Author + information
- Received March 8, 2012
- Revision received June 25, 2012
- Accepted August 21, 2012
- Published online December 4, 2012.
- William B. Hillegass, MD, MPH⁎,
- Manesh R. Patel, MD†,
- Lloyd W. Klein, MD‡,
- Hitinder S. Gurm, MD§,
- J. Matthew Brennan, MD†,
- Kevin J. Anstrom, PhD†,
- David Dai, PhD†,
- Eric L. Eisenstein, DBA†,
- Eric D. Peterson, MD, MPH†,
- John C. Messenger, MD∥ and
- Pamela S. Douglas, MD†,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Pamela S. Douglas, 7022 North Pavilion DUMC, Duke University Medical Center, PO Box 17969, Durham, North Carolina 27715
Objectives The purpose of this study was to characterize long-term outcomes of percutaneous coronary intervention (PCI) in elderly diabetic patients in routine practice.
Background Although drug-eluting stent (DES) implantation in diabetic patients is common practice, pivotal randomized trials enrolled <2,500 diabetic patients, most of whom were <65 years of age.
Methods Data from 405,679 patients ≥65 years old (33% had diabetes mellitus, of whom 9.8% had insulin-treated diabetes mellitus [ITDM], and 23.3% had noninsulin-treated diabetes mellitus [NITDM]) undergoing PCI from 2004 to 2008 at 946 U.S. hospitals were linked with Medicare inpatient claims data.
Results Over 18.4 months median follow-up (25th to 75th percentile: 8.0 to 30.8 months), ITDM/NITDM were associated with significantly increased adjusted hazards of death (hazard ratio [HR]: 1.91 [95% confidence interval (CI): 1.86 to 1.96], p < 0.001/HR: 1.32 [95% CI: 1.29 to 1.35], p < 0.001) and myocardial infarction (HR: 1.87 [95% CI: 1.79 to 1.95], p < 0.001/HR: 1.29 [95% CI: 1.25 to 1.34], p < 0.001) compared with nondiabetic patients. The adjusted hazard of undergoing additional revascularization procedures (HR: 1.14 [95% CI: 1.10 to 1.18, p < 0.001/HR: 1.08 [95% CI: 1.05 to 1.10], p < 0.001) and subsequent hospitalization for bleeding (HR: 1.40 [95% CI: 1.31 to 1.50], p < 0.001/HR: 1.18 [95% CI: 1.13 to 1.24], p < 0.001) were also significantly increased. Compared with nondiabetic patients, there were similar excess risks associated with ITDM/NITDM in patients selected for DES and BMS use; selection for use of DES was associated with reductions in death in ITDM/NITDM and myocardial infarction in ITDM, but not NITDM. There were no significant interactions between diabetes status and stent type for revascularization or bleeding.
Conclusions One-third of older patients undergoing PCI have diabetes. After adjustment for other comorbidities, diabetes, particularly ITDM, remains independently and strongly associated with increased long-term adverse events after both DES and BMS implantation.
In the balloon angioplasty and bare-metal stent (BMS) eras, diabetes mellitus conferred increased risk of death, myocardial infarction (MI), and subsequent revascularizations in the 2- to 5-year follow-up after percutaneous coronary intervention (PCI) (1–3). Diabetic patients over the age of 65 years had a particularly elevated risk of events, including 60% increased mortality at 2 years (adjusted for baseline comorbidities), compared with nondiabetic patients (1). Fewer than 800 diabetic patients over the age of 65 were enrolled in pivotal randomized controlled trials (RCTs) that examined drug-eluting stents (DES) versus BMS (4,5). Furthermore, the 2- to 5-year outcomes of treatment with DES or BMS in the contemporary DES era have not been well characterized in a large cohort of older diabetic patients in routine practice.
To measure longer-term “real-world” cardiovascular outcomes in older diabetic patients undergoing PCI in the DES era in the United States, data from the National Cardiovascular Data Registry (NCDR) CathPCI Registry were linked to the Center for Medicare and Medicaid Services (CMS) national inpatient claims databases. This consecutive population-based registry permits measuring: 1) the prevalence of insulin-treated diabetes mellitus (ITDM) and noninsulin-treated diabetes mellitus (NITDM) in older patients undergoing PCI; 2) the 2- to 4-year rates of death, MI, revascularization, and hospitalization for bleeding after PCI with both DES and BMS stratified by diabetes status in an all-comers older population; and 3) the differences in baseline characteristics and their relationship to outcomes of older diabetic patients selected for DES and BMS implantation in the DES era in routine clinical practice.
The CathPCI Registry, which is cosponsored by the American College of Cardiology (ACC) and the Society for Cardiovascular Angiography and Interventions (SCAI), catalogs data on patient and hospital characteristics, clinical presentation, treatments, and in-hospital outcomes for PCI procedures from >1,000 U.S. sites. Data reported in NCDR-certified software undergoes comprehensive data quality monitoring, including auditing. The prospectively defined NCDR variables are available at: http://www.ncdr.com.
This study included all Medicare-linked patients ≥65 years of age undergoing PCI who were enrolled in the CathPCI Registry from January 1, 2004, to December 31, 2008 (6,7). Percutaneous coronary intervention procedure codes were used to identify index procedures in the Medicare files, which were then linked to NCDR records using indirect identifiers, as previously described (8). Patients receiving both BMS and DES or missing diabetes status were excluded from the analysis (Fig. 1). Patients were categorized as: 1) nondiabetic; 2) ITDM; or 3) NITDM. The Duke University Medical Center institutional review board granted a waiver of the informed consent and authorization for this study.
Four primary clinical endpoints were examined: 1) death; 2) MI; 3) additional revascularization procedures; and 4) follow-up bleeding requiring hospitalization. Clinical endpoints were defined post-discharge with the Medicare claims file using the primary International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes for the hospital admission (listed in Online Table 1). Only revascularizations occurring after discharge from the index hospital stay were included as revascularization endpoints.
Baseline characteristics for the overall population were categorized by stent type (i.e., DES vs. BMS) and diabetes status (i.e., no diabetes, NITDM, and ITDM) and summarized as counts and percentages for categorical variables and means with standard deviations for continuous variables. Differences between groups were compared using chi-square tests for categorical variables and the Kruskal-Wallis test for continuous variables. Statistical significance was defined as p < 0.05, with no correction for multiple comparisons. The SAS statistical software version 9.2 (SAS Institute, Cary, North Carolina) was used for analyses.
Estimates of cumulative incidence rates by diabetes category and stent type for time-to-event clinical outcomes were based upon Gray's method (9). To estimate the prognostic differences between diabetic patients and nondiabetic patients undergoing coronary stenting, Cox proportional hazard models were used within strata of BMS and DES for each of the 4 primary endpoints. All baseline characteristics with statistically significant differences across diabetes status groups were included as covariates to estimate the adjusted hazard ratio (HR) of ITDM and NITDM compared with nondiabetic patients. A Cox model including stent type, diabetes status, and the interaction of stent type by diabetes status was created to evaluate for significant interaction between stent type and diabetes status for the 4 outcomes.
To examine whether the differences observed in outcomes (mortality, myocardial infarction, additional revascularization, and subsequent hospitalization for bleeding) between older diabetic patients treated with DES versus BMS could be explained by the baseline patient and procedural characteristics measured in the CathPCI Registry, 2 statistical methods were employed. First, an inverse probability-weighted (IPW) Cox model was derived for the entire patient cohort (n = 405,679). In this model, each patient's contribution is inversely weighted by their predicted probability of receiving a DES. The IPW adjusted HRs were calculated according to the approach of Cole and Hernan (10).
Second, a subcohort (n = 200,302) matched on propensity scores was derived. Three different propensity score models were created, for: 1) nondiabetic patients (n = 134,752); 2) ITDM (n = 19,876); and 3) NITDM (n = 45,674). Propensity scores represent the estimated probabilities of patients receiving DES versus BMS stratified by diabetes status, which was conditioned upon 102 observed covariates (Online Table 2). Drug-eluting stent and BMS patients with similar propensity scores were matched using the Greedy 5→1 digit matching algorithm (11). Within the propensity score-matched cohorts, estimates of adjusted HR for DES versus BMS were obtained using Cox models.
From 2004 through 2008, 672,617 patients ≥65 years of age underwent stent implantation, and 447,419 (67.0%) were linked to Medicare longitudinal records. After exclusions (Fig. 1), the study population included 405,679 patients from 946 sites. Except being less likely to have commercial insurance (3% vs. 15%), the baseline characteristics of the Medicare-linked CathPCI Registry patients were very similar to those that failed to link in the probabilistic matching, as reported previously (8). The median follow-up was 18.4 months (25th to 75th percentile: 8.0 to 30.8 months) with a mean follow-up of 20 ± 13.8 months).
Baseline patient and procedural characteristics
The prevalence of diabetes was approximately one-third of Medicare patients undergoing PCI. Of the linked cohort undergoing PCI, 94,537 (23.3%) had NITDM, 39,770 (9.8%) had ITDM, and 271,372 (66.9%) were nondiabetic. Baseline characteristics of the 405,679 patients stratified by diabetes status and implanted stent type are shown in the Table. Within this older cohort undergoing PCI, the ITDM (73.5 ± 6.1 years) and NITDM (74.2 ± 6.4 years) were only slightly younger than the nondiabetic patients (75.2 ± 6.8 years). As compared with nondiabetic patients, those with diabetes had higher baseline rates of important comorbidities. In contrast to these differences in baseline comorbidities, procedural characteristics were not markedly dissimilar between diabetic patients and nondiabetic patients. Overall, 73.3% (297,269 patients) received DES. The frequency of DES use was similar among diabetic and nondiabetic patients, with 73.1% DES implantation in ITDM, 74.2% in NITDM, and 73.0% DES in nondiabetic patients. The frequency of pre-procedural aspirin and clopidogrel treatment, glycoprotein IIb/IIIa therapy during PCI, number of stents deployed, frequency of type C lesions, and multivessel intervention were also similar between nondiabetic patients and diabetic patients.
Patients selected for DES were slightly younger, more likely to be female, and less likely to smoke than patients treated with BMS. Patients receiving DES also had lower rates of renal insufficiency, stroke, coronary artery bypass graft surgery, peripheral vascular disease, and lung disease, but were more likely to have previously undergone PCI, compared with BMS patients. Patients presenting with STEMI were less likely to receive DES (58.8%) compared with patients without STEMI (75.3%) (Table 1).
Diabetes mellitus, stent type, and outcomes
The unadjusted cumulative incidence curves of death, MI, additional revascularization procedures, and hospitalization for bleeding stratified by diabetes status and type of stent implanted are shown in Figure 2A to 2D. Within strata of DES and BMS, the graded adverse association observed between ITDM, NITDM, and no diabetes with death, MI, additional revascularizations, and hospitalization for bleeding are highly significant between ITDM, NITDM, and no diabetes (p < 0.0001 for all comparisons).
Among older Medicare patients treated with DES, mortality at 3-year follow-up was 23.7% with ITDM, 14.2% for NITDM, and 11.1% for nondiabetic patients (p < 0.001). For patients treated with BMS, mortality at 3-year follow-up was 31.6% for ITDM, 20.8% for NITDM, and 17.6% for nondiabetic patients (p < 0.001). Adjusting for all baseline differences listed in Table 1, both ITDM (HR: 1.91 [95% confidence interval [CI]: 1.86 to 1.96], p < 0.001) and NITDM (HR: 1.32 [95% CI: 1.29 to 1.35], p < 0.001) remain significantly associated with higher adjusted hazards of death. This excess mortality hazard associated with ITDM and NITDM was similar regardless of implanted stent type. Among the 297,269 older patients selected for DES, ITDM (HR: 1.98 [95% CI: 1.91 to 2.04], p < 0.001) and NITDM (HR: 1.34 [95% CI: 1.31 to 1.38, p < 0.001) were associated with a significantly increased adjusted risk of death compared with nondiabetic patients. In the 108,410 older patients selected for BMS in the DES era, ITDM (HR: 1.76 [95% CI: 1.67 to 1.85], p < 0.001) and NITDM (HR: 1.26 [95% CI: 1.20 to 1.31], p < 0.001) were also associated with a similar significantly increased adjusted risk of death compared with nondiabetic patients. A significant protective interaction was observed in the association between the presence of both ITDM (p < 0.001) and NITDM (p = 0.001) and DES implantation on adjusted hazard for mortality. The main effect of ITDM and NITDM is an association with a higher adjusted hazard for mortality compared with nondiabetic patients. Given the presence of ITDM and NITDM, the interaction suggests selection for DES is associated with some mitigation of this increased mortality risk compared with selection for BMS. Again, this protective interaction between diabetes and selection for DES on mortality hazard may arise from unmeasured confounders.
The higher absolute mortality risk observed among patients selected for BMS compared with DES was time dependent (Fig. 3). After an initial period of 15 to 18 months of declining quarterly incidence of death for the cohort, a plateau of near-constant quarterly incidence of death is observed within all strata of diabetes and stent type. The early (p < 0.001) and background plateau (p < 0.01) absolute mortality rates are significantly higher for ITDM than for NITDM patients, which are both higher than for nondiabetic patients.
Similar to mortality, older ITDM (HR: 1.87 [95% CI: 1.79 to 1.95], p < 0.001) and NITDM (HR: 1.29 [95% CI: 1.25 to 1.33], p < 0.001) patients undergoing PCI had a significantly higher adjusted hazard of MI in follow-up compared with nondiabetic patients regardless of stent type. Among the 297,269 DES treated patients, ITDM (HR: 1.93 [95% CI: 1.84 to 2.03], p < 0.001) and NITDM (HR: 1.27 [95% CI: 1.22 to 1.32], p < 0.001) were associated with a significantly increased risk of MI. Among the 108,410 older patients selected for BMS, ITDM (HR: 1.70 [95% CI: 1.57 to 1.85], p < 0.001) and NITDM (HR: 1.33 [95% CI: 1.25 to 1.42], p < 0.001) were also associated with a similar increased risk of MI compared with nondiabetic patients. There was no significant interaction between NITDM and stent type compared with nondiabetic patients on the adjusted hazard of subsequent MI (p = 0.72.); however, there was a significant protective association between ITDM and DES placement on the subsequent adjusted hazard of MI (p < 0.001).
Additional revascularization procedures
Older ITDM (HR: 1.14 [95% CI: 1.11 to 1.18, p < 0.001) and NITDM (HR: 1.08 [95% CI: 1.05 to 1.11], p < 0.001) patients undergoing PCI had higher adjusted hazard of subsequent revascularization procedures with either PCI or coronary artery bypass graft surgery than nondiabetic patients regardless of stent type implanted. After selection for DES implantation, the additional revascularization rates observed at 18 months of follow-up (a time point at which events related to restenosis have typically become manifest) were 15.9% for ITDM, 14.5% for NITDM, and 12.8% for nondiabetic patients (p < 0.001). For DES-treated patients, the adjusted hazard for additional revascularization procedures in ITDM (adjusted HR: 1.14 [95% CI: 1.10 to 1.18], p < 0.001) and NITDM (adjusted HR: 1.07 [95% CI: 1.05 to 1.10], p < 0.001) was higher compared with nondiabetic patients. For BMS-treated patients, additional revascularization rates at 18 months of follow-up were 15.5% for ITDM, 15.0% for NITDM, and 13.3% for nondiabetic patients (p < 0.001). The excess hazard of additional revascularization associated with diabetes among those selected for BMS with ITDM (adjusted HR: 1.14 [95% CI: 1.07 to 1.21]) and NITDM (adjusted HR: 1.08 [95% CI: 1.04 to 1.13]) were similar to diabetic patients selected for DES. There was no significant interaction between ITDM (p = 0.126), NITDM (p = 0.763), and stent type compared with nondiabetic patients on the adjusted hazard of additional revascularizations.
Subsequent hospitalization for bleeding
Subsequent hospitalization for bleeding ranged from 3.1% among nondiabetic patients receiving DES to 6.4% among ITDM patients treated with BMS over 30 months of follow-up. Patients with ITDM (adjusted HR: 1.40 [95% CI: 1.31 to 1.50], p < 0.001) and NITDM (adjusted HR: 1.18 [95% CI: 1.13 to 1.24], p < 0.001) had significantly higher hazard for subsequent hospitalization for bleeding after PCI, compared with nondiabetic patients (Fig. 4).
Among the 297,269 older patients selected for DES, ITDM (adjusted HR: 1.26 [95% CI: 0.99 to 1.62], p = 0.065) and NITDM (adjusted HR: 1.18 [95% CI: 1.00 to 1.42], p = 0.052) had only a trend toward independent association with a significantly increased risk of hospitalization for bleeding compared with nondiabetic patients at 30-day follow-up. However, over 1 year of follow-up, the typical minimum prescribed length of treatment with dual antiplatelet therapy in those receiving DES, ITDM (adjusted HR: 1.30 [95% CI: 1.18 to 1.44] , p < 0.001), and NITDM (adjusted HR: 1.19 [95% CI: 1.11 to 1.28], p < 0.001) had significant increased association with subsequent hospitalization for bleeding.
Similar findings were also observed among the 108,410 older patients treated with BMS. At 30 days, follow-up corresponding to the typical minimum prescribed length of treatment with dual antiplatelet therapy after BMS, ITDM (adjusted HR: 1.17 [95% CI: 0.83 to 1.64], p = 0.38), and NITDM (adjusted HR: 1.07 [95% CI: 0.84 to 1.36], p = 0.59) were not independently associated with a significantly increased risk of hospitalization for bleeding compared with nondiabetic patients. Nevertheless, over 1 year of follow-up in patients treated with BMS, ITDM (adjusted HR: 1.43 [95% CI: 1.23 to 1.66], p < 0.001) and NITDM (adjusted HR: 1.23 [95% CI: 1.10 to 1.37], p < 0.001) had significant independent associations with subsequent hospitalization for bleeding. There were no significant interactions between stent type and diabetes status and the adjusted hazard of hospitalization for bleeding.
Comparison of DES and BMS outcomes in diabetic patients in routine practice
The unadjusted rates for subsequent death, MI, and hospitalization for bleeding are significantly lower for both older diabetic patients and nondiabetic patients selected for DES compared with BMS in routine practice (Figs 2 and 5).⇓ This is also true for additional revascularization procedures, except for the ITDM subgroup.
However, as described previously, there are highly significant baseline differences in the patients selected for DES versus BMS implantation in routine clinical practice regardless of diabetes status. As depicted in Figure 5, the adjusted HRs remain significantly less for DES compared with BMS for all strata of diabetes and for all 4 major endpoints with IPW adjustment.
Propensity score matching of patients receiving DES and BMS within strata of diabetes yields 2 groups with very comparable baseline characteristics. In the propensity score-matched subcohort (n = 200,302), there were only small residual measured baseline differences between the BMS and DES recipients (Online Table 3). Except for subsequent hospitalization for bleeding in diabetic patients and additional revascularization procedures in ITDM, selection for DES remains associated with significantly lower adjusted hazards of death, MI, and subsequent revascularizations with propensity score matching.
In this national cohort, diabetes was present in one-third of older patients undergoing PCI in the DES era. Diabetic patients had a substantially higher prevalence of important baseline comorbidities. After adjustment for these known baseline differences, the presence of ITDM was associated with a doubling of subsequent relative hazards for death and MI, a 17% relative increase in the hazard of subsequent revascularization procedures, and a 39% relative increase in the hazard of hospitalization for bleeding compared with nondiabetic patients. Having NITDM also remained independently associated with increased relative hazards of death (32%), MI (28%), additional revascularization procedures (8%), and hospitalization for bleeding (18%) in follow-up after stent implantation compared with nondiabetic patients.
Consistent with prior studies in the balloon angioplasty and BMS era as well as smaller, selected DES cohorts, ITDM and NITDM still confer substantial independent risk for adverse cardiovascular outcomes over 3- to 4-year follow-up in older patients undergoing PCI in the DES era (12–14). The relative magnitude of incremental risk conferred by ITDM or NITDM remains similar, regardless of DES or BMS implantation. The mechanisms for this incremental risk of adverse cardiovascular events in older diabetic patients compared with nondiabetic patients, particularly for death and MI after PCI with both DES and BMS, is likely multifactorial. Hypotheses include a greater underlying burden of atherosclerosis, microvascular disease, a prothrombotic state, more neointimal hyperplasia, greater vascular inflammation, and/or further accumulation of diabetes-related end-organ damage and comorbidities during the 30- to 50-month follow-up period (12–18).
Medicare-aged diabetic patients undergoing PCI were not observed to be substantially more likely (73.9%) than nondiabetic patients (73.0%) to be treated with DES in routine practice, which is a surprising observation given the 55% reduction in subsequent target vessel revascularization with DES versus BMS in diabetic patients documented in meta-analysis of the 22 randomized trials. Since less than one-third of the 2,500 diabetic patients enrolled in the RCTs were ≥65 years old, the applicability of the RCT data to unselected older diabetic patients encountered in routine practice is not well characterized (4,5,13,14). Patients selected for DES in routine practice had significantly lower measured comorbidities than did patients treated with BMS in this large cohort. Coupled with the substantially greater baseline comorbidities of the diabetic patients, this explains the similar utilization of DES in diabetic patients compared with nondiabetic patients observed in consecutive patients treated with PCI in routine practice.
Yet, not all of the observed difference in longer-term outcomes in diabetic patients selected for DES compared with BMS can be explained by these known baseline differences in comorbidities. Adjustment for age, sex, clinical presentation, left ventricular ejection fraction, number of vessels diseased, cardiogenic shock, renal function, dialysis, number of lesions and vessels treated, number of stents implanted, chronic obstructive pulmonary disease, peripheral vascular disease, congestive heart failure history, prior stroke, MI, coronary artery bypass graft surgery, and PCI among 102 covariates does not fully explain the observed differences in outcomes of death and MI between patients selected for DES versus BMS in routine practice. For example, among ITDM, the unadjusted relative hazard for mortality is 32% (95% CI: 28% to 36%) lower with selection for DES than BMS. Adjustment for measured baseline differences reduces this to 18% (95% CI: 14% to 22%); therefore, the 18% lower relative hazard of longer-term mortality after selection for DES versus BMS implantation is not explained by the available baseline and procedural covariates in the CathPCI Registry.
Largely by design, the set of information collected in the CathPCI Registry has been demonstrated to be highly predictive of index hospitalization events and outcomes (19). Despite the extensive set of covariates collected in the CathPCI Registry, the residual differences in these important longer-term outcomes with stent type suggest the need for additional factors to explain these differences. Among BMS-treated patients across all strata of diabetes, the higher early incidence of death and MI suggests other unmeasured (but important) factors are almost certainly being appropriately considered in stent implantation decisions.
The lower subsequent hazard of additional revascularization with selection for DES versus BMS may reflect the efficacy of DES as demonstrated in the randomized trials. Nevertheless, the difference in additional revascularization rates observed in routine practice between DES and BMS are considerably smaller than target vessel revascularization rate differences in RCTs. This may be explained in part by proof-of-concept RCTs necessarily excluding patients likely to need subsequent procedures for additional lesions and vessels. In addition to appropriate operator selection biases based on the estimated likelihood of restenosis that we have not measured, implantation of BMS in the DES era may be a marker of patients less suitable for pursuing an invasive strategy in the future. This notion is indirectly supported by the observation of higher prior PCI rates among patients receiving DES than BMS in this cohort.
A post-discharge follow-up major bleeding endpoint has rarely been evaluated in previous observational comparisons of DES and BMS treatment. The relatively small rates of hospitalization for bleeding are reassuring from a patient safety point of view. Given the longer duration of dual antiplatelet therapy typically prescribed with DES versus BMS treatment, one might expect a higher bleeding risk with the prolonged dual antiplatelet therapy used with DES, but we found that unadjusted bleeding rates were lower with selection for DES than BMS in this cohort. This almost certainly reflects operators considering additional factors in matching stent type to estimated patient bleeding risk. After adjusting for all covariates, including contraindications to antiplatelet agents and anticoagulants, as well as warfarin status in the propensity-matched cohort, the lower hazard of bleeding in diabetic patients selected for DES compared with BMS is largely explained. Conversely, diabetes status, particularly ITDM, is significantly associated with both a higher unadjusted and adjusted risk of hospitalization for subsequent bleeding compared with nondiabetic patients after stent placement.
Study strengths and limitations
The CathPCI Registry represents >1,000 U.S. hospitals, thereby capturing a significant portion of PCIs nationally. More than 50% of patients undergoing PCI are 65 years of age or older. This “all-comers” cohort includes older patients, many of whom would have been excluded from the pivotal trials because of age, comorbidities, or disease complexity such as additional lesions likely requiring future procedures (13). The large size of this cohort and length of follow-up perhaps allows formulation of more accurate expectations of outcomes in older diabetic patients treated with DES and BMS in the DES era in our routine practice.
In contrast to the RCTs and meta-analyses, however, these observational data have many inherent limitations for comparing the efficacy of DES and BMS. Particularly based on the early separation in the time-course of mortality and MI rates after PCI with DES versus BMS, there are almost certainly appropriate factors driving operator decisions between DES and BMS implantation that have not (or cannot) be readily captured. These unmeasured confounders might explain the differences in mortality, MI, and additional revascularization we have observed in routine practice. Candidate factors for additional research are those that are plausibly related to longer-term outcomes, including competing noncardiovascular comorbidities, measures of thrombotic tendency and inflammation, functional status, socioeconomic status, measures of adherence to medical therapy, and patient frailty.
While this large observational registry does contain clinical judgments as to contraindication to antiplatelet and anticoagulant therapies as well as warfarin status, it is limited by the absence of information on utilization and duration of dual antiplatelet therapy for the bleeding endpoint.
In a large national consecutive cohort study of Medicare beneficiaries undergoing PCI, 33% of older patients have diabetes. A strong independent association was observed between diabetes (particularly ITDM) and increased cardiovascular events in the 3 to 4 years after PCI, regardless of BMS or DES implantation. These data quantitatively define the expected 3- to 4-year outcomes of death, MI, additional revascularization, and subsequent hospitalization for bleeding in older diabetic patients undergoing either DES or BMS implantation in the DES era compared with patients without diabetes.
This information is available only because of the diligent and dedicated work of all the participating NCDR CathPCI Registry centers, data coordinators, and operating/patient care teams. The authors would like to thank Erin LoFrese for her editorial contributions to this manuscript. Ms. LoFrese did not receive compensation for her assistance, apart from her employment at the institution where this study was conducted.
For supplemental tables, please see the online version of this article.
This project was sponsored by the Agency for Healthcare Research and Quality (AHRQ), U.S. Department of Health and Human Services, Rockville, Maryland, as part of the Cardiovascular Consortium and funded under project ID 24-DKE-3 and work assignment number HHSAA290-2005-0032—TO4-WA3 as part of the Developing Evidence to Inform Decisions About Effectiveness (DEcIDE) program. Additional support was obtained from the National Cardiovascular Data Registry, American College of Cardiology, Washington, DC. This research was conducted through a Government contract with the AHRQ, an operating division of the U.S. Department of Health and Human Services. Dr. Patel is a consultant and member of the advisory board of Genzyme, Bayer, Jansen, Baxter, and Otsuka; and has received research support from Johnson & Johnson, the National Heart, Lung, and Blood Institute; AHRQ, and AstraZeneca. Dr. Anstrom receives research and salary support from Alexion, AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Company, Inc., Innocoll Pharmaceuticals, Medtronic, Pfizer, and Proctor & Gamble (modest); is on data safety monitoring boards of Pfizer and Vertex (modest); and provides consulting services to Pacific Therapeutics, Bristol-Myers Squibb, and AstraZeneca (modest). Dr. Eisenstein receives research funding from Medtronic and Eli Lilly & Company, Inc. (significant). Dr. Peterson has received research funding from BMS/Sanofi, Merck, Lilly, Johnson & Johnson, Society of Thoracic Surgeons, and American College of Cardiology (significant). Dr. Messenger is the site Principal Investigator for the Resolute Study. Dr. Patel receives research grants from Johnson & Johnson, NHLBI, AHRQ, and AstraZeneca; and is a consultant to Genzyme, Bayer, Jansen, Baxter, and Otsuka. Dr. Peterson has received research support from Eli Lilly and Janssen Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- American College of Cardiology
- bare-metal stent(s)
- confidence interval
- Centers for Medicare and Medicaid Services
- cerebrovascular accident
- drug-eluting stent(s)
- hazard ratio
- International Classification of Diseases-Ninth Revision-Clinical Modification
- inverse probability weighted
- insulin-treated diabetes mellitus
- myocardial infarction
- National Cardiovascular Data Registry
- non-insulin-treated diabetes mellitus
- percutaneous coronary intervention
- randomized controlled trial
- Society for Cardiovascular Angiography and Interventions
- Received March 8, 2012.
- Revision received June 25, 2012.
- Accepted August 21, 2012.
- American College of Cardiology Foundation
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