|
|
Home >
Health Conditions > Hypertension >
First Line Treatment"
First Line Treatment for Hypertension?
I feel that Micardis
(telmisartan) (ARBs) with Altace (ramipril) (an
ACE inhibitor, if two drugs are required),
are the way to go for the least side effects. I'm not a doctor,
just someone that's done a lot of reading and experimenting with
different blood pressure medications. Consult your doctor before
taking any supplement or medication. See:
- Con:
Popular
blood pressure pills linked to cancer - MSNBC, 6/13/10 -
"experts found a link between people taking
medicines known as angiotensin-receptor blockers ... one extra cancer case
will occur for every 105 people taking the medications for about four years
... The maker of the most-used drug in the study ... it had "internal safety
data" contradicting the Lancet study. According to studies run by the
pharmaceutical, there was no link between increased cancer risk and Micardis
... Scientists aren't sure why ARBs might raise the possibility of
developing cancer, though some animal studies suggest the medications help
produce new blood vessels, which would speed tumor growth" - Note:
New blood vessels can be a good thing
like with heart disease
(2)
and
PAD and increased
endurance so it may be sacrificing one thing for another.
-
Would VALUE Cancer Data
Negate Findings of Report? - Medscape, 6/25/10 -
"from a pathophysiological viewpoint, the finding in the meta-analysis
of increased cancer with ARBs in such a short time period--two to four
years--does not make sense: it takes around 10 years to develop lung and
other cancers from smoking, the hypertension doctors argue. Some said
they had discussed the findings with oncologists, who think the concept
is farfetched"
-
New Review
Reassures on ARB/Cancer Risk, But Questions Linger - Medscape,
11/30/10 - "A new meta-analysis of almost 325
000 individuals from 70 clinical trials has found no excess risk of
cancer or cancer death with any single antihypertensive drug ...
However, a statistically significant increase in cancers among patients
taking an ARB in combination with an ACE inhibitor of roughly 10% means
the authors "cannot rule out" an increased risk of cancer with the
combination of these two medications"
-
Common hypertension medications may reduce colorectal cancer risk - AHA,
7/6/20 - "those who took hypertension medications such
as ACE-i or ARBs had a 22% lower risk of developing colorectal cancer in the
subsequent three years"
-
Does an ARB a Day Keep
Dementia at Bay? - Medscape, 7/26/19 - "Multiple
studies show a statistical correlation between memory preservation and the use
of ARBs in patients with hypertension. And although no large-scale prospective,
randomized, controlled studies have defined the magnitude of cognitive decline
(or preservation) with ARBs relative to other antihypertensive drugs, it seems
prudent to start patients with hypertension or diabetes and a strong family
history of dementia on therapy with ARBs versus ACEIs or other antihypertensive
drugs. Unfortunately, the widespread recalls of popular ARBs contaminated with
the potential carcinogen N-methylnitrosobutyric acid has limited the number of
ARBs available for patients initiating or switching to this class. If this issue
is resolved, it seems likely that the popularity of ARBs over ACEIs will
continue to grow. However, any therapy should be individualized and tempered by
other compelling concurrent disease state considerations."
-
Anti
hypertensive drug use was associated with a decreased dementia risk -
Science Daily, 6/3/19 - "The use of angiotensin II
receptor blockers (odds ratios [ORs] ranging from 0.74 to 0.79), ACE inhibitors
(ORs ranging from 0.85 to 0.88), calcium channel blockers (ORs ranging from 0.82
to 0.89), and beta blockers (OR=0.88) was associated with a decrease in dementia
incidence. In patients treated with calcium channel blockers, increasing the
duration of treatment decreased the incidence of dementia"
-
Comparative effects of
ACE inhibitors and ARBs on response to a physical activity intervention in older
adults: results from Lifestyle Interventions for Elders (LIFE) study - J
Gerontol A Biol Sci Med Sci. 2019 May 9 - "Participants age 70-89 years were
randomized to a physical activity (PA) or health education (HE) intervention.
Outcomes included incident and persistent major mobility disability (MMD),
injurious falls, Short Physical Performance Battery (SPPB), and gait speed ...
Compared to ACEi users, ARB users had 28% lower risk (HR=0.72 [0.60-0.85]) of
incident MMD and 35% (HR=0.65 [0.52-0.82]) lower risk of persistent MMD while no
interaction between medication use and intervention was observed. Risk of
injurious falls and changes in SPPB or gait speed were not different between ARB
and ACEi users"
-
Observational Study of
Brain Atrophy and Cognitive Decline Comparing a Sample of Community-Dwelling
People Taking Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor
Blockers Over Time - J Alzheimers Dis. 2019 Mar 18 -
"The baseline association of ACEi and ARB use with total brain volume was
similar in both groups. However, those taking an ARB had a slower rate of brain
atrophy than those taking an ACEi (p = 0.031). Neither ACEi nor ARB use was
associated with baseline cognitive function or cognitive decline ... These
results support the theory that ARB may be preferable to ACEi to reduce brain
atrophy"
-
Time to Ditch ACE
Inhibitors for CVD? - Medscape, 4/5/18 - "There is
"little, if any, clinical reason" to use angiotensin-converting enzyme (ACE)
inhibitors for the treatment of hypertension or other cardiovascular indications
because angiotensin receptor blockers (ARBs) are just as effective with fewer
side effects"
-
Telmisartan:
A multifaceted antihypertension drug - Curr Med Res Opin. 2016 Apr 7:1-9 -
"Among various antihypertensive drugs, angiotensin
receptor blockers (ARBs) have an established efficacy and safety, making them a
favourable choice. However, all ARBs do not share the same qualities.
Telmisartan, beyond its inherent favourable effects of the ARB class, has shown
some additional promising pleiotropic effects. Indeed, telmisartan has been
associated with favourable outcomes regarding glucose metabolism, dyslipidaemia
as well as adipose tissue redistribution. As a result, hypertensive patients
with multiple CVD comorbidities may have additional benefits when treated with
telmisartan"
-
Effects of
telmisartan on fat distribution: a meta-analysis of randomized controlled trials
- Curr Med Res Opin. 2016 Mar 24:1-24 - "The findings
suggest that telmisartan affected fat distribution, inducing visceral fat
reduction, and thus, could be useful in hypertensive patients with
obesity/overweight, metabolic syndrome, or glucose intolerance"
-
New class of blood pressure meds as effective as old, analysis shows -
Washington Post, 1/4/16 - "The new analysis, published
in Mayo Clinic Proceedings on Monday, involves a second look at 106 randomized
trials with 254,301 patients that took place after 2000 and shows that during
this time period patient outcomes on the two medications were remarkably
similar. The one difference they found was that ARBs tend to be better tolerated
by patients, meaning that they have fewer side effects or result in fewer
adverse events. ACE inhibitors are poorly tolerated by many patients because
they can produce a bothersome dry cough, and some end up stopping medication as
a result ... The other piece of good news regarding the medications is that ACE
inhibitors, as well as many ARBs, are now generic -- meaning that the cost
difference is minimal"
-
TBI
triggers liver to produce protein tied to inflammation; hypertension drug blocks
it - Science Daily, 9/21/15 - "in an animal model,
brain injury produces an inflammatory response in the blood and body's organs,
especially the liver. The liver responds with increased production (up to a
thousand-fold) of a protein that ramps up inflammation in the brain, leading to
chronic inflammation, nerve cell death and reduced blood flow ... The
investigators also discovered that in mice, small doses of telmisartan, a
hypertension drug, blocked production of one of the molecules in the protein's
biological pathway, leading to substantial reduction in inflammation. The brain
can then possibly heal"
-
Blood Pressure Meds May Cut Alzheimer’s Risk - WebMD, 9/14/15 -
"People with early thinking and memory issues who took
an ACE inhibitor or an ARB medication for their high blood pressure were less
likely to get Alzheimer’s disease than those on other BP drugs ... A 2009 study
also found that people taking ACE inhibitors that were crossing the brain
barrier had a 65% lower risk of getting the disease compared to people taking
other kinds of BP drugs"
-
Prevention
of metabolic disorders with telmisartan and indapamide in a Chinese population
with high-normal blood pressure - Hypertens Res. 2014 Oct 2 -
"The acquisition cost for telmisartan was ~1.86 times
higher than for indapamide for a similar antihypertensive effect. The
intervention for high-normal blood pressure with telmisartan and indapamide
appeared to be feasible and reduced the risk of metabolic syndrome. Telmisartan
was more effective, whereas indapamide had better pharmacoeconomic benefits"
-
Telmisartan
Exerts Sustained Blood Pressure Control and Reduces Blood Pressure Variability
in Metabolic Syndrome by Inhibiting Sympathetic Activity - Am J Hypertens.
2014 May 28 - "the magnitudes and durations of BP
control differ across ARBs ... Telmisartan exerted a longer-lasting BP-lowering
effect and greater attenuation of BP variability in SHRcp than valsartan.
Telmisartan decreased low frequency power of systolic BP and increased
spontaneous baroreflex gain in SHRcp during both the dark and light periods more
than valsartan. Telmisartan reduced 24-hour urinary norepinephrine excretion
more than valsartan"
-
Angiotensin-Converting
Enzyme Inhibitor Therapy and Colorectal Cancer Risk - J Natl Cancer Inst.
2014 Jan 15 - "A nested case-control study was conducted
using EPIC's General Practice Research Database (1987-2002) ... The adjusted
odds ratios (ORs) of CRC were 0.84 (95% confidence interval [CI] = 0.72 to 0.98;
P = .03) for or more years of ACE-I/ARB therapy and 0.75 (95% CI = 0.58 to 0.97;
P = .03) for 5 or more years of exposure. The strength of this association
increased with high-dose exposure (OR = 0.53; 95% CI = 0.35 to 0.79; P = .003
for ≥3 years of high-dose exposure). Among patients receiving antihypertensive
medications, the association with long-term therapy was no longer statistically
significant for ≥5 years), but the benefit of high-dose therapy remained (OR =
0.59; 95% CI = 0.39 to 0.89; P = .01 for ≥3 years of high-dose exposure)"
-
Angiotension
receptor blockers reduce the risk of dementia - J Hypertens. 2014 Jan 8 -
"a population-based cohort study with data from the
Taiwan National Health Insurance Research Database. A total of 24 531 matching
pairs (1 : 1) of ARB-exposed and non-ARB-exposed patients were included. Each
patient was individually tracked from 1997 to 2009 to identify incident cases of
dementia (onset in 1999 or later) ... The multivariate-adjusted hazard ratios
for dementia, Alzheimer's disease and vascular dementia were 0.54 (95% CI
0.51-0.59), 0.53 (95% CI 0.43-0.64) and 0.63 (95% CI 0.54-0.73) for patients
with ARB treatments, respectively. In terms of cumulative dosage, patients with
more than 1460 defined daily dose of ARBs had less risk than those patients with
less than 1460 defined daily dose (hazard ratio 0.37 vs. 0.61; P < 0.05) ...
These results suggest that ARB may be associated with a reduced risk of dementia
in high vascular-risk individuals. Patients exposed to ARBs for higher
cumulative doses experienced more protection from dementia and the subtypes"
-
ACE Inhibitors, ARBs Lower
AF Risk in Hypertension - Medscape, 1/8/14 -
"Compared with a beta-blocker and diuretic, the use of an ACE inhibitor reduced
the incidence of atrial fibrillation 88% and 49%, respectively. There was no
reduction in the incidence of atrial fibrillation when those treated with ACE
inhibitors were compared with those who received calcium-channel antagonists.
When the same analysis was repeated with ARBs, ARB use reduced the risk of
atrial fibrillation 90% and 57%, respectively, when compared with beta-blockers
and diuretics. Similarly, there was no reduction in risk when ARBs were compared
with calcium-channel antagonists ... When the ARB-treated patients were compared
with those who received an ACE inhibitor, the risk of atrial fibrillation was
reduced 32%. None of the five medication classes tested differed with regard to
the risk of stroke"
-
Clear
association between ACE inhibitors, acute kidney injury - Science Daily,
11/6/13 -
"ACE inhibitors and related drugs known as angiotensin
receptor antagonists (ARAs or 'sartans') are the second most frequently
prescribed medicines in UK clinical practice, and are used to treat common
conditions such as high blood pressure, heart disease and kidney problems,
especially in people with diabetes ... They compared the admission rates for
acute kidney injury to English hospitals with the prescribing rates of ACE
inhibitors and ARAs. From 2007/8 to 2010/11, there was a 52 per cent increase in
acute kidney injury admissions. During this same period of time, there was an
increase in the number of prescriptions for ACE inhibitors and ARAs issued by GP
surgeries by 16 per cent ... The results show a clear association between the
increase in prescriptions and the increase in hospital admissions" -
Note: It sounds like they call ARBs ARAs in England. From what I've read, I
don't think that kidney problem exists with telmisartan (an ARB).
-
Telmisartan
Reduces Mortality and Left Ventricular Hypertrophy With Sympathoinhibition in
Rats with Hypertension and Heart Failure - Am J Hypertens. 2013 Oct 5 -
"telmisartan (TLM) ... reactive oxygen species (ROS) ...
rostral ventrolateral medulla (RVLM) ... stroke-prone spontaneously hypertensive
rats (SHRSPs) ... candesartan cilexetil (CAN) ... Compared with the control
group, TLM improved survival to a greater extent than CAN. At 4 weeks after
treatment, ROS in the RVLM and uNE were significantly lower in the TLM-treated
group than in the CAN-treated group, despite the similar depressor effects. At 8
weeks after the treatments, LVH and LVEDP were attenuated in the TLM-treated
group compared with the CAN-treated group"
-
Two
Blood Pressure Drugs Linked to Lower Risk of Heart Disease in Diabetics -
Science Daily, 7/8/13 - "there is some evidence from
small trials that telmisartan has slightly different properties than other
angiotensin-receptor blockers and may improve cardiovascular health ...
telmisartan and valsartan were associated with a significantly lower risk of
hospitalization for heart attack, stroke or heart failure compared with other
angiotensin-receptor blockers ... at clinically attainable serum concentrations,
telmisartan is unique among these drugs in its ability to structurally interact
with and activate the PPARg receptor, a ligand-activated transcription factor
that regulates lipid metabolism and insulin sensitivity"
-
A
meta-analysis of randomized trials of telmisartan versus losartan for reduction
of ambulatory blood pressure - Hypertens Res. 2013 Aug 15 -
"MEDLINE, EMBASE and the Cochrane Central Register of
Controlled Trials were searched through July 2012 ... telmisartan therapy
appears to reduce ambulatory BP more than losartan therapy in patients with
hypertension"
-
Antihypertensive drugs decrease risk of Alzheimer disease: Ginkgo Evaluation of
Memory Study - Neurology. 2013 Aug 2 - "Secondary
longitudinal data analysis of the Ginkgo Evaluation of Memory Study in older
adults at least 75 years of age with normal cognition (n = 1,928) or MCI (n =
320) over a median 6.1-year period ... Hazard ratio for incident AD dementia
among participants with normal cognition was 0.51 in diuretic (95% confidence
interval [CI] 0.31-0.82), 0.31 in ARB (95% CI 0.14-0.68), 0.50 in ACE-I (95% CI
0.29-0.83), 0.62 in CCB (95% CI 0.35-1.09), and 0.58 in BB (95% CI 0.36-0.93)
users and was not significantly altered when mean systolic blood pressure was
above 140 mm Hg" - Note: Sounds like the ARB's left the others in the
dust.
-
Effects of
telmisartan therapy on interleukin-6 and tumor necrosis factor-alpha levels: a
meta-analysis of randomized controlled trials - Hypertens Res. 2012 Dec 13 -
"A recent meta-analysis of randomized head-to-head
trials suggests that therapy with telmisartan, an angiotensin II receptor
blocker (ARB) and partial agonist of peroxisome proliferator-activated
receptor-gamma, may increase adiponectin levels more strongly than other ARB
therapies. Therefore, telmisartan would be expected to reduce interleukin-6
(IL-6) or tumor necrosis factor-alpha (TNF-α) ... based on a meta-analysis of
nine randomized controlled trials, telmisartan therapy is likely effective in
reducing IL-6 and TNF-α levels"
-
Telmisartan
at 80 mg/Day Increases High-Molecular-Weight Adiponectin Levels and Improves
Insulin Resistance in Diabetic Patients - Adv Ther. 2012 Jul 20 -
"patients with type 2 diabetes and hypertension with
poor control of blood pressure by 40 mg/day telmisartan were randomly assigned
into the telmisartan 80 mg/day (Tel80) group (dose increase from 40 to 80
mg/day) or the telmisartan 40 mg + amlodipine 5 mg (Tel40 + Aml5) group ...
Although the antihypertensive effects of the two doses of telmisartan were
similar, a significant increase in HMW adiponectin levels was noted only in the
Tel80 group"
-
Prophylactic
treatment with telmisartan induces tissue-specific gene modulation favoring
normal glucose homeostasis in Cohen-Rosenthal diabetic hypertensive rats -
Metabolism. 2011 Aug 4 - "Telmisartan blunted the
development of hypertension, insulin resistance, and diabetes in prediabetic
Cohen-Rosenthal diabetic hypertensive rats through pleiotropic activity,
involving specific gene regulation of target organs"
-
Which is the preferred
angiotensin II receptor blocker-based combination therapy for blood pressure
control in hypertensive patients with diabetic and non-diabetic renal
impairment? - Cardiovasc Diabetol. 2012 Apr 10;11(1):32 -
"Telmisartan, a long-acting ARB with preferential
pharmacodynamic profile compared with several other ARBs, and the only ARB with
an indication for the prevention of CV disease progression, is available in two
SPC formulations, telmisartan/HCTZ and telmisartan/amlodipine"
-
Effect of
telmisartan vs. ramipril on 'dipping' status and blood pressure variability:
pooled analysis of the PRISMA studies - Hypertens Res. 2013 Sep 19 -
"dipper status (extreme dippers, dippers, non-dippers,
risers/reverse dippers) ... After 14 weeks' treatment, telmisartan had a greater
systolic BP (SBP) reduction and higher smoothness index in all four dipper
groups compared with ramipril. In addition, the tendency toward dipping was
significantly higher in patients treated with) telmisartan than ramipril
(P=0.032; odds ratio for telmisartan vs. ramipril: 1.27 (95% confidence
interval: 1.102-1.58)). In patients with an early morning SBP surge 35 mm Hg,
telmisartan treatment was associated with significantly greater reductions from
baseline in the night-time low mean, early morning mean and early morning SBP
surge compared with ramipril (P=0.026, P<0.0001 and P=0.0006, respectively). In
this retrospective analysis, telmisartan was shown to normalize the circadian BP
pattern to a dipper profile in a larger proportion of patients than ramipril,
and reduce early-morning SBP surge in high-risk patients, indicative of a
cardioprotective effect"
-
Systematic
review of the effect of telmisartan on insulin sensitivity in hypertensive
patients with insulin resistance or diabetes - J Clin Pharm Ther. 2011 Aug
17 - "Telmisartan is an angiotensin receptor blocker
(ARB) originally developed for the treatment of hypertension. It can also
partially activate peroxisome proliferator-activated receptor (PPAR)-γ, which
may improve insulin sensitivity. This effect may prove useful in hypertensive
patients with insulin resistance or diabetes mellitus. Such activity is more
marked than that observed with other ARBs ... Eight trials involving a total of
763 patients met the inclusion criteria. Telmisartan was superior to other ARBs
in reducing FPG level (mean difference, -8.63 mg/dL; 95% CI -12.29 mg/dL to
-4.98 mg/dL; P < 0.00001) and increasing adiponectin level (mean difference,
0.93 μg/dL; 95% CI 0.28 μg/dL to 1.59 μg/dL; P = 0.005). At 80 mg dose,
telmisartan may reduce FPI level and HOMA-IR. What is new and Conclusions: The
available evidence suggests a beneficial effect of telmisartan in improving
insulin sensitivity in hypertensive patients with insulin resistance or diabetes
as demonstrated by the decrease in FPG and increase in adiponectin levels. The
effect in decreasing FPG was greater with 80 mg dose than with the 40 mg dose.
FPI and insulin resistance may be improved with 80 mg of telmisartan"
-
Reduction of
circulating superoxide dismutase activity in type 2 diabetic patients with
microalbuminuria and its modulation by telmisartan therapy - Hypertens Res.
2011 Aug 4 - "Interestingly, the telmisartan treatment
not only reduced the circulating levels of two oxidative stress markers,
8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine (NT), but also enhanced
serum SOD activity. Notably, a significant correlation was observed between the
increase in serum SOD activity and the reduction in albuminuria. We further
compared the anti-oxidative effect of telmisartan with that of losartan, another
member of the ARB class, by implementing an 8-week interval crossover treatment
with these ARBs in another 12 microalbuminuric type 2 diabetic patients. The
patients showed higher serum SOD activity, and lower circulating levels of
8-OHdG and NT, during treatment with telmisartan than with losartan. These
results suggest that telmisartan has a more potent antioxidative effect through
its ability to enhance SOD activity in type 2 diabetic patients with
microalbuminuria"
-
Effects of
telmisartan and losartan on cardiovascular protection in Japanese hypertensive
patients - Hypertens Res. 2011 Jul 28 - "A total of
58 patients were enrolled in the present trial and the follow-up period was 1
year. There were no significant differences in blood pressure (BP) levels
between the telmisartan group and the losartan group throughout the trial. The
percentage of the patients treated with ARB monotherapy was significantly higher
in the telmisartan group compared with the losartan group. In addition, the
progression of intima-media thickness of common carotid artery was significantly
inhibited in the telmisartan group compared with the losartan group. Neither
group experienced significant changes in cardiac function and LV mass index.
There were no differences between the groups with respect to changes in
surrogate markers such as serum adiponectin, creatinine, homeostasis model
assessment index, plasminogen activator inhibitor-1 and high sensitivity
C-reactive protein. Although BP levels were equal and well controlled in both
groups, telmisartan showed more protective vascular effects than losartan"
- See telmisartan at
OffshoreRx1.com.
-
Influence of
telmisartan on insulin response after glucose loading in obese patients with
hypertension: ARB Trial of hypertension in obese patients with hyperinsulinemia
assessed by oral glucose tolerance test (ATHLETE) - Adv Ther. 2011 Jul 6 -
"In patients with hypertension and obesity showing
insulin resistance, treatment with telmisartan significantly improved the
hyperinsulin response to glucose loading. Telmisartan may therefore be
beneficial in these patients" - See telmisartan at
OffshoreRx1.com.
-
Telmisartan
for the management of patients at high cardiovascular risk - Curr Med Res
Opin. 2011 Jun 30 - "To date, telmisartan is the only
ARB indicated to reduce CV morbidity in a broad CV high-risk population"
- See telmisartan at
OffshoreRx1.com.
-
Value of
Angiotensin receptor blocker therapy in diabetes - J Clin Hypertens
(Greenwich). 2011 Apr;13(4):290-5 - "There are more
clinical trials investigating angiotensin receptor blockers (ARBs) in diabetes
than any other drug class, ranging from early "prevention" trials to the
treatment of individuals with advanced organ damage. In its earliest
manifestations, visceral adiposity predisposes to hypertension and hyperglycemia
(metabolic syndrome). In these individuals, ARB therapy delays the progression
to chronic hypertension and may also delay the progression to overt diabetes.
Based on the increased cardiovascular disease risk of the metabolic syndrome,
which is similar to stage 1 hypertension, both lifestyle modification and ARB
therapy are justifiable. ARB therapy has also been found to delay the onset of
microalbuminuria and retinopathy. In established diabetic nephropathy, ARB
therapy is recommended as a standard alternative to angiotensin-converting
enzyme inhibition to reduce macroalbuminuria and delay the progression to
end-stage disease. Finally, large trials in ischemic heart disease, heart
failure, and stroke have demonstrated clear benefits of ARB therapy. Because
ARBs have side effect rates equal to placebo and far lower than any other
antihypertensive drug class, the benefit/risk ratio is highly favorable across
the entire spectrum of diabetic disease. Thus, ARB therapy is a highly
attractive alternative for individuals at any stage of diabetes and with any
pattern of complications"
-
Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers and
Diabetes: A Meta-Analysis of Placebo-Controlled Clinical Trials - Am J
Hypertens. 2011 Feb 17 - "new onset diabetes (NOD) ...
Over an average follow-up of 4.0 +/- 1.0 years, there were 1,284/15,142 (8.5%)
cases of NOD in active-treated and 1,411/15,130 (9.3%) cases in placebo-treated
patients in the ACE inhibitor trials, and 2,330/18,756 (12.4%) cases in
active-treated and 2,669/18,800 (14.2%) cases in placebo-treated patients in the
ARB trials. Overall, active therapy reduced NOD compared to placebo (odds ratio
(OR) 95%, confidence interval (CI): 0.8 (0.8-0.9); P < 0.01). Both ACE
inhibitors (OR 95%, CI: 0.8 (0.7-1.0); P = 0.07) and ARBs (OR 95%, CI: 0.8
(0.8-0.9); P < 0.01) reduced NOD as compared to placebo. Active treatment
reduced CV mortality (OR 95%, CI: 0.9 (0.8-1.0); P < 0.01) and had a favorable
impact on non-CV mortality (OR 95%, CI: 0.7 (0.9-1.0); P = 0.2) as compared to
placebo.ConclusionsOur findings demonstrated that ACE inhibitors or ARBs should
be preferred in patients with clinical conditions that may increase risk of NOD,
since these drugs reduced NOD incidence. In addition, these drugs have favorable
effects on CV and non-CV mortality in high CV risk patients"
-
Inhibition
of intestinal cholesterol absorption might explain cholesterol-lowering effect
of telmisartan - J Clin Pharm Ther. 2011 Feb;36(1):103-10 -
"Recently, it has been demonstrated that telmisartan
also lowers the levels of total cholesterol and low-density lipoprotein (LDL)
cholesterol levels ... Our results suggest that the cholesterol-lowering effect
of telmisartan might be caused by inhibition of cholesterol absorption, whereas
that of statins is by inhibition of cholesterol synthesis. If confirmed,
co-treatment with the two agents may be useful for synergistically lowering
cholesterol in hypertensive patients"
-
Telmisartan Provides Better Renal Protection Than Valsartan in a Rat Model
of Metabolic Syndrome - Am J Hypertens. 2011 Mar 17 -
"spontaneously hypertensive rats (SHR) ... SHR were
fed either normal (SHR-NF, 7% fat) or high fat (SHR-HF, 36% fat) diet and
treated with an ARB for 10 weeks.ResultsBlood pressure was similar between
SHR-NF (190 +/- 3 mm Hg) and SHR-HF (192 +/- 4 mm Hg) at the end of the 10
week period. Telmisartan and valsartan decreased blood pressure to similar
extents in SHR-NF and SHR-HF groups. Body weight was significantly higher in
SHR-HF (368 +/- 5 g) compared to SHR-NF (328 +/- 7 g). Telmisartan but not
valsartan significantly reduced the body weight gain in SHR-HF. Telmisartan
was also more effective than valsartan in improving glycemic and lipid
status in SHR-HF. Monocyte chemoattractant protein-1 (MCP-1), an
inflammatory marker, was higher in SHR-HF (24 +/- 2 ng/d) compared to SHR-NF
(14 +/- 5 ng/d). Telmisartan reduced MCP-1 excretion in both SHR-HF and
SHR-NF to a greater extent than valsartan. An indicator of renal injury,
urinary albumin excretion increased to 85 +/- 8 mg/d in SHR-HF compared to
54 +/- 9 mg/d in SHR-NF. Telmisartan (23 +/- 5 mg/d) was more effective than
valsartan (45 +/- 3 mg/d) in lowering urinary albumin excretion in SHR-HF.
Moreover, telmisartan reduced glomerular damage to a greater extent than
valsartan in the SHR-HF.ConclusionsCollectively, our data demonstrate that
telmisartan was more effective than valsartan in reducing body weight gain,
renal inflammation, and renal injury in a rat model of cardiometabolic
syndrome"
-
Clinical
effectiveness of telmisartan alone or in combination therapy for controlling
blood pressure and vascular risk in the elderly - Clin Interv Aging.
2010 Dec 3;5:403-16 - "Two large clinical trials,
ONTARGET (Ongoing Telmisartan Alone in combination with Ramipril Global
Endpoint Trial) and TRANSCEND (Telmisartan Randomized AssessmeNt Study in
ACE-I iNtolerant subjects with cardiovascular disease) have assessed the
cardioprotective and antidiabetic effects of telmisartan. The collective
data suggest that telmisartan is a promising drug for controlling
hypertension and reducing vascular risk in high-risk elderly patients with
new-onset diabetes"
-
Molecular 'switch' contributes to cellular aging process: Discovery suggests
new treatments for metabolic diseases - Science Daily, 11/30/10 -
"in older animals SMRT acts like a "switch," turning
off the protective cellular activities of proteins known as peroxisome
proliferator-activated receptors (PPARs). PPARs help regulate genes that
promote fat burning to maintain lipid (blood fat) balance and reduce
oxidative stress. The researchers were able to reduce the negative effects
of oxidative stress by giving antioxidants or drugs known to turn the
protective activities of PPARs back on ... PPAR drugs have been used to
increase insulin sensitivity and lower blood lipid levels ... we believe
SMRT is one of the key players that causes age-dependent decline in
mitochondrial function by blocking PPAR activity, and we've found a way to
boost the body's ability to better handle metabolic and oxidative stress"
- Note: There are several PARR receptor activators such as the blood
pressure drug telmisartan and the diabetes medication
Actos (some doctors have
criticized me for years for taking it for anti-aging). I've started a
webpage on PPARs. When I get a chance I'll
search my site and put the articles on it.
-
Telmisartan: a Different Angiotensin II Receptor Blocker Protecting a
Different Population?
- J Int Med Res. 2009;37(6):1662-1679 - "Telmisartan
has a unique profile among ARBs, with a high affinity for the angiotensin II
type 1 receptor, a long duration of receptor binding, a high lipophilicity
and a long plasma half life. This leads to sustained and powerful blood
pressure lowering when compared with the first marketed ARBs, such as
losartan and valsartan. Some pharmacological properties of telmisartan
clearly distinguish it from other members of the ARB class and may
contribute to the clinical effects seen with telmisartan. A class effect for
ARBs cannot be assumed. To date, telmisartan is the only ARB that has been
shown to reduce cardiovascular risk in at-risk cardiovascular patients"
- See telmisartan at
OffshoreRx1.com.
-
Patient Compliance with Antihypertensive Therapy Appears Longer for Those
Taking Angiotensin II Antagonists - Doctor's Guide, 7/18/02 -
"The researchers found that the class of drug had a statistically
significant effect on the patients' persistence of compliance. Angiotensin
II antagonists had the highest rate of persistence followed by ACE
inhibitors, calcium channel blockers, beta-blockers, and diuretics"
-
Telmisartan
Prevents Weight Gain and Obesity Through Activation of Peroxisome
Proliferator-Activated Receptor-{delta}-Dependent Pathways - Hypertension.
2010 Feb 22 - "long-term administration of telmisartan
significantly reduced visceral fat and prevented high-fat diet-induced obesity
in wild-type mice and hypertensive rats but not in PPAR-delta knockout mice.
Administration of telmisartan did not influence food intake in mice ... We
conclude that telmisartan prevents adipogenesis and weight gain through
activation of PPAR-delta-dependent lipolytic pathways and energy uncoupling in
several tissues"
-
Telmisartan versus angiotension-converting enzyme inhibitors in the
treatment of hypertension: a meta-analysis of randomized controlled trials
- J Hum Hypertens. 2008 Nov 6 - "Telmisartan had
fewer drug-related adverse events than enalapril (RR 0.57, 95% CI
0.44-0.74), ramipril (RR 0.44, 95% CI 0.26-0.75), lisinopril (RR 0.70, 95%
CI 0.56-0.89) and perindopril (RR 0.52, 95% CI 0.28-0.98). The meta-analysis
indicates that telmisartan provides a superior BP control to ACEIs
(enalapril, ramipril and perindopril) and has fewer drug-related adverse
events and better tolerability in hypertensive patients"
-
Hypertension Drugs May Cut Alzheimer's Risk - WebMD, 1/12/10 -
"The patients taking an angiotensin receptor blocker had
a 19% lower risk of developing dementia compared to those taking lisinopril and
a 24% lower risk compared to use of other blood pressure/heart medications.
People taking both an ACE inhibitor and an angiotensin receptor blocker, which
both target the angiotensin system, had a 46% lower risk of dementia compared
with those taking other medications"
-
Neuroendocrine characterization and anorexigenic effects of telmisartan in diet-
and glitazone-induced weight gain - Metabolism. 2009 Sep 28 -
"Telmisartan prevents weight gain and decreases food
intake in models of obesity and in glitazone-treated rodents"
-
Effects of
angiotensin II receptor blockers on diabetic nephropathy - J Hypertens. 2009
Jul;27 Suppl 5:S15-21 - "Key beneficial effects of ARBs
and ACE inhibitors throughout the kidney disease continuum are primarily
explained by blood pressure lowering effects and partially by their direct
blockade of angiotensin II. Recent studies have shown that telmisartan, an ARB
with high lipophilicity and the longest half-life compared with other ARBs,
provides benefits on markers of cardiovascular risk, that is, microalbuminuria
and slowing of early-stage nephropathy"
-
Telmisartan ameliorates hyperglycemia and metabolic profile in nonobese
Cohen-Rosenthal diabetic hypertensive rats via peroxisome proliferator
activator receptor-gamma activation - Metabolism. 2010 Jan 12 -
"adiponectin was significantly (60%, P < .01)
increased by telmisartan ... The telmisartan-induced increase in adiponectin
was most probably associated with a decrease in glucose and tumor necrosis
factor alpha levels. Therefore, in addition to its hypotensive effect,
telmisartan demonstrated beneficial thiazolidinedione-like effects"
-
24-Hour BP Control
Better With Telmisartan Than With Ramipril - Medscape, 9/10/09
-
Clinical
evidence from ONTARGET: the value of an angiotensin II receptor blocker and
an angiotensin-converting enzyme inhibitor - J Hypertens. 2009 Jul;27
Suppl 5:S23-9 - "Telmisartan was better tolerated
than ramipril in this high-risk population: notably, the incidence of cough
and angioedema was significantly lower with telmisartan alone. Thus,
telmisartan provides comparable efficacy to ramipril with less adverse
events, which may encourage patient compliance"
-
Achieving blood pressure goals: should angiotensin II receptor blockers
become first-line treatment in hypertension? - J Hypertens. 2009 Jul;27
Suppl 5:S9-14 - "Recently, the ONgoing Telmisartan
Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET)
study established that telmisartan reduces morbidity and mortality in a
broad cross-section of patients at high risk for heart and vascular events,
to an extent similar to that of the angiotensin-converting enzyme inhibitor
ramipril. In addition, ONTARGET demonstrated that telmisartan is somewhat
better tolerated than ramipril. Attributes such as effective blood pressure
lowering, tolerability and convincing outcomes data mean that ARBs satisfy
the requirements for first-line antihypertensive agents"
-
Cognitive Deficit in Amyloid-{beta}-Injected Mice Was Improved by
Pretreatment With a Low Dose of Telmisartan Partly Because of Peroxisome
Proliferator-Activated Receptor-{gamma} Activation - Hypertension. 2009
Jul 27 - "Taken together, our findings suggest that
even a low dose of telmisartan had a preventive effect on cognitive decline
in an Alzheimer disease mouse model, partly because of PPAR-gamma
activation"
-
New
Blood Pressure Medication Has Fewer Side Effects, Global Study Suggests
- Science Daily, 3/31/08 - "The study found a new
drug telmisartan is as effective as the popular drug ramipril in reducing
cardiovascular death in high risk patients and it has fewer side effects"
- See telmisartan at
OffshoreRx1.com.
-
Telmisartan: The ACE of ARBs? - Sharma 47 (5): 822 -- Hypertension,
3/27/06 - "telmisartan also reduced weight gain,
increased total energy expenditure, and increased expression of key
mitochondrial enzymes (cyclooxygenase-1 and mitochondrial transcription
factor A) in skeletal muscle"
-
Blood Pressure
Linked to Erectile Dysfunction - WebMD, 5/16/05 -
"Men on older high blood pressure medications
(diuretics, beta-blockers) had higher rates and more severe erectile
dysfunction than men on newer medications (calcium antagonists, ACE
inhibitors, angiotensin II receptor blockers)"
-
Evidence-Based
Treatment of Hypertension: What's the Role of Angiotensin II Receptor
Blockers? - Medscape, 4/8/05 - "The
ARBs
themselves are very well tolerated and are not associated with the
side-effects known to cause compliance problems with beta blockers, ACE
inhibitors and calcium channel blockers such as impotence, dry cough and
peripheral oedema"
-
Blood
pressure drug reverses sexual dysfunction - Life Extension Magazine,
7/01 -
"the active ingredient in Cozaar and Hyaar (losartan)
can significantly improve sex lives of men who suffer from sexual
dysfunction"
- Does this pertain to other ARBs? The following indicates that it might:
-
Antihypertensive efficacy of telmisartan vs ramipril over the 24-h dosing
period, including the critical early morning hours: a pooled analysis of the
PRISMA I and II randomized trials - J Hum Hypertens. 2009 Feb 19 -
"The adjusted mean treatment differences in the last
6-h mean ambulatory SBP/DBP were -5.8/-4.2 mm Hg after 8 weeks and -4.1/-3.0 mm
Hg after 14 weeks, in favour of telmisartan (P<0.0001 for all four comparisons).
Secondary end point results, including the mean 24-h ambulatory BP monitoring,
day- and night-time BP and 24-h BP load, also significantly favoured telmisartan
(P<0.0001). Both treatments were well tolerated; adverse events, including
cough, were less common with telmisartan. These findings suggest that
telmisartan is more effective than ramipril throughout the 24-h period and
during the EMBPS; this may be attributable to telmisartan's long duration of
effect, which is sustained throughout the 24-h dosing period"
-
Telmisartan Increases the Permeability of Endothelial Cells through Zonula
Occludens-1 - Biol Pharm Bull. 2009 Mar;32(3):416-20 -
"telmisartan but not valsartan downregulated ZO-1
mRNA and protein levels, disrupted the distribution of ZO-1 in cultured
endothelial cells, and increased the permeability of endothelial cells in a
dose-dependent manner ... telmisartan disrupts the continuous pericellular
distribution of ZO-1, downregulates the expression of ZO-1 in endothelial
cells, and increases the permeability of endothelial cells at least partly
through PI3K and the peroxisome proliferator-activated receptor
gamma-dependent pathway"
-
Effects of telmisartan on adiponectin levels and body weight in hypertensive
patients with glucose intolerance - Metabolism. 2008 Oct;57(10):1473-8 -
"Telmisartan decreased body weight while increasing
serum adiponectin levels in hypertensive patients with glucose intolerance.
Candesartan did not achieve similar improvements in these patients. Among
ARBs, telmisartan may have a larger impact on obesity-related diseases that
can lead to cardiovascular disorders"
-
Telmisartan induces proliferation of human endothelial progenitor cells via
PPARgamma-dependent PI3K/Akt pathway - Atherosclerosis. 2008 Dec 31 -
"since endothelial progenitor cells (EPCs) are
thought to play a critical role in ischemic diseases, we investigated
effects of telmisartan on proliferation of EPCs ... These findings suggest
that telmisartan might contribute to endothelial integrity and
vasculogenesis in ischemic regions by increasing numbers of EPCs"
-
Effects
of Telmisartan and Ramipril on Adiponectin and Blood Pressure in Patients
with Type 2 Diabetes - Am J Hypertens. 2008 Oct 30 -
"There was a significant increase in adiponectin
levels in the telmisartan (0.68 (95% confidence interval (CI), 0.27 to 1.10)
microg/ml, P < 0.01) but not in the ramipril group" - See my
adiponectin page. An increase in
adiponectin is a good thing.
-
Angiotensin II type 2 receptor blockade increases bone mass - J Biol
Chem. 2008 Nov 11 - "Treatment with AT2 receptor
blocker significantly enhanced the levels of bone mass and this effect was
based on the enhancement of osteoblastic activity as well as the suppression
of osteoclastic activity in vivo"
-
Telmisartan improves insulin resistance in high renin nonmodulating
salt-sensitive hypertensives - J Hypertens. 2008 Dec;26(12):2393-8 -
"Nonmodulating (NMHT) is a high-renin subtype of
salt sensitive hypertension, which additionally develops insulin resistance
and oxidative stress. Conversely, modulating hypertensives (MHT) normally
regulates renal hemodynamics after high sodium intake without metabolic
impairment ... In NMHT, telmisartan, after 3 months treatment, significantly
reduced fasting and 120 min insulinemia (fasting: 8.4 +/- 2, 120 min: 25 +/-
10 muU%; P < 0.01) compared either to basal values or ramipril treatment.
Similarly, only in NMHT, compared with basal values and ramipril treatment,
telmisartan improved the HOMA-IR index in both MHT (2.76 +/- 0.16 to 2.24
+/- 0.18, P < 0.05) and NMHT (from: 4.4 +/- 1 to 2.3 +/- 0.7) and
triglyceride plasma levels (MHT: from 139 +/- 1.85 to 122 +/- 2.4 mg%, P <
0.05; NMHT: from: 223 +/- 12 to 146 +/- 10 mg%, P < 0.01). Finally, highly
sensitive C-protein-reactive protein values were higher in NMHT (0.33 +/-
0.07 mg.dl) than in MHT (0.14 +/- 0.06 mg.dl; P < 0.01). Both treatments
reduced highly sensitive C-protein-reactive protein in NMHT. (ramipril from
0.32 +/- 0.05 mg.dl to 0.26 +/- 0.06 m.dl (P < 0.05) and telmisartan from
0.34 +/- 0.05+/- to 0.20 +/- 0.05 mg.dl (P < 0.01). CONCLUSION: Our data
suggest that the improvement of the insulin sensitivity by telmisartan,
instead of a similar effect on blood pressure shown by both drugs, could be
ascribed to the PPAR agonistic action of telmisartan. This opens an
interesting therapeutic approach for patients with hypertension and altered
glycemic metabolism"
-
Medication To Lower Blood Pressure Reduces Outcome Of Cardiovascular Death,
Heart Attack Or Stroke, Study Suggests - Science Daily, 8/31/08 -
"Telmisartan reduced the outcome of cardiovascular
death, heart attack, stroke or hospitalization for heart failure by a
relative eight per cent ... However, when the outcome included
cardiovascular death, heart attack or stroke (and not hospitalization for
heart failure), telmisartan reduced that outcome by a significant 13 per
cent"
-
The angiotensin II
receptor blocker telmisartan improves insulin resistance and has beneficial
effects in hypertensive patients with type 2 diabetes and poor glycemic
control - Diabetes Res Clin Pract. 2008 Aug 8 -
"The telmisartan significantly improved HOMA-IR in hypertensive patients and
also significantly decreased HbA1c in type 2 diabetic patients especially in
the patients with poor glycemic control (HbA1c>==8.0%). These results
indicate that telmisartan improves insulin resistance and gives beneficial
effects in hypertensive patients with type 2 diabetes and a poor glycemic
control"
-
Comparison of the
effects of telmisartan and olmesartan on home blood pressure, glucose, and
lipid profiles in patients with hypertension, chronic heart failure, and
metabolic syndrome - Hypertens Res. 2008 May;31(5):921-9 -
"telmisartan had more beneficial effects on glucose
and lipid profiles in patients with relatively high HbA1c, serum total and
low-density lipoprotein cholesterol, and triglyceride levels. Therefore, we
concluded that telmisartan was more beneficial than olmesartan for
controlling blood pressure in the early morning, as well as for improving
glucose and lipid profiles in patients with hypertension, chronic heart
failure, and metabolic syndrome"
-
Telmisartan prevents aneurysm progression in the rat by inhibiting
proteolysis, apoptosis and inflammation - J Hypertens. 2008
Dec;26(12):2361-73 - "The angiotensin II type 1
receptor antagonist, telmisartan, prevents abdominal aortic aneurysm
progression independently of blood pressure reduction by inhibiting
proteolysis, apoptosis and inflammation in aortic tissue"
-
Telmisartan is more effective than losartan in reducing proteinuria in
patients with diabetic nephropathy - Kidney Int. 2008 May 21 -
"telmisartan is superior to losartan in reducing
proteinuria in hypertensive patients with diabetic nephropathy, despite a
similar reduction in blood pressure"
-
The angiotensin II
receptor blocker telmisartan improves insulin resistance and has beneficial
effects in hypertensive patients with type 2 diabetes and poor glycemic
control - Diabetes Res Clin Pract. 2008 Aug 8 -
"The telmisartan significantly improved HOMA-IR in hypertensive patients and
also significantly decreased HbA1c in type 2 diabetic patients especially in
the patients with poor glycemic control (HbA1c>==8.0%). These results
indicate that telmisartan improves insulin resistance and gives beneficial
effects in hypertensive patients with type 2 diabetes and a poor glycemic
control"
-
Telmisartan prevented
cognitive decline partly due to PPAR-gamma activation - Biochem Biophys
Res Commun. 2008 Aug 17 - "Pretreatment with a
non-hypotensive dose of telmisartan significantly inhibited such cognitive
decline. Interestingly, co-treatment with GW9662, a PPAR-gamma antagonist,
partially inhibited this improvement of cognitive decline. Another ARB,
losartan, which has less PPAR-gamma agonistic effect, also inhibited
Abeta-injection-induced cognitive decline; however the effect was smaller
than that of telmisartan and was not affected by GW9662. Immunohistochemical
staining for Abeta showed the reduced Abeta deposition in
telmisartan-treated mice. However, this reduction was not observed in mice
co-administered GW9662. These findings suggest that ARB has a preventive
effect on cognitive impairment in Alzheimer disease, and telmisartan, with
PPAR-gamma activation, could exert a stronger effect"
-
Angiotensin Receptor Blockers Are Lower Incidence, Progression Of
Alzheimer's Disease - Science Daily, 7/27/08 -
"Researchers at Boston University School of Medicine (BUSM) have, for the
first time, found that angiotensin receptor blockers (ARBs)—a particular
class of anti-hypertensive medicines—are associated with a striking decrease
in the occurrence and progression of dementia"
Effects of telmisartan, a unique angiotensin receptor blocker with selective
peroxisome proliferator-activated receptor-gamma-modulating activity, on
nitric oxide bioavailability and atherosclerotic change - J Hypertens.
2008 May;26(5):964-972 - "In addition to a class
effect of ARBs, telmisartan may have additional effects on nitric oxide
bioavailability and atherosclerotic change through its PPARgamma-mediated
effects in genetically hyperlipidemic rabbits"
-
Microalbuminuria Reduction with Telmisartan in Normotensive and Hypertensive
Japanese Patients with Type 2 Diabetes: A Post-Hoc Analysis of the Incipient
to Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2
Diabetic Nephropathy (INNOVATION) Study - Hypertens Res. 2008
Apr;31(4):657-64 - "The patients treated with either
dose of telmisartan showed lower transition rates from microalbuminuria to
overt nephropathy compared to the placebo group. In addition, more patients
on telmisartan reverted to normoalbuminuria (UACR<30 mg/g creatinine): 15.5%
of the 40 mg group, 19.6% of the 80 mg group, and 1.9% of the placebo group
... Side effects did not differ among the groups. The present study
demonstrates that telmisartan prevents the progression of microalbuminuria
(in some cases induces remission of albuminuria) in normotensive Japanese
patients with type 2 diabetes. Telmisartan is shown to be safe and well
tolerated in these patients"
-
Telmisartan, an Angiotensin II Type 1 Receptor Blocker, Improves Coronary
Microcirculation and Insulin Resistance among Essential Hypertensive
Patients without Left Ventricular Hypertrophy - Hypertens Res. 2008
Apr;31(4):615-22 - "Coronary flow velocity reserve
(CFVR) ... CFVR was improved in the telmisartan group (2.4+/-0.4 to
2.9+/-0.4; p<0.01), but there was no difference in the nifedipine group
(2.5+/-0.3 to 2.5+/-0.3; n.s.). HOMA-IR was improved in the telmisartan
group (3.1+/-1.1 to 1.6+/-0.7; p<0.01), but there was no difference in the
nifedipine group (2.8+/-1.1 to 2.4+/-0.7; n.s.). In conclusion, this study
demonstrates that antihypertensive therapy with telmisartan, but not
nifedipine, has a beneficial effect on coronary microcirculation and insulin
resistance among essential hypertensive patients"
-
Telmisartan but not candesartan affects adiponectin expression in vivo and
in vitro - Hypertens Res. 2008 Apr;31(4):601-6 -
"the changes in serum adiponectin and plasma glucose over 3 months were
significantly greater in the telmisartan group than in the candesartan
group. In vitro, although the protein level of adiponectin was not
significantly elevated, the mRNA expression of adiponectin was elevated
1.5-fold by telmisartan in 3T3-L1 adipocytes. Our findings suggest that
telmisartan may have beneficial effects in type 2 diabetes beyond its
antihypertensive effect"
-
Angiotensin
receptor blockers in the treatment of NASH/NAFLD: Could they be a
first-class option? - Adv Ther. 2008 Oct 29 -
"Nonalcoholic fatty liver disease (NAFLD) ... nonalcoholic steatohepatitis
(NASH) ... In our opinion there are two major advantages of ARBs that make
them a possible therapeutic option for treating NASH and MS: their specific
antihypertensive effect, and their impact on liver fibrosis. In light of
this, and based on the current evidence (including existent human studies),
we can speculate that some ARBs like telmisartan, candesartan, and losartan
can be beneficial in treating NASH/NAFLD and its consequences, and further
larger controlled clinical trials will bring consistent data into this
field"
-
Effect of irbesartan on erectile function in patients with hypertension and
metabolic syndrome - Int J Impot Res. 2008 Jul 3 -
"Erectile function increased significantly
(P<0.0001) after 6 months of treatment with irbesartan, irrespective of
dosage and independent of additional treatment with hydrochlorothiazide.
Prevalence of ED declined to 63.7% from 78.5% at baseline, along with a
significant increase in orgasmic function (P<0.001) and intercourse
satisfaction (P<0.001). Treatment with irbesartan alone, as well as in
combination with hydrochlorothiazide is associated with an improvement of
sexual desire, frequency of sexual contacts and erectile function in
hypertensive patients with the metabolic syndrome. These results suggest a
beneficial role of angiotensin receptor antagonists in the treatment of
metabolic syndrome, and ED" - Note: I've been suggesting telmisartan
(an ARB) for some time as the first line treatment for hypertension.
-
Telmisartan-Hydrochlorothiazide Outperforms Valsartan-Hydrochlorothiazide
for Blood Pressure Reduction - Doctor's Guide, 5/29/07 -
"The change in diastolic blood pressure was -18.2
mmHg for the telmisartan-hydrochlorothiazide group and -17.0 mmHg for the
valsartan-hydrochlorothiazide group. The change in systolic blood pressure
was -24.6 mmHg and -22.5 for the two groups, respectively"
-
Sustained Tubulo-interstitial Protection in SHRs by Transient Losartan
Treatment: An Effect of Decelerated Aging? - Am J Hypertens. 2008 Jan 10
- "Transient losartan treatment reduces
cell-turnover not only acutely but also for a prolonged period after drug
withdrawal. This results in the long-term in reduced aging and attenuated
tubulo-interstitial damage, suggesting there exists a modulating effect of
angiotensin II (ANGII)-antagonism on long-term cell turnover" -
Note: Losartan is an ARB. I would think that telmisartan (also and ARB and
my recommendation for hypertension) would give the same effect.
-
Telmisartan, an Angiotensin II Type 1 Receptor Blocker, Inhibits Advanced
Glycation End-product (AGE)-elicited Hepatic Insulin Resistance via
Peroxisome Proliferator-activated Receptor-gamma Activation - J Int Med
Res. 2008 Mar-Apr;36(2):237-43 - "Candesartan,
another ARB, did not affect AGEs-induced serine phosphorylation of IRS-1 at
serine-307 residues in Hep3B cells. Our study suggests that telmisartan
could improve AGE-elicited insulin resistance in Hep3B cells by inhibiting
serine phosphorylation of IRS-1, at least in part, via activation of
PPAR-gamma"
-
Metabolic effects of telmisartan and irbesartan in type 2 diabetic patients
with metabolic syndrome treated with rosiglitazone - J Clin Pharm Ther.
2007 Jun;32(3):261-8 - "Telmisartan seemed to
improve glycaemic and lipid control and metabolic parameters of the
metabolic syndrome better than irbesartan. These differences could be
relevant in the choice of therapy for this condition and diabetes"
-
Meta-analysis of Randomized Controlled Trials Comparing Telmisartan With
Losartan in the Treatment of Patients With Hypertension - Am J
Hypertens. 2008 May;21(5):546-52. Epub 2008 Mar 20 -
"In comparison with losartan, telmisartan provides superior control of BP
and has no association with increased risk of adverse events"
-
Telmisartan Superior to Ramipril in Preventing Morning Blood Pressure Rise
- Doctor's Guide, 5/19/05 - "Reductions were greater
and statistically significant in the highest quartile (34 mmHg), in whom
telmisartan reduced systolic surge by 12.4 mmHg and ramipril by 7.1 mmHg"
-
Telmisartan Provides Superior, Powerful Blood Pressure Reduction From
Morning to Morning Compared to Other Leading ARBS - Doctor's Guide,
6/15/06 - "telmisartan provides superior, powerful
blood pressure reduction from morning to morning compared to other leading
angiotensin II receptor blockers"
-
ONTARGET: ARB
Similar to ACE - Medscape, 3/31/08 - "The
angiotensin receptor blocker (ARB) telmisartan (Micardis, Boehringer
Ingelheim) was "noninferior" to the ACE inhibitor ramipril in patients with
vascular disease or high-risk diabetes in the landmark ONTARGET trial"
-
The role of telmisartan in the treatment of metabolic syndrome - Ter
Arkh. 2006;78(8):63-6 - "Telmisartan reduced all the
study parameters of blood pressure, body mass, fasting and post-prandial
hyperglycemia, postprandial hyperinsulinemia. Telmisartan raised peripheral
tissue sensitivity to insulin, normalized phases of insulin secretion. Total
cholesterol, LDLP cholesterol diminished while HDLP went up"
-
Blood Pressure Drug Telmisartan Shows Powerful Activity Against Stroke,
Study Suggests - Science Daily, 12/17/07 - "83
percent of rats given no medication showed signs of stroke, as did 56
percent of rats given ramipril alone. However, no strokes were noted in the
telmisartan-only or the telmisartan/ramipril combo groups ... Telmisartan's
ability to easily pass through the blood-brain barrier (something ramipril
cannot do) is likely behind the neuroprotective effect noted in the study"
-
Effects of telmisartan on fat distribution in individuals with the metabolic
syndrome - J Hypertens. 2007 Apr;25(4):841-8 -
"Systolic and diastolic blood pressure were
decreased in both groups to a comparable level. However, insulin and glucose
levels during an oral 75 g glucose loading were decreased only in the
telmisartan group. The visceral fat area, determined by abdominal computed
tomography scan, was reduced in the telmisartan group after 24 weeks'
treatment, but the subcutaneous fat area did not change in either group"
-
Bedtime Dosing of Atorvastatin and Valsartan Together Improves Overall
Anti-Hypertensive Effects - Doctor's Guide, 5/17/05 -
"When valsartan was dosed by itself during the day,
patients averaged a 9 mmHg fall in systolic blood pressure; daytime dosing
of both valsartan and atorvastatin resulted in a 17 mmHg reduction in the
24-hour mean of systolic and diastolic BP"
-
Valsartan Appears More Effective Than Telmisartan in Patients With Essential
Hypertension - Doctor's Guide, 6/25/04 -
"At the end of the study, the 24-hour mean BP was
statistically lower in the valsartan-treated group compared to
telmisartan-treated group"
- However:
-
Metabolic Effect of Telmisartan [Micardis] and Losartan [Cozaar] in
Hypertensive Patients with Metabolic Syndrome
- Cardiovasc Diabetol. 2005 May 15;4(1):6 -
"Telmisartan, but not losartan, significantly (p <
0.05) reduced free plasma glucose, free plasma insulin, homeostasis model
assessment of insulin resistance and HbAic. Following treatment, plasma
glucose and insulin were reduced during the oral glucose tolerance test by
telmisartan, but not by losartan. Telmisartan also significantly reduced
24-hour mean systolic blood pressure (p < 0.05) and diastolic blood pressure
(p < 0.05) compared with losartan"
-
Effect
of Telmisartan on Nitric Oxide-Asymmetrical Dimethylarginine System. Role of
Angiotensin II Type 1 Receptor and Peroxisome Proliferator Activated
Receptor {gamma} Signaling During Endothelial Aging - Hypertension. 2008
Feb 4 - "Telmisartan, in addition to blocking
angiotensin (Ang) II type 1 receptor (AT1R), activates peroxisome
proliferator activated receptor gamma (PPARgamma) signaling that interferes
with nitric oxide (NO) system. Because aging of endothelial cells (ECs) is
hallmarked by a reduction in NO synthesis, we hypothesized that telmisartan
increases NO formation by regulated asymmetrical dimethylarginine
(ADMA)-dimethylarginine dimethylaminohydrolase (DDAH)-system through
blocking AT1R and activating PPARgamma signaling ... During the process of
aging, PPARgamma protein expression decreased significantly, whereas the
expression of AT1R increased. Telmisartan reversed these effects and
dose-dependently decreased reactive oxygen species and 8-iso-prostaglandin
(PG) F2alpha formation ... telmisartan mainly by activating PPARgamma
signaling can alter the catabolism and release of ADMA as an important
cardiovascular risk factor. We therefore propose that telmisartan
translationally and posttranslationally upregulated DDAH expression via
activation of PPARgamma signaling, causing ADMA to diminish and increase NO
synthesis sufficient to delay senescence"
-
Telmisartan But Not Valsartan Increases Caloric Expenditure and Protects
Against Weight Gain and Hepatic Steatosis - Hypertension. 2006 Mar 27 -
"Telmisartan, but not valsartan, promoted increases
in caloric expenditure and protected against dietary-induced weight gain ...
Telmisartan reduced the accumulation of visceral fat and decreased adipocyte
size to a much greater extent than valsartan and was also associated with a
significant reduction in hepatic triglyceride levels"
-
Evidence-Based
Treatment of Hypertension: What's the Role of Angiotensin II Receptor
Blockers? - Medscape, 4/8/05 - "The ARBs are
highly effective in lowering blood pressure and reducing cardiovascular
mortality. They also appear to provide additional renal protection in
patients with diabetes, and this effect is independent of their effect on
blood pressure. Combinations of ARBs with drugs from other classes such as
ACE inhibitors have been found to be highly effective; they may permit lower
doses of ACE inhibitors to be used than in monotherapy, which may lower the
incidence of dose-related adverse effects. The ARBs themselves are very well
tolerated and are not associated with the side-effects known to cause
compliance problems with beta blockers, ACE inhibitors and calcium channel
blockers such as impotence, dry cough and peripheral oedema"
-
Angiotensin II receptor blockers downsize adipocytes in spontaneously type 2
diabetic rats with visceral fat obesity - Am J Hypertens. 2007
Apr;20(4):431-6 - "adipocyte
downsizing was significantly greater with telmisartan compared to valsartan.
The likely mechanism for this difference was thought to be the
PPAR-gamma-mediated action of telmisartan"
-
The Differential Effects of Angiotensin II Type 1 Receptor Blockers on
Microalbuminuria in Relation to Low-Grade Inflammation in Metabolic
Hypertensive Patients - Am J Hypertens. 2007 May;20(5):565-72 -
"There was a significant increase in high molecular
weight adiponectin in the telmisartan
group ... The reductions of microalbuminuria and high-sensitivity C-reactive
protein (hs-CRP) were significant in the telmisartan group"
-
Telmisartan shows an equivalent effect of vitamin C in further improving
endothelial dysfunction after glycemia normalization in type 1 diabetes
- Diabetes Care. 2007 Apr 24 -
"Combining insulin and vitamin C normalized
endothelial dysfunction and decreased oxidative stress to normal level.
Telmisartan significantly improved basal endothelial function and decreased
nitrotyrosine plasma levels. In patients treated with Telmisartan a near
normalization of both flow mediated vasodilation and oxidative stress was
achieved when glycemia was normalized, while adding vitamin C infusion did
not show further effect on endothelial function or nitrotyrosine plasma
levels"
-
Telmisartan Reduces Proteinuria More Than Losartan - Doctor's Guide, 5/28/07
- "Our findings suggest that at similar levels of blood
pressure control, telmisartan may confer greater protection against progression
to end-stage renal disease"
-
Preliminary Studies Suggest Potential Metabolic Effects of Micardis
(Telmisartan) - Doctor's Guide, 9/9/05 -
"The Micardis molecule is structurally similar to the
PPAR-gamma activator, pioglitazone,3 which has been approved for the treatment
of type 2 diabetes.7 Micardis partially activates PPAR-gamma resulting in
metabolic effects that differentiate it from other ARBs, according to
preclinical data.1-4 These data demonstrate that Micardis has a beneficial
effect on insulin resistance and blood lipids, independent of its effect on the
renin-angiotensin-aldosterone system"
-
Telmisartan and irbesartan therapy in type 2 diabetic patients treated with
rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis
factor-alpha - Hypertens Res. 2006 Nov;29(11):849-56 -
"The decrease in HbA1c and FPG at 12 months was
statistically significant only in the telmisartan group"
-
Novel ARB Provides Greater
Reductions in Proteinuria in Diabetics With Overt Nephropathy
- Medscape, 5/22/07 - "One year of treatment with the
novel angiotensin receptor blocker (ARB) telmisartan provided greater reductions
in proteinuria when compared with losartan, a drug approved for the treatment of
diabetic nephropathy to prevent renal-disease progression"
-
New treatment strategies for patients with hypertension and insulin resistance
- Am J Med. 2006 May;119(5 Suppl 1):S24-30 - "the
ability of telmisartan both to activate PPAR-gamma and to block the angiotensin
receptor may provide added value not only in the treatment of the metabolic
syndrome and prevention of type 2 diabetes but also in prevention and treatment
of atherosclerotic cardiovascular disease"
-
Angiotensin II Antagonist
Telmisartan Fights Stiffening Arteries In Hypertensive Diabetics - Doctor's
Guide, 4/6/01 -
"not only effectively lowered blood pressure compared
with placebo, but also significantly decreased arterial stiffness"
-
The effects of telmisartan and amlodipine on metabolic parameters and blood
pressure in type 2 diabetic, hypertensive patients - J Renin Angiotensin
Aldosterone Syst. 2006 Dec;7(4):243-6 -
"Group A: rosiglitazone (RSG) 4 mg + Telm 80 mg; Group
B: RSG 4 mg + Aml 10 mg ... Lower values of glucose, HbA1C, HOMA index and
higher adiponectin levels were observed in Group A compared to Group B ...
insulin sensitivity may confer make Telm particularly suitable in the treatment
of the metabolic syndrome"
-
The effects of irbesartan and telmisartan on metabolic parameters and blood
pressure in obese, insulin resistant, hypertensive patients - J
Endocrinol Invest. 2006 Dec;29(11):957-61 -
"The greater impact on the improvement of the
metabolic profile showed by telmisartan and the inverse correlation between
adiponectin levels and blood pressure may be partly due to the action as
partial PPARgamma agonist displayed by telmisartan"
-
BP Lowering May Halt Descent Into Dementia
- Clinical Psychiatry News, 12/02 -
"those in the candesartan arm had a mean 0.5-point
decline in MMSE scores during follow-up, compared with a 6-point drop in those
on a diuretic. The cognitive benefit was even more pronounced in patients over
age 85"
- Does this pertain to other ARBs? I don't know.
-
Dyslipidemia and Concurrent Medications Improve Likelihood of Persistence to ACE
Inhibitor Therapy - Doctor's Guide, 10/27/05 -
"The adjusted rate ratio of therapy discontinuation was
consistently higher for all other ACE inhibitors relative to ramipril"
-
Telmisartan May Help Preserve Renal Function in Patients With Hypertension,
Diabetes - Medscape, 6/1/07 -
"In patients with hypertension and type 2 diabetes,
telmisartan and ramipril both may help preserve cardiovascular and renal
function by increasing nitric oxide (NO) activity of the renal endothelium"
-
Telmisartan Provides Superior, Powerful Blood Pressure Reduction From
Morning to Morning Compared to Other Leading ARBS - Doctor's Guide,
6/15/06 - "telmisartan provides superior, powerful
blood pressure reduction from morning to morning compared to other leading
angiotensin II receptor blockers"
-
Telmisartan Lowers Early Morning Blood Pressure in Patients With Hypertension
More Effectively Than Does Valsartan - Doctor's Guide, 4/12/04 -
"telmisartan reduced BP during the last 6 h of the dosing period more
effectively than did valsartan (-11/-7.6 +/- 0.8/0.6 mm Hg vs. -8.7/-5.8 +/-
0.8/0.6 mm Hg"
-
Vitamin C
'benefits diabetics' - BBC News, 6/28/07 - "Vitamin
C neutralises free radicals, while Telmisarten stimulates the natural removal of
the molecules by cells"
-
Telmisartan, an Angiotensin II Type 1 Receptor Blocker, Inhibits Advanced
Glycation End-product (AGE)-induced Monocyte Chemoattractant Protein-1
Expression in Mesangial Cells Through Downregulation of Receptor for AGEs via
Peroxisome Proliferator-activated Receptor-gamma Activation - J Int Med Res.
2007 Jul-Aug;35(4):482-9 - "Candesartan, an Ang II type
1 receptor blocker, did not suppress AGEs-induced superoxide generation.
Telmisartan and the antioxidant, N-acetylcysteine, completely inhibited
AGEs-induced MCP-1 overproduction by mesangial cells"
Arguments for Ramipril:
-
Combination ACE inhibitor therapy increases risk of kidney failure and death,
study finds - Science Daily, 3/21/11 - "The
researchers looked at 32,312 seniors in Alberta, Canada, aged 65 and older who
were prescribed an ACE inhibitor and/or an ARB. They compared patients receiving
both drugs together with patients who received only one of the drugs. They found
a higher risk of adverse events such as high creatinine levels, end-stage renal
disease and death in people taking combination therapy"
-
Effects of Ramipril on Endothelial Function and the Expression of
Proinflammatory Cytokines and Adhesion Molecules in Young Normotensive Subjects
With Successfully Repaired Coarctation of Aorta A Randomized Cross-Over Study
- J Am Coll Cardiol. 2008 Feb 19;51(7):742-749 -
"Ramipril reversed the impaired endothelial function and decreased the
expression of proinflammatory cytokine IL-6, sCD40L, and adhesion molecules in
normotensive subjects with SCR. These findings imply that ramipril treatment may
have antiatherogenic effects in subjects with SCR, even in the absence of
arterial hypertension"
-
Keeping Seniors
Independent - WebMD, 3/14/02 -
"the average three-year decline in walking speed among
those women who used ACE inhibitors was 10 times lower than it was in the other
groups ... Researchers think several factors may explain these drugs' beneficial
effect on delaying disability: ACE inhibitors increase blood flow to the
muscles, reduce inflammation, and promote healthy eating habits and better
nutrition by inhibiting a substance known to reduce appetite"
-
Blood Pressure Drugs
May Help People Avoid 'Type 2' Disease, but Healthy Habits Still Best -
WebMD, 10/16/01 -
"people at high risk for developing
diabetes who take the drug Altace [ramipril] were 34% less likely to develop
diabetes than those who did not get the drug"
-
Not All ACE Inhibitors Have
the Same Effect on Mortality - Medscape, 7/28/04 -
"enalapril, fosinopril, captopril, quinapril, and
lisinopril were associated with higher mortality than was ramipril"
-
Angiotensin-converting Enzyme
Inhibitors, Beta Blockers May Postpone Kidney Failure - Doctor's Guide,
10/13/00 -
"The ACE inhibitor ramipril (Altace®) or the
beta-blocker metoprolol (Toprol®) significantly reduced the risk of kidney
failure compared to the CCB amlodipine (Norvasc®) in a group of patients who had
at least one gram of protein in a 24-hour sample of urine when they joined the
African American Study of Kidney Disease and Hypertension (AASK). Blood
pressures were comparable."
-
Ramipril Reduces Advanced Glycation End Products In Non-Diabetic Nephropathy
- Doctor's Guide, 4/21/03 -
"Ramipril also mildly decreased levels of
advanced glycation end products"
-
Some
Hypertension Drugs May Help Reduce Dementia Risk - Science Daily, 5507 -
"Centrally acting drugs include captropril (Capoten®),
fosinopril (Monopril®), lisinopril (Prinivil® or Zestri®), perindopril (Aceon®),
ramipril (Altace®) and trandolapril (Mavik®) ... The study found a link between
taking centrally active ACE inhibitors and lower rates of mental decline as
measured by the Modified Mini-Mental State Exam, a test that evaluates memory,
language, abstract reasoning and other cognitive functions"
-
Effect of antihypertensive agents on plasma adiponectin levels in hypertensive
patients with metabolic syndrome - Nephrology (Carlton). 2007
Apr;12(2):147-53 - "Ramipril and valsartan increased the
plasma adiponectin levels significantly
higher than the other regimens"
-
BP Reduction in
the Metabolic Syndrome and Type 2 Diabetes - Medscape, 2/13/06 -
"Beta blockers are now widely regarded as having
worse outcomes than other major classes of antihypertensive agents, though
this view is heavily influenced by a single drug, atenolol.[29] Furthermore,
the thiazide/beta blocker combination has been associated with an increased
risk of the emergence of new-onset diabetes.[30] This has been strongly
reinforced by the ASCOT trial, where the likelihood of new diabetes was 30%
greater in the thiazide/beta blocker patients as compared to those taking
calcium channel blockers with an ACE inhibitor.[31] Conversely, a very
recent meta-analysis has shown that overall ACE inhibitors and ARBs reduce
the risk of diabetes by about 25%"
-
Blood Pressure
Drugs Counter Cancer? - WebMD, 5/23/06 -
"After crunching the numbers, the risk reduction in
veterans taking ACE inhibitors was 53% for colon cancer, 52% for pancreatic
cancer, and 46% for esophageal cancer"
-
Prevention of Type 2 diabetes: fact or fiction? - Expert Opin
Pharmacother. 2007 Dec;8(18):3147-58 - "the DREAM
(Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication)
study (n = 5269) demonstrated that rosiglitazone at 8 mg once/day in
subjects with prediabetes (IGT and/or impaired fasting glucose) was
effective in reducing the risk of diabetes by 60%"
- Keeping Seniors
Independent - WebMD, 3/14/02 -
"the average three-year decline in walking speed
among those women who used ACE inhibitors was 10 times lower than it was in
the other groups ... Researchers think several factors may explain these
drugs' beneficial effect on delaying disability: ACE inhibitors increase
blood flow to the muscles, reduce inflammation, and promote healthy eating
habits and better nutrition by inhibiting a substance known to reduce
appetite"
-
ACE Inhibitors May Protect Against Mental Decline - Clinical Psychiatry
News, 8/07 - "The group of patients on an
antihypertensive other than an ACE inhibitor had a mean decline in exam
scores of 0.64 points per year. Those on an ACE inhibitor had a mean decline
of 0.38 points per year ... It is thought that some ACE inhibitors protect
from dementia and mental decline by decreasing oxidative stress and
inflammation in the brain"
Arguments for/against
combining ARBs and ACE inhibitors:
-
ACE + ARB = Adverse
Events - Medscape, 12/17/13 - "patients
receiving the active drug combination had an excess occurrence of
hyperkalemia and acute kidney injury. The hazard ratio for hyperkalemia was
2.8, and for acute kidney injury, it was 1.7. No benefit, excess risk, and
the study was stopped early"
-
Ambulatory Blood Pressure Values in the Ongoing Telmisartan Alone and in
Combination with Ramipril Global Endpoint Trial (ONTARGET) -
Hypertension. 2012 Oct 15 - "Twenty-four-hour
systolic BP was similarly reduced by R (-2.0 mm Hg) and T (-2.1 mm Hg),
whereas the reduction was more than twice as large in the T+R group (-5.3 mm
Hg), which showed a lower on-treatment 24-hour BP also in additional
patients (n=408) in whom ambulatory BP was performed only on-treatment.
Twenty-four-hour systolic BP was ≈14 mm Hg lower than clinic systolic BP at
baseline, whereas during treatment the 2 values became progressively closer
as clinic systolic BP was more tightly controlled and superimposable when
clinic systolic BP was <120 mm Hg. Similar results were obtained for
diastolic BP. These findings provide evidence on the relationship of clinic
and ambulatory BP target drug treatment. They also show that in the Ongoing
Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial,
failure of the R+T combination to enhance cardiovascular and renal
protection was not because of inability to more effectively control daily
life BP"
-
Are ACE Inhibitor/ARB
Combinations Beneficial? - Medscape, 5/16/12 -
"several trials comparing ACE inhibitor monotherapy vs combined treatment
with an ARB used suboptimal doses of ACE inhibitors, were relatively short
in duration, and had small sample sizes. Combination therapy may have a
benefit in reducing proteinuria in patients with hypertensive nephropathy.
Whether the long-term BP effects of ACE inhibitors and ARBs are additive or
synergistic is still not completely confirmed. Nonetheless, the Ongoing
Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial
(ONTARGET) study demonstrated that reductions in BP, as seen with
combination ACE inhibitor and ARB treatment, does not necessarily correlate
to improved morbidity and mortality, even in high-risk patients"
-
Telmisartan, ramipril and their combination improve endothelial function in
different tissues in a murine model of cholesterol-induced atherosclerosis
- Br J Pharmacol. 2011 Feb 16 - "Erectile
dysfunction correlates with cardiovascular disease and its common risk
factors due to the development of endothelial dysfunction. Positive effects
on endothelial and erectile function have been described for substances
inhibiting the renin-angiotensin-system ... Wildtype (WT, C57/B6) and
ApoE(-/-) mice were treated with a cholesterol-rich diet for 8 weeks.
ApoE(-/-) mice were supplemented with either telmisartan (20mg/kg/day),
ramipril (2.5mg/kg/day) or the combination thereof. Key results: Systolic
blood pressure significantly decreased in treatment groups (p < 0.001), with
significantly smaller reduction under ramipril monotherapy (p < 0.05).
Endothelial function (assessed by pharmacological stimulation of aortic
rings and CC in organ bath chambers) was impaired in ApoE(-/-) mice compared
to WT animals, which was improved by all three treatments to a comparable
extent (p < 0.05). Atherosclerotic lesion size in the ascending aorta and
aortic sinus (p < 0.001), the amount of lipid peroxides in cavernosal and
aortic tissue (p < 0.05) and free radical load (DHE-stain) (p < 0.05) were
enhanced in untreated ApoE(-/-) mice in comparison to WT animals and were
significantly reduced by either treatment. In penile tissue, expression of
eNOS could be restored by RAAS-blockade. Conclusions and implications:
Telmisartan and ramipril significantly improved endothelial function of
aortic and cavernosal tissues in ApoE(-/-) via reduction of oxidative
stress. Combination of both agents does not enhance beneficial effects
significantly"
-
Effects
of telmisartan added to Angiotensin-converting enzyme inhibitors on
mortality and morbidity in hemodialysis patients with chronic heart failure
a double-blind, placebo-controlled trial - J Am Coll Cardiol. 2010 Nov
16;56(21):1701-8 - "In hemodialysis patients, CHF is
responsible for a high mortality rate ... At 3 years, telmisartan
significantly reduced all-cause mortality (35.1% vs. 54.4%; p < 0.001),
cardiovascular death (30.3% vs. 43.7%; p < 0.001), and hospital admission
for CHF (33.9% vs. 55.1%; p < 0.0001). With Cox proportional hazards
analysis, telmisartan was an independent determinant of all-cause mortality
(hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.32 to 0.82; p <
0.01), cardiovascular mortality (HR: 0.42; 95% CI: 0.38 to 0.61; p <
0.0001), and hospital stay for deterioration of heart failure (HR: 0.38; 95%
CI: 0.19 to 0.51; p < 0.0001). Adverse effects, mainly hypotension, occurred
in 16.3% of the telmisartan group versus 10.7% in the placebo group"
- Note: It makes me wonder if similar effects on mortality might be seen in
people without kidney disease.
-
ARB Plus ACE Not for
Heart Failure - Medscape, 9/10/09
-
Combining ACE Inhibitors With Angiotensin Receptor Blockers May Not Be
Optimal for Treating Hypertension - Doctor's Guide, 5/11/09
-
Beneficial Effects of Combination Therapy with Angiotensin II Receptor
Blocker and Angiotensin-Converting Enzyme Inhibitor on Vascular Endothelial
Function - Hypertens Res. 2008 Aug;31(8):1603-10 -
"these results suggest that the angiotensin
I-converting enzyme inhibitor perindopril is superior to the calcium channel
blocker amlodipine for reducing vascular endothelial dysfunction when
co-administered with angiotensin receptor blockers in patients with
essential hypertension"
-
Use of Combination ACE
Inhibitors and ARB Therapy in Patients With CKD - Medscape, 9/29/08
-
Effects of Angiotensin Converting Enzyme Inhibitor and Angiotensin II
Receptor Antagonist Combination on Nitric Oxide Bioavailability and
Atherosclerotic Change in Watanabe Heritable Hyperlipidemic Rabbits -
Hypertens Res. 2008 Mar;31(3):575-84 - "1) vehicle
(control), 2) the ACEI enalapril (E: 3 mg/kg/day), 3) the ARB losartan (L:
30 mg/kg/day) and 4) enalapril (1.5 mg/kg/day) + losartan (15 mg/kg/day)
(E+L). Intra-aortic infusion of ACh produced an increase in plasma NO
concentration, which was significantly greater with all the drug treatments
than with the control. E increased ACh-induced NO significantly more than L
(by 6.9 nmol/L, and 4.7 nmol/L, respectively). E+L increased ACh-induced NO
by 9.5 nmol/L, significantly more than either E or L ... the combined
treatment with an ACEI and an ARB may have additive protective effects on
endothelial function as well as atherosclerotic change"
-
Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, or
Both for Patients With Proteinuria? A Best Evidence Review - Medscape,
5/20/08 - "Most significantly, the addition of ACEIs
to ARBs reduced proteinuria to a greater degree than ARBs alone (ratio of
means 0.76 at 1 to 4 months and 0.75 at 5 to 12 months). Combination therapy
was also superior to treatment with ACEIs alone ... The 2 important
conclusions that can be drawn from this meta-analysis are that ARBs are not
superior to ACEIs in improving proteinuria, and that the combination of
these 2 treatments appears superior in this outcome compared with either
treatment alone ... Two of the biggest safety concerns regarding the
combination therapy include the risks for hyperkalemia and acute worsening
of renal function. A review of the literature, however, suggests that these
risks may not be significantly worse with combination treatment vs
monotherapy"
-
ACE Inhibitors Plus ARBs Reduce Proteinuria But Increase Kidney Damage -
Doctor's Guide, 8/15/08 - "in people at high
vascular risk, telmisartan's effects on major renal outcomes are similar to
[those of] ramipril. Although combination therapy reduces proteinuria to a
greater extent than monotherapy, overall it worsens major renal outcomes"
-
Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events
- N Engl J Med. 2008 Mar 31 - "Telmisartan was
equivalent to ramipril in patients with vascular disease or high-risk
diabetes and was associated with less angioedema. The combination of the two
drugs was associated with more adverse events without an increase in
benefit" - Yeah but if you have to go with two drugs it sure seems
like it's the least of all the evils regarding side effects.
-
ACE Inhibitors May Protect Diabetics From Cancer, Peptic Ulcer -
Medscape, 12/19/08 - "There was a significant
association between ACE inhibitor use and the risk for cancer, with an
adjusted odds ratio of 0.59 ... The rate of cancer among users of ACE
inhibitors was 10% vs 15% for nonusers ... There was also a significant
association between ACE inhibitor use and peptic ulcer disease, with an odds
ratio of 0.68 ... The rate of peptic ulcer disease among ACE inhibitor users
was 12% vs 16% among nonusers"
-
Establishing A New Option for Target-organ Protection: Rationale for ARB
Plus ACE Inhibitor Combination Therapy - Am J Hypertens. 2008 Jan 24 -
"Combination therapy targeting RAS activation may
reduce target-organ damage and provide superior blood pressure (BP) control;
combining angiotensin-converting enzyme (ACE) inhibitors and angiotensin II
receptor blockers (ARBs) represents one possible approach"
-
Rationale for double renin-angiotensin-aldosterone system blockade - Am
J Cardiol. 2007 Aug 6;100(3A):25J-31J - "The
clinical benefits of both angiotensin-converting enzyme (ACE) inhibitors and
angiotensin receptor blockers (ARBs) extend beyond blood pressure reduction
to encompass tissue-protective effects in target organs, such as the heart,
vasculature, and kidneys, that underlie the reductions in cardiovascular
mortality and morbidity seen in large outcome trials. However, these effects
are achieved by different mechanisms. ACE inhibitors reduce circulating and
tissue angiotensin II levels and potentiate the beneficial effects of
bradykinin, including generation of nitric oxide (NO). By contrast, the
protective effects of ARBs are owing to the blockade of the angiotensin II
type 1 (AT(1)) receptors and possibly also to the stimulation of angiotensin
II type 2 (AT(2)) receptors, again resulting in NO release. In addition,
some ARBs, such as telmisartan, are selective activators of peroxisome
proliferator-activated receptor-gamma (PPAR-gamma), thereby increasing
insulin sensitivity. In contrast to other PPAR-gamma ligands, such as the
thiazolidinediones, activation of this receptor by telmisartan does not
result in weight gain. The complementary mechanisms of action of ACE
inhibitors and ARBs create a rationale for combination therapy in high-risk
patients"
-
New opportunities in cardiovascular patient management: a survey of clinical
data on the combination of angiotensin-converting enzyme inhibitors and
angiotensin receptor blockers - Am J Cardiol. 2007 Aug 6;100(3A):45J-52J
- "Angiotensin-converting enzyme (ACE) inhibitors
and angiotensin receptor blockers (ARBs) differ in their actions on the
renin-angiotensin-aldosterone system (RAAS). ACE inhibitors prevent the
formation of angiotensin II, although angiotensin II may still be generated
by alternative pathways. However, ACE inhibitors interrupt bradykinin
breakdown, which in turn potentially enhances nitric oxide and prostacyclin
mechanisms. In contrast, ARBs selectively prevent the binding of angiotensin
II to the angiotensin type 1 (AT(1)) receptor while leaving the potentially
beneficial effects of the AT(2) receptor unaffected. The supposition is that
dual blockade of the RAAS effectively overcomes the harmful effects of
angiotensin II mediated by the AT(1) receptor while offering the additional
effects of the ACE inhibitor"
-
Do we use an ACE, an ARB, or both? What clinical trials tell us -
Patient Care, 4/1/05 - "Combining ACEs and ARBs can
improve outcomes, particularly for patients with heart failure and those who
have hypertension with diabetes"
-
Impact of Telmisartan Versus Ramipril on Renal Endothelial Function in
Patients with Hypertension and Type 2 Diabetes - Diabetes Care. 2007 Mar
2 - "In patients with type 2 diabetes telmisartan
and ramipril both increased NO activity of the renal endothelium
significantly that in turn may support the preservation of cardiovascular
and renal function"
-
Addition of an angiotensin receptor blocker to full-dose ACE-inhibition:
controversial or common sense? - Eur Heart J. 2005 Nov;26(22):2361-7 -
"combination of a full-dose ACE-inhibitor and an ARB
can be a rational choice in selected patients"
- [full
article]
-
Combination ACE inhibitor and angiotensin receptor blocker therapy - future
considerations - J Clin Hypertens (Greenwich). 2007 Jan;9(1):78-86. -
"The individual gains seen with each of these drug
classes have led to speculation that their combination might offer additive
if not synergistic outcome benefits. The foundation of this hypothesis,
although biologically possible, has thus far not been sufficiently well
proven to support the everyday use of these 2 drug classes in combination.
Additional outcomes trials, which are currently proceeding to their
conclusion, may provide the necessary proof to support an expanded use of
these 2 drug classes in combination"
-
Do ACE
inhibitors and ARBs mix well? Analysis urges caution - theheart.org,
10/10/07 - "patients receiving both an ACE inhibitor
and an ARB were more likely not to comply with therapy due to side effects,
which included hypotension, cough, angioedema, worsening renal function as
defined by a change in serum creatinine >0.5 mg/dL, hyperkalemia as defined
by serum potassium level changes >5.5 mEq/L, and symptomatic hypotension"
- See
telmisartan
and
ramipril
at OffshoreRx1.com.
|
|