VASST trial

VASST trial

- Evaluate the role of vasopressin in septic shock being treated with conventional vasopressors.

What they did? Read it here
http://www.nejm.org/doi/full/10.1056/NEJMoa067373

Refractory septic shock in this study was defined as
- septic shock resistant to 500 mL of fluid and low dose norepinephrine (and required other vasopressors).

So are these patients really having REFRACTORY septic shock?
From http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectious-disease/sepsis/ : Refractory septic shock is a persistently low mean arterial blood pressure despite vasopressor therapy and adequate fluid resuscitation

Look at their mean MAP: it is about 70 mmHg (River's protocol MAP is 65 mmhg)
Look at their lactate: mean is 3.5

My opinion is: these patients were quite well resuscitated prior to randomization. They responded to whatever pressors given to them. So this is a study of vasopressin's role in septic shock in which you are considering to take off norepinephrine early, not really a study of vasopressin in REFRACTORY shock.

BUT, after patients achieved the target MAP, they were started on studied drugs. Open-label pressors were only given if the MAP could not be maintained. Based on the dosage of pressors use, they subdivided the patients into severe vs less severe groups.
- They did not specifically mentioned what the pressors they have used. But I think they just continued what the patients were using prior to randomization.
- Almost 60% only required one vasopressor, 30% required two vasopressors and 10% did not need any vasopressors (in addition to the studied drugs) to maintain MAP. The proportions were divided equally among two groups.
- And they were evaluating whether vasopressin has any role in severe vs less severe septic patients in comparison to NE

Another thing to consider is, they only received 0.5 cc of fluid and if they did not respond, pressors were started. 0.5 cc was perhaps too less, maybe pressors were given at higher doses that these patients really required.
- NE were given at mean dose of 20.7 mcg/min before randomization.
- Epinephrine were given at a mean dose of 8.6 mcg/min in NE group vs 14.6 mcg/min in vasopressin group.

How many of these patients ended in severe vs less severe septic group?
- 200 each from NE and vasopressin group were in severe group
- 182 vs 196 were in less septic group.
- So basically, whatever the patients received. around 200 ended up in severe vs less severe septic group (the drugs used weren't really important); BUT the drug used was important in determining whether the patients survived.
- In less severe group, vasopressin was better (reached statistical significance). In more severe group, neither was superior. However, test of interaction and post-hoc analysis did not find significant p-value between vasopressin and sepsis severity.

Anyway, what they found ?
Low-dose vasopressin did not reduce mortality rates as compared with norepinephrine among patients with septic shock who were treated with catecholamine vasopressor

My thoughts:
- This study did not tell us the role of vasopressin if septic shock didnt respond to catecholamines.

- The mortality in this study was lower than expected. Perhaps reflecting the better care nowadays.

- Epinephrine was of higher dose in vasopressin group. Perhaps this affected the mortality at 28 days. Perhaps this is why NE infusion doses were lower in vasopressor group.

- In less severe septic shock, perhaps vasopressin is better (better vasoconstriction). But role within 6 hours is not known. Role substituting catecholamines is not known.

- In severe septic shock, NE is better. In fact, mortality was marginally better in the study in NE group. Perhaps related to its effect to improve microperfusion

TRANSFER-AMI trial

TRANSFER AMI study

Evaluate role and optimal timing of routine PCI after fibrinolysis (role of rescue PCI).

1059 patients with STEMI who were receiving fibrinolytics were assigned to standard treatment (rescue PCI or delayed angio if needed) or early PCI group (transfer to PCI facility within 6 hours). 

All groups received standard medical treatments.

Primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening CHF, or cardiogenic shock within 30 days

Study found that early PCI group had better outcome than standard treatment group. (17.2% vs 11.0%, Relative risk reduction of 0.64, p = 0.004)

Definition of terms:

1) Facilitated PCI : PCI done RIGHT AFTER fibrinolysis within 2 hours window. In this study, the median time from lysis-balloon inflation was about 4 hours.

2) Rescue PCI : life-saving PCI done if lysis has failed/contraindicated/cardiogenic shock.

- This is what this study was about, comparing rescue PCI vs patients who got routine PCI after fibrinolysis.

My conclusion:

- Group with routine PCI after fibrinolysis had significantly lesser primary end points, but mostly driven by lesser recurrent ischemia and to a lesser extent new/worsening CHF. Death and re-infarction did not reach statistical significance.

• But perhaps if more patients were enrolled, re-infarction would reach statistically significant reduction in early PCI group.

Take note that:

- Note that most of them had Killip class I. So this did not apply to patients who had cardiogenic shock as the initial presentation (in fact these patients were excluded).

- They also presented early (median time of 2 hours from symptom onset) and received fibrinolysis within 30 minutes of hospital presentation.

- More important is the study did not recruit enough patients and was underpowered to detect any difference in mortality.

- More patients in early PCI group had stroke/TIA, while more in standard tx group has prior CHF. 

- More patients in early PCI group received clopidogrel.

- There was higher rate of bleeding in early PCI group, but mostly were mild bleeding.

My opinion is:
If you can transfer AMI patients from non-PCI to a PCI facility within 6 hours of fibrinolysis, there maybe a benefit.

• Within 6 hours is the key, not sure if there is a benefit after 6 hours.
• PCI should be done after at least 3 hours of fibrinolysis.

Pathophysiologically, it makes sense, you are trying to save heart muscles which are not yet necrotic if you do early PCI.

References

Routine Early Angioplasty after Fibrinolysis for Acute Myocardial Infarction, NEJM 2009