Ovidiu Dressler

Strut coverage and late malapposition with paclitaxel-eluting stents compared with bare metal stents in acute myocardial infarction: optical coherence tomography substudy of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) Trial.

Background— The safety of drug-eluting stents in ST-segment elevation myocardial infarction (STEMI) continues to be debated. Pathological studies have demonstrated an association between uncovered struts and subsequent stent thrombosis. Optical coherence tomography can detect stent strut coverage in vivo on a micron-scale level. We therefore used optical coherence tomography to examine strut coverage in patients with STEMI treated with paclitaxel-eluting stents (PES) and bare metal stents (BMS). Methods and Results— In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, patients with STEMI were randomized 3:1 to PES or BMS implantation. In a formal substudy, optical coherence tomography at 13 months was performed in 118 consecutive randomized patients (89 PES, 29 BMS) in whom 188 stents were assessed (146 PES and 42 BMS). A total of 44 139 stent struts were analyzed by an independent core laboratory blinded to stent assignment. The primary prespecified end point, the percentage of uncovered stent struts per lesion at follow-up, was 1.1±2.5% in BMS lesions versus 5.7±7.0% in PES lesions (P<0.0001). Malapposed struts were observed in 0.1±0.2% of BMS lesions versus 0.9±2.1% of PES lesions (P=0.0003). Percentage net volume obstruction was 36.0±15.4% with BMS and 19.2±11.3% with PES (P<0.0001). Conclusions— In patients with STEMI undergoing primary percutaneous coronary intervention, implantation of PES as compared with BMS significantly reduces neointimal hyperplasia but results in higher rates of uncovered and malapposed stent struts as assessed by optical coherence tomography at 13-month follow-up. Further studies are required to determine the clinical significance of these findings. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Strut Coverage and Late Malapposition With Paclitaxel-Eluting Stents Compared With Bare Metal Stents in Acute Myocardial Infarction

Background— The safety of drug-eluting stents in ST-segment elevation myocardial infarction (STEMI) continues to be debated. Pathological studies have demonstrated an association between uncovered struts and subsequent stent thrombosis. Optical coherence tomography can detect stent strut coverage in vivo on a micron-scale level. We therefore used optical coherence tomography to examine strut coverage in patients with STEMI treated with paclitaxel-eluting stents (PES) and bare metal stents (BMS). Methods and Results— In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, patients with STEMI were randomized 3:1 to PES or BMS implantation. In a formal substudy, optical coherence tomography at 13 months was performed in 118 consecutive randomized patients (89 PES, 29 BMS) in whom 188 stents were assessed (146 PES and 42 BMS). A total of 44 139 stent struts were analyzed by an independent core laboratory blinded to stent assignment. The primary prespecified end point, the percentage of uncovered stent struts per lesion at follow-up, was 1.1±2.5% in BMS lesions versus 5.7±7.0% in PES lesions (P<0.0001). Malapposed struts were observed in 0.1±0.2% of BMS lesions versus 0.9±2.1% of PES lesions (P=0.0003). Percentage net volume obstruction was 36.0±15.4% with BMS and 19.2±11.3% with PES (P<0.0001). Conclusions— In patients with STEMI undergoing primary percutaneous coronary intervention, implantation of PES as compared with BMS significantly reduces neointimal hyperplasia but results in higher rates of uncovered and malapposed stent struts as assessed by optical coherence tomography at 13-month follow-up. Further studies are required to determine the clinical significance of these findings. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Incidence, Mechanisms, Predictors, and Clinical Impact of Acute and Late Stent Malapposition After Primary Intervention in Patients With Acute Myocardial Infarction An Intravascular Ultrasound Substudy of the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) Trial

Background— The incidence and mechanisms of acute and late stent malapposition after primary stent implantation in ST-segment elevation myocardial infarction remain unclear. Methods and Results— The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial was a dual-arm, factorial, randomized trial comparing paclitaxel-eluting stents (PES) and otherwise equivalent bare metal stents (BMS) in ST-segment elevation myocardial infarction patients. The intravascular ultrasound substudy enrolled 241 patients with 263 native coronary lesions (201 PES, 62 BMS) with baseline and 13-month follow-up imaging. Postintervention acute stent malapposition (ASM) occurred in 34.3% PES- and 40.3% BMS-treated lesions. Of these, 39.1% PES- and 40.0% BMS-treated lesions resolved at follow-up, especially within the stent body (66.7%); complete resolution was accompanied by a reduction in external elastic membrane area. An ASM area >1.2 mm2 best separated persistent from resolved ASM. At follow-up, a higher frequency of late stent malapposition was detected in PES-treated lesions (46.8%) mainly because of more late acquired stent malapposition (30.8%) compared with BMS-treated lesions. Late acquired stent malapposition area correlated to the decrease of peri-stent plaque in the subset of lesions without positive remodeling and only to change in external elastic membrane in the group with positive remodeling. Independent predictors of late acquired stent malapposition were plaque/thrombus protrusion (odds ratio, 5.60; 95% confidence interval [CI], 2.32 to 13.54) and PES use (odds ratio, 6.32; 95% CI, 2.15 to 18.62). Conclusions— The incidence of ASM was similar in PES- and BMS-treated lesions, but late acquired stent malapposition was more common in PES-treated lesions. The reason for resolved ASM was negative remodeling, with larger ASM areas separating persistent from resolved ASM. Late acquired stent malapposition was due mainly to positive remodeling and plaque/thrombus resolution. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Prospective, Randomized, Multicenter Evaluation of a Polyethylene Terephthalate Micronet Mesh-Covered Stent (MGuard) in ST-Segment Elevation Myocardial Infarction The MASTER Trial

OBJECTIVES This study sought to evaluate the potential utility of a novel polyethylene terephthalate micronet mesh-covered stent (MGuard) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). BACKGROUND Suboptimal myocardial reperfusion after PCI in STEMI is common and results in increased infarct size and mortality. The MGuard is a novel thin-strut metal stent with a polyethylene terephthalate micronet covering designed to trap and exclude thrombus and friable atheromatous debris to prevent distal embolization. METHODS A total of 433 patients with STEMI presenting within 12 h of symptom onset undergoing PCI were randomized at 50 sites in 9 countries to the MGuard (n = 217) or commercially available bare metal or drug-eluting stents (n = 216). The primary endpoint was the rate of complete (≥70%) ST-segment resolution measured 60 to 90 min post-procedure. RESULTS Baseline characteristics were well matched between the groups. The primary endpoint of post-procedure complete ST-segment resolution was significantly improved in patients randomized to the MGuard stent compared with control patients (57.8% vs. 44.7%; difference: 13.2%; 95% confidence interval: 3.1% to 23.3%; p = 0.008). By core laboratory analysis, the MGuard stent compared with control stents also resulted in superior rates of Thrombolysis In Myocardial Infarction 3 flow (91.7% vs. 82.9%, p = 0.006) with comparable rates of myocardial blush grade 2 or 3 (83.9% vs. 84.7%, p = 0.81). Mortality (0% vs. 1.9%, p = 0.06) and major adverse cardiac events (1.8% vs. 2.3%, p = 0.75) at 30 days were not significantly different between patients randomized to the MGuard stent and control stent, respectively. CONCLUSIONS Among patients with acute STEMI undergoing emergent PCI, the MGuard micronet mesh-covered stent compared with conventional metal stents resulted in superior rates of epicardial coronary flow and complete ST-segment resolution. A larger randomized trial is warranted to determine whether these benefits result in reduced infarct size and/or improved clinical outcomes. (Safety and Efficacy Study of MGuard Stent After a Heart Attack [MASTER]; NCT01368471).

Intravascular Ultrasound Findings of Early Stent Thrombosis After Primary Percutaneous Intervention in Acute Myocardial Infarction A Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) Substudy

Background— Small stent area and residual inflow/outflow disease have been reported as the strongest intravascular ultrasound (IVUS) predictors of early stent thrombosis (ST) in patients with stable angina. IVUS predictors of early ST in patients with acute myocardial infarction have not been studied. Methods and Results— In the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) study, a formal substudy included poststent and 13-month follow-up IVUS at 36 centers. Twelve patients with baseline IVUS who had definite/probable early ST ≤30 days after enrollment were compared with 389 patients without early ST. Significant residual stenosis was a lumen area <4.0 mm2 with ≥70% plaque burden ≤10 mm from each stent edge. Significant edge dissection was more than medial dissection with lumen area <4 mm2 or dissection angle ≥60°. Randomization to bivalirudin ( P =0.29) or paclitaxel-eluting stent ( P =0.74) was not related to early ST. Minimum lumen area was smaller in patients with versus without early ST (4.4 mm2 [3.6, 6.9] versus 6.7 mm2 [5.3, 8.0], respectively, P =0.014). Minimum lumen area <5 mm2, significant residual stenosis, significant stent edge dissection, and significant tissue (plaque/thrombus) protrusion (more than the median that narrowed the lumen to <4 mm2) were more prevalent in patients with early ST, but significant acute malapposition (more than the median) was not. Overall, 100% of patients with early ST had at least 1 of these significant features: minimum lumen area <5 mm2, edge dissection, residual stenosis, or tissue protrusion versus 23% in patients without early ST ( P <0.01). Conclusions— Smaller final lumen area and inflow/outflow disease (residual stenosis or dissection) but not acute malapposition were related to early ST after acute myocardial infarction intervention. Clinical Trial Registration— URL: . Unique identifier: [NCT00433966][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00433966&atom=%2Fcirccvint%2F4%2F3%2F239.atomBackground— Small stent area and residual inflow/outflow disease have been reported as the strongest intravascular ultrasound (IVUS) predictors of early stent thrombosis (ST) in patients with stable angina. IVUS predictors of early ST in patients with acute myocardial infarction have not been studied. Methods and Results— In the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) study, a formal substudy included poststent and 13-month follow-up IVUS at 36 centers. Twelve patients with baseline IVUS who had definite/probable early ST ⩽30 days after enrollment were compared with 389 patients without early ST. Significant residual stenosis was a lumen area <4.0 mm2 with ≥70% plaque burden ⩽10 mm from each stent edge. Significant edge dissection was more than medial dissection with lumen area <4 mm2 or dissection angle ≥60°. Randomization to bivalirudin (P=0.29) or paclitaxel-eluting stent (P=0.74) was not related to early ST. Minimum lumen area was smaller in patients with versus without early ST (4.4 mm2 [3.6, 6.9] versus 6.7 mm2 [5.3, 8.0], respectively, P=0.014). Minimum lumen area <5 mm2, significant residual stenosis, significant stent edge dissection, and significant tissue (plaque/thrombus) protrusion (more than the median that narrowed the lumen to <4 mm2) were more prevalent in patients with early ST, but significant acute malapposition (more than the median) was not. Overall, 100% of patients with early ST had at least 1 of these significant features: minimum lumen area <5 mm2, edge dissection, residual stenosis, or tissue protrusion versus 23% in patients without early ST (P<0.01). Conclusions— Smaller final lumen area and inflow/outflow disease (residual stenosis or dissection) but not acute malapposition were related to early ST after acute myocardial infarction intervention. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

SYNTAX Score Reproducibility and Variability Between Interventional Cardiologists, Core Laboratory Technicians, and Quantitative Coronary Measurements

Background— In the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial, the SYNTAX score was useful in risk stratifying patients with complex coronary artery disease. The reproducibility of this score may affect its clinical utility. We therefore assessed SYNTAX score interobserver and intraobserver variability among a group of interventional cardiologists (ICs) and an experienced group of angiographic core laboratory (ACL) technicians. Methods and Results— After basic training from the SYNTAX score website, 3 ICs and 4 ACL technicians, each working independently, assessed the SYNTAX score of 30 multivessel disease angiograms. The ICs then underwent an intensive training session with ACL technicians, after which the SYNTAX score from 50 additional angiograms were assessed independently by both groups. Interobserver Fleiss &kgr; statistic values were determined. A third assessment was performed using quantitative coronary angiography (QCA). The ACL technician interobserver strength of agreement from both periods was substantial or greater (k=0.82; 95% CI [0.72, 1.00] and 0.84 [0.76, 1.00]) and not different than QCA. The IC interobserver agreement was initially estimated to be at least slight (k=0.33 [0.18, 0.44]), improving to substantial or greater after advanced training (k=0.76 [0.64, 1.00]). Despite advanced training, ICs underscored the number of lesions, bifurcations, and small-vessel disease (P<0.001), resulting in a lower score than ACL technicians (mean difference=7.5, P<0.001). Conclusions— Highly reproducible SYNTAX score measurements were quickly achieved by experienced ACL technicians. In contrast, agreement among ICs after the basic tutorial was initially poor but improved considerably after further training with the ACL, although differences still remained in interpretation of several lesion types. These findings have important implications for adoption of SYNTAX score methodology in routine practice and future clinical trials.

Intravascular Ultrasound Findings of Early Stent Thrombosis After Primary Percutaneous Intervention in Acute Myocardial Infarction

Background— Small stent area and residual inflow/outflow disease have been reported as the strongest intravascular ultrasound (IVUS) predictors of early stent thrombosis (ST) in patients with stable angina. IVUS predictors of early ST in patients with acute myocardial infarction have not been studied. Methods and Results— In the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) study, a formal substudy included poststent and 13-month follow-up IVUS at 36 centers. Twelve patients with baseline IVUS who had definite/probable early ST ≤30 days after enrollment were compared with 389 patients without early ST. Significant residual stenosis was a lumen area <4.0 mm2 with ≥70% plaque burden ≤10 mm from each stent edge. Significant edge dissection was more than medial dissection with lumen area <4 mm2 or dissection angle ≥60°. Randomization to bivalirudin ( P =0.29) or paclitaxel-eluting stent ( P =0.74) was not related to early ST. Minimum lumen area was smaller in patients with versus without early ST (4.4 mm2 [3.6, 6.9] versus 6.7 mm2 [5.3, 8.0], respectively, P =0.014). Minimum lumen area <5 mm2, significant residual stenosis, significant stent edge dissection, and significant tissue (plaque/thrombus) protrusion (more than the median that narrowed the lumen to <4 mm2) were more prevalent in patients with early ST, but significant acute malapposition (more than the median) was not. Overall, 100% of patients with early ST had at least 1 of these significant features: minimum lumen area <5 mm2, edge dissection, residual stenosis, or tissue protrusion versus 23% in patients without early ST ( P <0.01). Conclusions— Smaller final lumen area and inflow/outflow disease (residual stenosis or dissection) but not acute malapposition were related to early ST after acute myocardial infarction intervention. Clinical Trial Registration— URL: . Unique identifier: [NCT00433966][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00433966&atom=%2Fcirccvint%2F4%2F3%2F239.atomBackground— Small stent area and residual inflow/outflow disease have been reported as the strongest intravascular ultrasound (IVUS) predictors of early stent thrombosis (ST) in patients with stable angina. IVUS predictors of early ST in patients with acute myocardial infarction have not been studied. Methods and Results— In the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) study, a formal substudy included poststent and 13-month follow-up IVUS at 36 centers. Twelve patients with baseline IVUS who had definite/probable early ST ⩽30 days after enrollment were compared with 389 patients without early ST. Significant residual stenosis was a lumen area <4.0 mm2 with ≥70% plaque burden ⩽10 mm from each stent edge. Significant edge dissection was more than medial dissection with lumen area <4 mm2 or dissection angle ≥60°. Randomization to bivalirudin (P=0.29) or paclitaxel-eluting stent (P=0.74) was not related to early ST. Minimum lumen area was smaller in patients with versus without early ST (4.4 mm2 [3.6, 6.9] versus 6.7 mm2 [5.3, 8.0], respectively, P=0.014). Minimum lumen area <5 mm2, significant residual stenosis, significant stent edge dissection, and significant tissue (plaque/thrombus) protrusion (more than the median that narrowed the lumen to <4 mm2) were more prevalent in patients with early ST, but significant acute malapposition (more than the median) was not. Overall, 100% of patients with early ST had at least 1 of these significant features: minimum lumen area <5 mm2, edge dissection, residual stenosis, or tissue protrusion versus 23% in patients without early ST (P<0.01). Conclusions— Smaller final lumen area and inflow/outflow disease (residual stenosis or dissection) but not acute malapposition were related to early ST after acute myocardial infarction intervention. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

The Relationship Between Attenuated Plaque Identified by Intravascular Ultrasound and No-Reflow After Stenting in Acute Myocardial Infarction The HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) Trial

OBJECTIVES The aim of this study was to understand the impact of attenuated plaque on distal embolization during stent implantation in patients with acute myocardial infarction (AMI). BACKGROUND Attenuated plaques identified by grayscale intravascular ultrasound (IVUS) might predict transient deterioration in coronary flow and/or no-reflow during percutaneous coronary intervention (PCI). METHODS We analyzed clinical, angiographic, and IVUS data from 364 patients (n = 364 infarct-related arteries) enrolled in the randomized HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial. No-reflow was final Thrombolysis In Myocardial Infarction (TIMI) flow grade ≤2 in the absence of mechanical obstruction. Attenuated plaque was hypoechoic or mixed atheroma with ultrasound attenuation without calcification. A mean attenuation score was created by measuring the angle of attenuation each 1 mm, scoring the angle as 1 to 4 (corresponding to <90°, 90° to 180°, 180° to 270°, or 270° to 360°, respectively), summing the scores, and normalizing for analysis length. RESULTS Overall, 284 (78.0%) patients had attenuated plaques; no-reflow occurred in 37 (10.2%). Patients with no-reflow had a higher mean attenuation score (median [interquartile range] 2.2 [0.0 to 2.8] vs. 1.3 [0.7 to 1.8], p < 0.001), lower baseline left ventricular ejection fraction (52.8% [43.2% to 61.5%] vs. 61.4% [52.2% to 68.1%], p = 0.002), and more baseline angiographic thrombus (89.2% vs. 74.1%, p = 0.043) with no differences in post-PCI stent expansion versus patients without no-reflow. Multivariate analysis indicated that mean attenuation score was the strongest predictor of no-reflow. The mean attenuation score that best predicted no-reflow was ≥2 points (90° to 180°, sensitivity of 81.5%, and specificity of 80.5%). CONCLUSIONS Attenuated plaque was present in three-quarters of patients with AMI. The amount of attenuated plaque strongly correlated with no-reflow; the larger the attenuated plaque, the greater the likelihood of no-reflow. (Dual Arm Factorial Randomized Trial in Patients w/ST Segment Elevation AMI to Compare the Results of Using Anticoagulation With Either Unfractionated Heparin + Routine GP IIb/IIIa Inhibition or Bivalirudin + Bail-out GP IIb/IIIa Inhibition; and Primary Angioplasty with stent implantation with Either a Slow Rate-release Paclitaxel-eluting Stent [TAXUS™] or Uncoated Bare Metal Stent [EXPRESS2™]; NCT00433966).

Definitions and Methodology for the Grayscale and Radiofrequency Intravascular Ultrasound and Coronary Angiographic Analyses

OBJECTIVES In a prospective study of the natural history of coronary atherosclerosis using angiography and grayscale and radiofrequency intravascular ultrasound (IVUS)-virtual histology (VH), larger plaque burden, smaller luminal area, and plaque composition thin-cap fibroatheroma emerged as independent predictors of future adverse cardiovascular events. BACKGROUND The methodology for IVUS-VH classification for an in vivo natural history study and the prospective image mapping by angiography and grayscale and IVUS-VH have not been established. METHODS All culprit and nonculprit lesions (defined as ≥ 30% angiographic visual diameter stenoses) were analyzed. Three epicardial vessels as well as all ≥ 1.5-mm-diameter side branches were divided into 29 CASS (Coronary Artery Surgery Study) segments. Each CASS segment was then subdivided into 1.5-mm-long subsegments, and dimensions were analyzed. All grayscale and IVUS-VH slices from the proximal 6 to 8 cm of the 3 coronary arteries were analyzed, with lesions defined as having more than 3 consecutive slices with ≥ 40% plaque burden categorized as: 1) VH thin-cap fibroatheroma; 2) thick-cap fibroatheroma; 3) pathological intimal thickening; 4) fibrotic plaque; or 5) fibrocalcific plaque. The locations of angiographic and grayscale and IVUS-VH lesions were recorded in relation to the corresponding coronary artery ostium and nearby side branches. RESULTS The 3-year cumulative rate of major adverse cardiovascular events was 20.4%. Events were adjudicated to culprit lesions in 12.9% of patients and to nonculprit lesions in 11.6%. On multivariate analysis, nonculprit lesions associated with recurrent events were characterized by a plaque burden ≥ 70% (hazard ratio: 5.03; 95% confidence interval: 2.51 to 10.11; p < 0.0001), a minimal luminal area ≤ 4.0 mm(2) (hazard ratio: 3.21; 95% confidence interval: 1.61 to 6.42; p = 0.001), and IVUS-VH phenotype of a thin-cap fibroatheroma (hazard ratio: 3.35; 95% confidence interval: 1.77 to 6.36; p < 0.001). CONCLUSIONS Three-vessel multimodality coronary artery imaging was feasible and allowed the identification of lesion-level predictors for future events in this natural history study.

Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI): a multicentre, randomised, double-blind, placebo-controlled trial

BACKGROUND Incomplete revascularisation is common after percutaneous coronary intervention and is associated with increased mortality and adverse cardiovascular events. We aimed to assess whether adjunctive anti-ischaemic pharmacotherapy with ranolazine would improve the prognosis of patients with incomplete revascularisation after percutaneous coronary intervention. METHODS We performed this multicentre, randomised, parallel-group, double-blind, placebo-controlled, event-driven trial at 245 centres in 15 countries in Europe, Israel, Russia, and the USA. Patients (aged ≥18 years) with a history of chronic angina with incomplete revascularisation after percutaneous coronary intervention (defined as one or more lesions with ≥50% diameter stenosis in a coronary artery ≥2 mm diameter) were randomly assigned (1:1), via an interactive web-based block randomisation system (block sizes of ten), to receive either twice-daily oral ranolazine 1000 mg or matching placebo. Randomisation was stratified by diabetes history (presence vs absence) and acute coronary syndrome presentation (acute coronary syndrome vs non-acute coronary syndrome). Study investigators, including all research teams, and patients were masked to treatment allocation. The primary endpoint was time to first occurrence of ischaemia-driven revascularisation or ischaemia-driven hospitalisation without revascularisation. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT01442038. FINDINGS Between Nov 3, 2011, and May 27, 2013, we randomly assigned 2651 patients to receive ranolazine (n=1332) or placebo (n=1319); 2604 (98%) patients comprised the full analysis set. After a median follow-up of 643 days (IQR 575-758), the composite primary endpoint occurred in 345 (26%) patients assigned to ranolazine and 364 (28%) patients assigned to placebo (hazard ratio 0·95, 95% CI 0·82-1·10; p=0·48). Incidence of ischaemia-driven revascularisation and ischaemia-driven hospitalisation did not differ significantly between groups. 189 (14%) patients in the ranolazine group and 137 (11%) patients in the placebo group discontinued study drug because of an adverse event (p=0·04). INTERPRETATION Ranolazine did not reduce the composite rate of ischaemia-driven revascularisation or hospitalisation without revascularisation in patients with a history of chronic angina who had incomplete revascularisation after percutaneous coronary intervention. Further studies are warranted to establish whether other treatment could be effective in improving the prognosis of high-risk patients in this population. FUNDING Gilead Sciences, Menarini.