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NCS Currents Sept 2016

JOURNAL WATCH Journal Watch By Aimee Aysenne, MD, MPH and Chitra Venkatasubramanian, MBBS, MSc Welcome to Journal Watch. Recently, several studies were published on intracerebral hemorrhage and are actively changing the way we practice. The NEWS on the NCS website has publications and full reviews on these and other topics. Feel free to email us your comments and feedback. Platelet transfusion after ICH is associated with worse 3-month outcomes Baharoglu MI, Cordonnier C, Al-Shahi Salman R, et al. Lancet 2016;387:2605-2613. PATCH (platelet transfusion after ICH) is a multicenter, international, randomized open label, blinded endpoint assessment study. Patients with spontaneous supratentorial ICH who were on antiplatelet agent(s) for ≥7 days prior to ICH were randomized 1:1 to standard care with/without platelet transfusions. Patients on aspirin, carbasalate calcium ± clopidogrel were given one unit of platelet concentrate whereas those on dipyridamole received two units. ICH volume was measured on CT at admission and at 24 ± 3 hours. Aimee Aysenne, MD, MPH The primary endpoint was 3-month mRS. Secondary outcomes were survival and poor outcome (mRS 4-6 or 3-6). Other endpoints were median absolute ICH growth at 24 hours, complications of platelet transfusion and other safety events. Ninety- seven participants were assigned to the platelet transfusion group and 93 to standard care. Median ICH score was 1. Median ICH volume was 13 cc in the platelet group and 8.5 cc in the standard group. The majority of patients were on aspirin. Patients treated with platelet transfusions were more likely to be dead or dependent at 3 months than those without transfusions (adjusted OR 2.05, p=0.0114). More participants in the platelet group had mRS 4-6 at 3 months (72% vs. 56%, p=0.019). Median ICH growth at 24 hours and hospital mortality were the same. More adverse events were seen in the platelet group (42% versus 29%), due to ICH enlargement or infections. In this randomized trial, platelet transfusions in antiplatelet related ICH was associated with a nearly twofold increase in the odds of death or dependence at 3 months. This effect was consistent regardless of type of antiplatelet agent, baseline ICH volume, and other known prognostic factors. Platelet transfusions did not affect ICH growth. Since the majority of patients were on aspirin, it is unclear if the results are generalizable to ADP inhibitors (clopidogrel). Stored platelets can have unpredictable functionality, but they can also become activated with resultant prothrombotic and inflammatory properties, which could explain the increase in adverse events that offset any potential benefits. Conversely, the degree of ICH expansion in patients on antiplatelet agents may not be as clinically significant as in anticoagulation-associated ICH so the potential benefit of platelet transfusions is negligible. This pragmatic study provides new evidence against platelet transfusions in ICH. Aggressive blood pressure lowering after spontaneous ICH does not improve outcomes Qureshi AI, Palesch YY, Barsan WG, et al. NEJM 2016; Jun 8 (epub). ATACH-2 is a randomized, open label, multicenter, international trial of spontaneous ICH patients with GCS ≥5, ICH volume <60 cc, and one systolic blood pressure (SBP) reading >180 mmHg before initiation of antihypertensive medications but not <140 mmHg before randomization. Patients were randomized 1:1 to either the intensive group (SBP goal 110-139 mmHg) or standard group (SBP goal 140-179 mmHg) with intravenous nicardipine started within 4.5 hours of onset and maintained for 24 hours. Admission and 24-hour follow up non-contrast head CTs were compared. Follow-up at 1 month and in person at 3 months included modified Rankin score (mRS) and European Quality of life (EQ-5D). The primary endpoint was the proportion of patients who had a mRS of 4-6 (i.e., death or severe disability) at 3 months. The study was halted early for futility after the second pre-specified interim analysis. One thousand patients (500 in each group) were enrolled. Median ICH volume was 10 cc with only 10% of ICH >30 cc and 90% of hemorrhages were deep (thalamus or basal ganglia). Mean SBP during the first 2 hours post-randomization was 128.9 ± 16 mmHg in the intensive group and 141.1 ± 14.8 mmHg in the standard group. There was no difference in the death or functional neurologic outcomes in any prespecified subgroup analyses. Rates of ICH expansion, death at 3 months, and neurologic deterioration at 24 hours were similar between groups. The intensive group had more significant adverse events and a higher rate of renal adverse events in the first 7 days. ATACH-2 – the second largest multicenter, randomized trial of aggressive blood pressure lowering after ICH to a target of SBP 110-139 mmHg – did not improve functional outcome at 3 months when compared to a target SBP of 140-179 mmHg. The mean SBP in the intensive group in INTERACT-2 study was similar to that in the standard group in ATACH-2. Despite more aggressive BP lowering in ATACH-2 study, there was no improvement in functional outcomes. ATACH-2 allowed for use of antihypertensive therapy prerandomization in accordance with existing guidelines. A high proportion of patients had favorable baseline characteristics including GCS of 15 and small ICH volume so any additional intervention such as BP lowering may have had a negligible impact on improving outcome. The results of this trial cannot be applied to patients with large ICH. Combining the results of INTERACT-2 and ATACH-2, it is likely that the “sweet spot” for SBP lowering after ICH is perhaps around 140 mmHg and not any lower. Chitra Venkatasubramanian, MBBS, MSc 26


NCS Currents Sept 2016
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