Primer

Evolution of Coronary Stenting

Even though India was far behind the West when it started developing stents, currently, our technology is quite ahead of them.

Dr Balram Bhargava

Since the advent of balloon angioplasty in 1977 by the pioneering work of Andreas Gruentzig in Switzerland, interventional cardiology has advanced tremendously. The immediate problem of acute closure of arteries following balloon angioplasty was a major limitation. Intracoronary scaffolds or stents were first used by Ulrich Sigwart (1986), again in Switzerland. The stents solved the problem of abrupt closure of arteries and prevented immediate heart attacks. However, stents were limited by the problem of acute thrombosis which was tackled by the use of antiplatelets (aspirin and ticlopidine) and high pressure stent deployment. This led the approval of stents by the US Food and Drug Administration (FDA) in 1994.

The First Wave

Coil Stents: Stents were first used in India at the All India Institute of Medical Sciences (AIIMS) in 1991. Stents were shown to reduce restenosis or reblockage when compared to plain balloon angioplasty. However, in-stent restenosis (ISR) remained a major problem with rates in clinical practice up to 37 per cent. Although stents prevented the acute closure or collapse of the arteries, the metal evoked a tissue response which triggered uncontrolled growth of tissue (neointimal hyperplasia) and fibrosis inside the artery similar to a keloid. Several metals, coatings, drugs, and different stent designs were tested to reduce neointimal hyperplasia. The metals tested in the development of stents include surgical quality stainless steel (316L), tantalum and nitinol. No local or distant toxicity was demonstrated with any of these alloys. Since the stents prevented recoil of the artery and acute closure, they were being widely used across the world; but the delayed problem of ISR remained.

At this time (1994-1995), none of the stents were manufactured in India and both the internationally accepted stents i.e. the Palmaz Schatz stent (Johnson and Johnson) and the coil design Wiktor stent (Medtronic) were manufactured in USA and imported to India and the rest of the world. In 1996, a novel homemade stent was developed by me and my brother-in-law (a jeweller in Mumbai). This stent was made of a platinum-iridium alloy (Pt-Ir was chosen as it had the potential to become radioactive to reduce ISR). It was implanted in animals and was found to be very effective and more bioacceptable than the gold standard Palmaz Schatz (Johnson and Johnson, USA) stent. This stent was developed around the same time when the Kalam-Raju stent (K-R) was developed in Hyderabad. The Pt-Ir stent was tested in animals but the K-R stent was tested in humans and was found to be effective; but no scientific clinical trial was performed. Both these stents were not very successful as they were coil designs with less radial strength and recoil. At this point, the gap in technology between India and the West was at least five to seven years.

The Second Wave

Slotted tube laser cut stents: The coil stents were replaced by the laser cut slotted tube stents and several stents developed across the world. Intracoronary radiation developed and both beta and gamma radiation were used in India for the first time in 1999-2000 at AIIMS. Subsequently, we partnered with Professor Raju at the Care Hospitals, Hyderabad to further develop and test Indian stents more scientifically. At this point in time, three slotted tube cost-effective Indian stents were developed: Matrix (Sahajanand Medicals; Surat) Prostent (Vascular Concepts, Bangalore) and Legend (Relisys, Hyderabad). These stents were cost-effective but were not investigated in randomised clinical trials. At this point (around the year 2000), the gap in technology between India and the West was about three to five years. These Indian stents were exported to countries around India and North Africa. The slotted tube stents continued to have a problem of restenosis. Intracoronary radiation also went out of favour because of the problem of late thrombosis or late occlusion of the artery due to incomplete healing. This problem was partly solved by the use of prolonged antiplatelet medications. However, the patients who presented with late thrombosis had a very poor prognosis.

The Third Wave

Drug eluting stents (DES): In 2002, Johnson and Johnson and in 2003 Boston Scientific, USA got approvals by the FDA for their DES (Cypher:Sirolimus; Taxus:Paclitaxel). These medicated stents were found to be much more effective than the slotted tube bare metal stents (BMS). These stents were basically BMS coated with a plastic polymer and the drug was loaded on this polymer to provide a controlled and effective release of the antiproliferative drugs. This triggered a revolution for the use of DES. About 50 per cent of the implants in India and more than 90 per cent of the implants in the US were DES. However, these were very expensive costing over a lakh of rupees each. At the same time, three Indian companies developed medicated stents; Infinnium (Sahajanand Medicals; Surat) Pronova (Vascular Concepts, Bangalore) and Release-T (Relisys, Hyderabad). At this point (around the year 2003), the gap in technology between India and the West was about one to three years.

Scientifically conducted studies of the medicated Indian stents were published. In 2006, it was reported that although DES reduce restenosis, they are more prone to late stent thrombosis or sudden closure of the artery with devastating outcomes of heart attack and even death. This was observed with all the types of DES and resulted in marked reduction of the use of DES in the USA from 90 per cent to 60 per cent. This problem could partly be resolved by selective and judicious use of these stents and the use of prolonged antiplatelet therapy.

The Final Wave

Non polymeric nanocarbon coated DES: This led us to develop a non polymeric nanocarbon coated DES. This obviated the use of the polymer and the medication could be loaded effectively on the nanocarbon coating itself. Subsequently, the first animal evaluation of the non polymeric nanocarbon coated paclitaxel stent was done and showed excellent results. This led to the start of the first Indian investigator driven multicentric clinical trial on this nanocarbon coated non polymeric stent study (Corel-C Study approved by the DCGI, Government of India). The cost of this stent is less than half of the international medicated stents. Simultaneously, animal and clinical evaluation of the Sirolimus coated biodegradable polymer coated Indian stent was done at Sri Chitra Institute, Trivandrum and at AIIMS (Supralimus; Sahajanad, Surat).

The results of this stent are also very exciting and comparable to the best international stents with the advantage of not having any polymer (the polymer has been implicated in the late complications of these medicated stents). At this time, technology in India is ahead of the West!

Email:balrambhargava@yahoo.com