Aspirin / statin for preventing coronary heart disease in prediabetes?

Question

If a person has prediabetes what are the risks of taking aspirin and/or statins to prevent risk of coronary heart disease (angina, heart attack, sudden death)?

Answer 1

It is difficult to say, because the matter is controversial and in both cases it is still being investigated. The general rule for any medicine is that the benefits should outweigh the risks. (1) Both types of medicines that you ask about have some potentially serious side-effects. For aspirin they go from gastrointestinal disturbances, mucosal damage and slight asymptomatic blood loss to increased bleeding time and hemorrhagic stroke. (2,3) Statins, on the other hand, can also cause gastrointestinal disturbances, hepatitis and pancreatitis. Rhabdomyolysis, although rare is a very serious potential side-effect. (2)

Now, what about the potential benefits?

Aspirin

As for aspirin, some studies have shown that aspirin is effective in primary prevention and recommendations for its use are (3):

If an annual risk of coronary heart disease of < or =0.6% exists, aspirin is normally not indicated; for a risk of 0.7-1.4% the facts should be discussed with the patient. If a risk of > or =1.5% exists, aspirin should be given.

Some authors state that in diabetic patients the annual risk is always higher than 1.5% and therefore aspirin should be indicated in there patients. (4) However, the same study reports evidence from scientific literature showing that:

cardiovascular mortality of diabetic patients is as high as in nondiabetic patients with known coronary artery disease

Another meta-analysis concludes (5):

Whereas estimates of benefit among patients with diabetes remain imprecise, our analysis suggests that the relative benefit of aspirin is similar in patients with and without diabetes.

(emphasis mine)

This is in line with The European Society of Cardiology and European Association for the Study of Diabetes (EASD) guidelines published in 2007 (6):

Aspirin should be given for the same indications and in similar dosages to diabetic and non-diabetic patients.

Note that all of these studies are for patients with diabetes, not pre-diabetes. So, we can probably conclude that pre-diabetes on its own, without other proven risk factors for cardiovascular disease is not sufficient to indicate preventive use of aspirin.

Statins

European recommendations state:

• In diabetic patients with CVD, statin therapy should be initiated regardless of baseline LDL cholesterol, with a treatment target of <1.8–2.0 mmol/L (<70–77 mg/dL)

• Statin therapy should be considered in adult patients with type 2 diabetes, without CVD, if total cholesterol >3.5 mmol/L (>135 mg/dL), with a treatment targeting an LDL cholesterol reduction of 30–40%

(emph. mine)

So the presence of risk factors additional to diabetes are clearly required.

Another review says that several studies have (4):

demonstrated that patients with diabetes showed similar relative risk reductions compared with those without diabetes ranging from 19 to 58%, dependent on the study population and the statin used.

The same study cites:

The authors of the Collaborative Atorvastatin Diabetes Study trial even suggested that the debate about whether all patients with type 2 diabetes warrant statin treatment should now focus on whether any patients can reliably be identified as being at sufficiently low risk for statin treatment to be withheld.

As long as there are those, or as long as we don't know if there are such patients, it would be irresponsible to make a stiff guideline to prescribe these medicines without consideration of risks and benefits. If there are no other risk factors, it seems that evidence of benefits in pre-diabetic patients doesn't outweigh the risks of such therapy.

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One of the studies does suggest that (4):

Co-administration of aspirin and statins shows additional effects in reducing cardiovascular mortality.

But this can be used as an argument for making combination medicines known as fixed-dose combination medicines. The only true benefit is the convenience of taking one pill instead of two. A huge disadvantage is the inability to individualise the dose, along with potential interactions and double-dosing. The cost and cost-effectiveness over single active ingredient medicines depends solely on the manufacturer and other manufacturers in the field. Sometimes combination medicines are cheaper, sometimes they are more expensive.

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References:

1. Concepts in Risk-Benefit Assessment: A Simple Merit Analysis of a Medicine?

2. Martindale: The Complete Drug Reference, 34th edition

3. Primary prevention of coronary heart disease with aspirin

4. Should We Prescribe Statin and Aspirin for Every Diabetic Patient? Is it time for a polypill?

5. Aspirin for the Primary Prevention of Cardiovascular Events A systematic review and meta-analysis comparing patients with and without diabetes

6. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary