'Bioactive Stents Are Safer Regarding Thrombosis'

Dr Ganesh Kumar believes that there is no controversy regarding DES

The mid-term CSI PTCA registry reported the usage of 67,000 number of stents in India, of which Drug Eluting Stents(DES) were 53 per cent in the year 2005. However, the use of DES has come under the scanner after speakers at the World Congress of Cardiology (WCC), Barcelona suggested that DES carries a higher risk of potentially fatal blood clots than bare-metal stents (BMS). It is stated that DES "may increase death, Q-wave myocardial infarction and cancer deaths." Besides, according to reports in the Wall Street Journal, a recent Swiss study found 3.3 more heart attacks and deaths per 100 patients with DES than with the bare-metal ones. Dr Ganesh Kumar, Interventional Cardiologist, Dr L H Hiranandani Hospital, spoke to Rita Dutta about the ripple effects of the controversy among Indian interventional cardiologists

Questions have been raised about the efficacy of DES, wondering whether they are as safe as projected by the manufacturers. How have Indian interventional cardiologists reacted to the revelations?

The result shown with the long-term follow-ups on DES at WCC, Barcelona is surely of concern. Having said that, let me state that DES is definitely an answer for restenosis, which is of major concern since the use of BMS from the early 1990s. DES, without doubt, has shown a major decrease in restenosis rates, though at the cost of some cases of late thrombosis. The answer to this is right selection of cases for the use of DES (diabetics, long length lesions and small calibre vessels). One can still use BMS in 40-60 per cent (with almost comparable results) of cases, which do not fall in the above subset. Therefore, the concern is not of increase in MI or death due to late thrombosis, but it of over-use of DES. Of late, in my clinical practice, on many occasions when I wanted to use BMS for low-risk patients for restenosis, patients have demanded DES due to the hype surrounding it.

Please comment on the recent Swiss study that found 3.3 more heart attacks and deaths per 100 patients with DES than with the bare-metal ones.

The results which are seen with DES Vs BMS show more MI and death in DES group due to the non-re-endothelialisation with DES even at 33 months. Endothelialisation is a thin layer which is protective in nature and is supposed to grow within the stent in one month after stent implantation. The drug which is eluted from the first generation DES not only inhibits the smooth muscle cell proliferation of the vessel wall, but it non-selectively inhibits the growth of endothelium, sometimes permanently, unlike in BMS and now the more recent second generation stents. Therefore, when the free flowing blood is exposed to underlying naked stent (devoid of endothelium), it has a tendency to form clot.

On most occasions, this is taken care by the long-term usage of dual antiplatelets (blood thinners). The question is for how long to take these antiplatelets. Another hypothesis for late restenosis is the presence of a polymer which remains permanently on the stent, even after the elution of drug is complete. However, the BMS tend to endothelialise in one to two months after implantation. Let me also state that even BMS has some incidence of stent thrombosis, though early. Most patients who are resistant to Aspirin and /or Clopidogrel will have a possibility of stent thrombosis, irrespective of the stent type used.

Evidence from an 18-month patient follow-up programme has suggested that DES might be worthwhile in just one of three cases. Please comment

Yes, correct patient selection is of utmost importance. We must keep in mind that restenosis does not kill a person, it only increases need for repeat revascularisation. Early stent thrombosis is not a big issue as it can be seen in all types of stents, including BMS. However, most of us will admit that late stent thrombosis resulting in MI/death is definitely of some concern. Presently, imparting patient education for need to continue long-term dual antiplatelets is of prime importance to avoid late thrombosis phenomenon in those patients necessarily requiring DES.

Is DES too hyped?

Not really. Every landmark technology/ breakthrough is always a big welcome to mankind. But advanced technology always comes with some problems attached to it. This is applicable to all fields of scientific progress. We should be bold enough to admit the problems so that it helps in betterment of technology.

Reportedly, in the US, doctors have tapered their use of DES in the last six months. Will Indian cardiologists do the same?

I do not think most Indian cardiologists overuse DES. There is still a huge BMS market, and I guess it will continue for times to come, till we have some more data with the second generation stents.

What impact will the controversy have? Will it give BMS market a boost?

To start with, I do not believe that there is any controversy. The established first generation DES will still hold in 40-60 per cent of high risk (for restenosis) group. Rather than BMS getting a boost, many cardiologists are looking for other alternatives.

One such alternative is the polymer devoid second generation DES, which many cardiologists have started using. Initial data appears encouraging, in fact in some types, the Clopidogrel can safely be stopped as early as two months. We do not have data for more than 24 months for these stents, hence, it will be a bit early to compare the long-term results available with the first generation DES. However, like in all technological progress, the second generation stents would eventually replace the first generation one, once long-term safety data is available.

Also, we are talking about encouraging results of so called 'bioactive' stents, which in strict sense are not DES, but are metal stents coated with bioactive materials like titanium nitrous oxide which are presently in commercial use. Data has shown that these bioactive stents have lesser restenosis than BMS (but slightly more that DES) and also much safer on stent thrombosis issue. In the future, we can look at 'bio-absorbable' stents, which are currently under research.

In the weeks following the controversy, have you been flooded with queries from patients and their relatives about DES?

Like most patients in our country are not aware of problems with DES to start with, similarly most of them are not aware of any controversies about it. Despite it being in the news, there has been no real phobia surrounding it.

What about patients who already have the device?

The need for dual antiplatelet therapy for a long-term period is going to be important for such patients. I and most of my colleagues believe that if the dual antiplatelets are continued religiously, it is not of any issue. Problems will come up only if for any non-cardiac surgery that these patients with previously implanted DES have to undergo, the dual antiplatelets are to be discontinued. My take as a cardiologist is to accept a slightly higher risk of bleeding and continue the antiplatlets in most surgeries, if not all.

Will Indian cardiologists be cautious while using DES now?

Caution is not the word, selection of right cases is the key.

Are Indian cardiologists not affected by the controversy in anyway? Should they adopt a conservative approach, awaiting more data?

In our country, long-term follow-up on the patients post angioplasty is an issue. I think that it is better for us to exercise caution and to be careful since death is irreversible. Data collection and availability is an ongoing process throughout our lives. It always helps in improving technology. This does not mean that we have to adopt a conservative approach.

Do we need more long-term studies to establish facts?

We have facts in front of us, hence the 'controversies'.

When so many patients' lives are affected, why are most Indian cardiologists avoiding to take any stand in the controversy? Are they afraid of spoiling relations with the DES manufacturers?

I am not. I cannot comment about others.

What is the future of DES in India?

Good. Even though you don't have to use DES for every patient, but because the sheer number of cases requiring percutaneous coronary interventions are increasing every year due to the increasing disease burden, I foresee greater usage of DES.

How has the constitution and design of stents changed over the years? What kind of research is going on in stents?

From heavier designed stents in earlier days, to more sleeker stents now with much less metal to artery surface ratio without compromising much on radial strength, the designs have changed majorly. Even the stent composition has undergone major transformation from stainless steel to nitinol, to tantalum, platinium and cobalt cromium stents. Then we had bioactive stents like heparin-coated to phosphotidyl-coated, carbon-coated (to make them more inert) to the present titanium-nitride-oxide-coated stents. Finally, we have the first generation polymer-based DES to more recent DES without polymer. And now, research is being conducted on bioabsorbable stents.

rita@expresshealthcaremgmt.com