Should beta blockers remain first choice in the treatment of primary hypertension

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Should beta blockers remain first choice in the
treatment of primary hypertension?

• (aka, See, Teresa!
• We listen.)

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PRESENTATION OVERVIEW

• Review the background data
• Established roles, Proposed role
• Study the study
• Relevance, Validity, Results
• Discussion points

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BACKGROUND

• The Claim ? blockers are good.
• Outcome studies have demonstrated the value of ?
  blockers in patients.

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BACKGROUND? blockers are good.

• After myocardial infarction
• A 1999 systematic review found that the overall
  mortality after myocardial infarction in 31
  long-term trials was 10.1 percent beta blockers
  reduced the odds of death by 23 percent (95 CI
  15-31 percent).
• Freemantle N Cleland J, et al. ß-Blockade after
  myocardial infarction systematic review and meta
  regression analysis. BMJ 1999 Jun
  26318(7200)1730-7.

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BACKGROUND? blockers are good.

• With heart failure
• A 2001 meta-analysis found that ß-blockers
  reduced mortality in CHF patients at 1 year (odds
  ratio 0.65, 95 CI 0.53-0.80) and 2 years (odds
  ratio 0.72, 95 CI 0.61-0.84). ß-blockers also
  reduced hospitalization for HF (odds ratio 0.64,
  95 CI 0.53-0.79).

Brophy JM Joseph L, et al. Beta-blockers in
congestive heart failure. A Bayesian
meta-analysis. Ann Intern Med 2001 Apr
3134(7)550-60.
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BACKGROUND? blockers are good.

• With angina pectoris
• They improve exercise capacity, reduce
  exercise-induced ST depression, decrease the
  frequency of anginal episodes, and diminish the
  requirement for sublingual nitroglycerin.

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BACKGROUND

• The Question But are they that good?
• Some clinicians have argued that, since ?
  blockers are effective for secondary prevention,
  they should be effective in primary prevention in
  hypertensive patients.
• In other words

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THE STUDY

• Should beta blockers remain first choice in the
  treatment of primary hypertension?
• A meta-analysis.
• Lindholm LH, Carlberg B, Samuelsson O.
• Lancet. 2005 Oct 29-Nov 4366(9496)1545-53.

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STUDY RELEVANCE

• The Real Question Are you one of those
  clinicians?
• Do you use ? blockers as your first choice in the
  treatment of primary hypertension?

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STUDY RELEVANCE

• The Other Real Question
• Do your patients care?
• Are outcomes such as stroke and myocardial
  infarction important to your patients?

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STUDY VALIDITY

• Search strategies
• Cochrane Library,
• PubMed, and
• ASCOT-BPLA trial.

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STUDY VALIDITY

• Inclusion criteria
• Randomized controlled trial
• Treatment of primary hypertension
• ? blocker as 1st-line drug in at least 50 of all
  patients in one treatment group
• outcome data for all-cause mortality,
  cardiovascular morbidity, or both

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STUDY VALIDITY

• Analysis
• Heterogeneity between the studies was assessed
  with ?2 test and the chosen summary statistic
  variable was the reduction in relative risk (RR).
  
• When the p value for heterogeneity in any
  analysis was 0.10, the random model was used for
  calculations.
• (Uh Dave?)

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STUDY VALIDITY
Several 1st line rx options but which had a
beta-blocker in at least 50 of pts in one
treatment group
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STUDY RESULTS

• ß-blockers vs. Other drugs
• Relative risk of stroke was 16 higher with
  ß-blockers (95 CI 4-30 p0.009)
• Atenolol 26 (15-38 plt0.0001)
• Mixed trials 9 (-2-21 p0.13)
• Non-atenolol inconclusive
• RR of all-cause mortality trended similarly
  3 higher with ß-blockers (-1-8 p.14)
• RR of MI showed no difference

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STUDY RESULTS

• ß-blockers vs. Placebo or No treatment
• Relative risk of stroke was 19 lower with
  ß-blockers (95 CI 7-29)
• 1 Mixed trial 45 (15-65)
• Atenolol, Non-atenolol similar findings.
• RR of all-cause mortality and MI showed no
  difference.

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AUTHORS INTERPRETATION

• In comparison with other antihypertensive drugs,
  the effect of ß-blockers is less than optimum,
  with a raised risk of stroke.
• Hence, we believe that ß-blockers should not
  remain first choice in the treatment of primary
  hypertension and should not be used as reference
  drugs in future randomised controlled trials of
  hypertension.

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DISCUSSION

• Re-visiting Validity
• Pitfalls of meta-analysis Losing your marbles
• The value of enlarging large studies

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DISCUSSION

• Re-visiting Relevance
• Do you use ? blockers as your first choice in the
  treatment of primary hypertension?
• Selected patients?

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DISCUSSION

• Re-visiting Relevance
• Did the authors build a straw man?
• JNC 7 Report Thiazide-type diuretics should be
  used in drug treatment for most patients with
  uncomplicated hypertension, either alone or
  combined with drugs from other classes.

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DISCUSSION

• Re-visiting Relevance
• JNC 7 Report Compelling indications

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DISCUSSION

• Re-visiting Relevance
• Do your patients care?
• Untreated hypertension
• Increased stroke risk?