Impact of the SYNTAX scores I and II in patients with diabetes and multivessel coronary disease: a pooled analysis of patient level data from the SYNTAX, PRECOMBAT, and BEST trials.

AIMS: To assess the impact of the SYNTAX scores I and II in outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) for patients with diabetes and multivessel disease (MVD). METHODS AND RESULTS: We performed a patient-level pooled analysis of three large randomized trials of patients with MVD. The impact of coronary anatomic complexity as measured by the SYNTAX score in the differences in outcomes following PCI and CABG was assessed at a median follow-up of 5 years. We also assessed the performance of the SYNTAX II score model in patients with and without diabetes. From the 3280 patients enrolled in the three trials, a total of 1068 (32.6%) had diabetes. The rate of the composite of death, myocardial infarction (MI), or stroke was similar in the PCI and CABG arms in patients with low-intermediate (≤32) SYNTAX scores (15.1% vs. 14.9%, respectively; P = 0.93) while it was significantly higher in the PCI arm in patients with high (≥33) SYNTAX scores (24.5% vs. 13.2%, respectively; P = 0.018). The SYNTAX score II showed good calibration and moderate discrimination ability in patients with diabetes (c-index = 0.68) as well as in those without (c-index = 0.67). CONCLUSIONS: Differences in 5 years outcomes following PCI and CABG for patients with MVD and diabetes were influenced by anatomic complexity as measured by the SYNTAX score. The SYNTAX score II mortality prediction model showed similar performance regardless of the diabetes status.

Optical coherence tomographic analysis of in-stent neoatherosclerosis after drug-eluting stent implantation.

BACKGROUND: We report findings from optical coherence tomography (OCT) of in-stent neoatherosclerosis as a cause of drug-eluting stent (DES) failure. METHODS AND RESULTS: Optical coherence tomography and grayscale and virtual histology intravascular ultrasound were performed in 50 patients (30 stable, 20 unstable angina) with 50 DES in-stent restenosis lesions and intimal hyperplasia >50% of stent area. Median follow-up time was 32.2 months. Overall, 26 lesions (52%) had at least 1 OCT-defined in-stent thin-cap fibroatheroma (TCFA)-containing neointima and 29 (58%) had at least 1 in-stent neointimal rupture. Patients presenting with unstable angina showed a thinner fibrous cap (55 µm [interquartile range 42 to 105 µm] versus 100 µm [interquartile range 60 to 205 µm], P=0.006) and higher incidence of OCT-defined TCFA-containing neointima (75% versus 37%, P=0.008), intimal rupture (75% versus 47%, P=0.044), thrombi (80% versus 43%, P=0.010), and red thrombi (30% versus 3%, P=0.012) than stable patients. Fibrous cap thickness negatively correlated with follow-up time (r=-0.318, P=0.024). Compared with DES <20 months after implantation (the best cut-off to predict TCFA-containing neointima), DES ≥20 months after implantation had a higher incidence of TCFA-containing neointima (69% versus 33%, P=0.012) and red thrombi (27% versus 0%, P=0.007). Patients with unstable (versus stable) angina had an increasing number of unstable OCT findings including TCFA-containing neointima, neointima rupture, and thrombus (P=0.027). The rate of agreement between grayscale intravascular ultrasound and OCT for detecting intimal rupture was 50% and for detecting thrombus was 44%. The agreement between virtual histology intravascular ultrasound and OCT for identifying TCFA-containing neointima was 78%. CONCLUSIONS: In-stent neoatherosclerosis may be an important mechanism of DES failure, especially late after implantation.

Long-term clinical outcomes after sirolimus-eluting stent implantation for treatment of restenosis within bare-metal versus drug-eluting stents.

BACKGROUND: Sirolimus-eluting stents have been increasingly used for treatment of restenosis after implantation of bare metal stents (BMSs) or drug-eluting stents (DESs), but little is known regarding their long-term outcomes. METHODS: We compared long-term clinical outcomes in 295 patients treated with sirolimus-eluting stents for post-BMS (n = 224) vs. post-DES (n = 71) restenosis. All follow-ups were at least 12 months, and the primary endpoint was major adverse cardiac events (MACE), defined as cardiac death, nonfatal myocardial infarction (MI) or target lesion revascularization (TLR). RESULTS: Baseline characteristics were similar between the two groups, except that mean lesion length (28.0 +/- 16.2 vs. 19.5 +/- 13.6, P < 0.01) and mean stented length (35.4 +/- 19.2 vs. 25.7 +/- 14.7, P < 0.01) were significantly longer in the post-BMS group. Major in-hospital complications occurred in 2 patients. During a mean follow-up of 31.3 +/- 11.1 months, there were 9 deaths (4 cardiac, 5 noncardiac), 3 nonfatal MIs, and 25 TLRs. Late stent thrombosis was documented in 2 patients (1 in each group). There were no between group differences in cardiac or total deaths, but there were trends toward less frequent cardiac death/MI or TLR in the post-BMS group. The cumulative probability of MACE-free survival was significantly better for the post-BMS group (95.0% +/- 1.5% vs. 87.3% +/- 4.0% at 1 year; 93.0% +/- 1.7% vs. 81.0% +/- 5.2% at 2 years; Log Rank P = 0.016). In multivariate analysis, post-DES restenosis was the only significant predictor of MACE (OR 3.29, 95%CI 1.13-9.61, P = 0.029). CONCLUSIONS: Sirolimus-eluting stents were effective for treatment of in-stent restenosis, but post-DES restenosis was associated with poorer outcomes than post-BMS restenosis.

Mechanisms of in-stent restenosis after drug-eluting stent implantation: intravascular ultrasound analysis.

BACKGROUND: We used intravascular ultrasound (IVUS) to (1) clarify the mechanisms of luminal loss after drug-eluting stent (DES) implantation and (2) classify morphological patterns of in-stent restenosis (ISR). METHODS AND RESULTS: On the basis of IVUS-identified luminal narrowing (in-stent minimum lumen area <4 mm(2)), IVUS-defined ISR was classified as focal (luminal narrowing ≤10 mm in length), multifocal (≥1 focal lesions), and diffuse (luminal narrowing >10 mm in length) with or without stent edge involvement. Significant intimal hyperplasia (IH) was defined as IH area >50% of stent. Overall, 76 lesions had IVUS-defined ISR; 32 (42%) had stent underexpansion (minimal stent area <5 mm(2)); and 71 (93%) had IH area >50% of stent. Total stent length negatively correlated with minimal stent area (r=-0.613, P<0.001) as well as with stent area at the minimum lumen site (r=-0.436, P<0.001) but not with minimum lumen area (r=-0.084, P=0.472). Underexpansion was present at the minimum lumen site in 15 of 43 (35%) lesions with stent length >28 mm, even though there was significant IH in 34 (79%) lesions; conversely, in 32 of 33 (97%) lesions with stent length ≤28 mm, the minimum lumen site was not associated with stent underexpansion but significant IH. IVUS-defined focal ISR was most common (47%). Compared with focal ISR, normalized vessel, stent, lumen, and plaque volumes were smaller in diffuse and multifocal than focal ISR, with no difference in IH extent. CONCLUSIONS: In most DES restenosis, IH was the dominant mechanism of ISR. Nevertheless, underexpansion associated with longer stent length remained an important preventable mechanism of ISR.

Impact of bleeding on subsequent early and late mortality after drug-eluting stent implantation.

OBJECTIVES: The aim of this study was to assess the impact of early and late bleeding on subsequent mortality after drug-eluting stent (DES) implantation. BACKGROUND: Little is known about the impact of late bleeding after DES implantation. METHODS: With a time-updated Cox model, the impact of bleeding and myocardial infarction (MI) on 3-year mortality was analyzed in 3,148 consecutive patients who underwent DES implantation for coronary disease. RESULTS: Bleeding, defined according to STEEPLE (Safety and Efficacy of Enoxaparin in PCI Patients, an International Randomized Evaluation) minor or major criteria, occurred in 6.5% of patients over 3 years. Patients with bleeding were older; were more likely to be female; had higher rates of diabetes mellitus, hypertension, and extensive coronary disease and lower ventricular function; and underwent more complex procedures than those without bleeding. The 3-year adjusted hazard ratios (HRs) for mortality were 5.81 (95% confidence interval [CI]: 3.92 to 8.60; p < 0.001) for patients with bleeding and 2.53 (95% CI: 1.62 to 3.96; p < 0.001) for patients with MI. When the timings of events were separated, the HRs for mortality were 4.89 (95% CI: 3.08 to 7.78; p < 0.001) and 7.81 (95% CI: 4.39 to 13.89; p < 0.001) for patients with bleeding within and after 30 days, respectively. By contrast, the HRs for mortality were 1.85 (95% CI: 1.09 to 3.14, p = 0.022) and 10.33 (95% CI: 4.91 to 21.75, p < 0.001) for patients with MI within and after 30 days, respectively. CONCLUSIONS: Bleeding is closely associated with mortality during both the early and late periods after DES implantation. Therefore, in addition to carefully assessing bleeding after stenting, evidence-based treatment should be implemented to offer the best balance of benefit and harm.