Is Delhi burning? Not exactly but a couple of buses did get torched yesterday in south Delhi by angry protestors against the Citizenship Amendment Act. The Assamese too are more than irate at the new “Citizenship Amendment Bill “that was recently successfully thrust though the Indian parliament. Remarkably, there was little or no unrest while with National Register of Citizens exercise was going on in Assam. The affected folks were of course terrified.There was little to write home about after 19 lakh people were declared non residents or “illegal” occupants of the land. Even the realisation that of the these 19 lakh “illegal migrants” 15 lakhs were Hindus did not appear to cause great concern. The government however was obviously deeply concerned and swiftly moved into action. The “Citizenship Amendment Bill” got approved by both houses of parliament and shall soon be autographed by the president in Rashtrapati Bhawan. The citizens of Assam seem now to be acutely aware that the NRC exercise has served to purpose, they are back dealing with the same people they wanted out in the first place. Worse this time they shall not be dealing with “illegals” but those officially converted to “legals”, courtesy CAB. Small wonder the short lived sense of NRC relief has turned into a rage that has translated into violent protests, including the death of at least 5 people so far.
“The point is that it makes 200 million Muslims feel as if somehow their religion is not as valid or as Indian as the others. That’s not a good recipe for harmony.” That is Professor and Nobel Laureate Venky Ramakrishnan (2009 chemistry Nobel winner) on CAB in his interview to The Quint. He went on to say despite not being a local citizen he has “deep affection” for India and he wants ‘India to do well.”
It is impossible to be bored in modern India, every new day is an event. Probably diversion is needed from the mundane narrative of a rapidly declining economy, they say sales of both toothpaste and underwear are down; forget about selling a house. More than 10 lakh flats lie unsold in major cities of the country. There manifestly is no money going around and hence little appetite for consumption. Apparently unlike the Chinese economy that is based on manufacturing , Indian fiscal health depends on purchase. But what do you buy when you are broke ?
A much smaller seismic event has taken place in the world of cardiology with little notice by the Indian media. It concerns the left main (LM) coronary artery, which is the most important artery of the heart because it supplies good to more than two thirds of heart muscle. It divides into the left anterior descending and left circumflex coronary arteries. Blockage in the left main artery is of great concern because death is imminent if no treatment is provided. This is one blockage that mandates intervention either by coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) by stenting. Stents are tiny metallic tubes inserted into blocked arteries to make them patent. For many years CABG had been the only option for LM blockage or disease. Randomised trials done in the eighties of the last century had established superiority of CABG over medical treatment. The situation is much the same despite substantial improvement in medical therapy; left main disease can only be tackled by intervention; medicines do not work. The last decade however has witnessed the emergence of stenting as a viable alternative to CABG in the treatment of LM blockage or disease. Both American and European cardiology associations recommend PCI with stenting in LM disease of mild or moderate complexity based on the SYNTAX score, the recommendations are made based on clinical outcomes of high quality clinical trials. The first such trial to demonstrate equipoise between CABG surgery and PCI with stenting was the SYNTYAX trial, which randomised almost 800 patients of LM disease to CABG or stenting. The ten year long followup was recently published in the Lancet; the results suggested that mortality was the same whether a patient with left main disease underwent surgery or stenting. There was no significant difference in the death rate, even after 10 years.
The other big trial called “EXCEL”, however has become a huge controversy. The BBC beamed a documentary on accusations made by an author of the paper that vital data was concealed while publishing the paper in the prestigious New England Journal of Medicine journal. Professor David Taggart has been the “whistle blower” ; Taggart has withdrawn his name from the authorship of the paper because he believes that the incidence of heart attack has been withheld by the other investigators involved with the EXCEL paper. According to Taggart there were more heart attacks and more deaths in the stenting group as compared to patients undergoing CABG surgery, and that this data has been deliberately buried by the investigators of the EXCEL paper. EXCEL published its 5 years follow up recently, it recorded no significant difference in heart attack or death between CABG or stenting. Taggart’s allegations have been taken quite seriously by the European Association of Cardio-thoracic Surgeons (EACTS), which has gone to the extent of no longer supporting guidelines recommending stenting as an alternative to CABG.
The EXCEL trial was led by Professor Greg stone; it included almost 19005patients with left main disease; randomised them to CABG or stenting; and concluded that at the end of 5 years there was no difference in the composite of death, heart attack or stroke between CABg and stenting. Death of any cause occurred more frequently with stenting than CABG (13% versus 10%), but importantly definite cardiovascular deaths were similar (5% versus 4.5%). Heart attacks too were similar , around 10% in both groups. This is the data provided in the New England Journal of Medicine paper.
So how do we adjudicate the allegations made by Professor Taggart ( who by the way is a cardiac surgeon) and the BBC Newsnight investigation. Actually it is not too complicated. The problem lie not in the stars but in the definition of heart attack. You will be astonished to learn that even now there is no clarity as to what constitutes a heart attack. In simplest terms a heart attack implies that heart muscle is damaged to the extent that it is dead our necrotic; a small or large part of heart muscle gets damaged when an artery large or small gets completely blocked. One can therefore have a small or a large heart attack, which is measured by the amount chemicals or cardiac enzymes released by the necrotic heart muscle cells. The larger the damage the greater in quantum the release of these enzymes. There are largely 2 types of enzymes; creatine kinase MB (CKMB) and troponin (Tr). So far so good. The problem is that there is “Universal Definition” of heart attack and there is also a heart attack definition proposed by the Society for Cardiovascular Angiography and interventions (SCAI). The SCAI definition, to put it lucidly has a higher threshold or a higher bar; SCAI defines a heart attack subsequent to a PCI or CABG as an increase of CKMB ten times above the normal limit or a Tr increase by 70 above the upper limit. The “Universal” definition has a much lower threshold or bar to define a heart attack; the 2018 version defines a procedure related heart attack as a troponin level increase of 5 times more than the upper normal limit accompanied by ECG changes, 2 D echo demonstration of a new ischemic segment or the presence of (on coronary angiography) a blocked vessel, dissection of an artery or distal embolisation). So a heart attack is present with a lower bar when the “Universal” definition is employed; hence more patients will be classified as having a heart attack following a procedure. The SCAI definition on the contrary, with the higher bar, will identify fewer heart attacks. Professor Taggart and BBC Newsnight is deeply concerned that investigators of the EXCEL trial have used the SCAI definite and not the “Universal” definition, and therefore the allegation that had the “Universal” been used there would have been 80 times more attacks in the stenting group. These heart attacks were as explained involved a small area of the heart with little clinical significance. The Australian investigators reported that almost half of heart attacks using the “Universal”definition were due to occlusion of arteries < 1mm.
The response of Professor Greg Stone was swift; he put up a lengthy mail explaining the position of the Excel investigators. In a nutshell he emphasises the different thresholds of the 2 heart attack definitions. The riposte has already been explained by an elegant Australian study done a few years ago. The investigators of this trial used both SCAI and the Universal definitions in patients undergoing stenting. The patients were divided into a group with procedure related hear attack or a group without procedure related heart attack.They found that albeit more procedure related heart attacks were noted using the “Universal” definition than with the SCAI definition, at the end of 2 years the number of deaths or heart attacks were significantly greater with the SCAI definition ( 25% with positive SCAI versus 11% with negative SCAI). There was however no significant deaths/heart attack at the end of 2 years in patients identified as having stenting related heart attack when a rise in troponin was used (“Universal”). The Australian investigators reported that almost half of heart attacks using the “Universal”definition were due to occlusion of arteries < 1mm. Professor Greg stone in his explanation has underlined the fact that he and his co investigators considered the SCAI definition more suitable in the EXCEL trial. There was in the EXCEL trial no difference in heart attack at the end of 5 years with application of there SCAI definition. But the data on heart attack as per the “Universal” definition will be published also to further clear the air. He also made the point that the European association of cardiac surgeons should have sought an explanation from him before withdrawing from the left main revascularization guidelines.
The European Society off Cardiology however has not changed it’s recommendations regarding stenting in left main disease despite the BBC Newsnight investigation. Professor Taggart being a cardiac surgeon may be a bit sceptical about stenting and shall need to be satisfied by revealing the “Universal” heart attack numbers in ESCEL at the earliest. The BBC has pointed out that Professor Greg Stone has heaps of conflicts of interest. Stone is connected to nearly 20 stent/device companies as an adviser or other financial treated positions. The EXCEL rial was first presented at the TCT meeting , which one of the largest interventional cardiology conferences in the world. The TCT meeting is supervised by Professor Greg Stone , the lead author of EXCEL, and also millions of dollars are provided to TCT by nearly all major interventional cardiology product (stent) manufacturers of the world. EXCEL was supported by ABBOT , the maker of everolimus eluting stents used in EXCEL. Worse , one of the authors of the EXCEL paper has moved on to become the vice president of Medtronic, which is a giant stent manufacturing company. It will take some time for the air to clear; the issues involve life and death of thousands of left main disease patients.
It is important to mention a meta analysis of 24 prospective studies including almost 45,000 patients published in the current issue of EuroIntervention that concludes even 3 fold increase in troponin above the upper limit is associated with all cause mortality. The authors of this large meta analysis do not however discuss cardiovascular mortality; also studies that were included albeit prospective were not randomised. The editors of Eurointervention have issued a disclaimer that responsibility of the contents of this paper lies with the authors.
For now stenting should be considered for patients with the least complex left main blockage, and CABG surgery for more complex lesions; for the air to clear we may have to wait for another BBC Newsnight investigation. The SYNTAX trial is remarkable for concluding that even after 10 years there was no difference in mortality between stenting and CABG; and especially so because the stents used in SYNTAX were the paclitaxel eluting ones that are currently considered obsolete.