Findings Support DAPT Duration Longer Than 3 Months in ACS Patients

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Dual antiplatelet therapy (DAPT) for longer than 3 months provides better protection against death, stroke, or reinfarction than shorter-term therapy in patients with acute coronary syndromes (ACS), according to findings published online October 11, 2013, ahead of print in the European Heart Journal.

Researchers led by Christoph Varenhorst, MD, PhD, of Uppsala University (Uppsala, Sweden), looked at 56,440 ACS patients enrolled in the SWEDEHEART registry who were prescribed DAPT and hospitalized between January 2006 and July 2010.

Patients were divided into treatment groups according to the number of dispensed clopidogrel tablets:

• 3 months of treatment (84-100 tablets)
• > 3 months of treatment (> 100 tablets)
• 6 months of treatment (168-200 tablets)
• > 6 months of treatment (> 200 tablets)

Better Outcomes with Longer DAPT

During the index hospitalization, the incidence of stroke, stent thrombosis, and reinfarction was low in all groups. When the Charlson comorbidity index and the REACH bleeding risk score were calculated, absolute differences were small, with patients who were treated longer more likely to have higher comorbidity and bleeding risk.

The combined primary endpoint (defined as all-cause death, stroke, or reinfarction) occurred in 654 patients in the > 3-month DAPT group compared with 858 in the 3-month DAPT group (P < 0.0001). Additionally, the benefit of longer therapy remained for the subgroup of patients revascularized at the index event, but not for those who did not receive revascularization (table 1).

Table 1. Death, Reinfarction, and Stroke

Similar results were seen when comparing patients treated with DAPT for 6 months with those taking it for longer than 6 months.

For reinfarction, treatment with  > 3 months of DAPT was associated with a lower event rate compared with 3 months treatment (adjusted HR 0.83; 95% CI 0.70-0.98; P = 0.03). However, for the individual endpoints of all-cause death and stroke, no such differences were seen.

The risk of bleeding was higher in groups with longer therapy duration (> 3 vs. 3 months adjusted HR 1.56; 95% CI 1.18-2.017; P = 0.0018). Reported bleeds were most commonly classified as gastrointestinal (76.1%), intracranial (12.9%), or nonspecified posthemorrhagic anemia (10.3%). The calculated incidence of bleeding was 11 events per 1,000 person-years in the longer duration DAPT group vs. 8 events per 1,000 person-years in the 3 months of DAPT group.

Short-term DAPT Issue Remains Unclear

“We cannot exclude the possibility that factors associated with longer DAPT duration, such as repeat revascularization, also contributed to increased bleeding in the > 3-month treatment duration group,” Dr. Varenhorst and colleagues write. “Despite adjusting for propensity scores including a high number of variables, the possibility remains that the treatment groups were different due to unknown confounders. Nonetheless, our study conclusions are strengthened by the fact that data collection was independent of both treatment and outcome.”

According to the study authors, while several independent but moderately large trials have suggested that shorter treatment duration after stenting may be as beneficial as longer duration therapy, limited sample size and the inclusion of primarily low-risk patients with low event rates in these trials lead to uncertainty over the safety of short-term DAPT.

Three large randomized trials are currently looking at this issue, they report, and may help provide more practical data. These trials (ISAR-SAFE, OPTIMIZE, and DAPT) are attempting to overcome some of the limitations of earlier trials by using larger real-world populations treated with several DES types, the authors conclude.

But in a telephone interview with TCTMD, Jeffrey W. Moses, MD, of Columbia University Medical Center/Weill Cornell Medical Center (New York, NY), said the study authors are “muddling” their message.

“Those 3 trials are all stent trials, and they are all DES, which is not relevant to the population being studied,” he said. “They lump ACS patients together and don’t give us a breakdown of the type of stents used, so any information from these forthcoming studies is not going to answer the general ACS question [regarding DAPT duration].”

Approximately 35% of patients in the study did not receive a stent.

“What I do think this study does is reinforce the message that in contemporary practice, longer duration DAPT is associated with better outcomes in ACS patients,” Dr. Moses said.

Study Details

Baseline characteristics were similar between groups. Ongoing medication was typical for a contemporary ACS population with more than 90% of patients on beta-blockers and statins, more than 80% on ACE-inhibitors, and approximately 40% using proton pump inhibitors.

 

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Source:
Varenhorst C, Jensevik K, Jernberg T, et al. Duration of dual antiplatelet treatment with clopidogrel and aspirin in patients with acute coronary syndrome. Eur Heart J. 2013;Epub ahead of print.

 

 

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