We examined patients from a regional contemporary U.S. practice with mandatory reporting in order to compare long term outcomes after drug-eluting or bare metal stent placement. Our primary goal was to evaluate whether DES were associated with increased rates of myocardial infarction and mortality in long term follow-up; however, we observed small absolute differences in myocardial infarction and mortality favoring DES. Repeat revascularization procedures were also lower.
Previous randomized controlled trials of approved DES vs. BMS have not shown significant differences in death or myocardial infarction in long term follow-up to date 3
. While the chief strength of such randomized comparisons is elimination of selection bias, these studies have been limited by power and generalizability to every day practice 7, 8
. Some pooled randomized trials have shown a lower rate of recurrent MI for one DES vs BMS 14
. Observational studies have had contradictory findings to date 5, 15
. Observational studies require more sophisticated methods than randomized studies to minimize bias, but may offer improved power and greater generalizability 16
. We captured all PCI performed in Massachusetts over an 18 month period and included a wide range of hospitals and operators – academic, non-academic, with and without surgical back up, lower and higher volume centers – and a wide variety of procedure types – elective and emergent procedures, and low and high lesion complexity. Because all percutaneous coronary intervention procedures in Massachusetts are subject to prospective mandatory reporting of patient and procedural characteristics and outcomes, this a powerful and reliable cohort.
Our study differed in several important ways from other population-based comparisons of DES and BMS. In contrast to populations where DES use may be restricted geographically, financially, or according to patient risk, 5, 15
our US study reflected a majority of DES use overall (65%). As a result our DES sample represents a broader patient population.
To avoid bias due to differential follow-up, we restricted our analysis to those patients who had complete follow-up at a fixed time point – 2 years. Although we have substantially longer follow-up in a subset of patients, we limited the analysis to a fixed time point to avoid inference on an incomplete sample and avoid changing conclusions as greater follow-up accrues 17
Regarding ascertainment of study endpoints, we observed somewhat higher rates of MI than other studies5, 15
, as we included periprocedural MI, even during the same hospitalization. The absolute difference in target vessel revascularization of approximately 5% is similar to recently reported registries in the United States 18
, but lower than reported in randomized controlled trials where surveillance angiography was frequent1, 2
. One mechanism to explain the reductions in MI and mortality may be that reduction in the occurrence of repeat revascularization procedures related to restenosis in a patient population of higher complexity had an impact on true clinical endpoints. 19, 20
Late stent thrombosis has been considered a potential mechanism for the increase in mortality in some studies of DES21
. We did not have sufficient data to accurately estimate rates of late stent thrombosis. This well-powered observational study would suggest that if a small difference in late stent thrombosis is present between DES and BMS, it is not readily detectable in a clinical endpoint (death or MI) because it represents a small proportion of these events. Given the relatively rare occurrence of stent thrombosis (<1% in the first year and rarer in later follow-up) 6
, it would seem unlikely that these events would overtake the constant hazard of adverse events related to disease progression 22
beyond 2 years.
Because the choice of stent was not randomly assigned, we used propensity score matching to select a group of patients who were essentially similar according to all measured baseline variables. As compared with other methods that use a propensity model to adjust for selection bias, a matched analysis is more likely to reduce power (by restricting the sample to closely matched patients) but has the advantage of more reliably reducing selection bias (as compared with regression-based propensity analysis). We were afforded this opportunity because the density of DES and BMS procedures performed in Massachusetts was high (>14000 PCI procedures per year per 6 million adults), and because the patterns of use of DES and BMS in our study spanned both low and high risk patients. We confirmed that the matched patients were similar for each of 63 baseline variables, and with this degree of similarity, matching of unmeasured confounders is expected 23
. However, we acknowledge the possibility of residual confounding. This was estimated to be small as measured by the 2-day mortality difference. Some sources of residual bias include varying completion of revascularization, limited ability to adjust for angiographic characteristics (lesion length and vessel diameter were not available), and concomitant medical therapy.
We collected information regarding use of and contraindications to dual antiplatelet therapy with aspirin and thienopyridine therapy because of its known relationships to mortality, myocardial infarction, and stent thrombosis 24-26
. Although we did not have pharmacy data to compare the duration of therapy and compliance in patients treated with DES and BMS, during the period under study, the existing cardiology society guidelines recommended a longer duration of thienopyridine therapy in patients with DES (3-6 months minimum) than with BMS (1 month minimum) 27
. We cannot exclude the possibility that a longer use of thienopyridine treatment that is recommended with DES selection could have contributed to a mortality and myocardial infarction benefit favoring DES over BMS. As the most recent national society recommendation is for 12 months dual-antiplatelet therapy for DES 28
, the associated effect of dual-antiplatelet therapy with DES selection compared with BMS may increase in future studies.
We combined patients treated with paclitaxel-eluting and sirolimus-eluting stents within the DES group. Differences in safety between drug-eluting stents remain controversial, and other population-based studies have not shown significant differences in mortality between these two stents 29
In conclusion, in a large population-based study reflecting a majority of DES use across a cohort with comprehensive follow-up after PCI, we found that DES were associated with lower mortality, myocardial infarction, and target vessel revascularization relative to BMS use at 2 years of follow-up. Longer term follow-up will be required to provide further reassurance of preserved safety in the broad patient population currently treated with these coronary devices.