1. Polypill x Aspirin Project Groups 3 and 4
Does a polypill which contains low doses of BP and lipid lowering drugs prevent morbidity and mortality from cardiovascular disease (CVD); and does aspirin reduce the risk of a composite outcome of CVD and cancer.
A 2x2 factorial study
I will review with you the current status of adjuvant therapy in colon cancer, describe ongoing trials, and then speak about studies that are in development. I will briefly, at the end, talk about rectal cancer, with regard to the current status of adjuvant therapy and then describe a couple of trials that are in development.

2. Polypill Rationale
The hypothesis is that lowering risk factors among individuals with high absolute risk of CVD but without an indication for treatment will be beneficial – a primary prevention effort among those without “high” levels.
Epidemiological data indicate risk is continuous down to at least 115/75 mm Hg of BP and to 135 mg/dl for total cholesterol.
Drug treatments for elevated BP and lipids have been studied for many years and are safe.
There is considerable uncertainty about whether the benefits of risk factor - lowering extend to primary prevention among those without “high” levels.

3. Aspirin Rationale
Aspirin has anti-inflammatory properties that are associated with reductions in CVD and cancer.
Aspirin is recommended for secondary prevention of CVD, but the benefit/risk for primary prevention is uncertain.

4. 25 Year CVD Mortality for Men Screened in MRFIT*
Serum Cholesterol (mg /dl)
JNC-VII BP Category
342,815 men and 32,845 CVD deaths
* Age-adjusted rate per 10,000 person years

5. Antiplatelet therapy
Yes No
Antihypertensive therapy
Residual neurological signs
Atrial fibrillation
<6 months
≥ 6 months
0.4
1.0
2.0
28% (17 to 38%) risk reduction
(2P<0.001)
Current smoker
Time since index event
24% SE 3
reduction
(2P< )
0.6
0.8
1.2
1.4
Aspirin
ACE inhibitor
Beta -
blocker
Calcium antagonist
ALL PATIENTS
Treated hypertension
Rate ratio & 95% CI
Active better
Placebo better
Hazard ratio & 95% CI
Reduction of vascular events with statin therapy in the Heart Protection Study
Reduction of stroke with ACE-inhibitor ± diuretic therapy in the PROGRESS study

6. Combined effects of three interventions that each reduce relative risk by 25%
Even if they work less when used together (say 20% rather than 25% RRR) the final result doesn’t differ much (5.4% vs. 4.2% absolute risk)
Three successive 20% RR reductions
Three successive 25% RR reductions
Number of interventions

7. Questions To Consider Amount of nutritional hygienic advice
Target population – definition of “above average risk”
Definition of CVD and cancer outcomes
Management of participants who have increase in BP and/or lipids
Potential for interaction