that bleeding happens in kidney disease patients, but so does MI. The events happen at similar rates but it looks like our decision-making is driven so much by the concern for bleeding, which is justifiable, that we may be depriving certain patients who could benefit from prasugrel.”

Patients with underlying renal impairment are at an increased risk for both thrombotic and bleeding events, which makes the choice of antiplatelet agent following PCI for ACS a difficult decision, he added. Additionally, patients with kidney disease make up a large part of clinical practice, with PCI registries suggesting that 20% to 40% of patients undergoing PCI, particularly for ACS, have underlying renal disease, said Baber.

In an editorial accompanying the study, Hitinder Gurm, MD (University of Michigan, Ann Arbor), writes that CKD patients have more extensive coronary disease, are less likely to undergo revascularization, and have worse short- and long-term outcomes after PCI. Given that, you’d expect more aggressive medical therapy to be used in these patients.

It’s not quite so simple, however.

“The fear of bleeding is a real concern,” Gurm told TCTMD. “The worry is that they’ll bleed, stop the dual antiplatelet therapy, and then they’ll have more problems. It’s something that’s obviously of major concern.”

The PROMETHEUS Study

In the present study, which was published online August 2, 2017 in the JACC: Cardiovascular Interventions, the researchers analyzed data from the PROMETHEUS study, a large multicenter, observational study comparing clinical outcomes with prasugrel versus clopidogrel in ACS patients undergoing PCI at eight academic medical centers in the United States. Of the 19,832 patients included in study, 28.3% had CKD. Patients with CKD were older than those without renal dysfunction and had significantly more comorbidities, including multivessel disease and diabetes.

Not surprisingly, the CKD patients fared worse at 90 days and 1 year than patients without CKD. At 90 days, CKD patients had a 25% higher risk of MACE, including a 25% higher risk of MI and a 59% higher risk of death. The CKD patients also had a 51% higher risk of bleeding compared with non-CKD patients. At 1 year, the results were similar.

Among the CKD patients, 4,996 were treated with clopidogrel following PCI for ACS and 617 patients received prasugrel. To TCTMD, Baber noted that the frequency of prasugrel use by subgroups didn’t impact the choice of antiplatelet agent. CKD patients presenting with STEMI, as well as those with diabetes, multivessel disease, and small vessels were all less likely to receive prasugrel compared with patients without renal impairment.

Like in the overall PROMETHEUS results, investigators did not observe a clinical difference in outcomes among CKD and non-CKD patients treated with prasugrel or clopidogrel once they adjusted for confounding variables. Baber cautioned, however, these results are observational and not the primary intent of this analysis. Instead, their goal was to get a snapshot of what antiplatelet agent physicians were selecting for CKD patients.

The results suggest that the fear of bleeding with prasugrel is driving decision-making, with physicians shying away from the stronger antiplatelet in high-risk CKD patients. 

“There was a consistent pattern where the patients with kidney disease were much less likely to get the potent agent,” said Baber. “Even when you selected out the highest-risk thrombotic milieu, they were still much less likely to get prasugrel. And it wasn’t a mild difference either.”

For physicians tasked with selecting antiplatelet therapy following PCI in CKD patients, Baber suggests estimating their risk of thrombosis and bleeding to determine treatment. For example, in a CKD patient with diabetes presenting with STEMI, most physicians would presume the risk of thrombosis exceeds the risk of bleeding in the first year and select prasugrel over clopidogrel. He added that dedicated studies are needed in this area to better guide practice, though. 

‘Double Jeopardy’ in Play

To TCTMD, Gurm said CKD patients remain challenging as they are typically excluded from clinical trials, calling the area a “data-free zone” when it comes to P2Y12 inhibition following PCI for those with significant renal impairment.  

Despite the “double jeopardy” of CKD patients having a heightened risk of thrombotic and bleeding events, Gurm noted that data from at least one clinical trial, PLATO, showed that use of ticagrelor (Brilinta, AstraZeneca) among CKD patients reduced the absolute risk of vascular death, MI, and stroke by 6% when compared with use of clopidogrel, a benefit that was not as pronounced in patients with normal renal function. Additionally, use of ticagrelor in CKD patients resulted in a 5.3% absolute reduction in total mortality.

“The benefit of ticagrelor is really impressive in patients with chronic kidney disease,” he said. “But in clinical practice, that hasn’t really sunk in.” Gurm noted that benefit is based on one trial, a subgroup analysis at that. “There’s always a caveat as to whether this is just a chance finding or if it’s the real deal.”