Meta-analysis: Long-Term DAPT Beneficial for Patients With History of MI


LONDON, England—Extending dual antiplatelet therapy (DAPT) beyond 1 year results in decreased adverse events among patients with a history of MI, according to results of a meta-analysis presented on August 31, 2015, at the European Society of Cardiology Congress and simultaneously published in the European Heart Journal.

Take Home: Meta-analysis: Long-Term DAPT Beneficial for Patients With History of MI

For the study, Jacob A. Udell, MD, MPH, of Women's College Hospital (Toronto, Canada), and colleagues looked at data from 33,435 patients (mean age 64 years; 24% women) with a history of MI enrolled in one of the following 6 trials:

  • CHARISMA (n = 3,846): 28 months of clopidogrel
  • PRODIGY (n = 1,465): 6 vs 24 months of clopidogrel
  • ARCTIC-Interruption (n = 323): 12 vs 24 months of clopidogrel or prasugrel
  • DAPT (n = 3,576): 12 vs 30 months of clopidogrel or prasugrel
  • DES-LATE (n = 3,063): 12 vs 24 months of clopidogrel
  • PEGASUS TIMI-54 (n = 21,162): 33 months of ticagrelor

Mean time from MI was 18 months overall, and very few patients had a history of either stroke/TIA (3%) or CABG (7%).

Those treated with extended DAPT fared better than those on aspirin alone in terms of the primary endpoint (cardiovascular death, MI, or stroke; RR 0.78; 95% CI 0.67-0.90) as well as each of its components. However, this came at the cost of increased major bleeding with long-term DAPT (table 1).

Table 1. Adverse Outcomes

There were no differences between the groups in any other bleeding events including fatal bleeds and intracranial hemorrhage or in noncardiovascular death.

These results were maintained among all prespecified subgroups, including age, sex, DAPT regimen, index ACS type, time from index MI, and history of PCI.

Appropriate Patient Selection Will Increase Benefit

Whittling down which “high-risk patients at low risk of bleeding” will benefit from extended DAPT is important, Dr. Udell said. “Typically across the trials these were patients who had 1 to 3 years with a troponin positive history of MI, often with additional cardiovascular risk factors. Patients were excluded if they had ongoing anticoagulation, had a history of recent bleeding, recent surgery, or any history of intracranial hemorrhage.”

He cautioned against treating patients with prior stroke or TIA with extended dual therapy because very few have been studied.

“Clinicians read about meta-analyses very frequently and then are sometimes surprised that there are fundamental differences with respect to how a meta-analysis is performed. And then that calls into question the strength of the conclusions that any meta-analysis might point towards,”observed session comoderator Patrick T. OGara, MD, of Brigham and Womens Hospital (Boston, MA), who asked for clarification as to why the numbers in this meta-analysis are so compelling.

Dr. Udell said it is best to start with a simple clinical question at the bedside. “If you look at the meta-analyses at this point, its been a heterogeneous patient population thats been studied,” he said. “We selected patients with the highest risk in terms of coronary milieu…and we looked systematically back at the literature without cherry picking potential positive trials from the negative,”he said. “Importantly, when youre looking at reviews and results, [the clinical question] gets buried and sometimes you want to look for heterogeneity. You want to look to see if there are some trials that are driving results or other trials that are the outliers.”

Dan Atar, MD, PhD, of Oslo University Hospital (Oslo, Norway), asked about clinical implications and reminded the audience that CHARISMA—“the second biggest trial that you included”—favored long-term therapy and did not change clinical practice.

“Hindsight is 20/20,”Dr. Udell responded. “It helps to take a pooled view to see whether theres consistency. There will be a healthy debate for a while to come about whether it is a class effect or whether there are particular antiplatelet agents that may offer more potential benefit in an extended term than others.”

With new trials on the horizon, “its only a matter of time until we see an all-cause mortality benefit,” Dr. Udell noted. “I hope it impacts the guidelines in appropriately selected patients.”


Source: 
Udell JA, Bonaca MP, Collet J-P, et al. Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials. Eur Heart J. 2015;Epub ahead of print.

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Disclosures
  • Dr. Udell reports serving on the advisory board for Merck, Novartis, and Sanofi Pasteur and receiving research grants through his institution from Brigham and Women’s Hospital, New York University, and Novartis.

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