6This 8-week, randomized, double-blind, controlled study compared efficacy and tolerability of telmisartan ⁄ amlodipine (T ⁄ A) single-pill combination (SPC) vs the respective monotherapies in 858 patients with severe hypertension (systolic ⁄ diastolic blood pressure [SBP ⁄ DBP] !180 ⁄ 95 mm Hg). At 8 weeks, T ⁄ A provided significantly greater reductions from baseline in seated trough cuff SBP ⁄ DBP ()47.5 mm Hg ⁄ )18.7 mm Hg) vs T (P<.0001) or A (P=.0002) monotherapy; superior reductions were also evident at 1, 2, 4, and 6 weeks. Blood pressure (BP) goal and response rates were consistently higher with T ⁄ A vs T or A. T ⁄ A was well tolerated, with less frequent treatmentrelated adverse events vs A (12.6% vs 16.4%) and a numerically lower incidence of peripheral edema and treatment discontinuation. In conclusion, treatment of patients with substantially elevated BP with T ⁄ A SPCs resulted in high and significantly greater BP reductions and higher BP goal and response rates than the respective monotherapies. T ⁄ A SPCs were well tolerated. J Clin Hypertens (Greenwich). 2012;14:206-215. Ó2012 Wiley Periodicals, Inc.Based on evidence from a number of large antihypertensive trials, 1-9 most guidelines acknowledge that combination therapy is needed to reduce blood pressure (BP) successfully to goal in the majority of patients; only a minority of patients achieve their BP goal with a single agent.10-14 Also, the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) study showed a significant reduction of cardiovascular (CV) events and death in hypertensive patients at high CV risk treated with a combination of an angiotensin-converting enzyme (ACE) inhibitor and a calcium channel blocker (CCB).15 Nevertheless, despite rigorous and comprehensive guidelines, and a trend towards an increase in the use of combination therapy in treatment practice, 16 several studies have demonstrated the persistence of poor BP goal rates in treated patients. [17][18][19] The impact of poor BP control is compounded by the often high prevalence of other CV risk factors in hypertensive patients (eg, hypercholesterolemia, obesity, type 2 diabetes mellitus [T2DM], and smoking).13 Therefore, an urgent need still remains to improve the management of hypertension. One logical approach would be to use 2 drugs from different classes and complementary mechanisms of action in combination. Such combinations may result in additional BP decreases and improved goal rates, compared with either agent used alone. 20-23Furthermore, single-pill combinations (SPCs) are known to increase treatment adherence and reduce health care costs. [24][25][26][27] A combination of a CCB and an angiotensin II receptor blocker (ARB) is a rational approach for managing hypertension and there is increasing evidence that this combination is effective. 11,13,28,29 The aim of the current study was to compare the efficacy and tolerability of the SPC of telmisartan 80 mg ⁄ amlodipine 10 mg (T80 ⁄ A10) with that of...
JACQUES FOSSEY, DANIEL LEFORT, MASSOUD MASSOUDI, JEAN-YVES NEDELEC et JEANINE SORBA. Can. J. Chem. 63, 678 (1985).Des hydrocarbures cyclohexane, Me-cyclohexane et adamantane sont hydroxylts par le peracide benzoi'que selon un processus radicalaire. La rtgiostlectivitt en faveur des alcools tertiaires atteint 60 B 90%. Pour les dkcalines cis et trans, la sttrtostlectivitt des dCcalols-9 peut atteindre 97%. Une trks bonne stCrCostlectivitC d'hydroxylation par un peracide ne signifie pas obligatoirement que la rLaction n'est pas radicalaire.JACQUES FOSSEY, DANIEL LEFORT, MASSOUD MASSOUDI, JEAN-YVES NEDELEC, and JEANINE SORBA. Can. J. Chem. 63, 678 (1985).Cyclohexane, methylcyclohexane, and adamantane are hydroxylated by a radical process using perbenzoic acid. A regioselectivity of 60-90% in favour of tertiary alcohols is noted. In the case of cis and trans decalins, stereoselection leading to 9-decalols can reach 97%. Such a stereoselectivity for hydroxylation by use of a peracid does not necessarily indicate lack of a radical pathway.[Journal translation] L'hydroxylation directe des liaisons C-H non activCes par les peroxyacides est une reaction d'intCrCt genCral en synthkse (1 -9), dont I'aspect regio-et stereosClectif recueille une attention particuliere. On sait Cgalement que le cytochrome P450 (10-13) ou les porphyrines metalliques (14, 15) catalysent cette rCaction en utilisant les hydroperoxydes ou les peracides comme source d'oxygkne.Cette reaction d'hydroxylation par les peracides peut Ctre decrite par un mCcanisme de type soit oxCnoi'de, soit radicalaire. Dans le premier cas on observe une tres bonne rCgio-et stCrCoselectivitC (6-8); par contre dans le second cas, les rCsultats sont de ce point de vue, beaucoup moins explicites (2-4). Pourtant les rCsultats de sClectivitC sont souvent utilisCs pour remonter au type de mecanisme mis en jeu: en clair, si une rCaction est trks rkgio-et surtout tres stCrCosClective, on en conclut en general que la rCaction n'est pas radicalaire.Nous nous sommes donc proposC d'apporter des riponses prCcises sur la rCgio-et stCrCosClectivitC d'hydroxylation d'un certain nombre d'hydrocarbures saturCs cycliques par le peracide benzoi'que, dans des conditions expkrimentales ou le mCcanisme est, sans ambiguitk, radicalaire.En effet, au cours des travaux que nous avons effectuCs sur la rCactivitC homolytique des peracides, nous avons montrC (16) que la dCcomposition du peracide benzo'ique en solution, a ebullition, conduit h.~l'hydroxylation du solvant, dans la mesure ou celui-ci est un donneur d'hydrogene, selon le mCcanisme en chalne dCcrit dans la fig. 1.Quand on utilise le cyclohexane comme solvant (R-H) on obtient une mole de cyclohexanol (R-OH) par mole de peracide mis en oeuvre, montrant ainsi l'efficacitk du processus.Comme hydrocarbures saturCs nous avons utilis-5 le cyclohexane, dont les resultats servent de references, le methylcyclohexane et l'adamantane, pour dkterminer la rCgiosClectivitC, et les decalines cis et trans pour obtenir des informations sur la stCrCosel...
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