Cheung, BMY

Hong Kong Medical Journal

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Title Sartans for hypertension - Implications of the ValsartanAntihypertensive Long-Term Use Evaluation (VALUE) trialAuthor(s) Cheung, BMYCitation Hong Kong Medical Journal, 2004, v. 10 n. 5, p. 359Issued Date 2004URL http://hdl.handle.net/10722/44948Rights Creative Commons: Attribution 3.0 Hong Kong LicenseHong Kong Med J Vol 10 No 5 October 2004      359COMMENTARYSartans for hypertension – implications of the ValsartanAntihypertensive Long-term Use Evaluation (VALUE) trialAngiotensin receptor blockers (ARBs), also known assartans, block the activation of angiotensin type 1 receptorsand have a recognised role in the treatment of heart failureand nephropathy. The Losartan Intervention For Endpointreduction in hypertension (LIFE) study1 and the Study onCognition and Prognosis in the Elderly (SCOPE)2 were twolarge clinical trials of ARBs in the treatment of hypertension.The LIFE study showed that a losartan-based regimenwas superior to an atenolol-based regimen in preventing car-diovascular events (mainly strokes) in hypertensive patientswith electrographic left ventricular hypertrophy. The favour-able results in LIFE study have led to claims that ARBs areespecially beneficial in patients with left ventricular hyper-trophy and especially good at preventing strokes. TheSCOPE study randomised elderly hypertensive patients intotwo groups: one group was given candesartan and the other,a placebo.2 Additional medications were allowed for bloodpressure control, so the difference in blood pressure in thetwo randomised groups was minimal. Unlike the LIFE study,the SCOPE study showed no statistically significant differ-ences in the main endpoints in the two groups. Thus, theresults of the Valsartan Antihypertensive Long-term UseEvaluation (VALUE) trial—in which valsartan was com-pared with amlodipine, a calcium channel blocker—wereeagerly anticipated. A positive result would propel ARBs tobecome the preferred treatment for hypertension.The results of VALUE have just been announced at the14th European Meeting on Hypertension in Paris andpublished.3 In terms of the primary composite endpoint,there was no significant difference between the treatments.In fact, when comparing the two groups, the patients treatedwith valsartan suffered more cases of myocardial infarctionand stroke (P=0.02 and P=0.08, respectively), instead ofreceiving greater protection from those diseases. On the plusside, there were fewer cases of new-onset diabetes in thevalsartan-treated group than in the amlodipine-treated group(13.1% versus 16.4%, P<0.0001).The findings in VALUE do not support claims that ARBsare particularly good for the heart or the brain. Instead, theyemphasise the importance of good blood pressure control.In the valsartan-treated group, the average blood pressurewas about 2.0 mm Hg/1.6 mm Hg higher in the valsartan-treated group over the course of the trial. The differencewas even greater in the first 6 months. The investigatorsattributed the negative results of the study to this bloodpressure difference and devised a new statistical test calledserial median matching to support their interpretation.Ironically, a similar mismatch of blood pressure in the treat-ment groups in the LIFE study1 and the Heart OutcomesPrevention Evaluation (HOPE) study4 had not underminedthe positive interpretation of these studies. Favourableresults in large clinical trials comparing antihypertensivedrugs increasingly depend on small and inconspicuous bloodpressure differences.It now seems clearer than ever that meticulous controlof blood pressure is important and worthwhile. A goodantihypertensive agent must at least do that. Hypertensionaffects about 20% of the general population and morethan half of the elderly.5 Unfortunately, just over halfof the hypertensive patients are on treatment, and goodcontrol is achieved in fewer than half of those beingtreated.6 The priority must surely be the detection of hyper-tension and other risk factors in the community, andachieving good blood pressure control. For the majority ofhypertensive patients, good control requires the use ofmore than one class of antihypertensive drugs. Angiotensinreceptor blockers are well tolerated and may reduce new-onset diabetes, whilst calcium channel blockers lower bloodpressure highly effectively in the Chinese. Both have a placein the formulary. Debating which antihypertensive drug isthe best is only of commercial, and not academic, interest.BMY Cheung, PhD, FHKAM (Medicine)(e-mail: mycheung@hkucc.hku.hk)Department of Medicine, The University of Hong KongQueen Mary Hospital, Pokfulam Road, Hong KongReferences1. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidityand mortality in the Losartan Intervention For Endpoint reductionin hypertension study (LIFE): a randomised trial against atenolol.Lancet 2002;359:995-1003.2. Lithell H, Hansson L, Skoog I, et al. The Study on Cognition andPrognosis in the Elderly (SCOPE): principal results of a randomizeddouble-blind intervention trial. J Hypertens 2003;21:875-86.3. Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensivepatients at high cardiovascular risk treated with regimens basedon valsartan or amlodipine: the VALUE randomised trial. Lancet2004;363:2022-31.4. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effectsof an angiotensin-converting-enzyme inhibitor, ramipril, on cardio-vascular events in high-risk patients. The Heart Outcomes PreventionEvaluation Study Investigators. N Engl J Med 2000;342:145-53.5. Cheung BMY, Man YB, Wat NMS, et al. Prevalence of hypertensionin the Hong Kong cardiovascular risk factor prevalence study cohort.Journal of the Hong Kong College of Cardiology 2004;12:33.6. Cheung BMY, Law FCY, Lau CP. Does the rule of halves applyin Chinese hypertensive patients? J Hypertens 2002;20 Suppl4:350S.

Sartans for hypertension - Implications of the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial

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Sartans for hypertension - Implications of the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial

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