ライフサイエンスコーパス: valsartan

1 bitor, and a component of LCZ696 (sacubitril/valsartan).

2 hese genes was preserved by naloxone but not valsartan.

3 ting the angiotensin II type I receptor with valsartan.

4 ion, a failure prevented by naloxone but not valsartan.

5 ied changes in CRP that were associated with valsartan.

6 r heart failure was significantly lower with valsartan.

7 s a BP-independent antiproteinuric effect of valsartan.

8 as no longer different from that noted after valsartan.

9 s before and after administration of the ARB valsartan.

10 sponse to Ang I was blunted significantly by valsartan.

11 reatment with enalapril than with sacubitril/valsartan.

12 weeks (14% reduction; P=0.03) compared with valsartan.

13 kers of heart failure severity compared with valsartan.

14 d AT1 Ang II receptor blockade (benazeprilat/valsartan, 0.05/3 mg x kg(-1) d(-1)) and rapid pacing (n

15 d AT1 Ang II receptor blockade (benazeprilat/valsartan, 0.05/3 mg x kg(-1) x d(-1)) and rapid pacing

16 1012], 12 weeks, 835 [710-981]; ratio LCZ696/valsartan, 0.77, 95% CI 0.64-0.92, p=0.005).

17 ments (systolic/diastolic 11.2/6.6 mm Hg for valsartan, 11.6/6.5 mm Hg for amlodipine) and at no time

18 s 29% lower in patients receiving sacubitril/valsartan (114 [7%] patients) compared with patients rec

19 were randomly assigned to LCZ696 and 152 to valsartan; 134 in the LCZ696 group and 132 in the valsar

20 (455), a combination of aliskiren 150 mg and valsartan 160 mg (446), or placebo (459) for 4 weeks, fo

21 receive once-daily aliskiren 150 mg (n=437), valsartan 160 mg (455), a combination of aliskiren 150 m

22 le-blind treatment with valsartan 80 mg BID, valsartan 160 mg BID, or placebo while receiving their u

23 e (-6.8 mm Hg; P=0.013) were observed in the valsartan 160 mg group compared with placebo.

24 Patients were randomized to receive valsartan 160 mg PO BID, captopril 50 mg PO TID, or vals

25 Compared with placebo, the first dose of valsartan 160 mg resulted in a significantly greater red

26 led trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in pa

27 odialysis to placebo, ramipril (5 mg/d), and valsartan (160 mg/d) for 7 days, with a washout period o

28 6 patients were randomly assigned to receive valsartan; 198 were randomly assigned to receive placebo

29 ted with adverse effects similar to those of valsartan; 22 patients (15%) on LCZ696 and 30 (20%) on v

30 e patients reversed to normoalbuminuria with valsartan (29.9% versus 14.5%; P=0.001).

31 mly assigned to enalapril than to sacubitril/valsartan (3.1 vs 2.2 per 100 patient-years; HR, 1.37 [9

32 han to those randomly assigned to sacubitril/valsartan (3.3 vs 2.3 per 100 patient-years; HR, 1.43 [9

33 ing (n=9), (3) AT1 Ang II receptor blockade (valsartan, 3 mg x kg(-1) x d(-1)) and rapid pacing (n=9)

34 9), (2) concomitant AT(1) receptor blockade (valsartan, 3 mg/kg per day) and rapid pacing (n=8), (3)

35 3) concomitant AT1 Ang II receptor blockade (valsartan, 3 mg/kg/d) and rapid pacing (n=9), (4) concom

36 d (n=11); (2) IABP and AT1R blockade (AT1RB; valsartan, 3 ng/kg/hr; n=6).

37 int, the combination of aliskiren 300 mg and valsartan 320 mg lowered mean sitting diastolic blood pr

38 iskiren 300 mg 9.0 mm Hg decrease, p<0.0001; valsartan 320 mg, 9.7 mm Hg decrease, p<0.0001), or with

39 1.2 mm Hg, 95% CI -2.3 to -0.1; p=0.030) and valsartan 320 mg/day (-4.4 mm Hg, -5.4 to -3.3; p<0.0001

40 rdial infarction, to additional therapy with valsartan (4909 patients), valsartan plus captopril (488

41 eated animals with animals treated with oral valsartan (50 mg/kg/d), oral enalapril (10 mg/kg/d), and

42 f therapy, plasma aldosterone was reduced by valsartan 80 mg BID (-52.1 pg/mL; P=0.001) and 160 mg BI

43 omly assigned to double-blind treatment with valsartan 80 mg BID, valsartan 160 mg BID, or placebo wh

44 A pressure reduction from valsartan 80 mg did not achieve statistical significance

45 an 160 mg PO BID, captopril 50 mg PO TID, or valsartan 80 mg PO BID plus captopril 50 mg PO TID betwe

46 mg/day), nebivolol (5 mg/day or 20 mg/day), valsartan (80 mg/day or 160 mg/day), or placebo.

47 th enalapril 10 mg twice daily or sacubitril/valsartan 97/103 mg twice daily (previously known as LCZ

48 (LVEF) </=40%] were randomized to sacubitril/valsartan 97/103 mg twice daily versus enalapril 10 mg t

49 Sacubitril/valsartan, a combination angiotensin receptor-neprilysin

50 Valsartan, a specific AT1 receptor antagonist inhibited

51 and assessed the effectiveness of sacubitril/valsartan across the LVEF spectrum.

52 Valsartan added to background therapy for heart failure

53 Most importantly, valsartan administration also attenuated the development

54 Neither ramipril nor valsartan affected BP during hemodialysis.

55 y profile similar to that with aliskiren and valsartan alone.

56 Treatment with valsartan also resulted in significant improvements in N

57 f blood pressure were complete, created 5006 valsartan-amlodipine patient pairs matched exactly for s

58 lity and morbidity in the subgroup receiving valsartan, an ACE inhibitor, and a beta-blocker raises c

59 56% (95% CI, 49.6 to 63.0) of baseline with valsartan and 92% (95% CI, 81.7 to 103.7) of baseline wi

60 or the syntheses of industrial precursors to valsartan and boscalid from chloroarenes with approximat

61 The interaction between valsartan and CKD was also tested.

62 rsus 17% of patients treated with sacubitril/valsartan and enalapril, respectively.

63 he wholesale acquisition cost for sacubitril/valsartan and enalapril.

64 nd/or beta-blocker (BB) were randomized into valsartan and placebo groups and followed for a mean of

65 Baseline LVIDd and EF for valsartan and placebo groups were similar: 3.6 +/- 0.5 v

66 and increase in EF were no different between valsartan and placebo groups.

67 Valsartan and placebo were compared by RRs for M + M.

68 Small but significant differences between valsartan and placebo were present for change in right v

69 ents on background therapy and randomized to valsartan and placebo, serial recordings of left ventric

70 Valsartan and ramipril both lowered D-dimer levels (P<0.

71 Valsartan and ramipril both lowered IL-6 levels during d

72 Both valsartan and tempol substantially attenuated mitochondr

73 tensin type 1 receptor blockers losartan and valsartan and the angiotensin-converting enzyme inhibito

74 rtan+LBQ augmented the inhibitory effects of valsartan and the highest doses completely abrogated ang

75 o) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitri

76 Rates of adverse events for losartan, valsartan, and candesartan users (N=136 177) aged >/=66

77 Among generic users of losartan, valsartan, and candesartan, there was an increase in rat

78 d 1.26 +/- 0.10 for no treatment, enalapril, valsartan, and SK-1080, respectively).

79 We compared the effects of captopril, valsartan, and their combination on atherosclerotic even

80 artan group died, as did 941 patients in the valsartan-and-captopril group and 958 patients in the ca

81 l, 0.90 to 1.11; P=0.98; hazard ratio in the valsartan-and-captopril group as compared with the capto

82 The valsartan-and-captopril group had the most drug-related

83 The Valsartan Antihypertensive Long-term Use Evaluation (VAL

84 The Valsartan Antihypertensive Long-term Use Evaluation (VAL

85 s effect was proposed after results from the Valsartan Antihypertensive Long-Term Use Evaluation (VAL

86 valuation (VALUE) trial, in which the use of valsartan (ARB) was compared with amlodipine in patients

87 found an excess of MIs among patients in the valsartan arm.

88 duced NT-proBNP to a greater extent than did valsartan at 12 weeks and was well tolerated.

89 and during follow-up in patients assigned to valsartan at a target dose of 160 mg twice daily or plac

90 The combination of aliskiren and valsartan at maximum recommended doses provides signific

91 CI 670-914], 12 weeks, 605 pg/mL [512-714]; valsartan: baseline, 862 pg/mL [733-1012], 12 weeks, 835

92 This stimulation was inhibited by valsartan, but not by PD 123319.

93 ibitory effects of the clinical AT1R blocker valsartan can be identified, whereas blockage of upstrea

94 Valsartan can slow progression and/or reverse early card

95 r mediated, because AT1 receptor antagonists valsartan, candesartan, and losartan inhibited Ang II-in

96 Valsartan, captopril, or the combination had comparable

97 randomly assigned to receive treatment with valsartan, captopril, or the combination; follow-up cont

98 trated consistent improvements in sacubitril/valsartan compared with enalapril through 36 months.

99 comes and on the effectiveness of sacubitril/valsartan compared with enalapril.

100 u by one year, and persisted to two years in valsartan compared with placebo patients, irrespective o

101 e better in patients treated with sacubitril/valsartan compared with those treated with enalapril, wi

102 The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across

103 e maximum recommended doses of aliskiren and valsartan, compared with each drug alone in patients wit

104 Moreover, high dietary potassium and valsartan each augmented the inhibitory effect of 11,12-

105 designed to test the hypothesis that the ARB valsartan, either alone or in combination with captopril

106 s, a high potassium intake or treatment with valsartan enhanced AA-induced inhibition of ENaC, an eff

107 of double-blind treatment with nebivolol and valsartan fixed-dose combination (5 and 80 mg/day, 5 and

108 Nebivolol and valsartan fixed-dose combination is an effective and wel

109 The application of 1% valsartan gel compared with other tested formulations an

110 One percent of valsartan gel-treated wounds also exhibited higher mitoc

111 ite endpoint occurred in 810 patients in the valsartan group (10.6%, 25.5 per 1000 patient-years) and

112 group and 0.26% (SD 1.25) in the sacubitril/valsartan group (between-group reduction 0.13%, 95% CI 0

113 weeks in the LCZ696 group compared with the valsartan group (LCZ696: baseline, 783 pg/mL [95% CI 670

114 ed by 23.8+/-3.0 pg/mL (SEM) (-17.4%) in the valsartan group (P<0.00001).

115 d by 0.60 (SD 1.4) cm/s from baseline in the valsartan group (p<0.0001) and 0.44 (1.4) cm/s from base

116 placebo group and 346 (13.8 percent) in the valsartan group (P<0.001).

117 ssure 4.0/2.1 mm Hg lower in amlodipine than valsartan group after 1 month; 1.5/1.3 mm Hg after 1 yea

118 .9) mm Hg reduction in blood pressure in the valsartan group and a 9.7 (17.0)/5.5 (10.2) mm Hg reduct

119 in the captopril group (hazard ratio in the valsartan group as compared with the captopril group, 1.

120 ollow-up of 24.7 months, 979 patients in the valsartan group died, as did 941 patients in the valsart

121 esults of Base-Case Analysis: The sacubitril-valsartan group experienced 0.08 fewer heart failure hos

122 At 8 months, sacubitril/valsartan group noted improvements in both KCCQ clinical

123 ns were persistently lower in the sacubitril/valsartan group than in the enalapril group over the 3-y

124 rtan; 134 in the LCZ696 group and 132 in the valsartan group were included in analysis of the primary

125 onfidence interval for the comparison of the valsartan group with the captopril group was within the

126 the valsartan group, and 37 in the aliskiren/valsartan group), mainly due to lack of therapeutic effe

127 In the valsartan group, aldosterone (baseline, 137+/-124 pg/mL,

128 group, 53 in the aliskiren group, 43 in the valsartan group, and 37 in the aliskiren/valsartan group

129 gator reported events 798), 587 (796) in the valsartan group, and 554 (756) in the combination group;

130 nd renal dysfunction were more common in the valsartan group, and cough, rash, and taste disturbance

131 (0.77, 0.58-1.02, p=0.073) in the sacubitril/valsartan group.

132 g; P=0.01) in the placebo group than in the valsartan group.

133 eased by a similar amount in the placebo and valsartan groups (P=0.94).

134 at a similar frequency in the captopril and valsartan groups.

135 ng-enzyme (ACE) inhibitors or beta-blockers, valsartan had a favorable effect in patients receiving n

136 olled in PARADIGM-HF who received sacubitril/valsartan had a greater long-term reduction in HbA1c tha

137 treated with a beta-blocker or randomized to valsartan had greater odds of being in the HFiEF group,

138 22 patients (15%) on LCZ696 and 30 (20%) on valsartan had one or more serious adverse event.

139 Sacubitril/valsartan has been approved for use in heart failure (HF

140 independent randomized clinical trials, the Valsartan Heart Failure Trial (Val-HeFT) (n=4053) and th

141 The Valsartan Heart Failure Trial (Val-HeFT) provided the fi

142 Of the 5010 subjects enrolled in the Valsartan Heart Failure Trial (Val-HeFT), 3519 had a bas

143 onths (n=1517) in patients randomized in the Valsartan Heart Failure Trial (Val-HeFT).

144 Retrospective analysis of Valsartan Heart Failure Trial data indicated that the qu

145 e of CRP in patients randomized in Val-HeFT (Valsartan Heart Failure Trial) and studied changes in CR

146 low-up in approximately 4300 patients in the Valsartan Heart Failure Trial.

147 ng changes in mortality and morbidity in the Valsartan Heart Failure Trial.

148 4 months (n=1345), and 12 months (n=1094) in Valsartan Heart Failure Trial.

149 The Valsartan in Acute Myocardial Infarction (VALIANT) Echo

150 ocardial infarction who were enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) echoc

151 4,703 patients with acute MI enrolled in the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial

152 entation for 1067 patients who had SD in the Valsartan in Acute Myocardial Infarction Trial (VALIANT)

153 as sudden death events in patients from the VALsartan In Acute myocardial infarctioN Trial (VALIANT)

154 events in 14,703 patients randomized in the Valsartan in Acute Myocardial Infarction Trial (VALIANT)

155 As part of the Valsartan in Acute Myocardial Infarction Trial (VALIANT)

156 The VALIANT (Valsartan in Acute Myocardial Infarction Trial) Echo stu

157 0 African-American patients) in the VALIANT (VALsartan In Acute myocardial iNfarcTion) trial were com

158 patients with HFrEF is reduced by sacubitril/valsartan in comparison with enalapril.

159 METHODS AND In the Valsartan in Heart Failure Trial (Val-HeFT), 5010 patien

160 In Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Researc

161 (LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Pre

162 The RR for M + M outcomes favored valsartan in the worse quartiles.

163 lol) and an angiotensin II receptor blocker (valsartan) in adults with hypertension.

164 Valsartan increased F(2)-isoprostane levels, and ramipri

165 In summary, during hemodialysis, valsartan induces a greater anti-inflammatory effect com

166 ration of the Ang II type 1 receptor blocker valsartan inhibited Ang II-induced ABCA1 mRNA repression

167 tensin receptor blocker component of LCZ696, valsartan inhibited both hypertrophy and fibrosis.

168 lockers interfere with AT1R-Gq coupling, and valsartan interferes with betaAR-Gs coupling.

169 Valsartan is as effective as captopril in patients who a

170 Limitation: The benefit of sacubitril-valsartan is based on a single clinical trial.

171 Dual valsartan+LBQ augmented the inhibitory effects of valsar

172 ure (PARADIGM-HF) trial, in which sacubitril/valsartan (LCZ696) reduced both death and HF hospitaliza

173 sin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696) reduced cardiovascular morbidity and

174 ht to determine if treatment with sacubitril/valsartan (LCZ696) reduces rates of hospital readmission

175 These findings demonstrate that sacubitril/valsartan leads to better HRQL in surviving patients wit

176 ined BP and the same degree of BP reduction, valsartan lowered UAER more effectively than amlodipine

177 Valsartan lowered UAER similarly in both the hypertensiv

178 The MicroAlbuminuria Reduction With VALsartan (MARVAL) study was designed to evaluate the BP

179 These data suggest that sacubitril/valsartan might enhance glycaemic control in patients wi

180 AAF, suggesting that the angiotensin blocker valsartan might prevent HAAF.

181 A total of 88 patients (valsartan, n=44; placebo, n=44) were enrolled in the tri

182 The effect of valsartan on estimated glomerular filtration rate was es

183 The beneficial effect of valsartan on first morbid events was similar in those wi

184 The effect of valsartan on mortality did not differ in patients with a

185 There was no significant treatment effect of valsartan on right ventricular ejection fraction, exerci

186 ned to evaluate the BP-independent effect of valsartan on UAER in type 2 diabetic patients with micro

187 ion, and the effect of LCZ696, compared with valsartan, on hs-TnT over 36 weeks.

188 ertension, were randomly assigned to 80 mg/d valsartan or 5 mg/d amlodipine for 24 weeks.

189 achieved blood pressures, regimens based on valsartan or amlodipine would have differing effects on

190 arallel-group comparison of therapy based on valsartan or amlodipine.

191 ndomly assigned to treatment with sacubitril/valsartan or enalapril.

192 line, 12 and 36 weeks after randomization to valsartan or LCZ696.

193 ine and another combination drug, sacubitril/valsartan or LCZ696.

194 Intervention: Treatment with sacubitril-valsartan or lisinopril.

195 emia, with or without concurrent exposure to valsartan or naloxone.

196 2 months between groups randomly assigned to valsartan or placebo depended on baseline ACE inhibitor

197 were randomly assigned to receive 160 mg of valsartan or placebo twice daily.

198 rt failure were randomly assigned to receive valsartan or placebo.

199 improved with either ANG II receptor blocker valsartan or superoxide dismutase/catalase mimetic tempo

200 were randomly assigned to receive captopril, valsartan, or both.

201 Treatment with the ACE inhibitor captopril, valsartan, or the combination of captopril plus valsarta

202 between Sprague-Dawley, untreated Ren2, and valsartan- or tempol-treated Ren2 rats.

203 The benefit of sacubitril/valsartan over enalapril was similar to the primary outc

204 The benefit of sacubitril/valsartan, over an angiotensin-converting enzyme inhibit

205 onal therapy with valsartan (4909 patients), valsartan plus captopril (4885 patients), or captopril (

206 Valsartan pretreatment blocked Fra2 binding to the ABCA1

207 Valsartan prevented CsA-induced oxidative stress as well

208 Conclusion: Treatment with sacubitril-valsartan provides reasonable value in reducing cardiova

209 Valsartan reduced estimated glomerular filtration rate c

210 and Morbidity in Heart Failure), sacubitril/valsartan reduced morbidity and mortality compared with

211 fraction, whether treatment with sacubitril/valsartan reduced NT-proBNP below specific partition val

212 Valsartan reduced the estimated glomerular filtration ra

213 ril did not reduce focal tracer uptake, oral valsartan resulted in partial blockade (infarct-to-remot

214 sartan, or the combination of captopril plus valsartan resulted in similar changes in cardiac volume,

215 of drugs for the treatment of heart failure: Valsartan/sacubitril (formerly known as LCZ696 and curre

216 g clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure w

217 bidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and

218 identify a PKG-dependent mechanism by which valsartan/sacubitril, a combination drug recently approv

219 We review here the mechanisms of action of valsartan/sacubitril, the pharmacological properties of

220 Compared with placebo, valsartan significantly (P<0.001) reduced the rate of in

221 hat preventive treatment of Tg2576 mice with valsartan significantly reduced AD-type neuropathology a

222 Valsartan significantly reduced arterial pressure in kno

223 Valsartan significantly reduced the RDS after 6 months v

224 Valsartan significantly reduces the combined end point o

225 ase were quartile-dependent and greater with valsartan than placebo at virtually all time points.

226 point, however, was 13.2 percent lower with valsartan than with placebo (relative risk, 0.87; 97.5 p

227 e effect of the angiotensin-receptor blocker valsartan, the ACE inhibitor captopril, and the combinat

228 There was no significant effect of 3-year valsartan therapy on systemic right ventricular ejection

229 Background: Sacubitril-valsartan therapy reduces cardiovascular mortality compa

230 ith moderate heart failure demonstrated that valsartan therapy taken with either ACEI or BB reversed

231 en improvements in mortality with sacubitril/valsartan, this analysis provides comprehensive assessme

232 to LCZ696 titrated to 200 mg twice daily or valsartan titrated to 160 mg twice daily, and treated fo

233 eive either the angiotensin receptor blocker valsartan (titrated to 320 mg once daily) or matched pla

234 stration of the angiotensin receptor blocker valsartan to intact mice results in a significant reduct

235 addition of the angiotensin-receptor blocker valsartan to standard therapy for heart failure.

236 In sacubitril/valsartan-treated patients, median NT-proBNP was signifi

237 Results of Sensitivity Analysis: Sacubitril-valsartan treatment was most sensitive to the duration o

238 ental costs and QALYs gained with sacubitril/valsartan treatment were estimated at $35512 and 0.78, r

239 -remodeling effect and clinical benefit with valsartan treatment.

240 independent of clinical variables, sST2, and valsartan treatment.

241 It has been demonstrated that Valsartan (Val) as an angiotensin receptor blocker has r

242 We studied the efficacy of valsartan (Val) to slow cardiovascular disease progressi

243 valuate the cost-effectiveness of sacubitril-valsartan versus angiotensin-converting enzyme inhibitor

244 oup, and 554 (756) in the combination group; valsartan versus captopril, p = 0.651 (0.965); combinati

245 Overall, the sacubitril/valsartan versus enalapril hazard ratio for the primary

246 imed to investigate the effect of sacubitril/valsartan versus enalapril on HbA1c and time to first-ti

247 rdiovascular risk factors were randomized to valsartan versus placebo and nateglinide versus placebo

248 Valsartan versus placebo changes from baseline in LVIDd

249 000 patients with HF treated with sacubitril/valsartan vs enalapril over 30 years.

250 e pressor response to Ang I before and after valsartan was also reevaluated in 11 patients after the

251 the placebo group; however, after 12 months, valsartan was associated with a decrease in CRP in patie

252 sin receptor neprilysin inhibitor sacubitril/valsartan was associated with a reduction in cardiovascu

253 Valsartan was associated with a similar frequency of sig

254 The effect of sacubitril/valsartan was consistent across all subgroups examined.

255 Sacubitril/valsartan was effective across the LVEF spectrum, with n

256 Sacubitril/valsartan was effective at reducing cardiovascular death

257 sin receptor neprilysin inhibitor sacubitril/valsartan was more effective than the angiotensin-conver

258 Treatment with sacubitril/valsartan was nearly twice as likely as enalapril to red

259 The effect of valsartan was similar in all subgroups, including those

260 we found that only 1 of the candidate drugs, valsartan, was capable of attenuating oligomerization of

261 However, candesartan and valsartan were the most potent at blocking AngII-induced

262 Combining valsartan with captopril increased the rate of adverse e

263 the Markov model calculated that sacubitril/valsartan would increase life expectancy at an ICER cons

264 is that for the same blood-pressure control, valsartan would reduce cardiac morbidity and mortality m

265 Sensitivity analyses demonstrated sacubitril/valsartan would remain cost-effective vs enalapril.