Thread by @dr_benoy_n_shah

The #ISCHEMIA trial has been popular again in recent days on Twitter, but amongst all the controversies & criticisms, it got me thinking about the #STICH trial.

These two trials actually have quite a lot in common and it's worth exploring that in a little detail

A thread...1/

STICH was a government funded trial designed to answer definitively - for once and for all - the role of revascularization in ischaemic cardiomyopathy. Numerous observational and/or retrospective studies suggested benefit on 'hibernating myocardium' but the jury was still out 2/

It was a well-intentioned study with enormous amount of thought put into planning methodology, ensuring only experienced surgeons with proven good outcomes took part, OMT had to be maximized etc etc

Tragically, like other RCTs, STICH suffered from enormous enrollment bias...3/

Younger patients with LV dysfunction & widespread viable myocardium, especially in the LAD territory, were often not put forward for randomization..."there's no way I'm risking this guy getting tablets only, he needs revasc!"

As a result, mean N per site was 2!

4/

STICH set out to put an issue to bed but, for multiple reasons, that isn't the way it worked out. Recruitment was a lot slower than anticipated. Other limitations have been highlighted... but essentially, despite best will in the world, role of revasc in ICM remains debated...5/

ISCHEMIA was also supposed to settle the issue, once and for all, whether revasc offers better outcome over modern OMT in patients with stable CAD. The COURAGE trial, ORBITA trial and many retrospective studies had suggested no benefit for PCI / CABG in this setting...6/

So, again, ISCHEMIA was hopefully going to put this issue to bed.

Despite a very elegant trial design and accepting 3 stress modalities (SE, SPECT & CMR), the trial also didn't recruit as quickly as expected. Again, enrollment bias came into play. Many of us know this 7/

because we saw it happen! Youngish guy presents with chest pain, stress test shows gross LAD territory ischaemia... some cardiologists felt "these patients need revasc!" so, again, many never made it into the trial

Other limitations of ISCHEMIA also already debated to death...8/

In any case, the end result is that two eye wateringly expensive government funded RCTs sadly didn't provide definitive answers to vital and specific questions as many hoped they would.

So the question is... will these questions ever get a definitive answer? I believe not...9/

What STICH & ISCHEMIA highlighted is the monumental challenge of running large scale multicentre RCTs. Despite very careful planning and thought these trials still encountered lots of problems. You cannot control which patients are put forward for a trial & which ones aren't..10/

I'd almost go as far as to say that it's virtually impossible to carry out the 'perfect' RCT...both these trials were supposed to be exactly that...

When we wrote a review article for EHJ on STICH many years ago, we spent an entire page explaining that we're didn't think...11/

that an 'ideal' trial could ever be run. The reviewers didn't like that...they asked us to remove that section and actually asked us to design an "ideal trial"...so we had to, even though inside we're thinking "STICH wasn't that far off the mark, you know!"

12/

For me the take home messages from these trials were that an individualised patient-by-patient approach will always be necessary because the issues are far too complex for a binary "Yes this works" or "No this doesn't work" approach

13/

The investigators of both trials deserve a lot of credit for what they aimed to achieve...but this is the REAL world, not an ideal world, in which even the best laid plans can come into trouble...14/

If physicians genuinely want answers to these questions, we need to engage with such trials and do our very best not to let our own beliefs influence our behaviours

15/

@BCIS_uk @TheBJCA @BJCA_Women_LTFT @WessexSpRs #cardiotwitter @ncurzen

@threadreaderapp please unroll, thank you.