Lipid and Renal Effects of Olmesartan and Candesartan
Lipid and Renal Effects of Olmesartan and Candesartan
Background: Angiotensin II receptor blockers (ARBs), including olmesartan and candesartan, are widely used antihypertensive agents. Many clinical studies have demonstrated that ARBs have organ-protecting effects, e.g., cardioprotection, vasculoprotection and renoprotection. However, the effect of prolonged olmesartan monotherapy on lipid metabolism in patients with hypertension is less well studied. We performed a retrospective observational study to compare the effects of olmesartan with those of candesartan, focusing on lipid metabolism and renal function.
Methods: We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between Nov 1, 2004 and Feb 28, 2011, to identify cohorts of new olmesartan users (n = 168) and candesartan users (n = 266). We used propensity-score weighting to adjust for differences in all covariates (age, sex, comorbid diseases, previous drugs) between olmesartan and candesartan users, and compared serum chemical data including serum triglyceride (TG), LDL-cholesterol (LDL-C), total cholesterol (TC), potassium, creatinine and urea nitrogen. The mean exposure of olmesartan and candesartan users was 126.1 and 122.8 days, respectively.
Results: After adjustment, there were no statistically significant differences in all covariates between olmesartan and candesartan users. The mean age was 60.7 and 61.0 years, and 33.4% and 33.7% of olmesartan and candesartan users were women, respectively. There were no statistically significant differences in mean values for all laboratory tests between baseline and during the exposure period in both olmesartan and candesartan users. In olmesartan users, the reduction of serum TG level was significant in comparison with that in candesartan users. Other parameters of lipid profile and renal function showed no statistically significant difference in the change from baseline to during the exposure period between olmesartan and candesartan users.
Conclusions: In this study, we observed a more beneficial effect on lipid metabolism, a reduction of serum TG, with olmesartan monotherapy than with candesartan monotherapy. However, there were no clinically significant changes in the levels of all test parameters between baseline and during the exposure period with both drugs. These results suggest that the influence of olmesartan or candesartan monotherapy on lipid metabolism and renal function is small, and that they can be safely used in patients with hypertension.
Angiotensin II receptor blockers (ARBs) are widely used antihypertensive agents that act through inhibition of angiotensin II type 1 (AT1) receptors. In addition to antihypertensive effects, ARBs have been shown to have organ-protecting effects, including vasculoprotection, cardioprotection and renoprotection. Peroxisome proliferator activated receptor gamma (PPAR-γ), an intracellular receptor that regulates glucose and lipid metabolism, is modulated by different ARBs. Thereby, ARBs have been considered to improve insulin resistance, and we reported that monotherapy with ARBs had a favorable effect on glucose metabolism. Differences in pharmacology and pleiotropic effects appear to exist across ARBs, which may be of clinical importance and help physicians make decisions on drug selection.
Hypertension and dyslipidemia are conditions that frequently coexist. They are both major determinants of cardiovascular disease, and together cause an increase in coronary heart disease-related events. In experimental models, some ARBs have demonstrated the ability to affect lipid metabolism in a modest but significant way. Whether ARBs have a favorable effect on lipid metabolism in humans may be of clinical significance, especially in treating patients with dyslipidemia. Candesartan, which binds more tightly to and dissociates more slowly from the AT1 receptor than other ARBs, had the weakest PPAR-γ modulatory activity. Our recent study showed that candesartan monotherapy at a therapeutic dosage had a minimal effect on lipid metabolism for long periods up to 12 months. Olmesartan medoxomil is an ARB that is characterized by strong blood pressure-lowering efficacy with a fast onset, prolonged duration of action and good tolerability. Olmesartan has moderate PPAR-γ modulator activity, and thereby has the possibility of affecting lipid metabolism. Some clinical studies have demonstrated that olmesartan has organ-protecting effects, including long-term renoprotection in patients with type 2 diabetes, and beneficial effects to reduce cardiovascular risk in patients with atherosclerosis. A few clinical studies reported the effect of olmesartan on lipid metabolism. However, their subjects were patients who were treated with olmesartan combined with other antihypertensive drugs or lipid-lowering drugs. Therefore, the effect of prolonged olmesartan monotherapy on lipid metabolism in patients with hypertension is less well studied. In this study, we examined changes in the plasma lipid profile of new users of generally prescribed doses of olmesartan medoxomil, and compared them with those in new users of candesartan cilexetil at doses that have previously shown a minimal effect on lipid metabolism. We also examined changes in serum potassium level in addition to serum creatinine level and serum urea nitrogen, as parameters of renal function.
Abstract and Introduction
Abstract
Background: Angiotensin II receptor blockers (ARBs), including olmesartan and candesartan, are widely used antihypertensive agents. Many clinical studies have demonstrated that ARBs have organ-protecting effects, e.g., cardioprotection, vasculoprotection and renoprotection. However, the effect of prolonged olmesartan monotherapy on lipid metabolism in patients with hypertension is less well studied. We performed a retrospective observational study to compare the effects of olmesartan with those of candesartan, focusing on lipid metabolism and renal function.
Methods: We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between Nov 1, 2004 and Feb 28, 2011, to identify cohorts of new olmesartan users (n = 168) and candesartan users (n = 266). We used propensity-score weighting to adjust for differences in all covariates (age, sex, comorbid diseases, previous drugs) between olmesartan and candesartan users, and compared serum chemical data including serum triglyceride (TG), LDL-cholesterol (LDL-C), total cholesterol (TC), potassium, creatinine and urea nitrogen. The mean exposure of olmesartan and candesartan users was 126.1 and 122.8 days, respectively.
Results: After adjustment, there were no statistically significant differences in all covariates between olmesartan and candesartan users. The mean age was 60.7 and 61.0 years, and 33.4% and 33.7% of olmesartan and candesartan users were women, respectively. There were no statistically significant differences in mean values for all laboratory tests between baseline and during the exposure period in both olmesartan and candesartan users. In olmesartan users, the reduction of serum TG level was significant in comparison with that in candesartan users. Other parameters of lipid profile and renal function showed no statistically significant difference in the change from baseline to during the exposure period between olmesartan and candesartan users.
Conclusions: In this study, we observed a more beneficial effect on lipid metabolism, a reduction of serum TG, with olmesartan monotherapy than with candesartan monotherapy. However, there were no clinically significant changes in the levels of all test parameters between baseline and during the exposure period with both drugs. These results suggest that the influence of olmesartan or candesartan monotherapy on lipid metabolism and renal function is small, and that they can be safely used in patients with hypertension.
Introduction
Angiotensin II receptor blockers (ARBs) are widely used antihypertensive agents that act through inhibition of angiotensin II type 1 (AT1) receptors. In addition to antihypertensive effects, ARBs have been shown to have organ-protecting effects, including vasculoprotection, cardioprotection and renoprotection. Peroxisome proliferator activated receptor gamma (PPAR-γ), an intracellular receptor that regulates glucose and lipid metabolism, is modulated by different ARBs. Thereby, ARBs have been considered to improve insulin resistance, and we reported that monotherapy with ARBs had a favorable effect on glucose metabolism. Differences in pharmacology and pleiotropic effects appear to exist across ARBs, which may be of clinical importance and help physicians make decisions on drug selection.
Hypertension and dyslipidemia are conditions that frequently coexist. They are both major determinants of cardiovascular disease, and together cause an increase in coronary heart disease-related events. In experimental models, some ARBs have demonstrated the ability to affect lipid metabolism in a modest but significant way. Whether ARBs have a favorable effect on lipid metabolism in humans may be of clinical significance, especially in treating patients with dyslipidemia. Candesartan, which binds more tightly to and dissociates more slowly from the AT1 receptor than other ARBs, had the weakest PPAR-γ modulatory activity. Our recent study showed that candesartan monotherapy at a therapeutic dosage had a minimal effect on lipid metabolism for long periods up to 12 months. Olmesartan medoxomil is an ARB that is characterized by strong blood pressure-lowering efficacy with a fast onset, prolonged duration of action and good tolerability. Olmesartan has moderate PPAR-γ modulator activity, and thereby has the possibility of affecting lipid metabolism. Some clinical studies have demonstrated that olmesartan has organ-protecting effects, including long-term renoprotection in patients with type 2 diabetes, and beneficial effects to reduce cardiovascular risk in patients with atherosclerosis. A few clinical studies reported the effect of olmesartan on lipid metabolism. However, their subjects were patients who were treated with olmesartan combined with other antihypertensive drugs or lipid-lowering drugs. Therefore, the effect of prolonged olmesartan monotherapy on lipid metabolism in patients with hypertension is less well studied. In this study, we examined changes in the plasma lipid profile of new users of generally prescribed doses of olmesartan medoxomil, and compared them with those in new users of candesartan cilexetil at doses that have previously shown a minimal effect on lipid metabolism. We also examined changes in serum potassium level in addition to serum creatinine level and serum urea nitrogen, as parameters of renal function.
