Jump to: Relative risk vs absolute risk | Data from SUSTAIN-6 | Does semaglutide reduce the risk of a heart attack? | How does semaglutide reduce the risk of a heart attack? | Take home message
A recent announcement from Novo Nordisk, the pharmaceutical company that manufactures Wegovy (semaglutide 2.4mg), declared that preliminary results from their latest trial had shown a 20% reduction in the number of major cardiovascular events (MACE), like a heart attack or stroke, compared to placebo.
As this was an announcement about the study, rather than its release, we can’t dig into the paper and analyse the numbers ourselves to outline what a ‘20% reduction’ means.
A 20% reduction sounds significant, but this is likely the relative risk reduction, which doesn’t give us a complete picture of the relationship between semaglutide and heart disease risk.
Ideally, we’d have the exact figures in the number of MACEs between the semaglutide group and the placebo group to determine what’s known as the ‘absolute risk’. We could also develop what’s known as a ‘normal frequency’ from these numbers.
Relative risk vs. absolute risk
Here’s a hypothetical example of what we mean: we’ll use a fake drug, known as drug ‘X’.
Drug X has been designed to prevent heart attacks. 200 people are split into two groups. Group 1 receives the drug; group 2 receives a placebo (a sugar pill that looks like the drug).
- 2 people out of 100 who received drug X experienced a heart attack after 3 years.
- 4 people out of 100 who received the placebo experienced a heart attack after 3 years.
- We divide 4/100 to get the baseline absolute risk in this placebo group (often referred to as the control group), which is 4%.
- We then divide 2/100 to get the absolute risk in the group taking the medication (often referred to as the exposure or intervention group), which is 2%.
- To understand the relative risk, we divide the exposed group with the placebo group: 2%/4% = 0.5%.
This means that drug X causes a 50% relative drop in the rate of heart attacks compared to the placebo group.
A 50% relative drop sounds significant; however, as the baseline risk in the placebo group was relatively low at 4%, the absolute risk difference between the two groups was only 2%.
To put that into a normal frequency, we could say:
For every 100 people taking the medication, we can save two heart attacks over a three-year period.
This isn’t to say that drug X doesn’t work. Two heart attacks saved for every 100 people treated may convince you to take drug X. But it’s a different proposition than saying, ‘Drug X lowers your risk of a heart attack by 50%’.
Additionally, these numbers might increase over time, and three years may not be long enough to determine the actual risk reduction benefit. But if this is the only data we have, that’s what we have to work from.
Fortunately, we have older research we can analyse also investigating the link between semaglutide and major cardiovascular events (MACEs) to provide a clearer picture of how semaglutide lowers the risk of a heart attack or stroke.
Data from SUSTAIN-6
A large human clinical trial randomised 3,297 participants living with type 2 diabetes to receive semaglutide 1mg (Ozempic) or a placebo for two years.
The study’s main findings were that compared to placebo:
- Semaglutide lowered the relative risk of a non-fatal heart attack by 26%
- It also lowered the relative risk of a stroke by 39%
- And lowered the relative risk of a major cardiovascular event by 26%
This sounds significant. However, there was no difference between the death rate from cardiovascular disease and hospitalisation from heart failure in the two groups.
Looking at the absolute figures, this is how the study breaks down:
- 47 (2.9%) patients on semaglutide experienced a non-fatal heart attack, compared to 64 (3.9%) on placebo. An absolute risk reduction of 1%. Or, as a normal frequency, semaglutide prevented 17 heart attacks after two years.
- 27 (1.6%) patients on semaglutide experienced a stroke, compared to 44 (3.9%) on placebo. An absolute risk reduction of 2.3%. Or, as a normal frequency, semaglutide prevented 17 strokes after two years.
- 44 (2.7%) of patients on semaglutide died due to causes related to cardiovascular disease, compared to 46 (2.8%) in the placebo group. An absolute risk reduction of 0.1%. Or, as a normal frequency, semaglutide treatment prevented two deaths after two years.
Another study analysing the data from the SUSTAIN and PIONEER trials also found a similar reduction in risk of experiencing a major cardiovascular event (MACE) with semaglutide.
It demonstrated a 23% relative reduction in MACEs with semaglutide compared to placebo. 222 (2.1%) patients in the semaglutide group experienced a cardiovascular event, compared with 251 (3.5%) in the placebo group. An absolute risk reduction of 1.4%.
Or, as a normal frequency, in a group of 10,508 people on semaglutide, it prevented 29 heart attacks over an average follow-up time of 1.32 years.
So, does semaglutide lower your risk of a heart attack?
Overall, yes. Current research suggests that over a two-year period, semaglutide leads to a reduction in major cardiovascular events but doesn’t reduce the risk of dying of cardiovascular disease during this time.
Likely, a two-year follow-up isn’t enough time to see a true reflection in reducing deaths from cardiovascular disease with semaglutide. Future trials will likely conduct longer-term follow-ups to get a clearer picture.
Additionally, heart disease is complicated, and while semaglutide may help to improve various risk factors causally linked to the condition, such as high blood sugar and obesity, it can’t impact all other risk factors, such as smoking, lack of physical activity, and poor emotional health.
How does semaglutide reduce the risk of a heart attack?
As mentioned above, heart disease is complicated, and hundreds of causal factors are linked to the condition’s development. However, semaglutide is likely to lower the risk of a heart attack in three areas:
- Improved insulin sensitivity
- Lower blood sugar levels
- Lower inflammation from weight loss (smaller fat cells)
These areas would require too much depth to investigate for this blog, but we’ll be looking into them in future guides, so stay tuned.
Take home message
Semaglutide does lower the risk of major cardiovascular events and strokes compared to placebo. However, the net benefit of the drug in terms of cardiovascular health and mortality is still to be determined in longer-term follow-up trials.
Additionally, the use of relative risk in headlines and announcements can exaggerate the effect of medications, which can be misleading for the public when deciding whether to take a medication.
By understanding the absolute risk and putting the numbers from trials into a normal frequency, people can better understand the impact of medications and make more informed decisions about treatment options.
