Differential treatment response does not explain higher survival in patients with obesity, PAH

Differential treatment response may not explain the survival benefit seen in some patients with pulmonary arterial hypertension and obesity, researchers reported in Chest.

In a meta-analysis of 17 trials, patients with PAH and overweight or obesity had reduced 6-minute walk distance and worse WHO functional class compared with patients with PAH and normal weight. While increased BMI did not modify the treatment response for the observed change in 6-minute walk distance, the researchers said higher BMI attenuated the treatment response for WHO functional class.

“We wanted to explore whether body size affected the treatment response in PAH and whether it could explain the survival benefit of obese patients with PAH over normal weight patients with PAH,” Nadine Al-Naamani, MD, MS, assistant professor of medicine in the division of pulmonary, allergy and critical care at the University of Pennsylvania Perelman School of Medicine, told Healio.

The meta-analysis included 17 randomized, placebo-controlled, phase 3 trials that assessed PAH treatments that were submitted for approval to the FDA from 2000 to 2015. In total, the trials included 5,440 patients with PAH. Patient weight status was defined by recorded BMI at the time of randomization in their respective trial and categorized as normal weight (BMI 18.5-25 kg/m²; n = 2,317; mean age, 46 years; 20.9% men), overweight (BMI 25-30 kg/m²; n = 1,664; mean age, 52 years; 26% men) or obesity (BMI 30 kg/m² or more; n = 1,459; mean age, 52 years; 18.2% men).

The primary outcomes were change in 6-minute walk distance and WHO functional class.

Patients with overweight or obesity had lower baseline 6-minute walk distance (17.9 m vs. 21.6 m; P < .001) and a higher likelihood of WHO functional class III or IV PAH (73% vs. 41%; P = .004) compared with patients with normal weight.

PAH treatment was associated with an increase of 27.01 m in 6-minute walk distance (P < .001) and lower odds of worse WHO functional class (OR = 0.58; 95% CI, 0.48-0.7; P < .001).

Six-minute walk distance was reduced by 0.66 m for every 1 kg/m² increase in BMI (P = .07). Every 1 kg/m² increase in BMI also raised the odds of worse WHO functional class by 3% while on PAH treatment (OR = 1.03; 95% CI, 1-1.06; P = .06).

Researchers observed no significant effect modification for treatment response on 6-minute walk distance by patients’ BMI (P = .34). At the end of the 12-week follow-up period, higher BMI was not associated with odds of worsening WHO functional class.

“There were no significant differences in response to treatment with pulmonary vasodilators by body size of patients with PAH. If anything, the obese patients with PAH were less likely to improve their functional class in response to therapy. Differential response to treatment does not explain the observed higher survival of obese patients with PAH as compared to normal-weight patients with PAH,” Al-Naamani told Healio.

According to Al-Naamani, the researchers expected that patients with obesity would derive greater benefit from pulmonary vasodilators.

“Whether adjustment of dosing depending on larger body size is warranted needs to be explored in future research,” Al-Naamani said.

Additional area for future research include ensuring that clinical trials enroll patients across the weight spectrum and exploring other causes that may explain the “obesity paradox,” Al-Naamani said.

For more information:

Nadine Al-Naamani, MD, MS, can be reached at nadine.al-naamani@pennmedicine.upenn.edu.