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Posts Tagged ‘reteplase’

Thrombolytic therapy ,  has been  the specific treatment  for STEMI for  many decades. Primary PCI*  is  shown to be  superior  than  thrombolysis  if   performed   early  by an experienced  team in a dedicated facility. (*Conditions apply). It is estimated ,   currently only a  a fraction  STEMI  population get primary PCI (<5%) in ideal conditions . Another fraction , get  primary PCI by inexperienced cardiologists  in low volume centres.

So , thrombolysis   remains, and  would continue to remain ,   the    primary  mode of therapy for STEMI  in the  present and near  future !

How do you assess the successful  thrombolysis ?

It should be recognised ,  there is a fundametal flaw in this  question !

The aim of thrombolytic therapy is  not  to   lyse  the thrombus  , but also  to restore the coronary blood flow to the  myocardium – also called reperfusion . One may wonder , why the term ,  thrombolysis  should ‘t be  used interchangeably with reperfusion. 

A successful thrombolysis  never guarantees  a good reperfusion , for the simple reason ,  distal blood flow in an  obstructed coronary artery  is dependent on ,  many factors  other than relief of obstruction.

Apart from the potency of drug,     other   important factors  that determine  successful  lysis &  reperfusion are  . . .

  • Timing of opening of artery , if the thrombolysis is delayed  ,  the distal myocardium is dead , and   it won’t allow blood flow to enter the mycardium.
  • Microvascular integrity is as vital as epicardial vessels.
  • Distal microvascualture  plugging by the thrombotic debri . This is called”no reflow “

So , we should  primarily assess myocardial reperfusion rather than epicardial thrombolyis ! following thrombolysis .

What are the parameters available to assess successful reperfusion /thrombolyis?

  1. Clinical : Relief from chest  pain. Angina relief  , though subjective is an indication for adequate reperfusion of ischemic myocardium.
  2. ECG-ST segment regression > 50%
  3. Cardiac enzymes: Early flushing of  intra myocytic CPK into systemic circulation and hence early peaking of CPK MB (<1ohours instead of 24h)
  4. Reperfusion arrhythmias(AIVR-Less specific) .Primary VF is now thought to be reperfusion related.
  5. Infract related artery(IRA) patency by coronary angiogram
  6. Distal TIMI flow/ myocardial blush score/ TIMI frame count

ECG ST regression ,  is a direct indicator  myocardial reperfusion   as the ST segment shifts  towards baseline ,  implies  of infarct current of injury . ST regression almost always correlate with good  recovery of LV function  in STEMI .

IRA patency , is an epicardial index , it  does not give information about myocardial blood flow . But ,  a good  distal TIMI flow generally indicates good reperfusion.This  again ,  is  not a fool proof  index,  as even many of the TIMI 3 flow patients  have severely damaged myocardium by echocardiography .

Final message

For the above reasons, one should always  make a distinction between successful lysis and successful reperfusion . Surprisingly ,  ECG  is  the gold standard for assessing successful reperfusion of myocardium ,  while CAG tell us  about epicardial patency and possibly reperfusion also.

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Failed thrombolysis is an important clinical  issue  in STEMI   as  successful thrombolysis  occurs  only in  about 50-60%  of pateints . The typical criteria to define failed thrombolysis is  the  regression  of less than 50% of sum total( or maximum)  ST elevation in infarct leads.

So what do you do for these patients with failed thrombolysis ?

It depends upon the patient’s symptom, hemodynamic stability, LV dysfunction .

They  should  get one of the following .

  1. Conservative medical management  with /without CAG
  2. Repeat thrombolysis
  3. Rescue PCI
  4. CABG

Medical management is  thought to be  too inferior a  management,  many of the interventional cardiologists  do  not want to talk about . But  , there is  an important  group of patients (Not often addressed in cardiology literature)  who  technically fulfill the criteria  of failed thrombolysis  , but   still  very  comfortable , asymtomatic  and in  class 1. These patients ,  have  a strong option for continuing the conservative management .

Repeat thrombolysis does not have a consistent effect but can  be  tried in some  stable patients. CABG  can be a genuine option in few

Rescue PCI

This terminology  has become  the  glamorous one since the  catchy word  rescue is tagged in the title  itself. For most of the cardiac physicians ,  this has become the default treatment modality.This is an unfortunate perception . What  one should realise   here is  , we are  tying to rescue  the myocardium and  the patient ,   not the patient’s coronary artery !

Opening up a coronary obstruction is not synonymous with rescue .

For rescue PCI ,  to be effective it should be done within the same time window as that for thrombolysis (ie within 6 or at the most  12 hours) .This timing  is  of vital importance  for the simple reason , there will be nothing to rescue after 12 hours as most of the muscle  would be  dead. Reperfusing a dead myocardium has been shown to be hazardous in some ,  as it converts a simple  infarct into a hemorrhagic  infarct.This softens the core of the infarct and  carry a risk of rupture. Further,   doing a complex emergency  PCI  ,  in  a thrombotic milieu with   presumed  long term  benefit ,  is  a  perfect recipe for a potential  disaster.

While the above statement may be seen as pessimistic view , the optimistic cardiologist would vouch for the“Curious  open artery hypothesis” .This theory simply states , whatever be the status  of the distal myocardium ( dead or alive !)   opening an obstruction in the concerened coronary artery  will benefit the patient !

It is  huge surprise , this concept   continues to  be alive even after  repeatedly shot dead by number of very good clinical trials (TOAT, CTO limb of COURAGE etc ).

The REACT study (2004) concluded undisputed benefit of rescue PCI for failed thrombolysis  , only if the rescue was done  within  5-10 hours after the onset of symptoms.The mean time for  pain-to-rescue PCI was 414 minutes (6.5hours)

Final  message

It is fashionable to talk about time window for thrombolyis but not for PCI  .The time window for rescue PCI is an redundant issue  for many  cardiologists ! . But ,  the fact of the matter is ,  it is not . . .

The concept of time window in rescue PCI  , is as important as ,   that of  thrombolysis. Please , think twice or thrice !  if some body suggest you to do a rescue PCI in a stable patient  ,  12hours after the index event .

Important note : This rule   does not (  or need  not  ) apply for patients in cardiogenic shock  or patient ‘s with ongoing iscemia and angina.

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