Constantly Bombarded with New Drugs: What's a Cardiologist to Do?

Every physician encounters a barrage of direct-to-consumer and direct-to-physician advertising and is faced with the daunting task of deciding which drugs to add to their clinical armamentarium and how and when to add them. The purpose of this Points to Remember is to present a commonsense approach to incorporating newer drugs, or perhaps new indications for older drugs, into our clinical practice. To illustrate these points, this article focuses on a single drug, empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor that has been highly marketed in lay and medical media and hence has been incorporated into professional society treatment guidelines.

Coenzyme Q10 for Patients With Cardiovascular Disease: JACC Focus Seminar.

Coenzyme Q10 (CoQ10) is a naturally occurring compound that is found in animals and all humans. It has a fundamental role in cellular energy production. Although it is produced in the body, tissue deficiency can occur due to medications such as statins, which inhibit the mevalonate pathway. The clinical syndromes of statin-associated muscle symptoms (SAMS) and some of the features observed in patients with heart failure (HF) may be related to blood and tissue deficiency of CoQ10. Numerous clinical trials of CoQ10 in SAMS have yielded conflicting results. Yet, the weight of evidence as reflected in meta-analyses supports the use of exogenous CoQ10 in SAMS. In patients with HF, large-scale randomized clinical trials are lacking, although one relatively contemporary trial, Q-SYMBIO, suggests an adjunctive role for CoQ10. The possibility that statin-related CoQ10 deficiency may play a role in patients with diastolic HF is an intriguing hypothesis that warrants further exploration.

Coenzyme Q10.

Coenzyme Q10 (CoQ10) is among the most widely used dietary and nutritional supplements on the market. CoQ10 has several fundamental properties that may be beneficial in several clinical situations. This article reviews the pertinent chemical, metabolic, and physiologic properties of CoQ10 and the scientific data and clinical trials that address its use in two common clinical settings: statin-associated myopathy syndrome (SAMS) and congestive heart failure (CHF). Although clinical trials of CoQ10 in SAMS have conflicting conclusions, the weight of the evidence, as seen in meta-analyses, supports the use of CoQ10 in SAMS overall. In CHF, there is a lack of large-scale randomized clinical trial data regarding the use of statins in patients receiving contemporary treatment. However, one relatively recent randomized clinical trial, Q-SYMBIO, suggests an adjunctive role for CoQ10 in CHF. Recommendations regarding the use of CoQ10 in these clinical situations are presented.

Low-dose sirolimus-eluting hydroxyapatite coating on stents does not increase platelet activation and adhesion ex vivo.

We previously found paclitaxel-eluting polymer-coated stents causing more human platelet-monocyte complex formation than bare metal stents in vitro. Presently, we examined patterns of platelet activation and adhesion after exposure to 6 nanofilm HAp-coated (HAp-nano) stents, 6 HAp-microporous-coated (HAp-micro) stents, 5 HAp sirolimus-eluting microporous-coated (HAp-SES) stents and 5 cobalt-chromium stents (BMS) deployed in an in vitro flow system. Blood obtained from healthy volunteers was circulated and sampled at 0, 10, 30 and 60 min. By flow cytometry, there were no significant differences in P-Selectin expression between the 4 stent types (HAp-nano = 32.5%; HAp-micro = 42.5%, HAp-SES = 10.23%, BMS = 7% change from baseline at 60 min, p = NS); PAC-1 antibody binding (HAp-nano = 11.8%; HAp-micro = 2.9%, HAp-SES = 18%, BMS = 6.4% change from baseline at 60 min, p = NS) or PMC formation (HAp-nano = 21.6%; HAp-micro = 4%, HAp-SES = 6.6%, BMS = 17.4% change from baseline at 60 min, p = NS). The 4 stent types did not differ in the average number of platelet clusters >10 µm in diameter by SEM (HAp-nano = 2.39 ± 5.75; HAp-micro = 2.26 ± 3.43; HAp-SES = 1.93 ± 3.24; BMS = 1.94 ± 2.41, p = NS). The majority of the struts in each stent group were only mildly covered by platelets, (HAp-nano = 80%, HAp-micro = 61%, HAp-SES = 78% and BMS = 52.1%, p = NS). The HAp-microporous-coated stents (ECD) attracted slightly more proteinaceous material than bare metal stents (HAp-micro = 35% struts with complete protein coverage, P < 0.0001 vs. other 3 stent types). In conclusion, biomimetic stent coating with nanofilm or microporous hydroxyapatite, even when eluting low-dose sirolimus, does not increase the platelet activation in circulating human blood, or platelet adhesion to stent surface when compared to bare metal stents in vitro.

In-hospital and 1-year outcomes among unselected percutaneous coronary intervention patients treated with either sirolimus- or paclitaxel-eluting stents: results from the EVENT (Evaluation of Drug Eluting Stents and Ischemic Events) registry.

OBJECTIVES: The aim of this study was to compare outcomes among unselected patients undergoing percutaneous coronary intervention (PCI) with either sirolimus-eluting (SES) or paclitaxel-eluting stents (PES). BACKGROUND: Although the benefits of both SES and PES are well-established, studies comparing these stents directly have yielded conflicting results. METHODS: We used data from the EVENT (Evaluation of Drug Eluting Stents and Ischemic Events) registry to compare in-hospital and 1-year outcomes among unselected patients undergoing nonemergent PCI with either SES or PES implantation. RESULTS: Between July 2004 and June 2006, 6,035 patients underwent PCI with either SES (n = 3,443) or PES (n = 2,592) at 47 U.S. centers. Baseline clinical and angiographic characteristics were generally similar for the 2 stent types. At 1-year, there were no differences in the primary end point of cardiac death or myocardial infarction (MI) between the SES and PES groups (9.1% vs. 10.0%, p = 0.11) or in any individual end points including cardiac death, nonfatal MI, or stent thrombosis. In unadjusted analyses, target lesion revascularization (TLR) was slightly more common with SES than with PES (4.4% vs. 3.3%, p = 0.048), but this difference was no longer apparent after adjusting for baseline characteristics as well as site-related factors (adjusted hazard ratio: 1.09, 95% confidence interval: 0.78 to 1.50). CONCLUSIONS: Among unselected patients undergoing PCI, adjusted rates of both ischemic complications as well as clinically important restenosis were similar for SES and PES. The unexpected finding that TLR was influenced by site characteristics suggests that the correlation between TLR and angiographic restenosis might be weaker than previously described and warrants further study.

Safety of sirolimus-eluting stenting and its effect on restenosis in patients with unstable angina pectoris (a SIRIUS substudy).

The SIRIUS study was a double-blinded, randomized trial of the sirolimus-eluting stent (SES) to evaluate its effect on the rate of restenosis. The present report is a retrospective analysis of short- and long-term outcomes of SESs compared with bare metal stents (BMSs) in a subgroup of patients with unstable angina enrolled in the trial. Of 1,058 patients randomized in SIRIUS, 533 (50.4%) had unstable angina pectoris and 490 had stable angina. In the unstable angina group, patients treated with SESs and BMSs had similar clinical and angiographic characteristics. The stenting procedure was highly successful in the 2 groups (95.9% and 97.4%, respectively) with similar immediate angiographic results and short-term (in-hospital) clinical event rates. At 1-year follow-up, compared with BMSs, patients with unstable angina treated with SESs had significantly lower rates of target lesion revascularization (5.5% vs 22.3%, p <0.0001), target vessel failure (10.9% vs 26.3%, p <0.0001), and major adverse cardiac events (8.4% vs 24.8%, p <0.0001). Stent thrombosis was a rare event, with only 1 patient (0.4%) in each group during the first 30 days. Late thrombosis occurred in 2 patients (0.7%) in the BMS group but in none of the SES group. In conclusion, in the higher risk subgroup of patients with unstable angina, SESs are as safe as BMSs in decreasing restenosis and the need for repeat revascularization. This is reflected by a significant decrease in major adverse cardiac events and target vessel failure. Patients with unstable angina undergoing percutaneous coronary intervention who meet the entry criteria of the SIRIUS study should be preferentially treated with SESs.

In vivo plaque characterization using intravascular ultrasound-virtual histology in a porcine model of complex coronary lesions.

OBJECTIVE: To determine the accuracy of detection of different tissue types of intravascular ultrasound-virtual histology (IVUS-VH) in a porcine model of complex coronary lesions. METHODS AND RESULTS: Coronary lesions were induced by injecting liposomes containing human oxidized low-density lipoprotein into the adventitia of the arteries. IVUS-VH imaging was performed in vivo at 8.2+/-1.6 weeks after injection. A total of 60 vascular lesions were analyzed and compared with their correspondent IVUS-VH images. Correlation analysis was performed using linear regression models. Compared with histology, IVUS-VH correctly identified the presence of fibrous, fibro-fatty, and necrotic tissue in 58.33%, 38.33%, and 38.33% of lesions, respectively. The sensitivity of IVUS-VH for the detection of fibrous, fibro-fatty, and necrotic core tissue was 76.1%, 46%, and 41.1% respectively. A linear regression analysis performed for each individual plaque component did not show strong correlation that would allow significant prediction of individual values. CONCLUSIONS: In a porcine model of complex coronary lesions, IVUS-VH was not accurate in detecting the relative amount of specific plaque components within each individual corresponding histological specimen.

Comparison of the efficacy of direct coronary stenting with sirolimus-eluting stents versus stenting with predilation by intravascular ultrasound imaging (from the DIRECT trial).

A direct coronary stenting technique using drug-eluting stents may decrease drug-eluting stent efficacy due to possible damage to the surface coating of the stent. The DIRECT is a multicenter, prospective, nonrandomized trial designed to evaluate the direct stenting strategy for the sirolimus-eluting Bx-Velocity stent compared with the historical control (SIRIUS trial, stenting with predilation). Volumetric and cross-sectional intravascular ultrasound analyses at 8-month follow-up were performed in 115 patients (DIRECT n= 64, control n = 51). Patient and lesion characteristics were comparable between groups. The DIRECT group achieved an equivalent uniform expansion index, defined as minimum stent area/maximum stent area x 100, compared with the control group (65.9 +/- 11.7 vs 63.1 +/- 12.7, p = NS). At 8-month follow-up, vessel, stent, lumen, and neointimal volume index (volume in cubic millimeters/length in millimeters) and percent neointimal volume were similar between the DIRECT and control groups (vessel volume index 13.9 +/- 4.40 vs 15.0 +/- 3.83; stent volume index 6.83 +/- 2.02 vs 6.94 +/- 2.04; lumen volume index 6.71 +/- 2.04 vs 6.81 +/- 2.07; neointimal volume index 0.14 +/- 0.24 vs 0.16 +/- 0.23; percent neointimal volume 3.73 +/- 6.97 vs 3.14 +/- 5.32, p = NS for all). In addition, in-stent neointimal hyperplasia distribution was significantly smaller near the distal stent edge (0.22 vs 0.098 mm(3)/mm, p = 0.01 for an average neointimal volume index within 3 mm from the distal stent edge). In conclusion, direct coronary stenting with the sirolimus-eluting Bx-Velocity stent is equally effective in terms of uniform stent expansion and long-term quantitative intravascular ultrasound results compared with conventional stenting using predilation. This strategy appears to be associated with less neointimal hyperplasia near the distal stent edge.

Initial impact of drug-eluting stent use on the spectrum of patients undergoing percutaneous coronary intervention.

BACKGROUND: The availability of drug-eluting stents was expected to expand the application of percutaneous coronary intervention to a wider group of patients and lesion types. We sought to determine whether drug-eluting stents' availability has changed the practices of operators performing percutaneous coronary intervention with regard to patient selection and procedural factors. METHODS: We compared the clinical and angiographic characteristics of patients who underwent percutaneous coronary intervention at the Methodist Hospital, Houston, Texas, during three periods: June 2002-March 2003, June 2003-March 2004 and June 2004-March 2005. Sirolimus-eluting stents were available during the latter two periods. Paclitaxel eluting stents became available during the third period. RESULTS: A greater proportion of patients undergoing diagnostic catheterization were referred for percutaneous coronary intervention during the latter two periods (26.8%, 30.4%, 30.4%, respectively, P<0.0001). Patients undergoing stent placement during the latter two periods were more likely to have hypertension, hyperlipidemia or to have undergone previous percutaneous coronary intervention. The average implanted stent length was greater during the latter periods (14.5+/-4.6, 16.4+/-5.2, 16.8+/-5.5 mm, respectively, P<0.0001) and the average stent diameter was smaller (3.23+/-1.22, 3.13+/-1.16, 3.02+/-0.6 mm, respectively, P<0.0001). The frequency of percutaneous coronary intervention involving long lesions (>20 mm) and Left Anterior Descending (LAD) lesions was higher in the latter two periods and the frequency of multivessel stenting was higher in the last period. CONCLUSIONS: The spectrum of patients and coronary lesions that have undergone stenting has changed, particularly in the third period when both drug-eluting stent types were available. We observed a gradual shift toward higher-risk clinical and lesion characteristics following the introduction of drug-eluting stents.

Oral rapamycin after coronary bare-metal stent implantation to prevent restenosis: the Prospective, Randomized Oral Rapamycin in Argentina (ORAR II) Study.

OBJECTIVES: The purpose of this study was to assess the role of oral rapamycin in decreased restenosis after bare metal stent implantation. BACKGROUND: Small observational studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation. METHODS: Between September 2003 and September 2004, 100 patients were randomized to either oral rapamycin (6-mg loading dose given 2.7 h before intervention followed by 3 mg/day for 14 days) plus diltiazem 180 mg/day or no therapy after the implantation of a coronary bare metal stent design. The primary study end point was incidence of angiographic binary restenosis and late loss at nine months. The secondary end points were target lesion revascularization, target vessel revascularization, and incidence of major adverse cardiovascular events at 1 year. RESULTS: Angiographic follow-up was completed in 87% of patients. In the rapamycin group, the drug was well tolerated (26% minor side effects) and was maintained in 96% of patients. At 9 months, the in-segment binary restenosis was reduced by 72% (11.6% rapamycin vs. 42.8% no-therapy group, p = 0.001) and the in-stent binary restenosis was reduced by 65% (12% rapamycin vs. 34.6% no-therapy group, p = 0.009). The in-segment late loss was also significantly reduced with oral therapy (0.66 vs. 1.13 mm, respectively; 43% reduction, p < 0.001). At 1 year, patients in the oral rapamycin group also showed a significantly lower incidence of target vessel revascularization (8.3% vs. 38%, respectively, p < 0.001), target lesion revascularization (7.6% vs. 37.2%, respectively, p < 0.001), and major adverse cardiovascular events (20% vs. 44%, respectively, p = 0.018). CONCLUSIONS: This randomized, controlled, and unblinded study showed that the administration of oral rapamycin during 14 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis.

Initial experience with a magnetic navigation system for percutaneous coronary intervention in complex coronary artery lesions.

OBJECTIVES: The aim of this study was to evaluate the feasibility of a magnetic-assisted navigation system during percutaneous coronary intervention (PCI) of tortuous and severely angulated coronary arteries. BACKGROUND: The magnetic navigation system consists of two 0.8-T permanent magnets which generate a magnetic field over the heart. Altering the magnetic vector deflects a coronary guidewire with a magnetic tip. METHODS: Patients were selected for magnetic-assisted intervention (MAI) for potentially difficult to cross lesions. The time required for placement of the guidewire, total procedure time, fluoroscopy time, and amount of contrast for the procedure were recorded. There were a total of 59 patients undergoing PCI of 68 lesions. RESULTS: Patients were grouped based on whether MAI was attempted as a first option ("primary attempt"; n = 46) or following failure to pass a conventional guidewire ("secondary attempt"; n = 13). The target lesion was successfully crossed in 49 of 55 lesions (89%) and 9 of 13 lesions (69%) in patients undergoing primary and secondary attempts, respectively. The procedural success rates were 84% and 62%, respectively. Most lesions were located in the circumflex artery territory (39% and 62% of lesions, respectively). The median (25th and 75th percentiles) time for crossing the lesion was longer in the secondary attempt group (14.8 [5, 15.5] vs. 28.9 [8, 38] min). Median fluoroscopy time and median contrast used were also higher among the secondary attempt group. CONCLUSIONS: This first report of MAI suggests that it may become a useful adjunct for wire placement in difficult coronary interventions.

Single perivascular delivery of mitomycin C stimulates p21 expression and inhibits neointima formation in rat arteries.

OBJECTIVE: Mitomycin C (MMc) is an antibiotic that exerts a potent antiproliferative effect in tumor cells. Because the proliferation of vascular smooth muscle cells (VSMCs) plays a prominent role in the development of restenosis after percutaneous coronary interventions, the present study examined the effect of MMc on VSMC proliferation and on neointima formation after arterial balloon injury. METHODS AND RESULTS: Treatment of cultured rat aortic VSMCs with MMc (1 nmol to 30 micromol/L) inhibited VSMC proliferation in a concentration-dependent manner. Whereas high concentrations of MMc (1 to 30 micromol/L) induced VSMC apoptosis, as reflected by DNA laddering and caspase-3 activation, lower concentrations of MMc (1 to 300 nmol/L) directly inhibited VSMC growth by arresting cells in the G2/M phase of the cell cycle. The antiproliferative action of MMc was associated with a selective increase in the expression of the cyclin-dependent kinase inhibitor p21, and with a decrease in cyclin B1-cyclin-dependent kinase-1 complex activity. Finally, the local perivascular delivery of MMc immediately after balloon injury of rat carotid arteries induced p21 expression and markedly attenuated neointima formation. CONCLUSIONS: These studies demonstrate that MMc exerts a potent inhibitory effect on VSMC proliferation and neointima formation after arterial injury. MMc represents a potentially new therapeutic agent in treating and preventing vasculoproliferative disease.

Effects of SolCD39, a novel inhibitor of Platelet Aggregation, on Platelet Deposition and Aggregation after PTCA in a Porcine Model.

INTRODUCTION: This study evaluated CD39 in a porcine model of balloon angioplasty and in plasma of patients undergoing percutaneous intervention. CD39 (E-NTPDase1), is the endothelial ecto-ADPase inhibiting platelet function via hydrolysis of released platelet ADP. METHODS AND RESULTS: A recombinant soluble form of CD39 (solCD39) given intravenously to pigs had an elimination half life of 5--7 days, increased the bleeding time to an extent similar to aspirin, and inhibits platelet aggregation by>90%. Platelet counts and clot retraction remained normal following solCD39 administration. In a pig model of acute coronary balloon injury, solCD39 resulted in non-statistically significant decreases in platelet (7.7+/-1.4 versus 11.7+/- 3.4) and fibrin (3.5+/- 0.4 versus 4.2+/- 0.7) deposition ratios. Adding ex vivo to human platelet rich plasma (PRP) solCD39 produced nearly 100% inhibition of ADP-induced platelet aggregation. A dose-response effect of solCD39 on platelet aggregation induced by collagen or a thrombin receptor activating peptide (TRAP(SFLLRN)) was noted in PRP obtained from volunteers and patients receiving aspirin, clopidogrel or ticlopidine. SolCD39 also provided additional and complete inhibition of TRAP-induced platelet aggregation in PRP from patients who had received abciximab, aspirin and clopidogrel. CONCLUSIONS: SolCD39, a novel inhibitor of platelet activation and recruitment with a relatively long half-life appears to be well tolerated and is a potent inhibitor of ADP-, collagen-, or TRAP-induced platelet activation. Its potential use in percutaneous coronary intervention requires further study. ABBREVIATED ABSTRACT: E-NTPDase1/CD39 is the endothelial ecto-ADPase responsible for inhibition of platelet function. A recombinant soluble form (solCD39) had an elimination half life of 5-7 days in pigs, elevated bleeding times similar to aspirin, did not affect clot retraction, and inhibited platelet aggregation by > 90%. When combined with standard heparin therapy in a pig model of acute coronary balloon injury, solCD39 resulted in a trend toward a decrease in platelet and fibrin deposition. SolCD39 added ex vivo to human platelet rich plasma yielded nearly 100% inhibition of ADP-induced platelet aggregation and provided further inhibition when combined with standard therapy.

Endovascular needle injection of cholesteryl linoleate into the arterial wall produces complex vascular lesions identifiable by intravascular ultrasound: early development in a porcine model of vulnerable plaque.

BACKGROUND: We attempted to create a pig model of complex arterial lesions through the percutaneous injection of cholesteryl linoleate into the vessel wall. METHODS AND RESULTS: A total of 81 arterial segments (27 arteries) underwent percutaneous intramural injection of cholesteryl linoleate, in eight pigs. Intravascular ultrasound (IVUS) analysis and corresponding histology were obtained for analysis at 2 and 4 weeks after injection. Overall, 18 out of 27 (67%) of the injected arterial segments displayed lesions identifiable by IVUS as an eccentric echolucent zone present within the deeper layer of the lesion. Quantitative IVUS analysis demonstrated that these lesions were non-occlusive (36+/-8% area stenosis), eccentric (eccentricity index, 0.78+/-0.07) and located into positively remodeled vessels (remodeling index, 1.45+/-0.24). By histology, these lesions were eccentric and comprised less than a third of the vessel circumference. Medial thickening and a thickened intima containing lipid droplets and mononuclear cells were consistently found. The presence of lipids or local wall thickening seen by histology colocalized with the presence of echolucent structures seen by IVUS in 65% of the coronary segments and 70% of the iliac segments. CONCLUSIONS: The intramural deposition of cholesteryl linoleate results in the development of complex, lipid-containing inflammatory lesions in less than 4 weeks. These lesions are already identifiable by IVUS at 2 weeks and colocalize with histologic findings. Further development of this model may allow the validation of technologies designed to detect and treat high-risk atherosclerotic lesions.

HIV-based vectors and angiogenesis following rabbit hindlimb ischemia.

BACKGROUND: Numerous medical and surgical options exist for the treatment of vessel ischemia, which some patients fail or cannot tolerate. These investigations were designed to determine the effects of lentiviral-delivered vascular endothelial-derived growth factor (VEGF) and angiopoietin-2 (Ang-2) on collateralization in a rabbit model of hindlimb ischemia. MATERIALS AND METHODS: Self-inactivating human immunodeficiency virus (HIV)-based vectors were constructed encoding VEGF or Ang-2, co-transfected with vesicular stomatitis virus glycoprotein (VSV G) into 293T cells, and vector supernatants (1 x 10(8) IU/ml after concentration) were harvested. New Zealand white rabbits had ligation of either the right or left external iliac artery and excision of the ipsilateral femoral artery. Ten days later, empty, VEGF, or VEGF+Ang-2 vector supernatant was injected intramuscularly (IM) into the ipsilateral thigh. Ankle systolic blood pressure (SBP) ratios were recorded and venous blood samples collected on postoperative days (POD) 10, 25, and 40. On POD 40, run-off angiography was performed to measure vessel collateralization. Capillary density was determined by thin sectioning of muscle. RESULTS: A significant increase was noted in SBP in the VEGF-treated animals over time. Capillary density was not elevated despite significantly increased large vessel collateralization in rabbits receiving VEGF, which was counteracted by Ang-2. Antibodies against vector components were detected in exposed serum. CONCLUSIONS: Arterial collateralization and SBP increased significantly following VEGF vector administration, which was reversed by the Ang-2 vector. Development of antibody against VSV G can limit repeated injections of vector. Future experiments will involve the addition of other pro-angiogenic factors, repeated vector administration, and alternative routes of vector delivery.

Intravascular ultrasound assessment of neointima distribution and the length of stent that was free of intravascular ultrasound-detectable intimal hyperplasia in paclitaxel-eluting stents.

Using data from the ASian Paclitaxel-Eluting Stent Clinical Trial, a 3-center, randomized, placebo-controlled trial of nonpolymeric paclitaxel-coated stents with a single center, 81-patient intravascular ultrasound (IVUS) substudy, the length of a stent that was free of IVUS-detectable intimal hyperplasia measured 3.2 +/- 4.8 mm in placebo stents, 6.1 +/- 5.6 mm in low-dose stents, and 8.7 +/- 6.1 mm in high-dose stents (p = 0.0029). IVUS percent neointima volume obstruction correlated with the length of this IVUS neointima-free segment (r = 0.785, p <0.0001); angiographic late lumen loss and follow-up diameter stenosis also correlated with the IVUS neointima-free length of the stents (r = 0.670, p <0.0001 and r = 0.679, p <0.0001, respectively.

Comparison of quantitative angiographic parameters with the magnitude of neointimal hyperplasia measured by volumetric intravascular ultrasound in patients treated with bare metal and nonpolymeric paclitaxel-coated stents.

We used data from the ASian Paclitaxel-Eluting Stent Clinical Trial (a 3-center, randomized, placebo-controlled trial of nonpolymeric paclitaxel-coated stents with a single-center intravascular ultrasound substudy) to compare angiographic indexes of drug-eluting stent efficacy with the magnitude of intimal hyperplasia (IH) assessed by intravascular ultrasound. Overall, percent IH (IH volume divided by stent volume) was larger in restenotic lesions than in nonrestenotic lesions (46 +/- 19% vs 15 +/- 13%, p <0.0001); angiographic late loss and follow-up diameter stenoses correlated strongly with percent IH.