Landmark studies Flashcards
What did the SHOCK trial tell us?
“Early Revascularization in Acute Myocardial Infarction Complicated by Cardiogenic Shock”. The New England Journal of Medicine. 1999.
Among patients who developed cardiogenic shock during acute MI, what are the benefits of early revascularization compared to initial medical stabilization on mortality?
Compared to initial medical stabilization, early revascularization was associated with a nonsignificant trend towards improved survival at 30 days among patients who developed cardiogenic shock during acute MI. However, early revascularization did confer a significant benefit by 6 months.
This studies outcome is reflected in the AHA 2013 STEMI guidelines “PCI in STEMI and cardiogenic shock/acute severe HF regardless of time since MI onset (class I, level B)”
What did the IABP-SHOCK II trial show?
“Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock”. The New England Journal of Medicine. 2012.
In patients with acute MI complicated by cardiogenic shock, does an intraaortic balloon pump (IABP) reduce mortality?
In patients with acute MI complicated by cardiogenic shock, there was no difference in 30-day mortality with IABP placement.
The 2004 ACC/AHA and 2010 ESC STEMI guidelines listed class IB and IC recommendations, respectively, for the use of IABP in patients with cardiogenic shock, despite a lack of RCTs establishing its benefit.
The Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial randomized 600 patients with acute MI complicated by cardiogenic shock to either IABP or no IABP. More than 95% underwent primary PCI with stent placement in 90%. At 30 days, there was no significant difference in the primary outcome of mortality between IABP and controls. There were no differences in process-of-care outcomes, including ICU LOS, duration of catecholamines, or time to hemodynamic stability. IABP was not associated with any significant increase in adverse events, including reinfarction, stent thrombosis, bleeding, sepsis or stroke. Although there were some limitations to the study, including its relatively small size and crossover rate, these results challenge the routine use of IABP for cardiogenic shock complicating acute MI.
Guidelines
Based upon results from the IABP-SHOCK pilot trial, the 2012 ESC STEMI guidelines downgraded the use of IABP in STEMI patients from 1C to 2B. The 2013 ACCF/AHA STEMI guidelines do not incorporate the outcomes of this trial.
What did the AKIKI Trial demonstrate?
“Initiation strategies for renal-replacement therapy in the intensive care unit”. The New England Journal of Medicine. 2016.
Among ICU patients with AKI, does early renal replacement therapy (RRT) reduce mortality as compared to delayed RRT?
Among ICU patients with AKI, there is no mortality difference between early or delayed RRT.
Renal replacement therapy (RRT) is a life-saving intervention among critically-ill patients with severe AKI. However, some of these patients with severe AKI spontaneously recover renal function and may not need urgent RRT. While RRT is generally well-tolerated, it is associated with procedure-related complications (eg, line infections). Conversely, early removal of uremic toxins may provide benefit among the critically-ill. As such, the timing of initiation of RRT was a matter of debate among critically-ill patients with severe AKI.
Published in 2016, the Artificial Kidney Initiation in Kidney Injury (AKIKI) trial randomized patients to received early (n=311) or delayed RRT (n=308). The primary outcome was overall survival at day 60. Early RRT did not reduce mortality as compared to delayed RRT (48.5% vs. 49.7%; P=0.79). There was a significant increase in catheter-related bloodstream infection in the early RRT group. In the delayed RRT group, 49% of patients never received RRT.
A post-hoc analysis of the timing of RRT initiation showed a higher mortality rate among those with delayed HD when compared to participants with earlier initiation or no initiation. However, those in the delayed initiation group were sicker at baseline and no mortality differences were seen when controlling for baseline characteristics. However, individuals in the delayed RRT received greater quantities of diuretics. Whether this may have contributed to worsening clinical status in these individuals is unclear. Ideally, accurate metrics predictive of renal recovery would help identify patients most likely to need RRT. Until such resources are available, a watchful waiting approach seems to be safe.
In the same year, the single-centered ELAIN trial reported that early RRT significantly reduced all-cause mortality as compared to delayed initiation at 90, but not 60, days. The contrasting results in these 2 recent trials have been attributed to different study designs, the threshold for initiating RRT and patient populations in each trial. For example, ELAIN enrolled ~95% surgical ICU patients and initiated RRT at KDIGO stage 2 while AKIKI enrolled ~80% medical ICU patients and initiated RRT at KDIGO stage 3. These trials were included in a pooled analysis that did not support early being better than late RRT (early vs. delayed RRT: OR 0.74; 95% CI 0.43-1.27; I2=70.5%). More recently, the 2018 IDEAL-ICU trial found no benefit with early initiation of RRT among ICU patients with septic shock.
