Search PubMed⌕ Search

PubMed · 15526243

The VALUE trial: a commentary.

Abstract

The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) Trial compared coronary heart disease outcome in two anti-hypertensive treatment strategies based on either an angiotensin receptor blocker, valsartan, or a calcium channel blocker (CCB), amlodipine. In both patient groups a diuretic was added, if necessary, in an attempt to achieve blood pressure (BP) goals. Follow-up of over 15,000 patients was maintained for 4.2 years. There were no differences in the primary composite endpoint of cardiac morbidity and mortality (which included interventional procedures, hospitalised heart failure, non-fatal myocardial infarction and fatal coronary heart disease, however myocardial infarction and stroke events occurred less commonly on amlodipine than on valsartan the former achieving statistical significance [p=0.02 and p=0.08 respectively]). There was a non-significant excess of hospitalised heart failure on amlodipine (p=0.012). However, lower BPs early in the trial probably accounted for most of the observed benefits in favour of the CCB. The angiotensin receptor blocker arm was associated with less new onset diabetes. The results of VALUE add further support to the evidence that blood pressure control is the major determinant in outcome in trials of antihypertensive therapy.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Peter Sever. 2004. The VALUE trial: a commentary.. https://doi.org/10.3317/jraas.2004.033

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Differential effects of AT1 receptor and Ca2+ channel blockade on atherosclerosis, inflammatory gene expression, and production of reactive oxygen species.

Angiotensin II receptor blockade has been shown to inhibit atherosclerosis in several different animal models. We sought to determine if this effect was the result of blood pressure reduction per se or a result of the anti-inflammatory effects of receptor blockade. ApoE-deficient mice were fed a high fat diet and treated with either an angiotensin II receptor antagonist, candesartan (0.5 mg/kg/day, s.c.) or a calcium channel blocker, amlodipine (7.5 mg/kg/day, mixed with food). Atherosclerotic lesion area, aortic inflammatory gene expression as well as aortic H2O2 and superoxide production were assayed. We found that candesartan but not amlodipine treatment dramatically attenuated the development of atherosclerosis despite a similar reduction in blood pressure. Similarly, candesartan treatment inhibited aortic expression of inflammatory genes and production of reactive oxygen species, effects not seen with amlodipine. These data demonstrate that angiotensin II receptor blockade inhibits atherosclerosis by reducing vascular oxidative stress and inflammatory gene production independent of blood pressure reduction.

Amlodipine↗

A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the estimation of amlodipine in human plasma.

A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the estimation of amlodipine in human plasma. Amlodipine was extracted from human plasma by using a solid-phase extraction technique. Imipramine was used as the internal standard. A Hypersil BDS C18 column provided chromatographic separation of analytes followed by detection with mass spectrometry. The method involves a rapid solid-phase extraction from plasma, simple isocratic chromatography conditions and mass spectrometric detection that enables detection at sub-nanogram levels. The proposed method has been validated for a linear range of 0.1-10.0 ng/mL with correlation coefficient >or=0.9990. The intrarun and interrun precision and accuracy were within 10.0%. The overall recovery for amlodipine was 63.67%. Total run time was 3.2 min only.

Amlodipine↗

G1 cell cycle arrest by amlodipine, a dihydropyridine Ca2+ channel blocker, in human epidermoid carcinoma A431 cells.

We demonstrated previously that amlodipine, a dihydropyridine Ca(2+) channel blocker, exhibits antitumor effects on human epidermoid carcinoma A431 cells both in vitro and in vivo, in part through inhibition of capacitative Ca(2+) entry. In this study, we examined the effects of amlodipine on cell cycle distribution and cell cycle regulatory molecules in A431 cells, since a rise in intracellular Ca(2+) is required at several points during cell cycle progression. Flow cytometric analysis revealed that treatment with amlodipine (20-30muM, for 24h) induced G1 phase cell accumulation. The amlodipine-induced G1 arrest was associated with a decrease in phosphorylation of retinoblastoma protein (pRB), a regulator of G1 to S phase transition, reduction of protein levels of cyclin D1 and cyclin dependent kinase 4 (CDK4), G1 specific cell cycle proteins, and increased expression of p21(Waf1/Cip1), an inhibitory protein of CDK/cyclin complexes. In vitro kinase assay revealed that amlodipine significantly decreased CDK2-, CDK4-, and their partners cyclin E- and cyclin D1-associated kinase activities. The amlodipine-induced reductions in cyclin D1 protein expression and in CDK2 kinase activity were reproduced by a dihydropyridine derivative, nicardipine, having an inhibitory effect on A431 cell growth, but not by nifedipine, lacking the antiproliferative activity. Our results demonstrate that amlodipine caused G1 cell cycle arrest and growth inhibition in A431 cells through induction of p21(Waf1/Cip1) expression, inhibition of CDK/cyclin-associated kinase activities, and reduced phosphorylation of pRB.

Amlodipine↗