Michael Weber, MD

1
Systolic hypertension not an isolated problem

• Michael Weber, MD
• Professor of Medicine Associate DeanDownstate
  College of MedicineState University of New
  YorkBrooklyn, NY
• George L Bakris, MD
• DirectorHypertension-Clinical Research
  CenterRush Medical CollegeChicago, IL

2
Systolic hypertension
Cardiovascular risk

• The association between systolic hypertension and
  cardiovascular risk is well recognized and has
  been seen in
• prospective clinical trials (eg, SHEP)
• multiple retrospective analyses
  (eg, Framingham data)
• analyses of cardiovascular risk data from renal
  patients with systolic hypertension

3
Systolic hypertension
Relative risk

• The evidence suggests that systolic blood
  pressure (SBP), especially in people gt 55 is a
  relatively more powerful predictor of
  cardiovascular events than is diastolic blood
  pressure (DBP).
• The Framingham data suggest that this difference
  in relative risk is 2-3 fold higher for SBP
  compared to DBP.

4
Systolic hypertension
The lower the better

• The old adage that systolic blood pressure should
  equal 100 plus your age is false.
• Prospective investigation has shown that in the
  older age groups, reducing SBP to 130-140 mm Hg
  reduces risk for cardiovascular events and
  mortality.

5
Systolic hypertension
Pathophysiology

• As the vasculature ages, relaxation is less
  likely to occur, and DBP rises.
• SBP pressure is also a reflection of the hardened
  posture of the vessels.
• Older vessels are less pliable and contribute to
  an increased pulse pressure which may be as
  important a predictor for cardiovascular events
  as an elevated SBP.

6
Systolic hypertension
Conclusions for management

• 1) Reducing SBP to around 140 or less gives
  better cardiovascular risk reduction than
  maintaining the SBP at 160-170.
• 2) The population that benefits the most from
  this reduction is the elderly.

7
The aging of America

• The population that will get the greatest
  benefit are actually the oldest patients, that is
  those patients that are 75-80 years of age, and
  with the aging of America, for that matter the
  world, at least the Western world, I think those
  are significant findings.
• George L Bakris, MD
• Director of the Hypertension/Clinical
• Research Center at Rush Medical College
• Chicago, IL

8
Systolic hypertension
Meeting the JNC-VI guidelines

• The JNC-VI (Joint National Commission) guidelines
  state that SBP should be less than 140 for
  everyone regardless of age.
• In the presence of comorbid conditions (diabetes,
  diabetic nephropathy), lower values (eg, 130) are
  recommended.
• Reaching these values is one of the most
  difficult tasks in clinical medicine.

9
Systolic hypertension
Treatment recommendations

• Prospective treatment trials (SHEP, Systolic
  Hypertension in the elderly program and Syst-Eur,
  Systolic Hypertension in Europe trial) used
  calcium channel blockers (CCBs) and diuretics to
  reduce SBP.
• Combination therapy, such as the additional use
  of ACE inhibitors in diabetics, or beta-blockers
  in patients with angina, is often required.
• Most patients will need to be controlled with 2-4
  different medications.

10
Which antihypertensive?

• So we shouldn't be arguing should it be a
  calcium channel blocker, should it be an ACE
  inhibitor, should it be a diuretic the fact is
  that most of our patients are going to require 2
  if not all 3 of those drugs. And sometimes even
  that isn't quite enough.
• Michael Weber, MD
• Immediate past president of the American Society
  of Hypertension

11
Systolic hypertension
Treat the elderly

• There does not appear to be an upper age limit
  for benefit in the treatment of SBP.
• The goal is to reduce stroke risk.
• A linear correlation exists between the level to
  which you've reduced blood pressure and the
  relative risk for stroke.

12
Systolic hypertension
SBP as an endpoint

• SBP and renal disease endpoints are becoming more
  important in drug development.
• The FDA approves medications for the treatment
  of hypertension which may be the treatment of
  DBP, SBP or both.

13
CCBs inferior?

• To say they provide no benefit is at best a
  stretch and the analysis used to come up with
  that conclusion is flawed in many respects, not
  the least of which being the trials that were
  selected.
• George L Bakris, MD
• on a meta-analysis showing CCBs to be
  inferior, presented by Dr Curt Furberg at the
  recent 2000 ESC meeting in Amsterdam

14
Ongoing clinical trials
Meta-analysis

• The first interim analysis from a prospective
  WHO/ISH meta-analysis of ongoing clinical
  trials (trials not published before 1995) in
  hypertension, coronary artery disease, and CHF
  analysis was reported at the International
  Society of Hypertension meeting (Chicago, August
  24, 2000).
• This interim analysis is based on 14 clinical
  trials involving 75 000 patients and gt6000
  cause-specific cardiovascular events.

15
The debate over CCBs

• Dr Steven MacMahon (Institute for International
  Health, University of Sydney, Australia) reported
  on the interim analysis. and drew two
  conclusions, as follows
•    
• 1) the newer agents, such as CCBs and ACE
  inhibitors, reduce cerebrovascular and
  cardiovascular complications, and
•       
• 2) only small differences exist between the
  different classes of drugs - diuretics, beta
  blockers, calcium antagonists and ACE inhibitors

Heartwire/Sep 1, 2000/Experts condemn Furberg's
meta-analysis showing calcium channel blockers to
be inferior.
16
Systolic hypertension
NORDIL study
The Nordic Diltiazem (NORDIL) study group
enrolled 10 881 patients aged 50 - 74 years with
a diastolic BP of gt 100 mm Hg. Patients were
randomly assigned to receive diltiazem,
diuretics, beta blockers, or a diuretic/beta
blocker combination. Endpoints included the
incidence of fatal and nonfatal stroke, MI, and
other cardiovascular death. The mean duration of
follow-up was 4.5 years.

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Systolic hypertension
NORDIL results
SBP and DBP were lowered effectively in all
groups, and diltiazem was as effective as
diuretics, beta blockers or both in preventing
all stroke, MI and other cardiovascular death.
All regimens were equally well-tolerated.

Hansson L, et al. Lancet 2000 356 359-365
18
Systolic hypertension
INSIGHT study
The Intervention as a Goal in Hypertension
Treatment, or INSIGHT trial compared the effects
of nifedipine with the combination amiloride and
hydrochlorothiazide on cardiovascular death, MI,
heart failure, or stroke. The trial randomized
6321 patients aged 55 to 80 years with BP gt150/95
mm Hg or gt160 mm Hg systolic and at least one
additional cardiovascular risk factor to either
of the two treatment arms.

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Systolic hypertension
INSIGHT results
As in the NORDIL trial, the effect on primary
outcomes was similar in the two groups, there
were an equal number of deaths, and both drugs
lowered BP equally effectively.

Brown MJ, et al. Lancet 2000 356 366-372