Between January 2004 and December 2006, 390,973 NCDR patients ≥ 65 years underwent stent implantation, and 76% were linked to longitudinal Medicare records. After exclusions, the study population included 262,700 patients from 650 sites. () Comparison of NCDR® patients who did and did not match to Medicare records revealed non-match patients to be slightly younger (73 vs. 74 yrs), and more likely to be male (62% vs. 58%) and to have commercial insurance (15% vs. 3%).
Overall, 45,025 patients received one or more BMS and 217,675 received one or more DES (54% paclitaxel eluting, 46% sirolimus eluting). Unadjusted baseline characteristics show significant differences between DES and BMS, these differences were reduced following propensity score weighting (). Sixty-nine percent of DES implantations were for non-FDA-approved indications. Mean follow-up for BMS patients was slightly longer (496 ± 371 days) than for DES patients (456 ± 302 days) due to the trends in stent use over the time period studied.
Unadjusted baseline characteristics of patients in study population
During the 30-month study period, 21,254 deaths occurred. Thirty-month overall mortality was higher in patients who received BMS than DES both before (17.9% vs. 12.9%; p<0.0001), and after adjustment for population differences (16.5% vs. 13.5%, HR 0.75; 95% CI, 0.72 to 0.79). () The adjusted mortality difference was statistically significant in the initial six months post-PCI, and continued to increase throughout the 30-month follow-up period.() The estimated hazard ratio obtained using an unweighted Cox proportional hazards mortality model with backward variable selection was similar at 0.79 with a 95%CI (0.76 to 0.81). In addition to the use of DES, other factors favorably influencing 30-month post-PCI survival included female sex and prior PCI or CABG. As expected, mortality was higher in those with diabetes, renal failure, STEMI or CHF.
Unadjusted and adjusted results from time-to-event analyses for prespecified endpoints. Shown as Hazard Ratio and 95% confidence interval.
Adjusted cumulative incidence for death with 6- and 12-month landmark display
There were 10,528 MIs during the study period. Unadjusted MI rates at 30-months were 10.0 / 100 patients in BMS vs. 7.3 / 100 patients in DES (p<0.0001) with similar results following adjustment (8.9 / 100 patients vs. 7.5 / 100 patients, HR 0.77; 95% CI, 0.72 to 0.81).() This result was driven by lower MI rates in DES patients during the first 12-months post-PCI,() with no difference between 12 and 30-months of follow-up. In a secondary analysis, DES patients experienced a small increase in STEMI events beyond 12 months.()
Adjusted cumulative incidence for MI with 6- and 12-month landmark display
Adjusted cumulative incidence for STEMI with 6- and 12-month landmark display
Revascularization (PCI or CABG) was performed in 34,751 patients with a total of 40,427 revascularizations; 30-month unadjusted revascularization rates for BMS and DES populations were 24.5 / 100 patients and 23.0 / 100 patients (p=0.007). With risk-adjustment, no difference in overall revascularization was observed in DES versus BMS patients at 30-months (23.5 / 100 patients vs. 23.4 / 100 patients, HR 0.91; 95% CI, 0.87 to 0.96).(; ) However, revascularization rates were lower in DES patients to twelve-months post-PCI (13.3 / 100 patients vs. 15.2 / 100 patients) followed by a late rebound in revascularization procedures in the DES group between 12 and 30-months (10.2 / 100 patients vs. 8.2 / 100 patients). When CABG and PCI revascularizations were examined separately, CABG was more common in BMS than DES over the 30-month follow up period (3.7 / 100 patients vs. 2.5 / 100 patients), while the rate of PCI was similar.
Adjusted cumulative incidence for revascularization with 6- and 12-month landmark display
Stroke and Major Bleeding
During follow-up, 4,010 strokes and 5,120 major bleeding events required hospitalization, with 59% of strokes and 49% of bleeds occurring within 6-months following PCI. Unadjusted and adjusted stroke rates were roughly 3 / 100 patients at 30-months in each group (HR 0.97; 95% CI, 0.88 to 1.07) and only a minimal difference was noted in bleeding (3.6 / 100 patients BMS vs. 3.4 / 100 patients DES, HR 0.91; 95% CI, 0.84 to 1.00). (; Figures and )
Adjusted cumulative incidence for bleeding with 6- and 12-month landmark display
Adjusted cumulative incidence for stroke with 6- and 12-month landmark display
Each of the composite endpoints tracked closely with its individual components, favoring DES over BMS treated patients both before and after statistical adjustment.() The unadjusted 30-month rates of death or MI (17% vs. 23%), death or MI or revascularization (32% vs. 38%), and death or MI or stroke (19% vs. 24%) were each lower in DES than BMS patients.
The 30-month DES survival advantage was present across all patient subgroups, independent of sex, age, comorbidities, and procedural indication or urgency.() This effect was somewhat less pronounced in those with a prior history of CABG and renal failure, with or without dialysis. Notably, patients receiving DES in 2005 and 2006 had a greater relative survival benefit than those receiving DES in 2004. Similarly, the 30-month risk of MI was lower in all patient subgroups except those with renal failure and insulin-dependent diabetes. ()
Subgroup results – Forest plot of Hazard Ratios for death
Subgroup results – Forest plot of Hazard Ratios for MI
Most patient subgroups experienced a slightly lower 30-month rate of revascularization with DES compared with BMS. () However, no benefit was observed in patients >75 years, or with diabetes, renal failure, heart failure, or 3-vessel disease. Revascularization rates were similar in patients undergoing PCI in 2006, in contradistinction to the slightly lower DES revascularization rates from 2004 and 2005. (Figures and )
Subgroup results – Forest plot of Hazard Ratios for revascularization
Subgroup results – Forest plot of Hazard Ratios for bleeding
Subgroup results – Forest plot of Hazard Ratios for stroke
Randomized trial cohort
The 49,355 NCDR® registry patients fitting the inclusion and exclusion criteria for the Taxus IV and SIRIUS DES randomized controlled trials had 30-month outcomes similar to those of the overall population such that those receiving DES had a lower 30-month risk of death (HR 0.62; 95% CI, 0.55 to 0.70), MI (HR 0.66; 95% CI, 0.55 to 0.80), death or MI (HR 0.64; 95% CI, 0.57 to 0.70) and revascularization (HR 0.87; 95% CI, 0.80 to 0.96) compared to BMS. No difference in stroke (HR 0.97; 95% CI, 0.74 to 1.28) or major bleeding (HR 0.87; 95% CI, 0.71 to 1.05) was noted between trial-eligible DES and BMS patients.
Cause of death
Presumed ‘cause’ was extrapolated in 19,132 (90%) deaths using the algorithm described above, and included 8451 inpatient and 10,591 outpatient deaths. Slightly more BMS deaths were attributable to MI (15.0% vs. 13.5%, p=0.01) and malignancy (6.7% vs. 5.5%, p=0.002) while more DES deaths were more attributable to chronic lung disease (2.5% vs. 1.9%, p=0.01) and cerebrovascular disease (5.3% vs. 4.2%, p=0.003). No significant differences were found for any of the remaining diagnoses. Overall, DES patients had a lower risk of CV-only (including CHF and MI) deaths compared with BMS patients (HR 0.80; 95% CI, 0.74 to 0.86), as well as non-CV death from all other causes (HR 0.74; 95%CI, 0.70 to 0.78).