The mandarins in the Indian health ministry have decided to include coronary stents in the National List of Essential Medicines (NLEM) to bring down the pricing by a staggering 50%. There were almost 500,00 coronary stents inserted across India in 2015. More than 60% of these stents were imported while the remainder were made in India. Health ministry officials insist that Indian stents are equal in efficacy and safety as compared to foreign stents, without a single head to head comparison of the device. But then one should never expect common sense or scientific temper from the bureaucrats hunched in Nirman Bhawan, Delhi.
Heart disease continues to be the biggest killer of the globe; more than 17.5 million die in a year. Millions of patients with heart disease get treated by coronary stents; including patients with stable angina and acute coronary syndrome. It is well recognized that drug eluting stents (DES) are more effective than bare metal stents (BMS) in preventing restenosis, and the newer generation DES have the lowest rate of stent thrombosis (ST). It has been suggested that the newer generation DES would therefore have the advantage of reduced rates of death and myocardial infarction.
The largest randomized trial comparing DES with BMS published this week in the NEJM, has however failed to find any difference in deaths and myocardial infarction when contemporary DES were compared to BMS in more than 9000 patients at a follow up of 6 years (NEJM 2016; 375:1242-52). At 6 years death and myocardial and myocardial infarction were seen in 16.6% with DES and 17.1% of the patients receiving BMS. There was no difference in quality of life measure between the 2 groups.
Stent thrombosis was observed in 0.8% of DES group and 1.2% in the BMS group; a 0.4% difference (p=0.0498). Rates of any repeat revascularization were 16.5% in the DES group versus 19.8% in the BMS patients (p<0.001).
Patients were randomly assigned to get a DES or BMS during percutaneous coronary intervention (PCI). More than 80% of DES were the latest generation everolimus eluting stents, all patients received 75 mg of aspirin life long and 75 mg of clopidogrel for at least 9 months. Multivessel disease was present in 40% of patients, stable angina was present in almost 30%, non ST-segment elevation myocardial infarction in about 31% and ST elevation myocardial infarction in 26% of patients. The Norwegian Coronary Stent Trial (NORSTENT) investigators conducted the trial.
The NORSTENT investigators have managed the complicated task of providing evidence that BMS have also improved over the years, with new stent design, different metal composition, and thinner struts. Crucially this trial was not sponsored by the industry. It would now no longer be easy to conclude that the era of BMS is over. Such a conclusion was derived from underpowered or observational studies that moreover had selected patients.
We now can advocate use of BMS in patients with large vessel diameter in whom restenosis rates are low, those patients who are unable or unwilling to take dual anti-platelet therapy for long duration, patients needing non-cardiac surgery soon after, and of course patients who cannot afford DES (that are far more expensive). The results of this trial will empower interventional cardiologists to deploy BMS in selected patients.
The researchers in their discussion include the Everolimus Eluting stent versus Bare Metal Stent in ST-Segment Elevation Myocardial Infarction (EXAMINATION) trial (involving 1504 patients) that showed no reduction in the primary end point of death from any cause, recurrent myocardial infarction, or revascularization at 1 year. Rates of ST and target lesion revascularization were significantly lower in the DES group (Lancet 2012; 380:1482-90).
It would be a tad difficult to concur with the conclusion, “Is This the Beginning of the End for Bare Metal stents” made by NEJM Journal Watch on August 30,2016. Nothing in fact can be further from the truth. Thousands of physicians must be influenced sadly by such unrivalled spin.
Mercifully, the editors of the NEJM permitted an editorial on the Norwegien trial that recommends insertion of BMS in appropriate patients. There would be many such patients in India. The health industry in India and the government of India while taking note of this important randomized trial, should ensure that sale of Indian BMS are permitted only and subsequent to the most rigorous clinical testing for safety and efficacy. This is easier said than done.