Bimmer E. Claessen

In-Stent Restenosis in the Drug-Eluting Stent Era

The introduction of the drug-eluting stent (DES) proved to be an important step forward in reducing rates of restenosis and target lesion revascularization after percutaneous coronary intervention. However, the rapid implementation of DES in standard practice and expansion of the indications for percutaneous coronary intervention to high-risk patients and complex lesions also introduced a new problem: DES in-stent restenosis (ISR), which occurs in 3% to 20% of patients, depending on patient and lesion characteristics and DES type. The clinical presentation of DES ISR is usually recurrent angina, but some patients present with acute coronary syndrome. Mechanisms of DES ISR can be biological, mechanical, and technical, and its pattern is predominantly focal. Intravascular imaging can assist in defining the mechanism and selecting treatment modalities. Based upon the current available evidence, an algorithm for the treatment approaches to DES restenosis is proposed.

Prognostic Impact of Staged Versus “One-Time” Multivessel Percutaneous Intervention in Acute Myocardial Infarction : Analysis From the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) Trial

OBJECTIVES The purpose of this study was to compare a one-time primary percutaneous coronary intervention (PCI) of the culprit and nonculprit lesions with PCI of only the culprit lesion and staged nonculprit PCI at a later date in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. BACKGROUND In patients with STEMI and multivessel disease, it is unknown whether it is safe or even desirable to also treat the nonculprit vessel during the primary PCI procedure. METHODS In the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, 668 of the 3,602 STEMI patients enrolled (18.5%) underwent PCI of culprit and nonculprit lesions for multivessel disease. Patients were categorized into a single PCI strategy (n = 275) versus staged PCI (n = 393). The endpoints analyzed included the 1-year rates of major adverse cardiovascular events and its components, death, reinfarction, target-vessel revascularization for ischemia, and stroke. RESULTS Single versus staged PCI was associated with higher 1-year mortality (9.2% vs. 2.3%; hazard ratio [HR]: 4.1, 95% confidence interval [CI]: 1.93 to 8.86, p < 0.0001), cardiac mortality (6.2% vs. 2.0%; HR: 3.14, 95% CI: 1.35 to 7.27, p = 0.005), definite/probable stent thrombosis (5.7% vs. 2.3%; HR: 2.49, 95% CI: 1.09 to 5.70, p = 0.02), and a trend toward greater major adverse cardiovascular events (18.1% vs. 13.4%; HR: 1.42, 95% CI: 0.96 to 2.1, p = 0.08). The mortality advantage favoring staged PCI was maintained in a subgroup of patients undergoing truly elective multivessel PCI. Also, the staged PCI strategy was independently associated with lower all-cause mortality at 30 days and at 1 year. CONCLUSIONS A deferred angioplasty strategy of nonculprit lesions should remain the standard approach in patients with STEMI undergoing primary PCI, as multivessel PCI may be associated with a greater hazard for mortality and stent thrombosis. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966).

Long-Term Outcome of Percutaneous Coronary Intervention for Chronic Total Occlusions

OBJECTIVES The aim of this study was to evaluate long-term clinical outcomes after percutaneous coronary intervention (PCI) for chronic total occlusions (CTO). BACKGROUND Despite technical advancements, there is a paucity of data on long-term outcomes after PCI of CTO. METHODS We evaluated long-term clinical outcomes in 1,791 patients who underwent PCI of 1,852 CTO at 3 tertiary care centers in the United States, South Korea, and Italy between 1998 and 2007. Median follow-up was 2.9 years (interquartile range: 1.5 to 4.6 years). RESULTS Procedural success was obtained in 1,226 (68%) patients. Stents were implanted in 1,160 patients (95%); 396 patients (34%) received bare-metal stents (BMS), and 764 patients (66%) received drug-eluting stents (DES). After multivariable analysis, successful CTO PCI was an independent predictor of a lower cardiac mortality (hazard ratio [HR]: 0.40, 95% confidence interval [CI]: 0.21 to 0.75, p < 0.01) and reduced need for coronary artery bypass graft surgery (HR: 0.21, 95% CI: 0.13 to 0.40, p < 0.01); it also correlated with a strong trend toward lower all-cause mortality (HR: 0.63, 95% CI: 0.40 to 1.00, p = 0.05) at 5-year follow-up. Among patients who underwent stent implantation, treatment with DES rather than BMS resulted in less target vessel revascularization at long-term follow-up (17.2% vs. 31.1%, p < 0.01); definite/probable stent thrombosis rates were similar (DES 1.7%, BMS 2.3%, p = 0.58). Within the DES subgroup, patients treated with paclitaxel-eluting stents and sirolimus-eluting stents had similar clinical outcomes. CONCLUSIONS Successful CTO PCI is associated with reduced long-term cardiac mortality and need for coronary artery bypass graft surgery. Treatment of CTO with DES rather than BMS is associated with a significant reduction in target vessel revascularization with similar rates of stent thrombosis. Paclitaxel-eluting stents and sirolimus-eluting stents had similar long-term safety and efficacy outcomes.

Safety and efficacy outcomes of first and second generation durable polymer drug eluting stents and biodegradable polymer biolimus eluting stents in clinical practice: comprehensive network meta-analysis

Objectives To investigate the safety and efficacy of durable polymer drug eluting stents (DES) and biodegradable polymer biolimus eluting stents (biolimus-ES). Design Network meta-analysis of randomised controlled trials. Data sources and study selection Medline, Google Scholar, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) database search for randomised controlled trials comparing at least two of durable polymer sirolimus eluting stents (sirolimus-ES) and paclitaxel eluting stents (paclitaxel-ES), newer durable polymer everolimus eluting stents (everolimus-ES), Endeavor and Resolute zotarolimus eluting stents (zotarolimus-ES), and biodegradable polymer biolimus-ES. Primary outcomes Safety (death, myocardial infarction, definite or probable stent thrombosis) and efficacy (target lesion and target vessel revascularisation) assessed at up to one year and beyond. Results 60 randomised controlled trials were compared involving 63 242 patients with stable coronary artery disease or acute coronary syndrome treated with a DES. At one year, there were no differences in mortality among devices. Resolute and Endeavor zotarolimus-ES, everolimus-ES, and sirolimus-ES, but not biodegradable polymer biolimus-ES, were associated with significantly reduced odds of myocardial infarction (by 29-34%) compared with paclitaxel-ES. Compared with everolimus-ES, biodegradable polymer biolimus-ES were associated with significantly increased odds of myocardial infarction (by 29%), while Endeavor zotarolimus-ES and paclitaxel-ES were associated with significantly increased odds of stent thrombosis. All investigated DES were similar with regards to efficacy endpoints, except for Endeavor zotarolimus-ES and paclitaxel-ES, which were associated with significantly increased the odds of target lesion and target vessel revascularisations compared with other devices. Direction of results beyond one year did not diverge from the findings for up to one year follow-up. Bayesian probability curves showed a gradient in the magnitude of effect, with everolimus-ES and Resolute zotarolimus-ES offering the highest safety profiles. Conclusions The newer durable polymer everolimus-ES and Resolute zotarolimus-ES and the biodegradable polymer biolimus-ES maintain the efficacy of sirolimus-ES; however, for safety endpoints, differences become apparent, with everolimus-ES and Resolute zotarolimus-ES emerging as the safest stents to date.

Prognostic impact of a chronic total occlusion in a non-infarct-related artery in patients with ST-segment elevation myocardial infarction: 3-year results from the HORIZONS-AMI trial

AIMS We sought to investigate the impact of multivessel disease (MVD) with and without a chronic total occlusion (CTO) in a non-infarct-related artery (IRA) on mortality in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS AND RESULTS In the HORIZONS-AMI trial, of 3283 patients undergoing primary PCI, 1524 patients (46.4%) had single-vessel disease (SVD), 1477 (45.0%) had MVD without a CTO, and 283 (8.6%) had MVD with a CTO in a non-IRA. Compared with SVD patients and MVD patients without a CTO, patients with a non-IRA CTO were significantly less likely to achieve post-procedural TIMI 3 flow (P = 0.0003), more often had absent myocardial blush (P = 0.0002), and less frequently achieved complete ST-segment resolution (P = 0.0001). By multivariable analysis, MVD with CTO in a non-IRA was an independent predictor of both 0- to 30-day mortality [hazard ratio (HR) 2.88, 95% confidence interval (CI) 1.41-5.88, P = 0.004] and 30-day to 3-year mortality (HR 1.98, 95% CI 1.19-3.29, P= 0.009), while MVD without a CTO was a significant predictor for 0- to 30-day mortality (HR 2.20, 95% CI 1.00-3.06, P = 0.049) but not late mortality. CONCLUSION In patients with STEMI undergoing primary PCI in the HORIZONS-AMI trial, MVD with or without a CTO in a non-IRA was an independent predictor of early mortality. The presence of a CTO in a non-IRA was also an independent predictor of increased late mortality to 3 years.

Impact of In-Hospital Major Bleeding on Late Clinical Outcomes After Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: The HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) Trial

OBJECTIVES We aimed to investigate the long-term prognosis of patients with in-hospital major bleeding (IHMB). BACKGROUND The effect of IHMB on the long-term prognosis of patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction is unknown. METHODS Primary PCI was performed in 3,345 (92.9%) of 3,602 patients in the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial; in-hospital protocol-defined non-coronary artery bypass graft-related major bleeding developed in 231 (6.9%). We examined medication use at discharge, mortality, and major adverse cardiovascular events (composite of death, reinfarction, stroke, or ischemic target vessel revascularization) at 3-year follow-up in patients with and without IHMB. RESULTS At 3-year follow-up, patients with IHMB had higher mortality (24.6% vs. 5.4%, p < 0.0001) and major adverse cardiovascular events (40.3% vs. 20.5%, p < 0.0001). The deleterious effect of major bleeding was observed within 1 month, between 1 month and 1 year, and between 1 and 3 years. IHMB was an independent predictor of mortality (hazard ratio: 2.80; 95% confidence interval: 1.89 to 4.16, p < 0.0001) at 3-year follow up. CONCLUSIONS Patients with IHMB after primary PCI have significantly increased 3-year rates of morbidity and mortality. Further investigation is warranted to understand the mechanisms underlying this relationship and to further improve outcomes in patients with ST-segment myocardial infarction. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966).

Two-Year Clinical, Angiographic, and Intravascular Ultrasound Follow-Up of the XIENCE V Everolimus-Eluting Stent in the Treatment of Patients With De Novo Native Coronary Artery Lesions The SPIRIT II Trial

Background—This article reports the 2-year clinical, angiographic, and intravascular ultrasound outcomes of the everolimus-eluting stent (EES) compared with the paclitaxel-eluting stent (PES) in the randomized SPIRIT II trial. Methods and Results—This was a prospective, single-blind clinical trial in which a total of 300 patients with de novo native coronary artery lesions were randomized to either EES or PES in a 3:1 fashion. Clinical follow-up was planned at 2 years in all patients. A subset of 152 patients underwent serial angiographic and intravascular ultrasound analyses at 6 months and 2 years. After 2 years, target lesion failure (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization) rates were 6.6% and 11% in EES and PES, respectively (P=0.31). At 6 months, a significant reduction in angiographic in-stent late loss and percentage volume obstruction measured by intravascular ultrasound was observed in the EES group. However, at 2-year follow-up, a late increased intimal hyperplasia growth after implantation of an EES was observed. There were no significant differences between EES and PES for in-stent late loss (EES, 0.33±0.37 mm versus PES, 0.34±0.34 mm; P=0.84) and percentage volume obstruction (EES, 5.18±6.22% versus PES, 5.80±6.31%; P=0.65) at 2 years. The incidence of stent thrombosis was low and comparable in both groups (EES, 0.9%; PES, 1.4%). Conclusions—Although the previously reported angiographic and clinical superiority of the EES has vanished over time, this report confirms and extends the previously demonstrated noninferiority in terms of in-stent late loss of the EES when compared with the PES up to 2-year follow-up. There were no significant differences between EES and PES in clinical, angiographic and intravascular ultrasound outcomes at 2 years.

Effect of Multivessel Coronary Disease With or Without Concurrent Chronic Total Occlusion on One-Year Mortality in Patients Treated With Primary Percutaneous Coronary Intervention for Cardiogenic Shock

Despite early revascularization, mortality remains high in patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock. It has been shown that the effect of multivessel disease (MVD) on mortality in patients with STEMI treated with primary percutaneous coronary intervention is mainly caused by the presence of chronic total occlusion (CTO) in a noninfarct-related coronary artery. Whether this association also exists in patients with STEMI with cardiogenic shock is unknown. In our institution, 292 consecutive patients with STEMI complicated by cardiogenic shock were admitted from 1997 to 2005 and treated with primary percutaneous coronary intervention. Patients were classified as having single vessel disease, MVD without CTO, and CTO. Cox regression analysis was used for multivariate analysis. The 1-year mortality rate of patients with single-vessel disease, MVD, and CTO was 31%, 47%, and 63%, respectively. After adjustment for possible confounders, MVD alone was not an independent predictor of 1-year mortality (hazard ratio 1.5, 95% confidence interval 0.98 to 2.3, p = 0.07). In contrast, CTO in a noninfarct-related artery was an independent predictor of 1-year mortality (hazard ratio 2.1, 95% confidence interval 1.5 to 3.1, p <0.01). In conclusion, the presence of CTO in a non-infarct-related artery was an independent predictor of 1-year mortality. In contrast, MVD alone lost its predictive significance after multivariate analysis.

Impact of Intravascular Ultrasound Imaging on Early and Late Clinical Outcomes Following Percutaneous Coronary Intervention With Drug-Eluting Stents

OBJECTIVES This study sought to assess the impact of intravascular ultrasound (IVUS)-guided versus angiography-guided drug-eluting stent (DES) implantation. BACKGROUND There are limited data on IVUS guidance in the DES era. Therefore, we investigated the impact of IVUS guidance on clinical outcomes in the MATRIX (Comprehensive Assessment of Sirolimus-Eluting Stents in Complex Lesions) registry. METHODS The MATRIX registry prospectively enrolled consecutive, unselected patients treated with sirolimus-eluting stents (SES) (n = 1,504); 631 patients (42%) underwent IVUS-guided stenting, and 873 (58%) had only angiographic guidance. We assessed 30-day, 1-year, and 2-year rates of death/myocardial infarction (MI), major adverse cardiac events (cardiac death, MI, or target vessel revascularization), and definite/probable stent thrombosis in 548 propensity-score matched patient pairs. RESULTS After matching, baseline and angiographic characteristics were similar in IVUS and no-IVUS groups. Patients in the IVUS group had significantly less death/MI at 30 days (1.5% vs. 4.6%, p < 0.01), 1 year (3.3% vs. 6.5%, p < 0.01), and 2 years (5.0% vs. 8.8%, p < 0.01). Patients in the IVUS group had significantly less major adverse cardiac events at 30 days (2.2% vs. 4.8%, p = 0.04) and numerically less major adverse cardiac events at 1 year (9.1% vs. 13.5%, p = 0.07) and 2 years (12.9% vs. 16.7%, p = 0.18). Rates of MI were significantly lower in the IVUS group at 30 days (1.5% vs. 4.0%, p < 0.01), 1 year (1.8% vs. 4.8%, p < 0.01), and 2 years (2.1% vs. 5.7%, p < 0.01). CONCLUSIONS IVUS-guided stent implantation appears to be associated with a reduction in both early and long-term clinical events. Further investigation in randomized controlled trials is warranted.

Long-term impact of chronic kidney disease in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial.

OBJECTIVES This study sought to investigate the impact of chronic kidney disease (CKD) in patients undergoing percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) with different antithrombotic strategies. BACKGROUND CKD is associated with increased risk of adverse ischemic and hemorrhagic events after primary PCI for STEMI. METHODS HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial was a multicenter, international, randomized trial comparing bivalirudin monotherapy or heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) during primary PCI in STEMI. CKD, defined as creatinine clearance <60 ml/min, was present at baseline in 554 of 3,397 patients (16.3%). Patients were followed for 3 years. Net adverse cardiac event (NACE) was defined as the composite of death, reinfarction, ischemia-driven target vessel revascularization (TVR), stroke or non-coronary artery bypass grafting (CABG)-related major bleeding. RESULTS Patients with CKD compared with patients without had higher rates of NACE (41.4% vs. 23.8%, p < 0.0001), death (18.7% vs. 4.4%, p < 0.0001), and major bleeding (19.3% vs. 6.7%, p < 0.0001). Multivariable analysis identified baseline creatinine as an independent predictor of death at 3 years (hazard ratio: 1.51, 95% confidence interval: 1.21 to 1.87, p < 0.001). Patients with CKD randomized to bivalirudin monotherapy versus heparin plus GPI had no significant difference in major bleeding (19.0% vs. 19.6%, p = 0.72) or death (19.0% vs. 18.4%, p = 0.88) at 3 years. In patients with CKD, there was no difference in the rates of TVR in bare-metal stents (BMS) versus drug-eluting stents (DES) at 3 years (14.1% vs. 15.1%, p = 0.8). CONCLUSIONS STEMI patients with CKD have significantly higher rates of death and major bleeding compared with those without CKD. In patients with CKD, there appears to be no benefit of bivalirudin compared with heparin + GPI, or DES versus BMS during primary PCI in improving clinical outcomes.