Renal Patients With ACS Don't Benefit From Antiplatelets

March 20, 2012

March 20, 2012 (Christchurch, New Zealand) — Chronic kidney disease (CKD) patients with acute coronary syndrome (ACS) do not appear to benefit from the use of antiplatelet agents for secondary prevention and may, in fact, be harmed by these drugs, according to a new meta-analysis of almost 10 000 patients, by Dr Suetonia C Palmer (University of Otago, Christchurch, New Zealand) and colleagues [1]. They report their findings in the March 20, 2012 issue of the Annals of Internal Medicine.

"We have shown, for the first time, that the potential benefits of antiplatelet drugs in people with renal disease may actually be outweighed by the harms, in particular bleeding," senior author Dr Giovanni FM Strippoli (Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy) told heartwire .

We have shown, for the first time, that the potential benefits of antiplatelet drugs in people with renal disease may actually be outweighed by the harms.

"In essence, the use of these agents, such as GP IIb/IIIa inhibitors and clopidogrel, in people with renal disease [and ACS] has virtually no effect on all-cause mortality or MI, so they would not prevent cardiac events, but they would increase major bleeding, primarily major intracranial bleeding, a very heinous occurrence," he added.

Palmer and colleagues also reviewed data on almost 12 000 patients with renal disease at risk for or with stable coronary disease: in this instance, antiplatelet agents did prevent MI but had uncertain effects on mortality and increased minor bleeding. "The benefits [of antiplatelets] are more relevant to those with CKD who have stable or no coronary disease as opposed to those who have ACS," says Strippoli.

First time anyone has extracted data on renal patients from cardiology trials

Strippoli explains that there have been no specific trials of antiplatelet agents in CKD patients, so treatment recommendations are made based on benefits seen in big cardiology studies. But nonatherosclerotic conditions — such as cardiac failure, sudden cardiac death, and arrhythmia — are more common causes of cardiovascular events in persons with CKD than in the general population.

Cardiologists and guideline committees look at the data from the cardiology trials, and if they're positive, they apply it to renal patients as well, which is wrong.

"Cardiologists and guideline committees look at the data from the cardiology trials, and if they're positive, they apply it to renal patients as well; they wouldn't really think renal patients are any different, which is wrong," he says. And because the big trials of antiplatelet agents have been done by cardiologists, nephrologists "are less informed" about these agents, he notes.

"What we did is we looked at the cardiology trials and we extracted the renal data, so our findings now apply specifically to the renal population," he explains.

Low-level evidence is "the best that we can do," should change practice

In their analysis, Palmer and colleagues included trials that compared antiplatelet agents with placebo, standard care, or no treatment in adults, for which data for participants with CKD could be extracted. Nine trials — all post hoc subgroup analyses for CKD — involving 9969 persons with ACS or who were undergoing PCI were included. A separate analysis of 31 trials involving 11 701 renal patients at risk of or with CVD was also performed.

In the ACS patients, they found that there was little benefit of antiplatelet agents in those with CKD, but around a 40% increased risk of major bleeding, which means that bleeding risk in those with renal disease is at least doubled compared with those without CKD, say the researchers. It is also important to remember that people in the real world may have even higher risks for bleeding than trial participants, they note.

Effects of antiplatelet agents on CV, mortality, and bleeding outcomes in persons with CKD and ACS or undergoing PCI

Outcome Relative risk* p
Fatal or nonfatal MI 0.89 0.41
Coronary revascularization 0.93 0.84
All-cause mortality 0.89 0.48
Major bleeding 1.40 0.09
Minor bleeding 1.47 0.001

*Summary effects are provided using random-effects meta-analysis

In those with renal disease at risk for or with stable coronary disease, fatal or nonfatal MI was reduced by 34% in those taking antiplatelets compared with standard treatment or placebo, but there were "uncertain" effects on mortality and increased minor bleeding, the researchers note.

Strippoli and colleagues acknowledge, however, that these results are "low-level evidence" based primarily on subgroup analyses from trials, but Strippoli says this is "the best we can do. We are providing people with accurate estimates based on the existing data."

And although ideally trials of antiplatelet agents should be conducted specifically in CKD sufferers, "this is probably going to be infeasible, unless a large agency becomes interested in funding such a trial," he notes.

He says that at his institution, "certainly our practice will change now," and he hopes that guideline committees will base new recommendations "on our in-depth review."

"The trade-off between benefits and harms should always be carefully assessed before prescribing these [antiplatelet] drugs to people with CKD," he concludes.

Palmer received support from an unrestricted Amgen Dompé Consorzio Mario Negri fellowship. Strippoli reports no conflicts of interest. Disclosures for the coauthors are listed in the paper.

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