Role of Coronary Stents

Non-Surgical Management of Coronary Artery Disease

Prof Upendra Kaul
Srinagar, Publish Date: Sep 12 2017 11:26PM | Updated Date: Sep 12 2017 11:26PM
Role of Coronary StentsRepresentational Pic

Percutaneous Coronary Angioplasty has become a well-established non- surgical method of treating patients with coronary artery disease. The technique was conceived off and first used in humans by Dr Andreas Gruentzig a German doctor on 14th September 1977 in Zurich, Switzerland. This was 10 years after the beginning of a regular program of coronary artery bypass surgery by Dr Favalaro at the Cleveland in USA. 

In the initial years the blockages were treated by inflating a contrast filled balloon at the site of obstruction and the procedure was called balloon angioplasty. The results were unpredictable and at least 10 per cent patients needed urgent bypass surgery. Another major limitation was recurrence of narrowing’s within a few weeks to months of at least 30% patients, a problem called “Restenosis”. New methods to remove the blockages were then introduced. Directional atherectomy , rotablator and burning the blockage by Lasers were some of them. These were aimed at either removing the fat deposit , drilling through it or burning and vaporizing it by laser energy. These methods neither improved the results of balloon angioplasty nor reduced the complications.

The first major breakthrough which made a difference in outcomes was the use of a tube like metal scaffold after dilating the lesion with a balloon. This was the beginning of the era of coronary stenting. It was Jacquez Puel and Ulrich Sigwart who implanted a stent successfully into the coronary artery of a patient in Toulouse, France in 1986. Coronary stenting then replaced balloon angioplasty for coronary angioplasty. With the growing use of stents a new problem became manifest and that was in stent restenosis. This was because of excessive healing of the tissues within the stent and producing recurrence of the blockage.  It was very difficult to treat because this tissue is very hard. It was therefore very clear that we needed to reduce or minimize this healing process. Only biological means therefore appeared to be promising solutions. For a brief period radiation therapy called brachy- therapy which is also used to treat cancers was tried. Although it seemed to work but was not a practical method because of the logistics and dangers associated with it. 

This brought in the era of Drug Eluting Stents in 2002. The concept was to coat the metal stents with a polymer mixed with drugs which prevent healing or kill cells which lead to recurrence by excessive growth. In the initial years 2 drugs were successful in achieving it : Sirolimus and Paclitaxel. This started the age of CYPHER (Sirolimus eluting stent) and TAXUS (Paclitaxel eluting stent). After a decade of their use it was clear from several clinical trials that Sirolimus eluting stents were safer and superior in their long term results as compared to paclitaxel eluting stents. Meanwhile a few more limus analogues became available: Everolimus , Zotarolimus and Biolimus  with results comparable to sirolimus.  Several varieties of stents using one of these drugs are available and have replaced bare metal stents in most instances and are called drug eluting stents (DES).

 

Drug eluting Stent 

The constituents of a typical DES are the metal platform in the form of a tube which consists of struts. The metal is stainless steel, chromium cobalt or platinum based alloys. This platform is mounted on an appropriately sized balloon. The balloon is connected to a shaft which is connected to an inflation device used to inflate the balloon. Expansion of the balloon deploys the stent at the pre-determined site of the blocked artery. The stent is coated with a polymer and drug combination. The polymer helps in a predictable release of the drug into the vessel wall. Polymers can be durable which last for ever or resorb able within a defined period of time, usually 3 to 9 months. The durable polymers used in the new generation DES are very inert and safe (ex: everolimus eluting DES, Xience). However it is desirable that the polymer after completing its function of delivering the drug gets resorbed leaving only the metal well covered with body tissue.

The qualities of a good stent are that it should be low in strut thickness, track able and conformable to the curvatures of the vessel wall. It should have a good radial strength so that the support to keep the artery open is adequate. The stents before being made available for patient use should have credible scientific data of efficacy and safety in Trials and Registries.

Bio-resorb able Stents 

Intuitively the concept, that if the stent completely degrades after completing its function of scaffolding appears very attractive. In this direction after a lot of bench work Bio-resorb able vascular scaffold (BVS) became a reality. The product became available internationally including in our country. Within a few years of their release however its limitations became apparent. It had very thick struts, limited sizes, difficulty in deployment and moreover a significantly higher chance of getting blocked with clot formation. These problems have markedly limited their use and they are no longer available in our country. Even in Europe their use is limited to clinical trials alone. It is hoped that the new generation BVS would address these issues and make this very promising technology available again. Their long term benefits should lead to restoration of the vessel to normalcy with all its advantages.

Need of the Country

The number of interventional cardiologists in the country is estimated to be 3 to 5 per million of population in contrast to 50 to 70 per million of population in USA. The number of cardiac catheterization laboratories is estimated to be around 960 in year 2016. Keeping in mind the burden of disease the facilities and infrastructure for invasive treatment modalities is inadequate. In spite of these short comings the number of percutaneous coronary interventions (PCI) performed is increasing steadily at a growth rate of 6% annually. The total number of PCI procedures done in year 2016 was 495,000 with an estimated number of 594,000 stents used (1.20 per procedure). In terms of usage 80% stents used are drug eluting stents with over 60% of these being supplied by multi-national companies.

The system of keeping the stents in the hospitals for use was through distributors with exorbitant profit margins leading to a big gap between the buying price and the selling price to the patient especially in privately owned hospitals leading to a big escalation in the final price. The average retail price for a bare metal stent used to be INR 45,000 (670 USD) while drug-eluding stents (DES) were priced at around INR 1.2 lakh (1800 USD) generating profit margins that ranged from 270 per cent to 1,000 per cent. 

In the absence of an organized insurance system and barring 6 out of 26 states and some Central Government health schemes up to 40 per cent of the patients pay for their medical expenses and that includes coronary stents. No body seriously challenged this practice till recently a Delhi lawyer who had to pay for the treatment for PCI of his father noted this exorbitant pricing and took up the case to judiciary and the government. The case forced the authorities to list the stents in the list of National List of Essential Medicines (NLEM) in 2016 and later that year included stents in the first Schedule of the Drug Prices Control Order. Finally, in February 2017, the prices of stents were capped at INR 7,260 (110 USD) for bare metal stents (BMS), and INR 29,600 (440 USD) for drug eluting stents after studying the economics of the prevailing supply chain system This pricing is being enforced strictly. The suppliers have been barred from taking back the stocks.  This ruling has resulted in a debate in the country. 

There is no doubt that with this policy the patients requiring stent implantations will benefit and more so those paying out of pocket. With multi-vessel stenting becoming cheaper more patients can afford multi vessel PCI with complete revascularization which typically has been more expensive as compared to coronary artery bypass grafting (CABG). 

Another positive of this pricing cap is the likely increase in the use of indigenously manufactured stents which currently have a market share of less than 40%. There are at least 3 Indian companies which have a substantial share of this. It is therefore time for these companies to prove to the cardiologists and the patients regarding the equivalent safety and efficacy of their products. There is a perception in the minds of cardiologists which gets passed on to the patients that imported stents are superior.  This can best be done by the Indian companies by sponsoring studies for having outcomes data in Registries and also Randomized trials with adequate numbers and publications in peer reviewed journals. A special emphasis needs to be given to diabetic patients who constitute around one third of the total PCI population in our country.  Currently there is a study in progress comparing an Indian DES with the international best seller chromium cobalt fluro-polymer everolimus eluting stent (Xience) in an all comers population in Europe. The study named TALENT is sponsored by Sahjanand Medical Technologies. The patient enrolment for this study comprising of 1420 patients has already been completed and the 1 year follow up results will be available by September 2018.

Conclusion:

DES’s have become an important part of the non-surgical management of ischemic heart disease. Over the years significant advancements have occurred in the technology improving the efficacy and safety of these devices. The demand for these devices is steadily increasing in our country. It is time for the indigenous industry to rise to the occasion and compete with the established international industry. This needs research and development, state of art manufacturing facilities and scientific data in the form of non-inferiority trials and well conducted registries. The future is bright for the “Make in India” concept.

Author is Chairman and Dean Academics and Research Batra Hospital and Medical Research Centre New Delhi.