The Recent Treatment Trials,, VALUE -- ASCOT Trophy -- Should the results of these studies change the approach

1. 1 The Recent Treatment Trials,, VALUE -- ASCOT � Trophy -- Should the results of these studies change the approach to Hypertension management?

2. 2 WHAT REALLY MATTERS IN DECIDING ON THERAPY? It is still the same old question Is it blood pressure lowering alone that makes the difference or specific medications?

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4. 4 Results of PLACEBO CONTROLLED TRIALS Effect of Antihypertensive Drug Treatment on Cardiovascular Events

5. 5 THE VALUE TRIAL

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8. 8 Primary Composite Endpointsin Value Study

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14. 14 ASCOT INVESTIGSTORS CONCLUSIONS �Contemporary therapy [ccb/ace] is superior to older therapy[bbl/diuretic] in the management of hypertension�--- �RESULTS ARE GENERALIZABLE�-

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18. 18 THERE IS LITTLE DOUBT THAT A combination of an ACEI and a CCB is effective and is a reasonable choice for therapy for many hypertensives. At present, however, there is no strong evidence that this is a preferred combination when compared to a diuretic/ ACEI or ARB

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23. 23 Conclusions were based solely on analyses of secondary endpoints. Messerli, � We should remember [as we were told by the ALLHAT investigators] that secondary endpoints are �soft data� that should not form a basis for main conclusions or lead to a labeling of a drug class as preferred� ---- WHAT ABOUT ASCOT?

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26. 26 THE MESSAGE IS CLEAR. WHILE THERE MAY BE some REASONS TO USE SPECIFIC DRUGS, MOST OF THE BENEFIT REPORTED IN THE CLINICAL TRIALS RESULTED FROM BP LOWERING with multiple drug therapy. TRIAL RESULTS ARE,THEREFORE, NOT REALLY CONFUSING.

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31. 31 JNC 7 Blood Pressure Classification

32. 32 �Prehypertension�

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34. 34 Baseline BP Predicts Progression to Hypertension

35. 35 High-normal blood pressure (BP) is associated with an increased risk for cardiovascular disease (CVD). The association between baseline BP and the incidence of CVD on follow-up was investigated in 6859 participants in the Framingham Heart Study who were initially free of hypertension and CVD [Vassan et al, 2001]. A stepwise increase in cardiovascular (CV) event rates was noted in subjects with higher baseline BP levels. The 10-year cumulative incidence of CVD in subjects aged 35 to 64 years with high-normal BP at baseline (systolic BP: 130-139 mm Hg; diastolic BP: 85-89 mm Hg) was 4% in women and 8% in men. In older subjects (aged 65 to 90 years), the CV incidence was 18% in women and 25% in men. Compared with optimal BP, high-normal BP was associated with a risk factor�adjusted hazards ratio of 2.5 in women and 1.6 in men.High-normal blood pressure (BP) is associated with an increased risk for cardiovascular disease (CVD). The association between baseline BP and the incidence of CVD on follow-up was investigated in 6859 participants in the Framingham Heart Study who were initially free of hypertension and CVD [Vassan et al, 2001]. A stepwise increase in cardiovascular (CV) event rates was noted in subjects with higher baseline BP levels. The 10-year cumulative incidence of CVD in subjects aged 35 to 64 years with high-normal BP at baseline (systolic BP: 130-139 mm Hg; diastolic BP: 85-89 mm Hg) was 4% in women and 8% in men. In older subjects (aged 65 to 90 years), the CV incidence was 18% in women and 25% in men. Compared with optimal BP, high-normal BP was associated with a risk factor�adjusted hazards ratio of 2.5 in women and 1.6 in men.

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37. 37 Sustained Effect of Early vs Late Treatment with ACEI in SHR

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39. 39 CAN FURTHER ELEVATIONS IN B.P. BE PREVENTED BY TREATING �PRE-HYPERTENSION�? --------- A NEW 4-YEAR TRIAL TO TEST THE HYPOTHESIS --------THE TROPHY TRIAL

40. 40 TROPHY STUDY PARTICIPANTS N= 809 Average age: 49 years old Average Blood Pressure: 134/85 mm Hg Average BMI: 29.9 kg/m2

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42. 42 Trends in Systolic BP

43. 43 Kaplan-Meier Curves of Clinical Hypertension in the Two GroupsNumbers under the graph refer to hypertension-free individuals

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46. 46 Reserpine causes breast cancer Diuretics increase heart attack risk CCBs cause GI hemorrhages and do not reduce CHD events ACE inhibitors should not be used in people with renal disease Diuretics cause ESRD B-blockers may no longer be indicated in the treatment of hypertension

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50. 50 LOWER THE BP CVD outcome will be improved Except for some specific instances, it is the achieved BP level, not specific medications, that makes the difference Most patients require multidrug therapy

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52. 52 Algorithm for Drug Treatment of Hypertension

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56. 56 Baseline Characteristics of the Intention to Treat Group (cont.)

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61. 61 VALUE: Analysis of Results Based on BP Control at 6 Months When pooled, the outcomes data indicate that patients who were controlled, regardless of treatment regimen, had significantly better outcomes than those whose blood pressure was not controlled at 6 months.1 Early blood pressure control was a powerful determinant of almost all endpoints (except myocardial infarction).1 1. Weber MA et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical values in the VALUE trial. Lancet. 2004;363:2047-49.When pooled, the outcomes data indicate that patients who were controlled, regardless of treatment regimen, had significantly better outcomes than those whose blood pressure was not controlled at 6 months.1 Early blood pressure control was a powerful determinant of almost all endpoints (except myocardial infarction).1 1. Weber MA et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical values in the VALUE trial. Lancet. 2004;363:2047-49.

62. 62 CONFUSING MESSAGES FROM THE HYPERTENSION TREATMENT TRIALS What and whom shall we believe?