Usman Baber, MD: TWILIGHT Subgroup Findings

New subgroup analyses data from the Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention for Acute Coronary Syndrome (TWILIGHT-ACS) study showed ticagrelor monotherapy significantly reduced major bleeding risk without increasing ischemic event risk over 1 year in high-risk patients.

The findings, presented at the American Heart Association (AHA) 2019 Scientific Sessions in Philadelphia, provide greater materials to influence treatment protocol in high bleeding risk patients, while giving cardiologists greater confidence in navigating the considerable treatment-emergent adverse event.

In an interview with MD Magazine® while at AHA 2019, presenting author Usman Baber, MD, a professor at the Icahn School of Medicine at Mount Sinai, detailed the TWILIGHT-ACS findings, and what they mean for the cardiovascular field.

MD Mag: What were the details of the TWILIGHT-ACS subgroup analysis presented at AHA?

Baber: Today we presented subgroup analysis data from the TWILIGHT trial. So, TWILIGHT was a large, randomized, double-blind, placebo-controlled trial. It was conducted in 197 sites and 11 countries. In TWILIGHT we enrolled patients who were at high risk, and all of these patient underwent PCI with drug-eluting stents. They received ticagrelor plus aspirin for 3 months, then were randomized to aspirin or placebo with continuation of ticagrelor thereafter.

And today, what we did was focus on those patients enrolled in TWILIGHT who presented with either unstable angina, or non-ST elevation MI, or non-ST acute coronary syndromes. The primary endpoint of our analysis was clinically relevant bleeding—that's type II, III, or V.

The secondary endpoint was all-cause death and stroke occurring between randomization and 1 year thereafter. The motivating reason for even doing this analysis is that at present, the current guidelines stipulate that dual anti-platelet therapy is necessary for at least 1 year in patients presenting with an acute myocardial infarction.

And therefore, we wanted to understand whether or not the benefits of an abbreviated duration of dual anti-platelet therapy with continuation ticagrelor alone would be beneficial with respect to both bleeding and ischemic events in these high-risk patients.

MD Mag: What were the study results?

Baber: We found over the course of 1 year, in these high-risk patients with non-ST acute coronary syndrome, that ticagrelor monotherapy reduced the risk of clinically relevant bleeding by 4% in absolute terms—in relative terms, by 53%. And those benefits were more consistent when we examined more severe bleeding, or if we used alternative bleeding scales.

Perhaps even more pertinent for a patient population with non-ST elevation with acute coronary syndrome is that of ischemic events. And we found that the rates of death from MI or stroke were virtually identical in the treatment arms—4.3% and 4.4%—indicating no incremental increase in the risk for thrombosis when you withdraw aspirin and continue ticagrelor alone.

In additional analyses examining these findings in relation to the number of higher risk features patients had, in patients who had numerous high-risk features—at least 6 or more, they displayed a one-year event rate of approximately 9%. And even in those high-risk patients, we found no excess risk with ticagrelor monotherapy compared to ticagrelor plus aspirin.

We also demonstrated the findings were consistent in patients presenting with unstable angina, or non-ST elevation MI.

MD Mag: How could these findings influence future treatment protocol or guidelines?

Baber: I think with respect to guidelines, we'll have to see how the writers adopt these. I think with these data, and in other trials and the subgroup analyses that have come from global leaders, we're seeing a consistent theme and message.

And in my opinion, I don't think it would be a very large stretch to consider this as a potential strategy in certain patient populations, wherein one could derive benefit from bleeding and not pay a penalty on the ischemic events.

I think more broadly, from adoption and in the context of clinical practice, I think we can provide some reassurance to the clinicians maybe concerned about bleeding—and rather than de-escalating to a less intense P2Y12 inhibitor, you can still provide patients the benefits despite dropping the aspirin after about 3 months.

What we don't know from this study is, at what point can we really safely withdraw aspirin. In TWILIGHT, it was 3 months. In the global leader's program, it was 1 month. I think that is still up to some peer speculation and debate. But certainly, the theme is concordant across studies.