IABP-SHOCK II
Intraaortic balloon support in ACS with early revascularization
- Included 598 patients acute coronary syndrome patients (70% STEMI) with cardiogenic shock and planned early revascularization (PCI or CABG)
- Randomized to intraaortic balloon pump (IABP) or no IABP (control)
- Primary endpoint (30-day all-cause mortality) was not different between IABP and control (39.7% vs. 41.3%, p=O.96)
- SAPS II scores were improved on days 2 and 3 with IABP, but there was no difference by day 4
- There was no difference in measures of tissue oxygenation and inflammation (serum lactate and C-reactive protein)
- There were no differences in any safety endpoints, including stroke, bleeding, sepsis, or peripheral ischemic complications
- The vast majority of patients underwent PCI (96%), with only 3.5% receiving emergent CABG
- Crossover rate from control to IABP was generally low (10%)
- The trial was underpowered (designed for a control mortality rate of 56%), thus being at-risk for a type II error
TBL
In patients with acute coronary syndromes and cardiogenic shock with planned early revascularization, the use of an intraaortic balloon pump did not improve 30-day mortality or tissue oxygenation.
IDEAL-ICU
[or]
Early vs. delayed renal replacement therapy in septic shock.
- Included 488 French ICU patients with early septic shock (onset within 48 hours) with acute kidney injury (AKI) who did not have an emergent need for renal replacement therapy (RRT) (e.g. hyperkalemia > 6.5 mEq/L, metabolic acidosis with pH < 7.15, or refractory pulmonary oedema)
- Acute kidney injury was defined as the “failure” category in RIFLE.
- Randomised patients to early RRT (within 12 hours of AKI) or delayed RRT (after 48 hours of AKI if renal function had not recovered). RRT was initiated immediately in any patient with an emergent indication.
- RRT modality was left to the discretion of the treating clinician. Intermittent HD was used as the first
RRT modality in 44% of patients and continuous RRT in 56% of patients. The median delivered continuous RRT effluent dose was about 26 mL/kg/hr. - The primary endpoint (90-day mortality) was not different between early and delayed RRT (58% vs. 54%, p=0.38).
- The trial was stopped early (prior to enrolling a planned 432 patients per group) for futility. The study’s post-hoc power was 51.44%, indicating the study was underpowered.
- Within a 28-day period, delayed RRT was associated with more days free of RRT (12 vs. 16 days, p=0.006). RRT was initiated in 97% of early RRT patients and only 62% in the delayed RRT group (p<0.001, NNT 3). In the delayed RRT group, 17% of patients were started on RRT before 48 hours of AKI onset due to meeting an emergent RRT indication.
- There were no differences between the two groups related to 28-day mortality, 180-day mortality, days free of mechanical ventilation, days free of vasopressors, the median length of ICU or hospital stay, fluid balance, or RRT dependence among survivors.
TBL
Among patients with septic shock and acute kidney injury without an urgent need for dialysis, early renal replacement therapy (RRT) did not improve mortality versus a delayed strategy but did result in higher
utilization of RRT.
INTERACT 2
Intensive vs. standard blood pressure in intracerebral hemorrhage
- Included 2839 patients with a spontaneous intracerebral hemorrhage and a systolic BP between 150-220 mmHg within 6 hours of symptom onset.
- The study excluded those with a low Glasgow coma score (GCS 3-5) on the basis of an expected poor outcome.
- Randomized patients to “intensive” BP treatment (goal SBP < 140 mmHg within 1 hour) or “standard” BP treatment (goal SBP < 180 mmHg).
- Specific antihypertensive treatment was recommended based on a study protocol and site-specific formularies.
- After 7 days, all patients were assigned to a SBP goal of < 140 mmHg.
- Primary endpoint (90-day death or major disability based on a modified Rankin scale) was not different between intensive and standard therapy (52% vs. 55.6%, p=O.06)
- An ordinal analysis (comparing each of the 7 Rankin scores rather than comparing a dichotomous “favorable” versus “unfavorable” score) did demonstrate a favorable shift in scores with intensive therapy (OR for a higher score 0.87 [95% Cl 0.77-
1.00, p=O.04]) - Quality of life at 90-days (as measured by EQ-5D between 0 [death] and 1 [perfect health]) was more favorable with intensive therapy (mean score 0.6 vs. 0.55 , 0=0.002)
- There was no difference in all-cause mortality or ICH-related mortality between the two groups
- No safety outcome (including severe hypotension, stroke, and neurologic deterioration) was different between the two groups
- There was no difference in 24-hour hematoma expansion between the two groups
- There were no differences in any subgroup analysis, including those with baseline hypertension
- The mean blood pressure prior to randomization was about 180/100 mmHg. At 1 hour, intensive patients had a lower SBP than standard patients (150 vs. 164 mmHg, p<0.001)
- Of note, the study only included spontaneous parenchymal hemorrhage (intracerebral). It did not include other types of intracranial hemorrhage such as subarachnoid, traumatic, aneurysmal, or subdural.
- The majority of the patients were from China and many received an antihypertensive drug called urapidil (not available in the US) — this may limit study external validity
- Although use of a variety of antihypertensives makes this a very pragmatic trial, there is concern that only certain antihypertensives may have contributed benefit in the trial (eg, through non-blood-pressure pleiotropic effects)
- Many patients received mannitol but ICP monitoring data was not provided.
- Because patients with elevated ICP may benefit from a higher blood pressure (to maintain cerebral perfusion pressure), it is not clear whether an “intensive” goal is appropriate for these patients.
- Given the results of ATACH-II (a similar trial published in 2016) showing no benefit with intensive BP control within the first 24 hours and the fact that INTERACT 2 did not demonstrate benefit in the primary endpoint, the ordinal analysis showing benefit in this trial should be interpreted with caution
TBL
Among patients with a spontaneous intracerebral hemorrhage, a lower blood pressure goal may have benefit for long-term disability outcomes and quality of life.
ISAT
Clipping vs. coiling for aneurysmal subarachnoid hemorrhage
- Included 2143 patients with subarachnoid hemorrhage due to a ruptured intracranial aneurysm that would be anatomically suitable for either endovascular or neurosurgical treatment
- Randomized patients to endovascular platinum coiling or neurosurgical clipping. All other elements of care were left to the discretion of the treating clinicians.
- Primary endpoint (death or dependence at 1 year based on the modified Rankin scale) was reduced in patients with endovascular treatment compared to neurosurgery (23.5% vs. 30.9%, p=O.0001, NNT 14)
- The benefit of endovascular treatment for the primary endpoint was significant for at least 7 years (Log- rank p=0.03)
- Pre-specified subgroups related to age, severity, and anatomical location were underpowered and either neutral or favored endovascular therapy
- Early rebleeding (within 30 days) was slightly more common with endovascular treatment (1.9% vs. 0.7%, RR 1.09-5.57). The long-term rebleeding risk was no different between the two groups (Log-rank p=O.22).
- Post-procedure in-hospital seizures were more common with neurosurgery (1.5% vs. 3.1%, RR 0.37-0.74)
- A significant number of patients (69% of those evaluated) were excluded because the anatomical location of the aneurysm was not equally appropriate for both procedures (usually not appropriate for coiling)
- Critics of the ISAT trial highlight that the study only included a specific segment of aneurysmal SAH patients and that the decision to pursue coiling or clipping involves many patient-specific factors that the study was not powered to evaluate
