Prof Dr Upendra Kaul, Executive, Dean and Executive Director, Cardiology and Academics and Research, Fortis Escorts Heart Institute and Fortis Flt Lt Rajan Dhall Hospital recently presented results of a randomised clinical trial executed across 46 centres in India, by Fortis Escorts Heart Institute (FEHI) at the Trans-catheter Cardiovascular Therapeutics (TCT). In an tête-à-tête with Raelene Kambli, Dr Kaul explains the highlights of the study and also talks about its benefits for India
There are mixed views on advising diabetic patients for stent implants. What is your opinion on the same?
Patients with multi-vessel disease with diabetes needing revascularisation (stenting vs CABG) has been a debatable issue. The data suggested that CABG has advantages in terms of long term benefits, including survival. The choice of procedure needs to be looked from several angles, which include: the type of disease including size of the arteries, patient’s preference and financial status, and choice of stent which is critical. Our TUXEDO study clearly suggests that the new generation everolimus stents are the best in terms of efficacy and safety.
What are the highlights of the ramdomised Indian clinical trial that you conducted?
Firstly, it is the largest study ever done, comparing one strength to another in diabetic patients. Secondly, the study which was initiated in 2010 started its execution in June 2011 and completed its one year follow up of 1830 in March 2015 and the analysis of the study was done after this study and the data of this study was presented as a ‘late breaking trial’ at the prestigious Trans-catheter Cardiovascular Therapeutics (TCT). The study was comparing paclitaxel eluting stents (TAXUS Element) v/s everolimus eluting stents (XIENCE PRIME) which indicated that one stent had better result in patient with diabetes.
What is the motive behind this study and clinical trial?
To resolve a decade old controversy regarding the results of paclitaxel vs everolimus eluting stents . There was a lingering debate on this subject with a large meta analysis from retrospective analysis showing that the two were equivalent with paclitaxel eluting stents having an advantage in insulin requiring diabetics. We conducted a 1830-patient study over 46 centres across India, the largest study so far in diabetic patients comparing stent vs stent to answer this issue.
Why have you selected these stents for comparison?
As these are the most commonly used stents in the market.
Which are the companies that manufacture them?
Paclitaxel eluting stents are manufactured by Boston Scientific and the everolimus eluting stents are manufactured by Abbott and Boston Scientific. It is also important to note that paclitaxel as a drug molecule was developed by Boston Scientific.
Who has funded this project?
Boston Scientific has funded this huge project.
Do they have any vested interest in this study?
They have no role in investigations in this study nor did they have any role in the execution of the study. In fact, as per our study, their paclitaxel eluting stents have proved to be inferior to the other.
What was the method used for this clinical trial?
We randomly assigned 1830 patients with diabetes mellitus and coronary artery disease who were undergoing PCI to receive either a paclitaxel-eluting stent or an everolimus-eluting stent. We used a non-inferiority trial design with a noninferiority margin of four percentage points for the upper boundary of the 95 per cent confidence interval of the risk difference. The primary end point was target-vessel failure, which was defined as a composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularisation at the one-year follow-up.
What are the results of the trial?
At one year, paclitaxel-eluting stents did not meet the criterion for non-inferiority to everolimus-eluting stents with respect to the primary end point (rate of target vessel failure, 5.6 per cent vs. 2.9 per cent; risk difference, 2.7 percentage points [95 per cent confidence interval {CI}, 0.8 to 4.5]; relative risk, 1.89 [95 per cent CI, 1.20 to 2.99]; P = 0.38 for non-inferiority). There was a significantly higher one-year rate in the paclitaxel-eluting stent group than in the everolimus-eluting stent group of target-vessel failure (P = 0.005), spontaneous myocardial infarction (3.2 per cent vs. 1.2 per cent, P = 0.004), stent thrombosis (2.1 per cent vs. 0.4 per cent, P = 0.002), target-vessel revascularisation (3.4 per cent vs. 1.2 per cent, P = 0.002), and target-lesion revascularisation (3.4 per cent vs. 1.2 per cent, P = 0.002).
Which means that in patients with diabetes mellitus and coronary artery disease undergoing PCI, paclitaxel-eluting stents were not shown to be non-inferior to everolimus-eluting stents, and they resulted in higher rates of target-vessel failure, myocardial infarction, stent thrombosis, and target-vessel revascularisation at one year.
What are your learnings from this study?
This study has given India the leverage of being a trusted source for conducting clinical trials and research. Also, that this study has been recognised by the TCT is a big honour. Another feather to our crown is that this study is going to be published in the New England Journal. I would finally say that this study has paved a path for more trusted clinical trials in India.