This document summarizes research on the effectiveness and cost-effectiveness of influenza vaccination, statin drugs, and aspirin for preventing cardiovascular events. It finds that influenza vaccination has been shown to reduce hospitalizations for cardiovascular disease by 6-12% and lower mortality by 48-50% based on observational studies. The cost per life saved from influenza vaccination is estimated to be $13,200, much lower than the $198,000 per life saved by statin drugs. The document concludes that influenza vaccination could be a highly cost-effective addition to prevention strategies given its low cost and potential population-level benefits.

1. Editorial Slides
VP Watch, April 8, 2003, Volume 3, Issue 13
Aspirin, Statin, or Flu Vaccine?
The Most Cost-Effective Therapy

2. –Several groups have reported beneficial
effect of influenza vaccination on sudden
cardiac death 1
, recurrent myocardial
infarction 2
, brain infarction 3
, and MACE
after PTCA 4
.
–Considering the tremendous impact of
cardiovascular disease on modern society
and the widespread annual epidemics of
influenza, this subject deserves special
attention with regard to public
cardiovascular health.

3. As featured in VPWatch of this week,
Nichol et al5
, in an observational study
involving 140,000 people over 1998-9 and
146,000 over 1999-2000 (all >65y), found
a decrease of hospitalization among
vaccinated individuals for cardiovascular
disease, cerebrovascular disease, and
pneumonia.
Amazingly, the risk of all-cause mortality
was 48-50% lower among vaccinated
compared to non-vaccinated individuals.

4. • No other therapy in
cardiovascular medicine has ever
been demonstrated to achieve
results as those described by
Nichol’s et al.
A cost-effective analysis may
further illustrate the public health
effect of this therapy.

5. Statin; the Magic Pill
• Statin has become the magic
therapy for primary and secondary
prevention of cardiovascular
events.
• Based on the Heart Protection
Ptudy8
, Hamilton-Craig9
, analyzed
the number of patients needed to
be treated in order to prevent one
cardiovascular event.

7. • As the table makes it clear, the absolute
increase in risk is dependent on the
baseline characteristics of the
population and the vascular event that
is prevented.
• The sicker the population and the
greater number of events to be
prevented, the smaller is the number of
patients needed to be treated to prevent
that outcome.

8. • According to Hamilton-Craig9
48
patients need to be treated by
statin to avoid one myocardial
infarction in this high risk
population/5year.
• In other words, each year 10
million people need to be treated
by statin to save 50,000 lives.

9. • At a cost of about
$1,000/patient/year, the
approximate price for
preventing a non-fatal
myocardial infarction with
statin is:
$1,000x48x5 = $240,000 /year

10. • Meyers reported that flu vaccine
results in 6-12% absolute risk
reduction in vascular events in the
high risk population.
• Meyers 6
has estimated that it
requires 23 to 45 persons to be
vaccinated to prevent one
cardiovascular or
cerebrovascular event.

11. Estimated Cost-Effectiveness Analysis
• All >60y = 33 million (USA)
• All >60y and high Cholesterol = 33 million x 15% = 4.95 million
• Annual CHD death in >60y population = 500,000
• Absolute risk reduction for CHD death by flu vaccine in >60y =
6%
• Absolute risk reduction for CHD death by statin in >60y = 5%
• 33 million x $10 cost of flu vaccine / (500,000 x 0.06) =
$ 13,200 to save one life by flu vaccine
• 4.95 million x $1000 cost of statin / (500,000 x 0.05) =
$ 198,000 to save one life by statin
If all >60y US population receive flu vaccine and those with high
cholesterol receive statin:
Naghavi et al. 2003 unpublished data

12. $198,000
$13,200
0
20,000
40,000
60,000
80,000
100,000
120,000
140,000
160,000
180,000
200,000
Cost/Life Saved
Statin
Flu Vaccine
$
Dollars Spent to Save One Life
Naghavi et al. 2003 unpublished data

13. • Troche et al 9597427
compared the costs of aspirin
treatment with statin treatment
for the German Health Care
System.
• In their analysis (Fig 2), the saving
of 40 life years would be obtained
with 5 million DM with aspirin but
13 million DM with statins.

15. .
statin
Aspirin
Aspirin
Statin
Cost-Effectiveness Balance

16. .
statin
Flu Vac
Flu Vaccine
Statin
Cost-Effectiveness Balance

17. Conclusion:
• Data continues to accumulate regarding the
beneficial effect of influenza vaccination on
cardiovascular morbidity/mortality and total
mortality.
• The low cost of the vaccine (~ $10/year)
makes influenza vaccination a highly cost-
effective add on to the arsenal of available
therapies for reduction of CVD mortality and
morbidity to a great degree at population
level.

18. • Knowing the massive
population effect of influenza
infection, clinical trials are
urgently needed to evaluate
the effects of influenza
vaccination on vulnerable
patients across different age
groups.
Conclusion:

19. Questions / Hypotheses
1. What is (are) the mechanism(s) for the
detrimental effect of influenza infection
on the cardiovascular system?
2. Are newer medications for influenza
infection beneficial on the
cardiovascular system considering
that often the cardiovascular
complication occurs 1-2 weeks after
the respiratory symptoms have begun
to subside?

20. 3. Could influenza vaccination slow down
the progression of atherosclerosis in a
significant number of individuals?
4. The age-adjusted mortality for
cardiovascular disease has been
declining since the late 1960’s. Could
influenza vaccination have been a
significant player in this trend?
Questions / Hypotheses

21. Questions / Hypotheses
We have little data concerning all these
important questions. Recently Naghavi
et al 7
showed striking pro-inflammatory
and pro-thrombotic effects of influenza
infection on aged apoE null mice.
Whether similar effect accounts for the
increased morbidity/mortality in humans
is still unknown.

22. Flu Vaccine Under-Utilized
• Although influenza vaccination has been
available for 3 decades, as late as 1989
the vaccination rate among the elderly
was only 33%.
• It has increased up to 52% with the
findings of the Medicare Demonstrations
Project in 1993 and has reached around
63-66% in the present time.

23. References:
• 1. Influenza vaccination and the risk of primary cardiac arrest.
• 2.
Association of influenza vaccination and reduced risk of recurrent myocardial infarction.
• 3.
Association between influenza vaccination and reduced risk of brain infarction.
• 4. Influenza vaccine pilot study in acute coronary syndromes and planned
percutaneous
coronary interventions: the FLU Vaccination Acute Coronary Syndromes (FLUVACS) Stud
• 5.
Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke amo
• 6.
Myocardial infarction, stroke, and sudden cardiac death may be prevented by influenza va
• 7. Influenza infection exerts prominent inflammatory and thrombotic
effects on the atherosclerotic plaques of apolipoprotein E-deficient mice.
• 8. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin
in 20,536 high-risk individuals: a randomised placebo-controlled trial.
• 9.
The Heart Protection Study: implications for clinical practice. The benefits of
statin therapy do not come without financial cost.