Editorial Slides VP Watch, April 8, 2003, Volume 3, Issue 13

Aspirin, Statin, or Flu Vaccine?The Most Cost-Effective Therapy

– 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.

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.

• 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.

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.

• 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.

• 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.

• 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

• 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.

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

$198,000

$13,200

020,00040,00060,00080,000

100,000120,000140,000160,000180,000200,000

Cost/Life Saved

StatinFlu Vaccine

$

Dollars Spent to Save One Life

Naghavi et al. 2003 unpublished data

• 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.

.

                     

statinAspirin

Aspirin

Statin

Cost-Effectiveness Balance

.

                     

statinFlu Vac

Flu Vaccine

Statin

Cost-Effectiveness Balance

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.

• 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:

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?

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

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.

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.

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) Study.

• 5. Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly.

• 6. Myocardial infarction, stroke, and sudden cardiac death may be prevented by influenza vaccination.

• 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.