More Than Half of CVD Studies Exclude Patients With Kidney Disease

Patients with kidney disease continue to be underrepresented in clinical trials testing cardiovascular medications or procedures, according to the results of a new systematic review.

The lack of representation in studies is troubling given that the population of patients with kidney and cardiovascular disease is growing and that strategies testing clinical interventions may have differing results in those with and without kidney disease.

“Cardiovascular disease is the biggest killer in patients with kidney disease,” Girish Nadkarni, MD, of the Icahn School of Medicine at Mount Sinai (New York), told TCTMD. “We don’t really know how to treat cardiovascular disease and its complications in patients with kidney disease because there is no good evidence. Most of the trials that have been performed predominantly in kidney-disease patients are smaller or unblended, and this leads to poorer-quality evidence.”

The analysis was published November 30, 2015, in JAMA: Internal Medicine.

Excluding Patients Leads to Evidence Gap

Speaking with TCTMD, Nadkarni said 2 previous reviews assessing the representation of patients with kidney disease in clinical trials have been performed. In one, more than half of the studies testing an intervention proven efficacious in cardiovascular disease excluded patients with kidney disease. In the second review, patients with moderate to advanced chronic kidney disease were excluded from 75% of cardiovascular studies.

Nadkarni noted that researchers may reasonably exclude individuals with kidney disease in trials testing new drugs, particularly if the drug is excreted by the kidney, as there are legitimate concerns about potential harms. That being said, there is a trend to exclude them from studies where there is little to no chance of harm to the kidney, such as lifestyle-interventions, certain cardiovascular procedures, or quality-improvement studies.

ACS, Heart Failure Studies Reviewed

To investigate the current state of inclusion in clinical trials, researchers by Ioannis Konstantinidis, MD, also of the Icahn School of Medicine at Mount Sinai, identified 371 RCTs testing clinical interventions in a total of 590,040 patients with ACS or heart failure.

Of the 371 studies, 212 (57%) excluded patients with kidney disease. Patients with kidney disease were more likely to be excluded from North American studies compared with European trials, as well as more likely to be excluded from trials testing procedures rather than those testing medications. Patients with kidney disease were more likely to be included in industry-funded trials than in government-funded studies. More than 52% of the studies used serum creatinine levels to estimate renal function when excluding patients compared with 9.9% that used the estimated glomerular filtration rate.

“Patients with kidney disease are different from those without kidney disease because the kidney is not only important for excretion—it also has many other functions, including maintaining homeostasis in the body,” said Nadkarni. “While that is true, we also have seen that in a subset of studies that did include patients with kidney disease, there wasn’t a lot of difference in terms of outcomes or harms.”

In their analysis, the researchers found that only 13.2% of the studies including kidney-disease patients showed an interaction between treatment and renal function, a finding that suggests  harm in these patients might be overestimated. Nadkarni suspects physicians and researchers might be overly cautious when testing clinical interventions in cardiovascular disease patients with kidney disease, although the present study was not designed to assess reasons for the exclusion.

Overall, Nadkarni said he was surprised by how many studies excluded individuals with impaired renal function, especially given the 2 previous reviews highlighting their underrepresentation in clinical studies and the growing prevalence of individuals with cardiovascular and kidney disease. Approximately 10% to 15% of individuals with cardiovascular disease would also have moderate or severe kidney disease, he said, and future studies should aim to include patients with different degrees of renal function in order to understand the risks and benefits of various treatments.

Konstantinidis I, Nadkarni GN, Yacoub R, et al. Representation of patients with kidney disease in trials of cardiovascular interventions. JAMA Intern Med. 2015;Epub ahead of print.

Michael O’Riordan is the Managing Editor for TCTMD. He completed his undergraduate degrees at Queen’s University in Kingston, ON, and…

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  • Konstantinidis and Nadkarni report having no conflicts of interest.