ALLHAT: What Outcomes Would Have Been Expected

1
ALLHAT What Outcomes Would Have Been Expected?

• Comparisons Among Placebo- or No Treatment
  Controlled Trials

2
Effect of Antihypertensive Therapy on CV Events
CVD deaths
Fatal/nonfatal strokes
Fatal/nonfatal CHD events
CHF
LVH
Percent decrease in events vs placebo
17 randomized, placebo-controlled trials using
diuretic or b-blocker (n48,000)
All reductions are statistically significant
Moser M et al. J Am Coll Cardiol.
1996271214-1218. Hebert PR et al. Arch Intern
Med. 1993153578-581.
3
Event Reduction with Low Dose Diuretic or
b-Blocker
ns
ns
?25-50 mg HCTZ
Psaty, et al. JAMA 1997277739-745
4
Event ReductionSHEP Syst-EurRandomized
Controlled Trials in Isolated Systolic
Hypertension (ISH)
ns separately, but plt.05 combined
ns
ns
SHEP Systolic Hypertension in the Elderly,
n4,736 1st drug chlorthalidone Syst-Eur
Systolic Hypertension in Europe, n4,695 1st
drug nitrendipine
Syst-Eur (1997) was the only randomized
placebo-controlled morbidity trial in
hypertension with a calcium channel blocker
5
HOPE Trial
Effect of ACE Inhibition vs Placebo on CV Outcomes
CV Death
Nonfatal MI
Nonfatal Stroke
P lt .001
New/Worsening CHF
Revascularization
Worsening Angina
P .001
Risk Reduction ()
Yusuf S, et al. N Engl J Med. 2000342145-53
6
Event Reduction in SHEP, Syst-Eur, and HOPE
SHEP Systolic Hypertension in the Elderly,
n4,736 chlorthalidone Syst-Eur Systolic
Hypertension in Europe, n4,695
nitrendipine HOPE Heart Outcomes Prevention
Evaluation Study, n9,297 ramipril
7
PROGRESS Study Design
Randomization (6105 patients)
Eligibility (7121 patients)
Study end
Active therapy
Patients with a History of Cerebrovascular
Disease
4mg perindopril ? indapamide (2.5mg)
perindopril run-in
2 mg qd
4 mg qd
Placebo
2 weeks
2 weeks
4 years
(open)
(double-blind)
(2 mg in Japan)
Neal B, MacMahon S. J Hypertens 1995131869-1873
8
Stroke Risk Reduction in PROGRESS All
participants
28 risk reduction
0.20 0.15 0.10 0.05 0.00
95 CI 17 - 38
Plt0.0001
Placebo
Active perindopril /- indapamide
Proportion with event
BP difference 9/4 mm Hg
(Years)
0
1
2
3
4
PROGRESS Collaborative Group. Lancet
20013581033-41
9
Stroke and Major CVD Reduction in PROGRESS
PROGRESS Collaborative Group. Lancet 2001 358
1033-41
10
ALLHAT What Outcomes Would Have Been Expected?

• Comparisons Among Active Comparator Trials
  Involving Diuretic /- Beta-Blocker (D/BB)

11
Large Hypertension Trials Comparing Two or More
Regimens CVD or CV Mortality

• Trial n BP? Outcomes
• CAPPP 10,985 3/1 captopril not
  superior to D/BB
• NORDIL 10,881 3/ 0 diltiazem not superior
  to D/BB
• CONVINCE 16,602 0/1 verapamil not
  superior to
• D/BB (?equivalent?)
• STOP-2 6,628 0/-1
  isradipine/felodipine
• 0/ 0 ACEIs not superior to D/BB
• INSIGHT 6,592 0/ 0 nifed GITS not
  superior to diuretic
• ANBP-2 6,083 1/0 ACEIs not
  superior to diuretics
• ALLHAT 42,418 -3/-1 chlorthalidone
  superior to doxazosin,
• -1/1,-2/ 0 amlodipine (HF only),
  lisinopril

12
ALLHAT vs. ANBP2Blood Pressure Endpoints
13
ALLHAT vs. INSIGHTBlood Pressure Endpoints
14
ALLHAT Compared to Other Large CVD Endpoint
Trials Conclusion

• Findings from other major trials are totally
  consistent with ALLHATs conclusion that
  diuretic-based antihypertensive treatment is
  unsurpassed in preventing major cardiovascular
  morbidity and mortality, and offer some support
  for its superiority in reducing risk of heart
  failure.