Cutting DAPT short not recommended for ACS

The standard 12-month duration of dual antiplatelet therapy (DAPT) remains the recommended regimen for patients receiving new-generation drug-eluting stents (DES) for the treatment of acute coronary syndrome (ACS) compared with a 3-month strategy despite the latter’s noninferiority to the former regimen, according to the results of the REDUCE* trial.

“[The 3-month DAPT] strategy is recommended only if clinically mandated (eg, high bleeding risk),” said the researchers. Given the numerically higher rates of death and stent thrombosis (ST) with the 3-month strategy, the study findings suggest that the 1-year regimen should still be recommended for ACS, they added.

“The optimal duration of DAPT after DES implantation in ACS is still a matter of debate, because thrombotic risk needs to be balanced with bleeding risk,” said the researchers. Despite the protective effect of prolonged DAPT against thrombotic complications, it entails a significant increase in bleeding which may counterbalance the net benefit. [N Engl J Med 2007;357:2001-2015; N Engl J Med 2009;361:1045-1057]

To evaluate the impact of an abridged DAPT regimen in this setting, the team randomized 1,496 ACS patients (mean age, 60 years) 1:1 to receive either 3 or 12 months of DAPT** following DES implantation. [Euro Intervention 2019;15:e990-e998]

The 3-month regimen was noninferior to the 12-month strategy in terms of the incidence of the primary endpoint*** at 1 year (8.2 percent vs 8.4 percent; hazard ratio [HR], 0.97; p_{noninferiority}<0.001). Adjustment for gender rendered no difference between the two strategies (adjusted HR, 0.96; p=0.80).

At 2 years, outcomes between the 3- and the 12-month regimen remained similar (11.6 percent vs 12.1 percent; HR, 0.96; p=0.76) even after adjusting for gender (adjusted HR, 0.95; p=0.81).

Of note were the numerically higher rates of cardiac death and ST associated with 3- vs 12-month DAPT, both at 1 year (1.8 percent vs 1.1 percent; HR, 1.62 [cardiac death] and 1.6 percent vs 0.8 percent; HR, 2.00 [ST]) and 2 years (1.1 percent vs 0.4 percent; HR, 2.71 and 1.2 percent vs 0.4 percent; HR, 3.04, respectively). However, given the study’s lack of power to assess low event rates, these should be interpreted with caution, noted the researchers. “[Moreover,] about half of the deaths were noncardiovascular and some were even observed when patients were still on DAPT. Nevertheless, these outcomes do not justify a liberal use of the shorter DAPT therapy.”

Another notable factor is the lower incidence of bleeding with the 3- vs the 12-month regimen (3.3 vs 4.0 percent), which appears to favour the shorter regimen given the likelihood of bleeding with prolonged DAPT. However, the researchers highlighted that this finding could have been influenced by the exclusion of patients with high bleeding risk, the younger patient sample, and the use of new adenosine-diphosphate antagonists in <60 percent of participants.

Other potential limitations are the lack of placebo arm and the heterogeneous use of P2Y₁₂ inhibitors. The findings may also not be extrapolated to other DES as only one stent was used in the study, noted the researchers.

Despite the disadvantages tied to a shorter DAPT regimen, the researchers underscored its potential to provide advantages in terms of cost especially on a larger scale.

Taken together, a shorter DAPT duration may be safe in this patient subset in case of intol­erance to a longer duration, said the researchers. “[However,] until more information becomes available, 1-year DAPT should still be recommended in ACS patients.”

Not for the faintheart

“[W]e should continue to adhere to the current guideline-recommended 12-month minimum DAPT duration following ACS,” echoed Dr Nino Mihatov from the Beth Israel Deaconess Medical at Harvard Medical School in Boston, Massachusetts, US, in an editorial. “Although noninferiority was technically achieved, the authors rightly exercised caution in [interpreting] the results.”

Mihatov identified the safety signals (ie, increased ST and cardiac death rates), which began to deviate after discontinuation of DAPT in the 3-month arm, as more concerning.

“Similar signals of harm observed in the SMART-DATE^# trial should give clinicians pause for thought before entertaining an abbreviated DAPT regimen in ACS patients … There is no free lunch to be gained through shorter DAPT durations – one must be prepared to accept higher ischaemic events with shortened DAPT duration,” said Mihatov.