Conrad Smith

A comparison of bare-metal and drug-eluting stents for off-label indications.

BACKGROUND Recent reports suggest that off-label use of drug-eluting stents is associated with an increased incidence of adverse events. Whether the use of bare-metal stents would yield different results is unknown. METHODS We analyzed data from 6551 patients in the National Heart, Lung, and Blood Institute Dynamic Registry according to whether they were treated with drug-eluting stents or bare-metal stents and whether use was standard or off-label. Patients were followed for 1 year for the occurrence of cardiovascular events and death. Off-label use was defined as use in restenotic lesions, lesions in a bypass graft, left main coronary artery disease, or ostial, bifurcated, or totally occluded lesions, as well as use in patients with a reference-vessel diameter of less than 2.5 mm or greater than 3.75 mm or a lesion length of more than 30 mm. RESULTS Off-label use occurred in 54.7% of all patients with bare-metal stents and 48.7% of patients with drug-eluting stents. As compared with patients with bare-metal stents, patients with drug-eluting stents had a higher prevalence of diabetes, hypertension, renal disease, previous percutaneous coronary intervention and coronary-artery bypass grafting, and multivessel coronary artery disease. One year after intervention, however, there were no significant differences in the adjusted risk of death or myocardial infarction in patients with drug-eluting stents as compared with those with bare-metal stents, whereas the risk of repeat revascularization was significantly lower among patients with drug-eluting stents. CONCLUSIONS Among patients with off-label indications, the use of drug-eluting stents was not associated with an increased risk of death or myocardial infarction but was associated with a lower rate of repeat revascularization at 1 year, as compared with bare-metal stents. These findings support the use of drug-eluting stents for off-label indications.

Impact of drug-eluting stents among insulin-treated diabetic patients: a report from the National Heart, Lung, and Blood Institute Dynamic Registry.

OBJECTIVES This study sought to evaluate the safety and efficacy of drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients with insulin- and noninsulin-treated diabetes. BACKGROUND Diabetes is a powerful predictor of adverse events after percutaneous coronary interventions (PCI), and insulin-treated diabetic patients have worse outcomes. The DES are efficacious among patients with diabetes; however, their safety and efficacy, compared with BMS, among insulin-treated versus noninsulin-treated diabetic patients is not well established. METHODS Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 1-year outcomes of insulin-treated (n = 817) and noninsulin-treated (n = 1,749) patients with diabetes who underwent PCI with DES versus BMS. RESULTS The use of DES, compared with BMS, was associated with a lower risk for repeat revascularization for both noninsulin-treated patients (adjusted hazard ratio [HR] = 0.59, 95% confidence interval [CI] 0.45 to 0.76) and insulin-treated subjects (adjusted HR = 0.63, 95% CI 0.44 to 0.90). With respect to safety in the overall diabetic population, DES use was associated with a reduction of death or myocardial infarction (adjusted HR = 0.75, 95% CI 0.58 to 0.96). However, this benefit was confined to the population of noninsulin-treated patients (adjusted HR = 0.57, 95% CI 0.41 to 0.81). Among insulin-treated patients, there was no difference in death or myocardial infarction risk between DES- and BMS-treated patients (adjusted HR = 0.95, 95% CI 0.65 to 1.39). CONCLUSIONS Drug-eluting stents are associated with lower risk for repeat revascularization compared with BMS in treating coronary artery disease among patients with either insulin- or noninsulin-treated diabetes. In addition, DES use is not associated with any significant increased safety risk compared with BMS. These findings suggest that DES should be the preferred strategy for diabetic patients.

Paclitaxel-Eluting Versus Sirolimus-Eluting Stents in Diabetes MellitusCLINICAL PERSPECTIVE

Background—Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry. Methods and Results—Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES (n=677) and PES (n=328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P=0.20), death and myocardial infarction (14.9% versus 13.6%, P=0.55), repeat revascularization (14.8% versus 17.8%, P=0.36), and stent thrombosis (1.3% versus 1.3%, P=0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed. Conclusions—PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice.Background— Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry. Methods and Results— Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES ( n =677) and PES ( n =328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P =0.20), death and myocardial infarction (14.9% versus 13.6%, P =0.55), repeat revascularization (14.8% versus 17.8%, P =0.36), and stent thrombosis (1.3% versus 1.3%, P =0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed. Conclusions— PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice. Received June 9, 2009; accepted October 22, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Paclitaxel-Eluting Versus Sirolimus-Eluting Stents in Diabetes Mellitus A Report From the National Heart, Lung, and Blood Institute Dynamic Registry

Background—Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry. Methods and Results—Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES (n=677) and PES (n=328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P=0.20), death and myocardial infarction (14.9% versus 13.6%, P=0.55), repeat revascularization (14.8% versus 17.8%, P=0.36), and stent thrombosis (1.3% versus 1.3%, P=0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed. Conclusions—PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice.Background— Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry. Methods and Results— Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES ( n =677) and PES ( n =328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P =0.20), death and myocardial infarction (14.9% versus 13.6%, P =0.55), repeat revascularization (14.8% versus 17.8%, P =0.36), and stent thrombosis (1.3% versus 1.3%, P =0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed. Conclusions— PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice. Received June 9, 2009; accepted October 22, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Strategies for drug-eluting stent treatment of bifurcation coronary artery disease in the United States: Insights from the e-Cypher S.T.L.L.R.Trial†

Objectives: Our goal is to report the first large multicenter data for percutaneous coronary intervention (PCI) of bifurcation disease with drug‐eluting stents (DES) in the United States. Background: Bifurcation PCI remains a challenge to this date. There are limited data on outcomes of patients treated with bifurcation DES implantation, particularly in the United States. Methods: There were 161 patients with bifurcation disease [side branch (SB) ≥2‐mm] treated with ≥1 sirolimus‐eluting stents at 41 centers participating in the Stent deployment Techniques on cLinicaL outcomes of patients treated with the cypheR™stent (STLLR) trial. There was no protocol mandated strategy for bifurcation PCI. One‐year outcome data were collected. Angiographic and clinical data were adjudicated independently. Results: There were 147 patients (91.3%) treated with single stent strategy. Only 14 (8.7%) patients received sirolimus‐eluting stents implantation in both branches. Among patients with single stent strategy, double wire strategy (DW) was selected in 27 (18.4%) patients whereas single wire strategy (SW) was selected in 120 (81.6%) patients. There were 48 (32.7%) Medina 1,1,1 bifurcations treated with SW (n = 34; 70.8%) and DW (n = 14; 29.2%). There were 26 procedures started with SW which had SB dilatation during the procedure, one as a bailout (TIMI‐1 grade flow in the SB). Overall 1‐year death, myocardial infarction, and target lesion revascularization occurred in 2.4, 4.0, and 5.6%, respectively. There was no significant difference in clinical outcomes between SW and DW. SB dilatation was associated with a high rate of stent thrombosis (8.6%). Conclusions: Main branch stenting without SB protection is the most common approach utilized in the STLLR study, which may reflect contemporary DES bifurcation strategies in the Unite States. This strategy was associated with an acceptable low incidence of adverse outcomes at 1‐year.

Impact of Drug-Eluting Stents Among Insulin-Treated Diabetic Patients A Report from the NHLBI Dynamic Registry

OBJECTIVES This study sought to evaluate the safety and efficacy of drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients with insulin- and noninsulin-treated diabetes. BACKGROUND Diabetes is a powerful predictor of adverse events after percutaneous coronary interventions (PCI), and insulin-treated diabetic patients have worse outcomes. The DES are efficacious among patients with diabetes; however, their safety and efficacy, compared with BMS, among insulin-treated versus noninsulin-treated diabetic patients is not well established. METHODS Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 1-year outcomes of insulin-treated (n = 817) and noninsulin-treated (n = 1,749) patients with diabetes who underwent PCI with DES versus BMS. RESULTS The use of DES, compared with BMS, was associated with a lower risk for repeat revascularization for both noninsulin-treated patients (adjusted hazard ratio [HR] = 0.59, 95% confidence interval [CI] 0.45 to 0.76) and insulin-treated subjects (adjusted HR = 0.63, 95% CI 0.44 to 0.90). With respect to safety in the overall diabetic population, DES use was associated with a reduction of death or myocardial infarction (adjusted HR = 0.75, 95% CI 0.58 to 0.96). However, this benefit was confined to the population of noninsulin-treated patients (adjusted HR = 0.57, 95% CI 0.41 to 0.81). Among insulin-treated patients, there was no difference in death or myocardial infarction risk between DES- and BMS-treated patients (adjusted HR = 0.95, 95% CI 0.65 to 1.39). CONCLUSIONS Drug-eluting stents are associated with lower risk for repeat revascularization compared with BMS in treating coronary artery disease among patients with either insulin- or noninsulin-treated diabetes. In addition, DES use is not associated with any significant increased safety risk compared with BMS. These findings suggest that DES should be the preferred strategy for diabetic patients.

Impact of Drug-Eluting Stents Among Insulin-Treated Diabetic Patients

OBJECTIVES This study sought to evaluate the safety and efficacy of drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients with insulin- and noninsulin-treated diabetes. BACKGROUND Diabetes is a powerful predictor of adverse events after percutaneous coronary interventions (PCI), and insulin-treated diabetic patients have worse outcomes. The DES are efficacious among patients with diabetes; however, their safety and efficacy, compared with BMS, among insulin-treated versus noninsulin-treated diabetic patients is not well established. METHODS Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 1-year outcomes of insulin-treated (n = 817) and noninsulin-treated (n = 1,749) patients with diabetes who underwent PCI with DES versus BMS. RESULTS The use of DES, compared with BMS, was associated with a lower risk for repeat revascularization for both noninsulin-treated patients (adjusted hazard ratio [HR] = 0.59, 95% confidence interval [CI] 0.45 to 0.76) and insulin-treated subjects (adjusted HR = 0.63, 95% CI 0.44 to 0.90). With respect to safety in the overall diabetic population, DES use was associated with a reduction of death or myocardial infarction (adjusted HR = 0.75, 95% CI 0.58 to 0.96). However, this benefit was confined to the population of noninsulin-treated patients (adjusted HR = 0.57, 95% CI 0.41 to 0.81). Among insulin-treated patients, there was no difference in death or myocardial infarction risk between DES- and BMS-treated patients (adjusted HR = 0.95, 95% CI 0.65 to 1.39). CONCLUSIONS Drug-eluting stents are associated with lower risk for repeat revascularization compared with BMS in treating coronary artery disease among patients with either insulin- or noninsulin-treated diabetes. In addition, DES use is not associated with any significant increased safety risk compared with BMS. These findings suggest that DES should be the preferred strategy for diabetic patients.

Paclitaxel-Eluting versus Sirolimus-Eluting Stents in Diabetes Mellitus: A Report from the NHLBI Dynamic Registry

Background—Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry. Methods and Results—Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES (n=677) and PES (n=328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P=0.20), death and myocardial infarction (14.9% versus 13.6%, P=0.55), repeat revascularization (14.8% versus 17.8%, P=0.36), and stent thrombosis (1.3% versus 1.3%, P=0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed. Conclusions—PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice.Background— Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry. Methods and Results— Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES ( n =677) and PES ( n =328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P =0.20), death and myocardial infarction (14.9% versus 13.6%, P =0.55), repeat revascularization (14.8% versus 17.8%, P =0.36), and stent thrombosis (1.3% versus 1.3%, P =0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed. Conclusions— PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice. Received June 9, 2009; accepted October 22, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Paclitaxel-Eluting Versus Sirolimus-Eluting Stents in Diabetes Mellitus

Background—Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry. Methods and Results—Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES (n=677) and PES (n=328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P=0.20), death and myocardial infarction (14.9% versus 13.6%, P=0.55), repeat revascularization (14.8% versus 17.8%, P=0.36), and stent thrombosis (1.3% versus 1.3%, P=0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed. Conclusions—PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice.Background— Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry. Methods and Results— Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES ( n =677) and PES ( n =328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P =0.20), death and myocardial infarction (14.9% versus 13.6%, P =0.55), repeat revascularization (14.8% versus 17.8%, P =0.36), and stent thrombosis (1.3% versus 1.3%, P =0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed. Conclusions— PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice. Received June 9, 2009; accepted October 22, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Paclitaxel-Eluting Versus Sirolimus-Eluting Stents in Diabetes MellitusCLINICAL PERSPECTIVE: A Report From the National Heart, Lung, and Blood Institute Dynamic Registry

Background—Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry. Methods and Results—Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES (n=677) and PES (n=328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P=0.20), death and myocardial infarction (14.9% versus 13.6%, P=0.55), repeat revascularization (14.8% versus 17.8%, P=0.36), and stent thrombosis (1.3% versus 1.3%, P=0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed. Conclusions—PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice.Background— Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry. Methods and Results— Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES ( n =677) and PES ( n =328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P =0.20), death and myocardial infarction (14.9% versus 13.6%, P =0.55), repeat revascularization (14.8% versus 17.8%, P =0.36), and stent thrombosis (1.3% versus 1.3%, P =0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed. Conclusions— PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice. Received June 9, 2009; accepted October 22, 2009. # CLINICAL PERSPECTIVE {#article-title-2}