Telmisartan does not improve walking performance in PAD

Walking performance in patients with peripheral artery disease (PAD) does not improve with telmisartan treatment, according to a recent study.

Researchers at two sites in the U.S. performed a randomized double-blind trial in patients with lower-extremity PAD to determine whether telmisartan, an angiotensin-receptor blocker, increased six-minute walk distance over six months. The original planned sample size was 240, but because enrollment was slower than expected, two combined telmisartan groups were compared with two combined placebo groups and the target sample size was changed to 112. Six-month change in six-minute walk distance was the primary outcome, with 8 to 20 m as the minimum clinically important difference. Secondary outcomes were maximal treadmill walking distance; Walking Impairment Questionnaire scores for distance, speed, and stair climbing; and physical function score on the 36-Item Short-Form Health Survey. The results were published Oct. 4 by JAMA.

Potential participants were asked to take telmisartan, 20 mg/d, for 14 days before randomization and were excluded if they did not take the drug for at least 10 days or developed new lightheadedness, a potassium level of 5.5 mmol/L or greater, a decrease of 30% or more in estimated glomerular filtration rate, or a systolic blood pressure below 100 mm Hg and a diastolic blood pressure below 50 mm Hg. One hundred fourteen patients were randomly assigned in a 2 × 2 factorial design to telmisartan plus exercise (n=30), telmisartan plus attention control (n=29), placebo plus exercise (n=28), or placebo plus attention control (n=27). Doses of telmisartan or placebo were assigned at 20 mg/d or 40 mg/d based on patients' blood pressure and potassium levels after the run-in period, with titration to a maximum of 80 mg/d as tolerated.

Patients' mean age was 67.3 years, 40.4% were women, and 71.1% were Black. One hundred five patients (92%) completed six-month follow-up. Adherence based on pill counts was 92.6% for telmisartan and 90.4% for placebo. At six months, telmisartan did not improve six-minute walk distance versus placebo (mean, 341.6 m to 343.0 m vs. 352.3 m to 364.8 m; within-group change, 1.32 m vs. 12.5 m). The adjusted between-group difference was −16.8 m (95% CI, −35.9 m to 2.2 m; P=0.08). No improvement was seen with telmisartan versus placebo in any of the secondary outcomes. Hospitalization for PAD was the most common serious adverse event, occurring in three patients (5.1%) in the telmisartan group and two (3.6%) in the placebo group. The results were adjusted for study site, six-minute walk distance at baseline, randomization to exercise versus attention control, sex, and history of heart failure at baseline.

The researchers noted that the trial may have lacked statistical power to show a significant detrimental effect of telmisartan on walking performance and that the target sample size was reduced because many potential participants were already taking an angiotensin-converting inhibitor or angiotensin-receptor blocker, among other limitations. They concluded that telmisartan did not improve six-minute walk distance at six-month follow-up versus placebo in patients with PAD and that their results do not support its use for improving walking performance in this population.

An accompanying editorial noted that additional research on PAD treatment is sorely needed and that therapies known to be effective, such as supervised exercise therapy and treatment with statins and cilostazol, continue to be underused. “Developing novel therapies has little potential to benefit patients with PAD unless clinicians are able to implement them in practice. A part of this gap is underdiagnosis,” the editorialists wrote. “…Rather than waiting for patients to report they have difficulty walking even short distances, clinicians need to ask, examine, and test with particular attention those at highest risk.”