Ideally, the introduction of a new treatment should answer the unmet needs of patients with a specific disease and, therefore, if really effective, it should have a measurable effect on the clinical outcomes or quality of life for the overall population of these patients.
In some fortunate historical moments, the availabilty of new technologies may immediately improve the clinical outcomes of a given population with a specific illness. There is no need for an RCT to demonstrate that the timely interruption of ventricular fibrillation with DC shock13
saves lives and improve the overall survival of patients with STEMI. Similarly, when a new treatment is really effective, even a small number of patients enrolled in a dedicated RCT may be enough: in patients with left main disease, CABG has demonstrated to improve survival, when compared with MT, after enrolling only 113 patients in an RCT.14
The role of RCTs is to compare the effectiveness of alternative treatment options, whereas, observational studies should assess interventions in real-world scenarios being frequently under-represented in RCTs. As above, when a new treatment is really effective, that is, the implementation of reperfusion strategies involving primary PCI in patients with STEMI, the impact on survival on the overall population of patients with STEMI may be much more evident in observational studies15
than in RCTs.17
With regards to DES, after the demonstration of their effectiveness in reducing the rate of restenosis2
and, therefore, reducing the need for repeated revascularisations, their utilisation in 2005 reached approximately 90% of interventional procedures in USA,1
despite the demonstrated absence of an impact on other major cardiovascular events,3
and despite their cost-effectiveness could be demonstrated in a limited number of patients, that is, those at high risk for restenosis.9
Moreover, most recent guidelines on myocardial revascularisation, recommend DES implantation in all patients treated with PCI, in the absence of contraindications to extend double-antiplatelet treatment (Class I LOE A).19
This recommendation is based on a number of randomised, as well as observational studies published in the last 10 years, all of them addressing only the populations of patients who actually underwent revascularisation and comparing DES with BMS or CABG. We were not able to find any publication in Pubmed addressing the impact of DES availabilty on the overall population of patients with coronary artery disease in a real-world practice, candidates, therefore, not only for percutaneous or surgical revascularisation but also for MT, and were unable to understand whether the DES availabilty had any global impact on treatment options and, as such, on the clinical outcomes of this population. Consequently, the study questions were: (1) did DES availability push the indications towards percutaneous interventions and, if so, what was their overall impact on clinical outcome? To find an answer, our comparison was made by extracting upstream two groups of consecutive patients hospitalised in the BMS and DES periods for ischaemic heart disease in the presence of at least one stenosis ≥50% at CA. All patients with a strong clinical indication for PCI (STEMI in the first 24 h and those with previous CABG) or for surgery (associated conditions necessitating surgical correction) were excluded. The patients were enrolled in 13 hospitals with the aim of generalising the findings and the DES period was delayed until the first quarter of 2005 in order to compare a BMS period with a ‘steady-state’ DES period. The completeness of the enrolment of consecutive patients, together with the accurate review of all medical records and angiographies, represents one particular strength in our study and allows to overcome limits inherent in both the analyses limited at administrative records (lack of clinical data) and observational clinical studies (limited coverage and consecutivity concerns).
The main finding of our study is that the availabilty of DES, being actually implanted in one-third of patients observed in the DES period, had no impact on any of the major cardiovascular events during a 4-year follow-up, including the need for further revascularisation, in the overall population of patients hospitalised because of ischaemic heart disease and with at least one coronary artery stenosis ≥50%. In a multivariable analysis, the 4-year survival as well as the combined end-point of mortality, myocardial infarction, stroke and further revascularisations, were unaffected by the availabilty of DES, whereas older age, severe renal failure, LV EF reduction, higher Syntax score and the choice of MT, had an independent negative impact on survival.
It is not possible to compare our findings to other similar studies, since all published studies investigated patients who actually underwent revascularisation with implantation of BMS or DES. The limitations of these observational studies were underscored by Yeh et al
, suggesting that in order to assess the clinical impact of DES, the comparison of a BMS period versus a DES period could be more reliable than comparing patients implanted with one or the other type of stent, in spite of complex statistical analyses.20
We took another step forward by taking into account all patients hospitalised because of ischaemic heart disease, and not only those who underwent revascularisation, in order to assess the overall clinical impact of DES availability, starting from the choice of initial treatment between MT or revascularisation with PCI or CABG.
Interestingly, our findings do not support the widespread belief that the availability of DES increased indications toward the PCI as the preferred treatment for patients with ischaemic heart disease; only in those with CAD of ‘intermediate’ complexity, that is, with a Syntax score of 23–32, we observed a significant increase of subjects undergoing PCI and a decrease of those left in MT or sent to CABG. This group represented only 17.6% of patients with demonstrated CAD and, therefore, any change of treatment options limited to this group will only marginally impact on the overall results on treatment choice. In our study, the shift toward the choice of PCI as the preferred treatment in this subgroup of patients did not impact on their clinical outcome.
Another finding of our study is that most of patients with demonstrated CAD showed a ‘low’ complexity disease, that is, Syntax score <23, therefore candidate to MT or PCI more easily then to CABG and with prognosis hardly to be influenced with any type of revascularisation.
As previously demonstrated in RCTs,3
no significant difference in mortality or rate of myocardial infarction can be expected in patients treated with DES and this finding was confirmed in our study. With regards to our finding that even further revascularisations were not decreased in the DES period, the only hypothesis we can formulate is that the occurence of clinical restenosis after PCI in a real-world population, during the BMS period immediately preceding the DES availability, was indeed not high: only 12% after 12 months in a series of 3146 consecutive patients.21
Even in the largest reported registry, accounting for 262 700 medicare patients, the use of DES had no impact on the further revascularisations when compared with BMS.8
Therefore, it may be difficult to demonstrate any meaningful difference in the need for further revascularisations associated with DES availability, observing the real-world population of patients with coronary artery disease as a whole.
Limitations of the study
The sample size was relatively small to reach statistical significance in some subgroup comparisons, for which the enrolment of a larger number of patients would have been required. On the other hand, if thousands and thousands of patients are to be enrolled to demonstrate any effect of a treatment, it is very likely that the treatment itself has a limited clinical meaning.
Most of patients had 1–2 vessel disease and/or Syntax score <23 and therefore with expected favourable prognosis as demonstrated in a multivariable analysis. It seems reasonable that further investigation regarding the impact of DES on clinical outcome should address mainly the group of patients with higher Syntax score.
The follow-up was based on administrative data; therefore, we had no information on the quality of life of patients enrolled in the BMS and DES periods.
In our study, DES were implanted in 57% of patients who underwent PCI in 2005 and we are unable to extrapolate our findings to different scenarios, that is, the use of DES in 90% of the patients treated. In any case, the most recent data in Italy regarding 2010 show that at least one DES was implanted in 54.8% of 141 916 PCI procedures,22
supporting the fact that our data can be generalised to contemporary real-world practice.