HYPERTENSION
Ultra-low doses of BP medication
combinations are effective, safer
V arious combinations of blood pressure (BP) medications given at
one-quarter of the standard doses were efficacious and resulted in
fewer adverse effects compared with standard doses of single-agent
BP medications, according to results of a large systematic review and
meta-analysis published in Hypertension.1
Background
Hypertension is extremely preva-
lent in the United States, and many
patients require several BP-lowering
medications to reach optimal targets.
Unfortunately, use of polypharmacy
to manage hypertension often leads to
unwanted adverse effects. Therefore,
effective BP control with fewer adverse
effects is the ultimate goal to successful
management of hypertension.
Data have suggested that low doses
of BP medications given in combination
may be the best option, as these regi-
mens provide clinical benefit with the
fewest number of adverse effects. To
test this hypothesis, researchers con-
ducted a large systematic review and
meta-analysis to assess the efficacy and
safety of quarter-dose BP medication
regimens compared with placebo and
standard-dose monotherapy regimens.
Systematic review,
meta-analysis
A total of 42 studies were included in
the analysis (n = 20,284), with 38 report-
ing on quarter-dose monotherapy, 7 on
dual quarter-dose combination therapy,
and 2 on quadruple quarter-dose com-
bination therapy compared with pla-
cebo or individual components given
at standard doses.1 No data were avail-
able on triple quarter-dose combination
therapy. The mean duration of the trials
was 7 weeks, mean age of the partici-
pants was 54 years, 61% were men, and
mean baseline BP was 154/101 mm Hg.
The data showed that compared with
placebo, single quarter-dose therapy
reduced in-office BP by 4.7/2.4 mm
Hg, dual quarter-dose therapy reduced
BP by 6.7/4.4 mm Hg, and quadru-
ple quarter-dose therapy reduced BP by
22.4/13.1 mm Hg. All of these reduc-
tions were statistically significantly bet-
32 PharmacyToday AUGUST 2017
Hypertension_08_17.indd 32
ment phase are maintained over the
ter than placebo (i.e., P < 0.001). When
compared with standard-dose mono-
therapy, single quarter-dose therapy
was less efficacious than standard-dose
monotherapy (+3.7/+2.6 mm Hg, P <
0.001), dual quarter-dose therapy was
as efficacious as standard-dose mono-
therapy (+1.3/0.3 mm Hg, P = NS),
and quadruple quarter-dose therapy
was more efficacious than standard-
dose monotherapy (13.1/7.9 mm Hg,
P < 0.001).
In terms of safety, the single and dual
quarter-dose therapies had an adverse
event profile similar to that of placebo
and significantly less than that of stan-
dard-dose monotherapy. Limited infor-
mation was available on the safety of
the quadruple quarter-dose therapy
compared with placebo or the standard-
dose monotherapy regimen.
Study limitations
An accompanying editorial highlighted
select limitations of the current analy-
sis,2 including the small number (18) of
patients in the quadruple quarter-dose
combination comparison with stan-
dard-dose monotherapy; the short dura-
tion (mean 7 wk) of the trials; and the
lack of data for triple quarter-dose com-
bination therapy. These authors wrote
that the short duration of the included
studies does not ensure that the favor-
able BP effects of low-dose combina-
tion treatment seen in the early treat-
long term.
In addition, they noted that the
effects of these ultralow-dose combi-
nation regimens need to be evaluated
on BP assessments made in the ambula-
tory setting, not just the in-office envi-
ronment.
Clinical implications
The results of this systematic review
and meta-analysis suggest that ultra-
low doses of combination BP medica-
tions may be a reasonable alternative
to standard single-agent monotherapy
for management of BP. The authors of
the analysis wrote, Use of dual quar-
ter-dose blood pressurelowering ther-
apy may be preferable to standard-dose
monotherapy, given comparable blood
pressure reduction with better toler-
ability. Alternatively, addition of a
single quarter-dose agent to existing
Effective blood pressure
control with fewer adverse
effects is the ultimate goal
to successful management
of hypertension.
therapy is likely to confer an extra 34
mmHg systolic blood pressure reduc-
tion without additional side effects and
thus could be preferable to doubling
the dose of the existing agent, which
on average confers only about a 12
mmHg extra systolic blood pressure
reduction at the expense of increased
side effects.1
The authors highlighted the low-dose
treatment options currently on the mar-
ket, such as a bisoprololhydrochloro-
thiazide combination and many quar-
ter doses of various beta-blockers.1 They
concluded that additional research is
needed to determine the effects of ultra-
low-dose BP medications not only on BP
control, but also on patient acceptability
and long-term adherence.
References
1. Hypertension. 2017;70(1):8593
2. Hypertension. 2017;70(1):3234
Maria G. Tanzi, PharmD, contributing writer
www.pharmacytoday.org
7/25/2017 4:19:56 PM