Metaanalysis of Effect of Statin Treatment on Risk of Sudden Death

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Meta-analysis of Effect of Statin Treatment on
Risk of Sudden Death
Giacomo Levantesi, Marco Scarano, RosaMaria
Marfisi, Giovanna Borrelli, Anne WS Rutjes,
MariaGiuseppina Silletta, Gianni Tognoni, Roberto
Marchioli
Am J Cardiol 20071001644-1650
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Background

• Currently, statins have been hypothesized to have
  several pleiotropic effects, including possibly
  antiarrhythmic action, in addition to their
  largely known lipid-lowering effect.
• Although many randomized controlled trials (RCTs)
  on statins enrolled patients with evidence of
  atherothrombotic disease, at high risk of sudden
  cardiac death (SCD), the evidence supporting such
  antiarrhythmic properties is limited.
• We therefore conducted a meta-analysis of all
  RCTs evaluating the effect of statins on SCD. In
  addition, we investigated whether a potential
  benefit of statins on SCD could be related to
  their lipid-lowering effects.

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Methods

• To retrieve published RCTs, a literature search
  constrained to human studies, without language
  restrictions, from January 1966 to July 2006, in
  the MEDLINE database was conducted. Moreover, a
  manual search of references cited by published
  studies and relevant review articles was
  performed.
• Studies were eligible for inclusion if
• the study design was a RCT
• the intervention consisted of a single treatment
  with a statin compared with placebo or no
  treatment
• the number of patients included in the study was
  100
• intervention duration was 6 months
• the number of events for SCD that occurred during
  the study were reported by intervention and
  control groups
• Exclusion criterion crossover design of the
  study.

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Study Selection
N1629 Potentially relevant RCTs identified in
1911 abstracts searched and screened for retrieval
N1062 RCTs excluded Reasons reviews, study
design without control group, trials not focusing
on clinical effects of statins, ongoing trials
N567 RCTs retrieved for more detailed evaluation
N447 RCTs excluded Reasons patients lt 100 or
follow-up lt 6 months
N120 Potentially appropriate RCTs to be
included in the meta-analysis
N110 RCTs withdrawn Reasons by outcome, no
reporting of sudden cardiac death
N10 RCTs definitely included
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Characteristics of studies, treatments, and
patients
AUS Australia B Belgium CDN Canada CerVE
cerebrovascular events D Germany F France I
Italy IL Israel MI myocardial infarction NL
Netherlands NZ New Zealand S Sweden SF
Finland ?TC total cholesterol levels changes in
treated patients UK United Kingdom USA United
States.
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Meta-analysis
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Subgroup analysis
Group not included in the heterogeneity
between-group test. Low lt1/year Moderate
1 to 3.5/year High gt3.5/year.
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Univariate linear regression analysis
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Conclusions

• During a mean follow-up of 4.4 years, statins
  reduced significantly (OR 0.81) the risk of SCD
  independently from baseline patient
  characteristics, with the only exception of age.
• The results of our meta-analysis in a large
  population of patients support the hypothesis
  generated by individual, sometimes small, and not
  randomized studies that part of the clinical
  benefit of statins could be due to a decrease in
  life-threatening arrhythmias.
• Hypothetical mechanisms
• decrease of the ischemic burden of myocardium
• stabilization of myocardium against
  proarrhythmic events mediated, also, by a
  normalization of sympathetic outflow.

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Implications

• The broad adoption of simple measures of
  aggressive treatment in subjects at higher
  cardiovascular risk may significantly reduce also
  Sudden Cardiac Death, one of the major public
  health problems.
• Statin seem to have the characteristics of such
  simple aggressive treatment.