Better Than Aspirin vs Cardiovascular Disease

Using daily low-dose aspirin to reduce cardiac risk (mostly: atherothrombosis) has been a popular American pastime for some decades now, and it does work!

However, there’s a catch:

Low-dose aspirin lowers the risk of atherothrombosis by inhibiting platelet aggregation, but at the cost of increasing bleeding risk (especially gastrointestinal). The tradeoff is further complicated by the fact that aspirin improves nonfatal cardiovascular outcomes but does not significantly reduce cardiovascular or all-cause mortality.

In other words: speaking in statistical generalizations of course, it may improve your recovery from minor cardiac events but is unlikely to help against fatal ones.

We wrote about this here: Aspirin, CVD Risk, & Potential Counter-Risks

The current prevailing professional (amongst cardiologists) consensus is that it may broadly be recommended for secondary prevention of atherosclerotic cardiovascular disease (ASCVD), i.e. if you have a history of CVD, but usually not for primary prevention (i.e. if you have no history of CVD). Note: this means personal history, not family history.

There are some more considerations than just that, though, and a simplified flowchart of those other considerations looks something like this:

• No for primary prevention ( (i.e. you have no history of ASCVD)
  • …except in select adults aged 40–70 (not above or below that range) with higher ASCVD risk and/but only if you also have no increased bleeding risk.
• Yes for secondary prevention (i.e. if you already have ASCVD)
  • …and if you want more details on this, please see the above-linked article!

yes, but…

For those in the “yes” category, there is now a strong argument for early discontinuation of low-dose aspirin use.

Researchers (Dr. Valeria Paradies et al.) investigated this in an open-label randomized controlled trial across 40 European centers with 1,942 myocardial infarction patients who had complete revascularization and one month of uneventful dual antiplatelet therapy (DAPT). In other words, exactly the people in the “yes” category above.

DAPT, by the way, is what it sounds like and refers to the use of two antiplatelet therapies at once, namely:

1. low-dose aspirin
2. some kind of P2Y12 inhibitor

The P2Y12 inhibitor is also what it sounds like (it inhibits P2Y12), but that’s not a very useful explanation, so: it blocks the P2Y12 receptor on platelets, so that platelets don’t get activated by passing adenosine diphosphate, so they don’t aggregate (stick together), so your blood doesn’t clot.

When we say “some kind of P2Y12 inhibotor”, we’re not being whimsical, by this we mean there are many kinds, but common kinds include:

• Clopidogrel: widely used, low bleeding risk, variable effect due to genetic metabolism differences
• Prasugrel: more potent, faster onset, higher bleeding risk, often avoided in older patients or those with prior stroke (including any transient ischemic attack)
• Ticagrelor: potent, reversible inhibitor, improves outcomes compared to clopidogrel but can cause breathing difficulties and increases bleeding risk

What they found: looking at various metrics (death, myocardial infarction, stent thrombosis, stroke, or major bleeding), the results showed:

• DAPT was not better than a P2Y12 inhibitor alone (some metrics were slightly better or worse in one group than the other, but the differences were minimal, often around 0.1% difference one way or the other, and if we average out the differences, the result is “no real difference”)
• P2Y12 inhibitor-only patients enjoyed significantly less bleeding (less than half the bleeding of the DAPT patients)

So, with all that in mind, the take-away here seems to be “add aspirin if you’d like to bleed 2x as much“

Now, the researchers are technically arguing only for this decision (“stop the aspirin”) to be made after one month of DAPT first.

Why one month of DAPT first? Because this study started after one month of uneventful DAPT, as their baseline, to screen out any patients who had something go wrong in the first month, which would be confounding.

In other words, while they’re saying “stopping aspirin after one month and continuing P2Y12 inhibitor alone is safe, maintains ischemic protection, and reduces bleeding risk”, this is because that is what their results show, and, being scientists, they can only speak for what the study actually tested, and cannot speak for the first, untested month.

It’s a bit like how antidepressants (for example) are only tested on people who have had depressive symptoms for a given period of time, but that in practical terms, that doesn’t really mean they only becomes safe and affective after that given period of time. It just means, science didn’t have the opportunity of testing it at day 1, so can only speak for “after t period of time”

Back to the study at hand, you can find the paper here: Early Discontinuation of Aspirin after PCI in Low-Risk Acute Myocardial Infarction

Which P2Y12 inhibitor?

Here’s a big (n=28,982) study in patients with established coronary artery disease that doesn’t put P2Y12 inhibitors head-to-head, but did test clopidogrel vs aspirin head-to-head, and found:

• 8% less bleeding in the clopidogrel-only group compared to the aspirin-only group
  • but, a high p-score (p=0.64), so this one cannot be strongly claimed, as the difference could be due to other factors
• 14% fewer major adverse cardiovascular or cerebrovascular events* in the clopidogrel-only group compared to the aspirin-only group
  • this time, a very low p-score (p=0.0082), meaning this can be very strongly claimed; the researchers are about as sure about it as scientists get about anything)

*i.e. cardiovascular death, myocardial infarction, or stroke

About p-scores (or p-values): this is the probability (p) of something happening by chance. So for example, p=0 means “this result is literally impossible” and p=1 means “this result is absolutely predetermined as definitely what will happen”. Generally speaking, a p-score being under 0.05 is considered statistically significant.

In short: clopidogrel certainly didn’t cause any extra bleeding compared to aspirin (in fact, the clopidogrel group had 8% less bleeding, the scientists are just being cautious about claiming causality with regard to the bleeding), and beat aspirin head-to-head for effectiveness (14% fewer major adverse cardiovascular or cerebrovascular events, and this time, the scientists are very confident about the significance of the association).

You can find this paper here: Clopidogrel versus aspirin for secondary prevention of coronary artery disease: a systematic review and individual patient data meta-analysis

Want to learn more?

On the topic of medications commonly prescribed for cardiac health that may not actually help (and indeed, may harm):

Beta-Blockers: Useless vs Heart Attacks & Worse For Women?

Take care!