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Home > Health Conditions > Hypertension > First Line Treatment"

First Line Treatment for Hypertension?

See telmisartan or ramipril at OffshoreRX.com.

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"
• 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"
• 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 OffshoreRX.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 OffshoreRX.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 OffshoreRX.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 OffshoreRX.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 OffshoreRX.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:
  • Valsartan Appears to Improve Sexual Function in Men and Women with Hypertension - Doctor's Guide, 5/18/03 - "Men and women being treated with the angiotensin II receptor blocker valsartan for mild-to-moderate hypertension appear to show improvements in sexual function and desire"
  • Impotent Patients on Valsartan Find Increased Interest in Sex; Use Sildenafil More Often: Presented at ASH - Doctor's Guide, 6/13/05 - "Hypertensive patients with erectile dysfunction who are taking the angiotensin II receptor blocker valsartan find they have increased sexual desire ... It could be related to the reactive stimulation of angiotensin cascade due to AT1 receptors blockade"
• 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:
  • 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"
• 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:

• 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 OffshoreRX.com.

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