Cardiovascular disease clinical trials often exclude patients with kidney disease

A systematic review found that patients with kidney disease were underrepresented in clinical trials of cardiovascular disease interventions.

“This finding is troubling since [kidney disease] and [cardiovascular disease] are independent risk factors leading to increased prevalence of [kidney disease] in patients with [cardiovascular disease] and vice versa,” lead author Ioannis Konstantinidis, MD, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues wrote.

Results were published online in JAMA Internal Medicine on Nov. 30.

The researchers reviewed trials from the top 10 medical journals ranked by impact factor that were included in MEDLINE between Jan. 1, 2006, and Dec. 31, 2014. They included trials that were randomized or controlled, treated heart failure or acute coronary syndrome and randomized at least 100 participants. Trials were excluded if they did not report mortality or were subgroup analyses.

Of the 371 trials in this analysis, 57.1 percent excluded patients with kidney disease. Patients with kidney disease were likely to be included in European trials versus North American and Canadian trials; in trials that tested medications versus those that tested procedures; in industry-funded trials versus government-funded trials; and in trials of patients with heart failure versus trials of patients with acute coronary syndrome.

Of the 212 trials that excluded patients with kidney disease, 52.4 percent used serum creatinine levels as the exclusion threshold, 9.9 percent used estimated glomerular filtration rate, 10.4 percent used creatinine clearance thresholds, 28.3 percent used renal replacement therapy of any form and 17.0 percent used nonspecific qualitative exclusion criteria.

Although the researchers hypothesized that trials may exclude patients with kidney disease because it may be a major confounder, but they found that only 13.2 percent of trials assessing effect by a kidney disease subgroup had an interaction.

“We urge trialists to include patients with [kidney disease] in trials of [cardiovascular disease] interventions and to both report and analyze outcomes by renal function to improve the understanding of the risks and benefits of interventions in this vulnerable population,” they wrote.