AIM: Antiplatelets may cause more harm than good in CKD patients
While antiplatelets have been found to reduce the risk of cardiovascular disease, a meta-analysis published in the March 20 issue of the Annals of Internal Medicine, found that for chronic kidney disease (CKD) patients, they may do more harm than good. In fact, researchers found that bleeding risks may outweigh the benefits of antiplatelet treatment in this patient population; however, research remains scarce.

It has been estimated that 10 percent to 15 percent of the population has CKD, and this number is likely to grow due to the increased incidence of diabetes and obesity. Of these patients, nearly 50 percent are 70 years or older; 33 percent to 50 percent also have acute MI.

Patients with early-stage CKD have a 25 percent to 30 percent increased risk of developing cardiovascular disease (CVD) and that risk becomes more than 30- to 50-fold higher in patients with end-stage kidney disease, the authors wrote.

Often antiplatelet regiments are prescribed to thwart CVD; however, CKD patients may have a higher risk of bleeding with these drugs. To better understand the impact of antiplatelet treatments on CKD patients, Suetonia C. Palmer, MB, PhD, of the University of Otago Christchurch in Christchurch, New Zealand, and colleagues looked at nine trials involving 9,969 patients with acute coronary syndromes undergoing PCI and 31 trials involving 11,701 patients with stable and no CVD.

Their aim was to evaluate cardiovascular events, mortality and bleeding. The analysis compared antiplatelet agents with standard care, placebo or no treatment.

“Health costs of treating a person with CKD are nearly three-fold higher than those for a person without CKD, and the cost of treating end-stage kidney disease is 10-fold higher,” Palmer et al wrote. “Together, increasing use of health resources, continued poor outcomes, and emergence of performance measures directed to the care of persons with CKD necessitate careful evaluation of all healthcare interventions in this growing population.”

After analysis, the researchers found “low-quality” evidence that antiplatelet treatment on top of standard care had “little or no effect on myocardial infarction (seven trials, 5,261 participants), with no evidence of significant heterogeneity.” Additionally, the authors found that trials involving glycoprotein IIb/IIIa inhibitors provided similar effects.

One trial included in the analysis showed that six strokes, fatal or nonfatal, occurred in 411 patients, alluding to the fact that clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) as an add-on to standard therapy had “uncertain” effect on stroke. Adding antiplatelet therapy to standard therapy also had little or no effect on all-cause mortality during the analysis. These effects were uncertain as they pertained to cardiovascular mortality.

The nine trials that included CKD patients with acute coronary syndromes who required PCI included bleeding event data. While the authors deemed the evidence as “low-quality,” they said the results showed that antiplatelet therapy plus standard care increased major and minor bleeding.

“Antiplatelet therapy increased major bleeding in analyses limited to trials reporting outcomes at one year or more,” the authors wrote. The authors also found that antiplatelet therapy had little or no effect on coronary artery revascularization, and no data were available on all-cause hospitalization, end-stage kidney disease or withdrawal from treatment, the authors added.

It was also reported that antiplatelet therapy did reduce MI; however, the researchers added that it had an "uncertain" effect on stroke. Of the trials included, 18 reported major bleeding events and eight reported minor bleeding events. However, no trials focused on reporting the details of hemorrhagic stroke.

“According to low-quality evidence, antiplatelet therapy significantly increased minor bleeding but had uncertain effects on major bleeding,” the authors added. In 10 of the trials, antiplatelet agents in trials one year or longer were linked to major bleeding.

“In general, evidence is of low or very-low quality, with considerable variation in trial duration; heterogeneity in the definitions and assessment of bleeding outcomes; reliance on subgroup data from major trials, particularly for antiplatelet treatment in acute cardiovascular disease; and substantial methodological limitations in data for adults with CKD and stable cardiovascular disease,” Palmer et al wrote.

“Antiplatelet treatment (generally glycoprotein IIb/IIIa inhibitors) given in addition to standard care in persons with acute coronary syndromes or those undergoing percutaneous coronary revascularization who also have CKD has little or no effect on myocardial infarction, death, or coronary revascularization but increases major and minor bleeding.”

The researchers said that little research exists that highlights the effect antiplatelet therapy has on stroke and CV death in CKD patients with acute coronary syndromes or who are undergoing PCI. And while it was noted that antiplatelets could reduce the rate of fatal or nonfatal MI by 33 percent in CKD patients, the data on how it impacts stroke or all-cause mortality are few and far between.

Additionally, taking 12 months of oral antiplatelet therapy could prevent MI in between 1 percent and 3 percent of those at risk for MI.

The authors said that more trials outlining the risks and benefits of administering antiplatelets to CKD patients are necessary. “Bleeding hazards and lack of clear efficacy in reducing cardiovascular morbidity and mortality need to be acknowledged when patients with CKD are being counseled about acute or long-term antiplatelet therapy,” the authors summed.