J Hypertens Suppl. 2006 Apr;24(2):S11-6.

Circadian rhythm of blood pressure and the relation to cardiovascular

events.
Giles TD1.

Author information

1
Louisiana State University Health Sciences Center, New Orleans, 70112, USA. tgiles4@cox.net

Abstract

Incidences of potentially life-threatening cardiovascular events display a diurnal pattern, tending to be higher
in the morning than at other times of day. The recording of blood pressure at pre-defined intervals under
everyday circumstances is facilitated by ambulatory blood pressure monitoring (ABPM). This technique
shows that systolic and diastolic blood pressures display a circadian rhythm in most individuals. Typically, at
the end of the night on arousal, blood pressure surges. This surge coincides with increased cardiovascular
events. A recent prospective study conducted in Japan, where the incidence of stroke is high, provides
further evidence for the link between cardiovascular events and morning blood pressure surge. Prevalence
of both silent ischaemic events and multiple cerebrovascular infarcts was highest among the elderly subjects
studied, with the largest increase in blood pressure on awakening. An increased risk of cardiovascular
morbidity and mortality is also seen in 'non-dippers' (i.e. individuals in whom the normal nocturnal fall in
blood pressure is absent or blunted). ABPM is superior to clinic blood pressure in predicting cardiovascular
morbidity and mortality, and this suggests that 24-h blood pressure control may be necessary to gain
complete benefit from blood pressure-lowering therapy. Antihypertensive agents with a long duration of
action have the potential to provide blood pressure control throughout the dosing interval and thus cover the
critical early morning period when the blood pressure surges. Clinical studies that have compared
telmisartan with shorter-acting angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors
demonstrate that telmisartan has a sustained duration of action, with proven efficacy over the entire 24-h
period between doses, including the critical early morning period.

PMID:
16601555
[PubMed - indexed for MEDLINE]

Hypertens Res. 2014 Mar;37(3):225-31. doi: 10.1038/hr.2013.141. Epub 2013 Oct 10.
Comparative effects of telmisartan and valsartan as add-on agents for
hypertensive patients with morning blood pressure insufficiently
controlled by amlodipine monotherapy.
Yoshida H1, Akasaka H1, Saitoh S1, Shimamoto K1, Miura T1; SPEED investigators.

Collaborators (73)

Shimamoto K, Miura T, Saitoh S, Yoshida H, Oimatsu H, Ooiwa H, Tanaka S, Nishimiya T, Hayashi M,

Matsuki T, Mori Y, Higashiura K, Yamaguchi T, Ogawa S, Kodama K, Furugen M, Ishimoto R, Saito N,
Fukuoka M, Hamabe K, Murakami H, Nakagawa M, Kikuiri K, Nishihara M, Sato S, Noto T, Tsuchida A, Ishii
K, Iwata M, Komakine T, Suzuki K, Nakamura Y, Nozawa Y, Kobayashi H, Togashi N, Shoji T, Ando T,
Yamauchi K, Kijima T, Sawai N, Nishizato K, Yamamoto H, Nakata T, Koyanagi T, Hotta H, Kyuma M,
Ohtomo T, Tobisawa T, Shinshi Y, Miyazaki S, Ohnuma Y, Hasegawa T, Takada A, Terashima Y, Yoshioka T,
Matsumoto T, Tsubokura T, Takagawa Y, Yoshida D, Sakamoto K, Nakamura Y, Koizumi T, Hagiwara M,
Urabe K, Marusaki S, Yoshida S, Kaneko N, Ura N, Sasaki H, Ise T, Nishitani T, Nishimura M, Togashi M.

Author information

1
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University, School
of Medicine, Sapporo, Japan.

Abstract

The aim of this study was to determine the efficacies of valsartan and telmisartan as add-on agents for the
control of morning blood pressure (BP) in patients already on amlodipine monotherapy. A total of 414
hypertensive patients were prospectively enrolled in a 4-week run-in period when they were treated with
amlodipine (5mg/day), and home BP was measured in the morning and evening. Patients with home systolic
BP (SBP) being 135-159mmHg in the morning at the end of the run-in period were randomized to additional
treatment with valsartan (80mg/day) or with telmisartan (40 mg/day) for 8 weeks. The primary endpoint was
the change in morning home BP, and secondary endpoints included variability of morning home BP. Of the
282 patients randomized, 262 patients (n=131, in each treatment) completed the protocols. Demographic
parameters and baseline morning SBP/diastolic BP (DBP) (146.37.1/84.89.3 vs. 146.07.1/84.29.1 mm
Hg) were comparable in the valsartan group and telmisartan group, and changes in SBP/DBP after 8-week
treatment were not significantly different between the two groups (-7.410.6/-3.96.1 vs. -8.39.9/-5.05.9
mmHg). Valsartan significantly increased individual standard deviation and variation coefficient of morning
SBP, but telmisartan did not change either of these indices of SBP variation. In subgroups with baseline SBP
being above the median (145.2mmHg), change in DBP was significantly larger by telmisartan than by
valsartan (-6.35.6 vs. -3.96.7mmHg, P<0.05). These results suggest that telmisartan is more useful than
valsartan as an add-on agent for reducing the level and variability of morning BP in patients on amlodipine
monotherapy.

Hypertens Res. 2013 Jul;36(7):627-33. doi: 10.1038/hr.2012.233. Epub 2013 Jan 24.
A meta-analysis of randomized trials of telmisartan vs. valsartan therapy
for blood pressure reduction.
Takagi H1, Niwa M, Mizuno Y, Goto SN, Umemoto T; ALICE (All-Literature Investigation of Cardiovascular
Evidence) Group.

Author information

1
Department of Cardiovascular Surgery, Shizuoka Medical Center, Shizuoka, Japan.
kfgth973@ybb.ne.jp

Abstract

A previous meta-analysis of six randomized head-to-head trials suggests that the blood pressure (BP)-
lowering capabilities of telmisartan may be comparable to those of valsartan. We performed an updated
meta-analysis of telmisartan vs. valsartan therapy for the reduction of BP in hypertensive patients.
MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through August
2012 using web-based search engines (PubMed, OVID). Eligible studies were prospective randomized
controlled trials examining telmisartan vs. valsartan therapy and reporting clinic BP as an outcome. For each
study, the data regarding changes from baseline to final clinic systolic BP (SBP) and diastolic BP (DBP) in
both the telmisartan and valsartan groups were used to generate mean differences (MDs) and 95%
confidence intervals (CIs). Of the 62 potentially relevant articles initially screened, 17 reports about
prospective randomized controlled clinical trials of telmisartan vs. valsartan therapy, including a total of 5422
patients with hypertension, were identified and included. Pooled analysis suggested significant differences in
BP reductions among the patients randomized to telmisartan vs. valsartan therapy (MD for SBP, -2.04 mm
Hg; 95% CI, -2.80 to -1.28 mm Hg; P<0.00001; MD for DBP, -1.08 mm Hg; 95% CI, -1.55 to -0.62 mm Hg;
P<0.00001). When data from the monotherapy and combination therapy (with hydrochlorothiazide) trials
were pooled separately, telmisartan therapy was associated with a statistically significant difference in BP
reductions relative to valsartan therapy in both the monotherapy and combination therapy groups. In
conclusion, telmisartan therapy appears to reduce BP more than valsartan therapy in patients with
hypertension.

PMID:
23344134
[PubMed - indexed for MEDLINE]

Chin Med J (Engl). 2012 Jun;125(12):2200-4.

Different effects of telmisartan and valsartan on human aortic vascular
smooth muscle cell proliferation.
Wang L1, Zhao L, Zhang D, Chen JZ, Xue JL.

Author information

1
Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, China.
trichina2007@126.com

Abstract

BACKGROUND:

Vascular smooth muscle cell proliferation is an important process in the development of atherosclerosis and
is associated with other cellular processes in atherogenesis. Telmisartan is reported to have partial
peroxisome proliferator-activated receptor (PPAR)- activating properties and has been referred to as
selective PPAR modulators, but valsartan just blocks angiotensin II (AngII) type 1 (AT1) receptors. This study
aimed to compare the different effects of telmisartan and valsartan on human aortic smooth muscle cells
(HASMCs) proliferation.

METHODS:

Ability of telmisartan and valsartan to inhibit proliferation of HASMCs was evaluated by the Cell Counting Kit-
8 (CCK-8) in continuous cell culture. Whether the antiproliferative effects of telmisartan and valsartan depend
on their effects on AngII receptors or activating the peroxisome PPAR- was also investigated in this study.

RESULTS:

Telmisartan inhibited proliferation of HASMCs by 52.4% (P < 0.01) at the concentration of 25 mol/L and the
effect depended on the dose of telmisartan, but valsartan had little effect on HASMCs proliferation (P > 0.05)
and no dose response. When tested in cells stimulated with AngII, telmisartan had the same inhibition of
HASMCs by 59.2% (P < 0.05) and valsartan also inhibited it by 41.6% (P < 0.05). Telmisartan and valsartan
had the same effect on down-regulating AT1 receptor expression and telmisartan was superior to valsartan
up-regulating AngII type 2 (AT2) receptor expression. Antiproliferative effects of telmisartan were observed
when HASMCs were treated with the PPAR- antagonist GW9662 but antiproliferative effects of the PPAR-
activator pioglitazone were not observed.

CONCLUSIONS:

Telmisartan, but not valsartan, inhibits HASMCs proliferation and has dose-dependent response without
stimulation of AngII. AT2 receptor up-regulation of telmisartan contributes to its greater antiproliferative
effects than valsartan. Its PPAR- activation does not play a critical role in inhibiting HASMCs proliferation.

J Clin Hypertens (Greenwich). 2002 Jul-Aug;4(4 Suppl 1):26-31.

Comparison of telmisartan vs. valsartan in the treatment of mild to
moderate hypertension using ambulatory blood pressure monitoring.
Bakris G1.

Author information

Department of Preventive Medicine and Internal Medicine, Rush Hypertension/Clinical Research

1

Center, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL, USA.

Abstract

A prospective, randomized, open-label, blinded end-point trial compared telmisartan and valsartan for
treating mild to moderate hypertension. Efficacy for 24-hour control of blood pressure was assessed using
ambulatory blood pressure monitoring. Mean changes in diastolic blood pressure for the last 6 hours before
dosing and the nighttime period were significantly greater with telmisartan than with valsartan (p<0.01 for the
last 6 hours before dosing; p<0.05 for the nighttime period). Mean changes in systolic and diastolic blood
pressures for the 24-hour interval, the morning, and the daytime periods were significantly greater with
telmisartan than with valsartan (p<0.01). The incidence of all adverse events and the most common adverse
events were comparable for patients receiving telmisartan and patients receiving valsartan. Neither treatment
was associated with cough. These data suggest greater efficacy for telmisartan than valsartan in controlling
blood pressure throughout the 24-hour dosing interval, including the last 6 hours before dosing, and the two
agents were similarly well tolerated.

Copyright 2002 Le Jacq Communications, Inc.

Blood Press Monit. 2004 Aug;9(4):203-10.

Sustained antihypertensive activity of telmisartan compared with

valsartan.
Lacourcire Y1, Krzesinski JM, White WB, Davidai G, Schumacher H.

Author information

1
Hypertension Research Unit, Centre Hospitalier l'Universit de Quebec, Ste Foy, Quebec, Canada.
yves.lacourciere@crchul.ulaval.ca

Abstract

BACKGROUND:

Early morning blood pressure (BP) surge and 24 h mean BP are linked to target-organ damage and
cardiovascular events. Antihypertensive agents should sustain BP control, particularly in the last 6 h of the
dosing interval or if dosing is missed. The efficacies of the long half-life telmisartan compared with shorter
half-life valsartan in the last 6 h of the dosing interval following active treatment and during 24 h after a
missed dose were compared.

METHODS:

In two identically designed multinational, randomized, double-blind, forced-titration studies, hypertensive

patients (seated diastolic blood pressure (DBP), 95-109 mm Hg, 24 h mean ambulatory DBP, > or = 85 mm
Hg) received once-daily telmisartan (40- 80 mg) or valsartan (80-160 mg) for a total of 8 weeks; uptitration
occurred after 2 weeks low-dose treatment. After 4 weeks high-dose treatment, patients were given either 1
days double-blind active therapy or placebo (that is, missed dose). Following a further 2 weeks active
treatment, a cross-over was performed: patients who had previously received 1 days placebo received active
therapy and vice versa. At baseline and after the two active or missed doses, 24 h ambulatory BP monitoring
was performed. Data from the studies were pooled, as prospectively planned and analyzed using the intent-
to-treat population.

RESULTS:

After active therapy, last 6 h mean DBP was reduced by 7.6+/-7.9 mm Hg with telmisartan (n=447) compared
with 5.8+/-7.8 mm Hg with valsartan (n=430) (P=0.0044). Last 6 h mean systolic blood pressure (SBP) was
reduced by 11.1 mm Hg with telmisartan compared with 9.1 mm Hg with valsartan (P=0.0066). After a
missed dose, 24 h mean DBP was reduced by 7.2+/-6.5 mm Hg with telmisartan (n=437) compared with
5.5+/-6.2 mm Hg with valsartan (n=431) (P=0.0004). The reduction in 24 h mean SBP after a missed dose
was 10.7 mm Hg with telmisartan and 8.7 mm Hg with valsartan (P=0.0024). Absence of treatment-by-study
interaction indicated that pooling of studies was appropriate. All 24 hourly mean reductions in DBP and SBP
were greater for telmisartan than valsartan. Both treatments were well tolerated.

CONCLUSIONS:

Due to its longer half-life, telmisartan offers more sustained BP control, especially at the end of the dosing
period and provides sustained efficacy in poorly compliant patients in the event of a missed dose with a
statistical superiority compared with valsartan.

Diab Vasc Dis Res. 2013 Jan;10(1):93-6. doi: 10.1177/1479164112444640. Epub 2012 May 4.
The effects of telmisartan treatment on the abdominal fat depot in
patients with metabolic syndrome and essential hypertension:
Abdominal fat Depot Intervention Program of Okayama (ADIPO).
Murakami K1, Wada J, Ogawa D, Horiguchi CS, Miyoshi T, Sasaki M, Uchida HA, Nakamura Y, Makino H.

Author information

Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine,
1

Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.

Erratum in

Diab Vasc Dis Res. 2013 Nov;10(6):554.

Abstract

Telmisartan partially activates the peroxisome proliferator-activated receptor (PPAR), which may
ameliorate the accumulation of visceral adipose tissues and sensitise insulin action. Nineteen patients with
essential hypertension and metabolic syndrome were randomly assigned to receive 40 mg of telmisartan
(TELMI group) once daily or 80 mg of valsartan (VAL group) once daily for 24 weeks. The visceral fat area
(VFA) measured by computed tomography (CT) was significantly reduced from 150.415.5 to 127.716.7
cm(2) in the TELMI group (p=0.049). Although VFA was also reduced in the VAL group from 169.814.8 to
155.314.8 cm(2), the change was not significant (p=0.173). There were no significant changes in body
weight, body mass index (BMI), waist circumference, subdermal fat area (SFA), fasting plasma glucose, and
homeostasis model assessment of insulin resistance (HOMA-IR) in comparison to the baseline and follow-up
data in both groups. In conclusion, telmisartan may have a benefit in the reduction of visceral adipose tissues
in comparison to valsartan.