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Alteplase in primary PCI fails to reduce MVO

Audrey Abella
21 Nov 2018
Dr Collin Berry discusses results of the T-TIME trial

The use of low-dose intracoronary alteplase, a tissue plasminogen activator (tPA), in patients with acute ST-elevation myocardial infarction (STEMI) at the time of primary percutaneous coronary intervention (PCI) was ineffective in reducing microvascular obstruction (MVO, or failed myocardial reperfusion), according to the T-TIME* trial results presented at AHA 2018.

“[MVO] is common after STEMI … [and] an independent predictor of all-cause death and heart failure,” said study author Dr Colin Berry from the University of Glasgow in Glasgow, Scotland. “No single intervention has been shown to have a convincing benefit.”

To evaluate the potential of alteplase in reducing MVO, 440 individuals (mean age 60.5 years, 15 percent female) with acute STEMI presenting ≤6 hours from symptom onset were randomized 1:1:1 to receive placebo or alteplase 10 or 20 mg by manual intracoronary infusion (20 mL) over 5–10 minutes after reperfusion but prior to stent implantation during PCI. A majority of participants received additional antiplatelet medications (ie, clopidogrel, ticagrelor, or prasugrel), with some adding intravenous [IV] or intracoronary glycoprotein IIb/IIIa antagonists to their regimen. Parametric MRI was obtained at 2–7 days post-MI. [AHA 2018, abstract 19547]

The amount of MVO (percentage of left ventricular mass) on MRI between days 2 and 7 was similar between groups (mean, 2.3, 2.6, and 3.5 percent for placebo, alteplase 10 mg and 20 mg, respectively; p=0.28).

Moreover, patients who received alteplase 20 mg presenting at 4–6 hours had an increase in MVO compared with placebo recipients (mean difference, 1.12, 95 percent confidence interval [CI], 0.42–1.82; p=0.002).

These findings appear to suggest a trend towards an increased MVO with treatment, noted Berry. “[Therefore, our] results do not support this therapeutic strategy … MVO remains an unmet therapeutic need.”

Berry also noted the “unexpected” increase in the area under the curve for troponin T at 2 and 24 hours in both treatment groups vs placebo (relative risk, 1.53, 95 percent CI, 1.16–2.01, p=0.002), which signified larger MIs.

“[T]he MIs were large, occupying 13 percent of the left ventricle (LV),” concurred discussant Dr Paul Armstrong from the University of Alberta in Edmonton, Alberta, Canada.

The timing of antiplatelet therapy and use of glycoprotein IIb/IIIa inhibitors should also be taken into account, added Armstrong. “[T]he combination of fibrinolytic and glycoprotein inhibitors is very effective in producing reperfusion at both myocardial and epicardial levels – regrettably with [excessive] haemorrhage,” Armstrong pointed out. “However, with intracoronary tPA, one might have achieved a different result going forward … We need a better taxonomy associated with MVO to provide more informed solutions.”

 

A tough nut to crack

MVO appears to be one “tough nut to crack”, as it occurs in nearly half of patients despite successful primary PCI, said one of the T-TIME investigators Dr Peter McCartney from the University of Glasgow in Glasgow, Scotland, in a separate video interview.

Only one trial on IV metoprolol has shown benefit in treating MVO; however, this was a post hoc analysis with a relatively small population, and MVO was not the primary endpoint, McCartney pointed out. “[An RCT] on IV metoprolol prior to reperfusion is [in the works] and we will await the results of that.”

“[MVO] is associated with adverse outcomes such as LV remodelling [leading to] larger infarcts, larger LV volumes, and reduced ejection fractions, [consequently resulting in] increased incidence of mortality and heart failure presentation … Hopefully, we [find] a treatment soon,” said McCartney.

 

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