DAPT superior to aspirin for outcomes after CABG

Dharam J. Kumbhani, MD, SM

This was an important meta-analysis. It shows that you can safely use DAPT compared with just aspirin alone in patients who are post-CABG and still have potentially better ischemic outcomes with no increase in bleeding outcomes. The authors included clinical trials as well as observational studies. They didn’t necessarily combine them in one summary estimate, which is right because otherwise that would be a problem statistically.

It is unclear if this study will have immediate implications for clinical practice.

There was a very important study on this topic called the DACAB trial, which was recently presented at the American Heart Association Scientific Sessions in November, and thus not included in this analysis. That showed something very similar, an improvement in ischemic outcomes post-CABG in a cohort of 500 patients. In some ways, it validates the findings of this meta-analysis.

Now there are several caveats. No. 1, the American College of Cardiology/AHA guidelines recommend that you can routinely use DAPT post-CABG, particularly among patients who undergo CABG surgery off-pump. In this study too, the majority of the benefit was among off-pump CABG patients, with little benefit among on-pump patients. Now again, we see the on-pump benefits is smaller, but that’s the key thing. The majority of the benefit even in earlier studies has been shown with off-pump patients, and you can see that in this meta-analysis as well. This analysis may thus just validate that DAPT may be reasonable mostly for patients undergoing off-pump CABG.

I’d like to see a couple of other things further researched. The proportion of patients who were enrolled who undergo CABG in the setting of ACS is also important; this included 75% of the DACAB cohort. For those patients, it’s a Class I indication to use DAPT for 1 year even if they don’t undergo angioplasty or stenting. In the present analysis, that information was missing for a lot of the studies included.

The question that remains is: Does it apply to every single patient who is undergoing CABG? Those are the nuances that need to be teased out.

Finally, the last issue is one of aspirin dosing, since there’s a lot of heterogeneity there as well.

When used as monotherapy, current CABG guidelines recommend 325 mg aspirin, but many of these studies were done using 81 mg of aspirin in the comparison group. That was certainly true of the DACAB trial as well. The point is if you really want to understand the utility of DAPT, you need to study it in patients where it’s not already indicated, and you need to use a dose of aspirin that’s routinely used post-CABG. The right population to study that in would be patients undergoing on-pump CABG for non-ACS indications and patients who are randomly assigned to clopidogrel 75 mg or any P2Y12 inhibitor and aspirin 81 mg compared with aspirin 325 mg, which is what the surgical practice has been.

This study is well done statistically. It’s a nice, helpful study that validates many of the things we’ve known from the studies before. Certainly, this is an area that is ripe for research.

Timothy J. Gardner, MD

While acknowledging the authors’ extensive efforts, this is another complex meta-analysis that may add more uncertainty about a role for DAPT in post-CABG patients. The reduction in the composite endpoint of MI, stroke and death in patients taking DAPT despite no difference in MI or stroke lessens confidence in the apparent CV-related benefit of DAPT.
In addition, while major bleeding is not reported to be higher in DAPT patients, this therapy is not safe and appropriate for all-comers after CABG, ie, elderly patients, patients with increased bleeding risk, etc.
I’m skeptical of the reduced graft occlusions reported with DAPT, since graft occlusion rates cannot be reliably determined by selective postoperative diagnostic testing.
The implications of this review are limited due to the diversity of clinical and patient-related factors in the CABG population. While some selected patients (young, extensive CAD, prior stents, etc) may benefit from DAPT with low bleeding risk, DAPT is not appropriate for many — perhaps for most — current CABG patients.
Even if we are to assume that DAPT is possibly better for some CABG patients than aspirin alone, what is the safe and appropriate duration for DAPT? Also, what is the ongoing or accumulative risk of bleeding with long-term DAPT for post-CABG patients?