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Do Statins Work?

This is an analysis of how much statins reduce the risk of atherosclerotic cardiovascular (ASCVD) risk over a 10-year horizon. Such risk events include strokes and heart attacks.

Previously, I benchmarked three models estimating cardiovascular risk.

Of the three benchmarked models, the most relevant is the ASCVD Risk Estimator Plus (ASCVD Plus) from the American College of Cardiology. This is because it is more sensitive to risk inputs than the MESA model. And, it does estimate the risk reduction impact of statins and other therapies. Meanwhile, the Framingham model does not.

We will review the following:

1. The risk reduction impact of statins aimed at lowering the risk of high cholesterol.
2. The risk reduction impact of blood pressure medication aimed at lowering the risk of high blood pressure.
3. The risk reduction impact of statins and blood pressure medication aimed at lowering the combined risk of high cholesterol and high blood pressure.

We will focus on otherwise healthy 65-year-old Caucasians. And, we will disaggregate the risk for men and women as women have a drastically lower risk than men, as reviewed in an earlier article.

Statin impact on ASCVD 10-year risk

To use the ASCVD Plus model and measure the impact of cholesterol, I focused on the 65-year-old caucasian population. I sensitized the total cholesterol from 200 to 260. I assumed that the LDL cholesterol level was 50% of total cholesterol. I assumed a constant HDL cholesterol of 70. I also assumed individuals had healthy blood pressure (125/85). All the mentioned default inputs are necessary to run the ASCVD Plus model.

The table above shows the impact of statin on reducing the ASCVD 10-year risk for men with high cholesterol.

A 65-year-old man with a total cholesterol of 260 has an ASCVD 10-year risk of 12.1%. Taking statins would reduce this risk level to 9.1%. This represents an absolute or nominal risk reduction of — 3.0% percentage points or a relative risk reduction of — 24.8%.

As described, the support for statins can be manipulated depending on what statistics you focus on. An absolute risk reduction of — 3.0% seems small. Meanwhile, a relative risk reduction of — 24.8% sounds a lot more impressive.

Now, moving on to the same risk reduction assessment for women.

The table above shows the impact of statin on reducing the ASCVD 10-year risk for women with high cholesterol. Notice that there are no values related to the impact of statin therapy associated with a total cholesterol level of 200. This is because the baseline risk of 4.8% is below 5.0%. And, the American College of Cardiology does not recommend any therapy when someone’s risk is below 5%.

A 65-year-old woman with a total cholesterol of 260 has an ASCVD 10-year risk of 5.5%. Taking statins would reduce this risk level to 4.1%. This represents an absolute or nominal risk reduction of -1.4% percentage points and a relative risk reduction of — 25.5%.

This is a situation where the relative risk reduction (-25.5%) if misinterpreted, can greatly exaggerate the merits of statins. Focusing on the minimal absolute risk reduction (-1.4%) may not support taking any statins. As estimated, this would suggest that women are nearly immune to the impact of high cholesterol. That’s what the ASCVD Plus model from the American College of Cardiology indicates.

Blood pressure medication impact on ASCVD 10-year risk

When focusing on blood pressure, I sensitized the systolic blood pressure from 130 to 160. I assumed that the diastolic blood pressure would be 66.66% of the systolic blood pressure. And, I assumed as default values the cholesterol metrics shown in the top table below.

The table above shows the impact of blood pressure medication on reducing the ASCVD 10-year risk for men with high blood pressure.

A 65-year-old man with a systolic blood pressure of 160 has an ASCVD 10-year risk of 15.2%. Taking blood pressure meds would reduce this risk level to 11.1%. This represents an absolute or nominal risk reduction of — 4.1% percentage points or a relative risk reduction of — 27.0%.

Now, moving on to women.

The table above shows the impact of blood pressure medication on reducing the ASCVD 10-year risk for women with high blood pressure.

A 65-year-old woman with a systolic blood pressure of 160 has an ASCVD 10-year risk of 7.7%. Taking blood pressure meds would reduce this risk level to 5.6%. This represents an absolute or nominal risk reduction of — 2.1% percentage points or a relative risk reduction of — 27.3%.

This is another situation where focusing on the relative risk reduction (-27.3%) may overstate the merit of such a drug.

Combined therapy impact on reducing ASCVD 10-year risk

Now we combine both risks (high cholesterol and high blood pressure). And, we look at the risk reduction impact of taking both a statin and a blood prescription med.

The table above shows the impact of a combined therapy on reducing the ASCVD 10-year risk for men who have both high cholesterol and high blood pressure.

A 65-year-old man with a total cholesterol of 260 and a systolic blood pressure of 160 has an ASCVD 10-year risk of 18.1%. Taking both a statin and a blood pressure med would reduce this risk level to 11.9%. This represents an absolute or nominal risk reduction of — 6.2% percentage points or a relative risk reduction of — 34.3%.

Moving on to women…

The table above shows the impact of combined therapy on reducing the ASCVD 10-year risk for women who have both high cholesterol and high blood pressure.

A 65-year-old woman with a total cholesterol of 260 and a systolic blood pressure of 160 has an ASCVD 10-year risk of 8.8%. Taking both a statin and a blood pressure med would reduce this risk level to 4.8%. This represents an absolute or nominal risk reduction of — 4.0% percentage points or a relative risk reduction of — 45.5%.

Quantitative caveat

Note how relative risk reduction measures convey a large risk reduction benefit for statins and other meds. This may overstate the true risk reduction merit of such drugs. This is especially the case when looking at women’s cholesterol-related risk. Regarding women’s cholesterol condition, statins do not seem to do much.

Qualitative caveat

This analysis focuses on these meds’ risk reduction of ASCVD events. This analysis is incomplete because it does not factor in other considerations such as:

• Risk of falls, fractures, etc. Blood pressure prescription meds do increase this risk.
• Other side effects.

Regarding critical considerations such as all-mortality risk and cognitive impairment, I understand these drugs may not represent a material danger, and they may have positive implications.

THE END

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