Aims: Whereas product labels of beta blockers list
peripheral arterial disease (PAD) as a contraindication, current
PAD guidelines state otherwise. We aimed to evaluate the clinical
efficacy and safety of the ß1 selective blocker
nebivolol in hypertensive patients with PAD.
Methods and results: This multicentre, prospective,
double-blind, active controlled, parallel-group study compared
once-daily treatment with nebivolol (Neb) 5 mg vs.
hydrochlorothiazide (HCTZ) 25 mg, in hypertensive patients with
Fontaine stage II (intermittent claudication). The primary endpoint
was the initial claudication distance (ICD) during treadmill
exercise after 24-week treatment in the per protocol population,
using a noninferiority statistical approach. A total of 177
patients (mean age was 66.3 ± 9.2 years, 76.7% men) were
randomized to study treatment and 127 completed the study; the
intent-to-treat (ITT) analysis was performed on 163 patients, the
per protocol analysis on 127 patients. Both drugs lowered blood
pressure significantly. After 24-week treatment, ICD increased in
the Neb group in the ITT population by 28.3% (95% CI
15.6–41.0) vs. in the HCTZ group by 26.5% (14.4–38.5),
and in the per protocol population in the Neb group by 26.4%
(13.4–39.4) vs. in the HCTZ group by 32.1% (18.4–45.7).
Thus, noninferiority of Neb could neither be confirmed nor
rejected. An increase of absolute claudication distance (ACD, mean
percentage increase after 24 weeks on Neb 15.8 ± 33.2 vs. on
HCTZ 20.2 ± 46.6) was observed without statistical differences
between groups. Ankle-brachial index (ABI) increased slightly in
both groups. Generally, both treatments were well tolerated.
Conclusion: The increases in ICD, ACD and ABI with
nebivolol suggest that this medication does not have negative
effects on hypertensive patients with symptomatic PAD, and can be
used for treatment of hypertension in these patients at high
cardiovascular risk without reducing the walking ability.
