PMID- 19014834
OWN - NLM
STAT- MEDLINE
DCOM- 20090209
LR  - 20151119
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 30
IP  - 10
DP  - 2008 Oct
TI  - Coadministration of valsartan 160 and 320 mg and simvastatin 20 and 40 mg in 
      patients with hypertension and hypercholesterolemia: a multicenter, 12-week, 
      double-blind, double-dummy, parallel-group superiority study.
PG  - 1782-93
LID - 10.1016/j.clinthera.2008.10.004 [doi]
AB  - BACKGROUND: Together, high blood pressure (BP) and high cholesterol levels 
      constitute a cumulative risk for coronary heart disease (CHD). Elevations in 
      cholesterol increase BP through upregulation of angiotensin type 1 receptors, 
      with a corresponding increase in cholesterol oxidation due to elevations in BP. 
      Hence, control of low-density lipoprotein cholesterol (LDL-C) and BP through 
      coadministration of an antihypertensive and a statin have potential benefit in 
      the management of CHD. OBJECTIVES: This study examined the dose response to 
      simvastatin 20 and 40 mg in reducing LDL-C and the efficacy and tolerability of a 
      high dose of valsartan (320 mg) when administered with simvastatin. METHODS: In 
      this multicenter, 12-week, double-blind, double-dummy, parallel-group superiority 
      study, patients with hypertension and hypercholesterolemia were randomized to 
      receive valsartan 160 mg along with simvastatin 20 or 40 mg. At week 6, valsartan 
      was titrated upward to 320 mg in both groups. The primary efficacy variable was 
      the change in LDL-C, calculated using the Friedewald formula or measured directly 
      (depending on triglyceride levels) and analyzed for superiority. Secondary 
      efficacy variables were the change in LDL-C and the proportion of patients 
      achieving LDL-C and BP control. Safety assessments included the occurrence of 
      adverse events (AEs) and serious AEs, and changes in hematology and biochemistry 
      variables, vital signs, and findings on physical examinations. RESULTS: Eight 
      hundred seventy-two patients were randomized to receive double-blind treatment, 
      and the intent-to-treat population included 838 patients. The combination of 
      valsartan 160 mg + simvastatin 40 mg was statistically superior to that of 
      valsartan 160 mg + simvastatin 20 mg in reducing LDL-C at week 6 (least squares 
      mean percent change from baseline: -38.5% vs -33.6%, respectively; P < 0.001); at 
      week 12, the corresponding values were -36.8% in the valsartan 320 mg + 
      simvastatin 40 mg group and -32.7% in the valsartan 320 mg + simvastatin 20 mg 
      group (P = 0.002). Rates of combined LDL-C and BP control at week 6 were 35.1% 
      (146/416) in the valsartan 160 mg + simvastatin 20 mg group and 37.4% (154/412) 
      in the valsartan 160 mg + simvastatin 40 mg group; at week 12, rates of combined 
      control were 50.7% (212/418) in the valsartan 320 mg + simvastatin 20 mg group 
      and 50.0% (206/412) in the valsartan 320 mg + simvastatin 40 mg group. AEs 
      occurred in 24.3% (102/420) of the valsartan 160/320 mg + simvastatin 20 mg group 
      and 22.2% (93/419) of the valsartan 160/320 mg + simvastatin 40 mg group. 
      CONCLUSIONS: In these patients with hypertension and hypercholesterolemia, 
      coadministration of valsartan and simvastatin was well tolerated and was 
      associated with significant reductions from baseline in BP and LDL-C. 
      Coadministered with valsartan 160/320 mg in the evening, simvastatin 40 mg had 
      superior LDL-C-lowering efficacy to simvastatin 20 mg.
FAU - Rump, Lars-Christian
AU  - Rump LC
AD  - Department of Internal Medicine/Nephrology, Heinrich-Heine-Universitat 
      Dusseldorf, Dusseldorf, Germany.
FAU - Baranova, Elena
AU  - Baranova E
FAU - Okopien, Boguslaw
AU  - Okopien B
FAU - Weisskopf, Marianne
AU  - Weisskopf M
FAU - Kandra, Albert
AU  - Kandra A
FAU - Ferber, Philippe
AU  - Ferber P
LA  - eng
SI  - ClinicalTrials.gov/NCT00254475
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Tetrazoles)
RN  - 80M03YXJ7I (Valsartan)
RN  - AGG2FN16EV (Simvastatin)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Aged
MH  - Anticholesteremic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Antihypertensive Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Blood Pressure
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Hypercholesterolemia/*drug therapy
MH  - Hypertension/*drug therapy
MH  - Lipoproteins, LDL/blood
MH  - Male
MH  - Middle Aged
MH  - Simvastatin/administration & dosage/adverse effects/*therapeutic use
MH  - Tetrazoles/administration & dosage/adverse effects/*therapeutic use
MH  - Valine/administration & dosage/adverse effects/*analogs & derivatives/therapeutic 
      use
MH  - Valsartan
EDAT- 2008/11/19 09:00
MHDA- 2009/02/10 09:00
CRDT- 2008/11/19 09:00
PHST- 2008/08/14 00:00 [accepted]
PHST- 2008/11/19 09:00 [pubmed]
PHST- 2009/02/10 09:00 [medline]
PHST- 2008/11/19 09:00 [entrez]
AID - S0149-2918(08)00325-1 [pii]
AID - 10.1016/j.clinthera.2008.10.004 [doi]
PST - ppublish
SO  - Clin Ther. 2008 Oct;30(10):1782-93. doi: 10.1016/j.clinthera.2008.10.004.