AIM: Older patients still underrepresented in HF trials

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Despite the fact that 80 percent of all heart failure (HF) cases affect patients over the age of 65, elderly patients go underrepresented in ongoing clinical trials evaluating the condition, according to an analysis published in the March 28 issue of the Archives of Internal Medicine.

As the baby boomer population begins to age, researchers have speculated that the number of adults over the age of 65 who are diagnosed with HF will double over the next 25 years and HF represents the condition responsible for the most hospital admissions.

Due to the fact that a multitude of HF research focuses on younger patients with the potential to have the condition, Antonio Cherubini, MD, PhD, of the University of Perugia Medical School in Perugia, Italy, and colleagues decided to evaluate the degree of exclusion of older patients in HF clinical trials.

To do so, Cherubini et al extracted data from the World Health Organization Clinical Trials Registry Platform to evaluate the exclusion criteria as justified or poorly justified and the proportion of trials that excluded patients above a certain age.

The authors assessed 251 clinical trials investigating HF, finding that 25.5 percent excluded patients by an arbitrary upper age limit. Of these trials, the upper age limit varied between 65 and 95 years.

These types of exclusions were more common in EU trials compared with U.S. trials, 32.3 percent vs. 16.2 percent and in drug trials that were sponsored by public institutions compared with private entities, 35.6 percent and 13.9 percent.

The research showed that 109 HF trials had one or more poorly justified exclusion criteria that could limit the inclusion of older patients. The researchers reported that the most common exclusion criteria were due to comorbidities such as renal or liver disease; this occurred in 80.1 percent of clinical trials.

Other exclusion criteria that could have limited the participation of older patients were reduced life expectancy, cognitive impairment, use of drugs and physical impairment, which occurred in 36.3 percent, 12.7 percent, 18.7 percent and 13.9 percent of clinical trials.

“We found that a significant proportion of trials (25.5 percent) are still limiting the participation of older patients using an arbitrary upper age limit, with similar figures to those observed in 1985-1989, 1990-1994 and 1995-1999 (21 percent, 35 percent and 27 percent, respectively),” the authors wrote. “Therefore, CTs [clinical trials] that will influence clinical practice in the near future continue to discriminate against older individuals.

“Randomized CTs are considered to stand at the pinnacle of the research method hierarchy for assessment of new interventions. However, their restrictive eligibility criteria may compromise their external validity,” the authors concluded.

While understanding how to include these older patients into clinical trials will be difficult, the authors said that a larger effort should be made to adapt clinical trial design to a larger number of patients.

In an accompanying editorial, Jerry H. Gurwitz, MD, and Robert J. Goldberg, PhD, wrote that “Substantial implications follow from the exclusion of older individuals from participating in clinical trials.”

In fact, Gurwitz and Goldberg offer that these types of age-related and other exclusion criteria may make clinical trials ungeneralizable to most patients with HF.

“Although the inadequate participation of older individuals in cardiovascular clinical trials has long been recognized, little has been done to address this ongoing problem,” Gurwitz and Goldberg wrote.

The editorial authors proposed the following approaches to improve evidence-based care of older patients with cardiovascular disease:
  • Eliminate arbitrary age-based exclusions in cardiovascular clinical trials;
  • Require strong justification for exclusion criteria that could adversely affect the inclusion of older individuals, including those criteria relating to comorbidity, medication use and functional and cognitive impairment;
  • Encourage the design and conduct of RCTs specific to older individuals through targeted funding; and
  • Report and publicize trends in the inclusion of elderly patients in cardiovascular clinical trials to assess progress in improving the generalizability of research findings to this high-risk population.