Length of DAPT, Reasons for Discontinuation Have Disparate Effects

AMSTERDAM, The Netherlands—The duration of and approach taken to dual antiplatelet therapy can have varying implications on patients, and the optimal length of treatment remains unknown, according to results of 2 studies presented on September 1, 2013, at the European Society of Cardiology Congress.

Disruption the Culprit in Most Events

For the PARIS (Patterns of non-adherence to Antiplatelet Regimens In Stented patients) registry, simultaneously published in the Lancet, Roxana Mehran, MD, of Mount Sinai Medical Center (New York, NY), and colleagues looked at 5,031 patients implanted with either BMS or DES and discharged on dual antiplatelet therapy from 15 centers in 5 countries between July 2009 and December 2010.

Mean duration of sustained dual antiplatelet therapy in patients without cessation was 686 days. Over 2 years, treatment cessation occurred at an incidence of 57.3% and included:

• Discontinuation (40.8%) at recommendation of a physician who felt the patient no longer needed therapy
• Interruption (10.5%) on a voluntary basis and guided by a physician due to surgery and reinstated within 14 days
• Disruption (14.4%) due to bleeding or noncompliance

The 2-year combined rate of cardiac death, definite or probable stent thrombosis, spontaneous MI, or clinically indicated TLR was 11.5%, most of which (74%) occurred while patients were taking dual antiplatelet therapy.

Compared with those on dual therapy, MACE risk was higher due to both interruption (adjusted HR 1.41; P = 0.10) and disruption (adjusted HR 1.50; P = 0.004)—especially highlighted in the first week (adjusted HR 7.04; P < 0.001) and 30 days (adjusted HR 2.17; P = 0.06) after disruption. By contrast, those who discontinued had a lower MACE risk than those who remained on dual therapy (adjusted HR 0.63; P = 0.004).

Overall, 5.4% of MACE events could be attributed to interruption or disruption of dual therapy; 15.0% for spontaneous MI, 7.7% for definite or probable stent thrombosis, 4.1% for TLR, and 7.4% for cardiac death.

Results were similar after excluding patients receiving BMS and when using a more restrictive MACE definition.

Extreme Heterogeniety

“The impact of DAPT cessation on cardiac risk after PCI is not uniform. It is extremely heterogeneous and varies substantially by the underlying mode or circumstance by which DAPT cessation occurs,” Dr. Mehran said. “The overall impact of DAPT cessation on adverse events is actually modest and may have been mitigated with our newer, safer drug-eluting stents.”

Discussant Stephan Windecker, MD, of Bern University Hospital (Bern, Switzerland), said the study had 3 key findings:

• Unexpected dual therapy cessation due to interruption or disruption occurred in every fourth or fifth patient undergoing PCI and “is therefore highly relevant”
• Physician-guided discontinuation or brief interruptions were not associated with increased risk of ischemic risk events
• Sustained therapy throughout 3 years did not improve outcomes compared with physician-guided discontinuation

Dr. Windecker noted a limitation of the study, however. “The association described between DAPT cessation and adverse events does not necessarily reflect a true cause and effect relationship, and this may be particularly true for the category of patients with DAPT interruption in the context of surgery,” he said.

Asked if there are specific time periods after PCI in which any type of therapy cessation is associated with high event risk, Dr. Mehran explained that the risks are higher within the first 6 months. “I wish I could have that answer,” she said, “but certainly we’re seeing that discontinuation under physician guidelines, even earlier with the newer generation DES, seems to be safe.”

Balancing Bleeding, Stent Thrombosis

In another presentation, Raban V. Jeger, of University Hospital Basel (Basel, Switzerland), outlined a comparison of dual antiplatelet therapy lengths in the BASKET and BASKET-PROVE trials.

While the trial endpoints were the same—major bleeding and stent thrombosis at 2 years—BASKET (n = 2,314) stopped dual antiplatelet therapy at 6 months and BASKET PROVE (n = 557) did so at 12 months. In addition, the former included all stented patients (with a greater percentage receiving BMS), while the latter only included those with stents measuring between 3.0 and 3.5 mm long (mostly DES).

At 2 years, there were more bleeding and fewer stent thrombosis events in patients receiving dual therapy through 12 months than those receiving it for 6 months.

With prolonged dual antiplatelet therapy, the risk of major bleeding was higher during months 7-12 vs. months 0-6 and 13-24 (P for interaction < 0.001 for TIMI 3; P for interaction = 0.046 for BARC ≥ 3) while the risk of stent thrombosis was lower (P for interaction = 0.145).

About one-third (31%) of deaths were due to stent thrombosis and 11% were due to bleeding; hence the researchers estimated 22 lives saved in 10,000 patients with 12 months of dual antiplatelet therapy.

With prolonged therapy, “there are more bleedings, but [they are] not that dangerous,” Dr. Jeger said.

Study Details 

For PARIS, most discontinuations (87%) were for a thienopyridine only—aspirin was almost always continued—whereas for most interruptions (70%) and half of disruptions (50%), both a thienopyridine and aspirin were stopped

Note: Dr. Mehran is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.

Sources:

1. Mehran R, Baber U, Steg PG, et al. Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study. Lancet. 2013;Epub ahead of print.
2. Jeger RV. Survival benefit with 12 versus 6-months dual antiplatelet therapy after coronary stent implantation: a report from BASKET and BASKET-PROVE. Presented at: European Society of Cardiology Congress; September 1, 2013; Amsterdam, The Netherlands.

Related Stories:

• PARIS: Early DAPT Nonadherence, A Small Problem with Big Consequences
• DAPT Cessation Within 1 Year Increased Risk for Major Adverse Events
• Meta-analysis Questions Benefit of Longer Dual Antiplatelet Therapy Post-PCI