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The Rationale for Initiating Therapy with Fixed-Dose Combinations in Hypertension. Thomas D. Giles, M.D. Tulane University School of Medicine New Orleans, LA.
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Thomas D. Giles, M.D.
Tulane University School of Medicine
New Orleans, LA
Disclosure: Grant support: Astra Zeneca, Amgen, Abbott, Novartis, The National Institutes of Health, Boehringer-Ingelheim, and Sankyo/Forest. Consultant for Novartis, Pfizer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Sankyo/Forest.This presentation is supported by Novartis Pharmaceuticals
Hypertension IncreasesMorbidity and Mortality
Treatment DecreasesMorbidity and Mortality
CHD Incidence Rate/1000 Person Years
Cumulative Fatal & Nonfatal Endpoints
The Framingham Study
The Vet. Adm. Study II
Ann Intern Med. 1961; 55:33–50.
JAMA. 1970; 213:1143–1152.
HCTZ, hydrochlorothiazide.Materson BJ et al. Hypertension. 1990;15:348-360.
Average Reduction in Events, %
Neal B et al. Lancet. 2000;356:1955–1964.
SBP/DBP (mm Hg)
*Individuals aged 40-69 years, starting at BP 115/75 mm Hg.
CV, cardiovascular; DBP, diastolic blood pressure;SBP, systolic blood pressure.
Lewington S et al. Lancet. 2002;360:1903-1913.
Chobanian AV et al. JAMA. 2003;289:2560-2572.
BP Differences of 10 mmHg Are Associated With Up to a 40% Effect on CV Risk
30% reduction in risk of IHD mortality
10 mmHg decrease in mean SBP
40% reduction in risk of stroke mortality
Lewington S et al. Lancet. 2002;360:1903–1913.
actively controlled trials.
placebo-controlled studies or trials with an untreated control group.
Negative values indicate tighter BP control on reference treatment.
UKPDS C vs A
HOT L vs H
HOT M vs H
Odds Ratio (experimental/reference)
UKPDS L vs H
Difference (reference treatment minus experimental treatment) in Systolic BP (mmHg)
Greater differences in BP reduction mean greater reductions in the risk of cardiovascular mortality.
BP, blood pressure
Staessen JA et al. Hypertension Research. 2005;28:385-407.
ABCD DBP <75
MDRD MAP <92
HOT DBP <80
AASK MAP <92
IDNT SBP <135/DBP <85
ALLHAT SBP <140/DBP <90
Multiple Antihypertensive Agents Are Needed to Achieve Target BP
Number of antihypertensive agents
Target BP (mm Hg)
DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure.
Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.
Lewis EJ et al. N Engl J Med. 2001;345:851-860.
Cushman WC et al. J Clin Hypertens. 2002;4:393-405.
Chobanian et al., JAMA 2003; 289:2560–72,