Symptom Duration May Be More Important Than D2B for STEMI, HORIZONS-AMI Substudy Suggests

Door-to-balloon (D2B) time has been a commonly used metric for system performance in STEMI patients because it is relatively easy to measure, but new data from a substudy of the HORIZONS-AMI trial suggest that more attention should be paid to symptom duration since it may more accurately reflect the risk not only of myocardial injury but also long-term mortality.

The findings have implications for how patients are manage both during the acute phase and down the road.

Next Step: Symptom Duration May Be More Important Than D2B for STEMI, HORIZONS-AMI Substudy Suggests

“The problem is that [D2B is] almost an automatic metric that people are fixated on and there’s a rush to action,” Michael A. Kutcher, MD, of Wake Forest School of Medicine (Winston-Salem, NC), told TCTMD. “It’s an easy metric to measure.”

HORIZONS-AMI, published in the Lancet in 2011, randomized more than 3,000 STEMI patients undergoing primary PCI to receive bivalirudin or heparin plus a glycoprotein IIa/IIIb inhibitor and then randomized again to DES or BMS. This subanalysis—by Roxana Mehran, MD, of the Icahn School of Medicine at Mount Sinai (New York, NY), and colleagues—looked at 2,056 of those patients who had complete symptom onset-to-balloon (S2B) and D2B time information.

The paper was published in the December 28, 2015, issue of JACC: Cardiovascular Interventions.

S2B times were ≤ 2, < 2 to 4, and > 4 hours in 7.9%, 47.4%, and 44.7% of patients, respectively. Delays were more frequently seen in the elderly, women, diabetics, those with prior angina, and patients with longer D2B times.

Longer S2B times were associated with increased microvascular injury—measured by 2 factors: myocardial blush grade (MBG) 0/1 and ST-segment resolution < 30%—regardless of whether patients had a low or high clinical risk profile. On multivariate analysis, there were several independent predictors of both injury measures including S2B time and anterior infarction.

Having a D2B of more than 2 hours was linked with a higher likelihood of MBG 0/1 (OR 1.63; 95% CI 1.16-2.30) but did not correlate with ST-segment resolution.

Lastly, both MBG 0/1 and ST-segment resolution < 30% correlated with higher mortality at 3 years. But only the former—along with diabetes, peripheral vascular disease, smoking history, and age—remained an independent predictor of 3-year death on multivariate analysis (OR 1.79; 95% CI 1.17-2.72).

D2B Not ‘Tapped Out’

The “time dependent” relationship discovered in the study between S2B duration and the chance of myocardial perfusion injury after primary PCI “may be a potential pathophysiological factor that might account for the higher mortality associated with longer [S2B time],” Mehran and colleagues write.

Though this association was independent of clinical and angiographic characteristics and HORIZONS-AMI involved universal use of stents, they continue, the “findings with regards to the relationship of [S2B time] and MBG resemble observations from [a prior study] in which stents were used in < 60% of cases.” This means that “optimal epicardial patency with routine use of stents does not [affect] myocardial perfusion,” the authors suggest.

D2B has been used as an important metric among hospital systems for years, but this substudy challenges its overall importance for some patients, Kutcher writes in an accompanying editorial. While D2B is not “tapped out,” he says, “we need to pay even more attention to adjunctive metrics such as the symptoms and signs of acute onset of acute coronary ischemia.”

Paying attention to these things enables physicians to approach a patient differently at the time of intervention, according to Kutcher. “There are things we can do at the time of the intervention if we know there’s been a protracted symptom-to-balloon time that we might not do if we’re just fixated on getting the artery open as fast as possible,” he said in the interview.

Lackluster Options Available

The “limited therapeutic options” currently available to reduce microvascular injury, the authors note, come from the “disappointing” TASTE and TOTAL trials looking at manual thrombectomy.

Even so, “selective aspiration may still be warranted” in patients with a prolonged S2B time or with low MBG and ST-segment resolution, Kutcher says. He also suggests “more aggressive adjunctive pharmacological therapy,” whether that be giving a bolus of intracoronary abciximab or tirofiban or a bolus of IV eptifibatide in the cath lab, which may “theoretically lead to less micro distal embolization.”

Periprocedural treatment with exenatide and cyclosporine infusion have likewise led to “favorable outcomes,” though further research is needed, Kutcher writes. Other solutions could come in the form of post-procedural IV bivalirudin or heparin infusions and transradial access.

A “major message” of this study is that myocardial perfusion injury correlates with mortality, he notes, and as such, “consideration should be given to keeping these patients on long-term dual antiplatelet therapy along with aggressive statin, beta-blocker, and afterload reduction therapy and close follow-up.” They should also be followed more closely than patients with shorter ischemia durations, Kutcher adds.

Priority on Early Symptom Recognition

Ultimately, the study “highlights the need to reconsider the role of [D2B] as a performance metric,” Mehran and colleagues say, but clinical trials are needed for prehospital treatment strategies to “examine the utility of a broader metric of systems delay such as first medical contact to balloon time as well as total ischemic time.”

A shift in approach may also be justified in certain situations, they continue, to allow physicians to focus more comprehensively on clinical evaluation and factor in comorbidities, bleeding risk, and DAPT duration to ensure diagnostic accuracy.

Kutcher also said that the interventional cardiology community should use this opportunity to further public education plans for early symptom recognition. “It’s an opportunity to also emphasize the [significance of] ischemia onset to EMS [and encourage them] to ask the basic question: ‘When did this start?’”

Note: Mehran and co-author Gregg W. Stone, MD, are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

1. Prasad A, Gersh BJ, Mehran R, et al. Effect of ischemia duration and door-to-balloon time on myocardial perfusion in ST-segment elevation myocardial infarction: an analysis from HORIZONS-AMI trial (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction). J Am Coll Cardiol Intv. 2015;8:1966-1974.
2. Kutcher MA. Door-to-balloon time as a process metric for treatment of ST-segment elevation myocardial infarction: time to “tap out”? [editorial]. J Am Coll Cardiol Intv. 2015;8:1975-1977.

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  • HORIZONS-AMI was sponsored by the Cardiovascular Research Foundation under an investigational device exemption from the US Food and Drug Administration, with funding from Boston Scientific and The Medicines Company.
  • Mehran reports receiving institutional research support from, serving as a consultant or an advisory board member to, and holding shares in several pharmaceutical and device companies.
  • Kutcher reports serving as a consultant to Medicure Pharma Inc.