CLINICAL
NEWS JACC in a FLASH
Featured topics in the current and recent
issues of the JACC family of journals
HCTZ No Longer an Acceptable
Option for Treating Essential
Hypertension?
Hydrochlorothiazide (HCTZ) is one of
the most commonly prescribed antihypertensive drugs in the world. However, a new study published in JACC is
questioning this practice.
HCTZ use has been influenced by
recommendations from reports out
of the Joint National Committee (JNC)
for Prevention, Detection, Evaluation,
and Treatment of High Blood Pressure,
which have all recommended thiazides
as the preferred therapy for hypertension. For most physicians, thiazide is
synonymous with HCTZ. However,
studies questioning the effectiveness of
HCTZ go back 30 years.
The current study, conducted in 54
Indian patients with stage 1 essential
hypertension, was led by Franz H.
Messerli, MD, of the Mount Sinai
Health Medical Center. Diagnosis of
hypertension was based on office blood
pressure (BP) and confirmed by 24hour ambulatory blood pressure monitoring (ABPM) measurements. Patients
were randomized to receive treatment
with a once-daily dose of chlorthalidone 6.25mg (n = 16), HCTZ 12.5 mg
(n = 18) or HCTZ- controlled release (CR)
12.5mg (n = 20). The controlled release
formula arm of the study was included
due to the fact that the antihypertensive
efficacy of HCTZ may be hampered
by its short half-life. Patients were told
to take their medication every morning. Comparative efficacy evaluations
were performed at baseline, week 4
and week 12 for 24-hour ABPM and at
baseline, week 2, week 4, week 8 and
week 12 for office BP measurements.
Patients treated with chlorthalidone
and HCTZ-CR experienced a significant
reduction in 24-hour ambulatory systolic BP and diastolic BP from baseline.
At weeks 4 and 12, the reduction was
not significant for patients treated with
conventional HCTZ. At weeks 4 and 12,
the 24-hour ambulatory systolic BP was
ACC.org/CSWN
significantly lower in patients treated
with chlorthalidone compared to those
treated with conventional HCTZ.
At weeks 4 and 12, all treatments
showed a significant reduction in mean
office systolic BP. There was no significant difference in change if systolic BP
or diastolic BP from baseline at week
4 and week 12 between groups. The
proportion of patients who met goal
BP levels did not significantly differ
between treatment groups. Tighter
BP control was observed in 25.0% of
chlorthalidone patients, 11.11% of
HCTZ patients and 15% of HCTZ-CR
patients.
At week 12, patients in all treatment groups showed a significant reduction in ambulatory daytime systolic
BP, but only patients from the chlorthalidone and HCTZ-CR groups showed a
significant reduction in ambulatory daytime diastolic BP. At week 12, the mean
ambulatory daytime systolic BP was
significantly lower for patients treated
with chlorthalidone than those treated
with conventional HCTZ. At week 12,
chlorthalidone and HCTZ-CR patients
showed significantly reduced ambulatory nighttime systolic BP and diastolic
BP. The change was not significant in
HCTZ patients. At weeks 4 and 12,
ambulatory nighttime systolic BP was
significantly lower in patients treated
with chlorthalidone than those with
conventional HCTZ.
All treatments were generally safe
and well-tolerated.
According to the authors, the discrepancy between ABPM and office BP
indicate that HCTZ lowers BP appropriately during the daytime, when patients
are seen by their doctor’s, but has little
to no effect during the night and early
morning hours. This time period is the
most critical as it coincides with the
highest risk of stroke and other cardiovascular events. Previous studies have
shown similar findings, demonstrating
that assessing the antihypertensive
efficacy of HCTZ by in-office BP is
deceptive. Chlorthalidone and HCTZCR provide BP control throughout the
diurnal cycle, unlike convention HCTZ.
Chlorthalidone also has well-documented benefits on cardiovascular morbidity
and mortality.
Messerli and colleagues conclude
that “low-dose chlorthalidone 6.25 mg
can be used as monotherapy, whereas
low-dose HCTZ should no longer be
considered an acceptable option for
treatment of essential hypertension.”
In a corresponding editorial comment, Hillel Sternlicht, MD, and
George L. Bakris, MD, question
whether the results are generalizable to
a broader population. Only one-third
of patients screened were enrolled and
each patient arm was small. “Additionally, because the study was conducted
in a Southeast Asian country, it remains
unclear whether the results can be
extrapolated to those on Western diets
or of other ethnicities,” they write.
Pareek AK, Messerli FH, Chandurkar NB,
et al. J Am Coll Cardiol. 2016;doi:10.1016/j.
jacc.2015.10.083.
Exercise at the
Extremes: Relationship Between
Exercise Volume and
Risk Reduction
Recent studies have found that both too
little and too much exercise can lead to
negative cardiovascular outcomes. So
how much exercise is needed to reduce
cardiovascular events? A recent paper
from the ACC’s Spo 'B