Meta-analysis of randomized trials on drug-eluting stents vs. bare-metal stents in patients with acute myocardial infarction

Aims To compare the efficacy and safety of drug-eluting stents vs. bare-metal stents in patients with acute ST-segment elevation myocardial infarction. Methods and results We performed a meta-analysis of eight randomized trials comparing drug-eluting stents (sirolimus-eluting or paclitaxel-eluting stents) with bare-metal stents in 2786 patients with acute ST-segment elevation myocardial infarction. All patients were followed up for a mean of 12.0-24.2 months. Individual data were available for seven trials with 2476 patients. The primary efficacy endpoint was the need for reintervention (target lesion revascularization). The primary safety endpoint was stent thrombosis. Other outcomes of interest were death and recurrent myocardial infarction. Drug-eluting stents significantly reduced the risk of reintervention, hazard ratio of 0.38 (95% CI, 0.29-0.50), P < 0.001. The overall risk of stent thrombosis: hazard ratio of 0.80 (95% CI, 0.46-1.39), P = 0.43; death: hazard ratio of 0.76 (95% CI, 0.53-1.10), P = 0.14; and recurrent myocardial infarction: hazard ratio of 0.72 (95% CI, 0.48-1.08, P = 0.11) was not significantly different for patients receiving drug-eluting stents vs. bare-metal stents. Conclusion The use of drug-eluting stents in patients with acute ST-segment elevation myocardial infarction is safe and improves clinical outcomes by reducing the risk of reintervention compared with bare-metal stent

5-Year Follow-Up After Primary Percutaneous Coronary Intervention With a Paclitaxel-Eluting Stent Versus a Bare-Metal Stent in Acute ST-Segment Elevation Myocardial Infarction A Follow-Up Study of the PASSION (Paclitaxel-Eluting Versus Conventional Stent in Myocardial Infarction With ST-Segment Elevation) Trial

The purpose of this study was to evaluate the long-term outcomes of the PASSION (Paclitaxel-Eluting Versus Conventional Stent in Myocardial Infarction with ST-Segment Elevation) trial. In primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction (STEMI), the use of drug-eluting stents (DES) is still controversial. Several randomized controlled trials of DES, compared with bare-metal stents (BMS), with short-term follow-up showed a reduction in target lesion revascularization (TLR), but no differences in rates of cardiac death or recurrent myocardial infarction. Moreover, the occurrence of (very) late stent thrombosis (ST) continues to be of major concern, and, therefore, long-term follow-up results are needed. We randomly assigned 619 patients presenting with STEMI to a paclitaxel-eluting stent (PES) or the similar BMS. The primary end point was the composite of cardiac death, recurrent myocardial infarction, or TLR. We performed clinical follow-up at 5 years. At 5 years, the occurrence of the composite of cardiac death, recurrent myocardial infarction, or TLR was comparable at 18.6% versus 21.8% in PES and BMS, respectively (hazard ratio [HR]: 0.82, 95% confidence interval [CI]: 0.58 to 1.18, p = 0.28). The incidence of definite or probable ST was 12 (4.2%) in the PES group and 10 (3.4%) in the BMS group (HR: 1.19, 95% CI: 0.51 to 276, p = 0.68). In the present analysis of PES compared with BMS in primary percutaneous coronary intervention for STEMI, no significant difference in major adverse cardiac events was observed. In addition, no difference in the incidence of definite or probable ST was seen, although very late ST was almost exclusively seen after the use of PES. (Paclitaxel-Eluting Versus Conventional Stent in Myocardial Infarction with ST-Segment Elevation [PASSION]; ISRCTN65027270

Lack of long-term clinical benefit of thrombus aspiration during primary percutaneous coronary intervention with paclitaxel-eluting stents or bare-metal stents: post-hoc analysis of the PASSION-trial

Although current clinical guidelines recommend the use of thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI), previous studies evaluating TA demonstrated contradictory results. The aim of this study was to evaluate long-term clinical outcome after TA in adjunct to PPCI for acute ST-segment myocardial infarction (STEMI), as compared with conventional treatment, with the use of paclitaxel-eluting stents or bare-metal stents. We analyzed data of the PASSION trial, in which 619 patients with STEMI were randomly assigned to a paclitaxel-eluting stent or a bare-metal stent. TA was performed in 311 patients (50.2%). Clinical endpoints at 2 years were compared between patients who received TA during PPCI with patients who underwent conventional PPCI. The primary outcome of interest was a composite of cardiac death, recurrent myocardial infarction (MI), or target-lesion revascularization (TLR). A propensity score model was made to account for baseline differences that could have affected the probability of performing TA. Complete follow-up was available for 598 patients (96.6%). The cumulative incidence of the combined outcome measure of cardiac death, recurrent MI, or TLR was 40 (13.0%) in the TA group and 41 (13.5%) in the conventional PPCI group (HR 0.96; 95% CI 0.62-1.47; P = 0.84). Also after adjusting for propensity score, no significant difference in event rate was observed between both treatment groups. In this post-hoc analysis of the PASSION trial, TA in adjunct to PPCI did not affect rates of major adverse cardiac events at 2 years follow-up, as compared with conventional PPC

Myocardial structure and function differ in systolic and diastolic heart failure

BACKGROUND: To support the clinical distinction between systolic heart failure (SHF) and diastolic heart failure (DHF), left ventricular (LV) myocardial structure and function were compared in LV endomyocardial biopsy samples of patients with systolic and diastolic heart failure. METHODS AND RESULTS: Patients hospitalized for worsening heart failure were classified as having SHF (n=22; LV ejection fraction (EF) 34+/-2%) or DHF (n=22; LVEF 62+/-2%). No patient had coronary artery disease or biopsy evidence of infiltrative or inflammatory myocardial disease. More DHF patients had a history of arterial hypertension and were obese. Biopsy samples were analyzed with histomorphometry and electron microscopy. Single cardiomyocytes were isolated from the samples, stretched to a sarcomere length of 2.2 microm to measure passive force (Fpassive), and activated with calcium-containing solutions to measure total force. Cardiomyocyte diameter was higher in DHF (20.3+/-0.6 versus 15.1+/-0.4 microm, P<0.001), but collagen volume fraction was equally elevated. Myofibrillar density was lower in SHF (36+/-2% versus 46+/-2%, P<0.001). Cardiomyocytes of DHF patients had higher Fpassive (7.1+/-0.6 versus 5.3+/-0.3 kN/m2; P<0.01), but their total force was comparable. After administration of protein kinase A to the cardiomyocytes, the drop in Fpassive was larger (P<0.01) in DHF than in SHF. CONCLUSIONS: LV myocardial structure and function differ in SHF and DHF because of distinct cardiomyocyte abnormalities. These findings support the clinical separation of heart failure patients into SHF and DHF phenotypes

Drug-eluting stents versus bare-metal stents in diabetic patients with ST-segment elevation acute myocardial infarction : a pooled analysis of individual patient data from seven randomized trials

INTRODUCTION AND OBJECTIVES: The performance of drug-eluting stents (DESs) in high-risk patients with diabetes and acute ST-elevation myocardial infarction (STEMI) who have undergone primary angioplasty has not been previously studied. The objective was to evaluate the efficacy and safety of DESs in diabetic patients with STEMI. METHODS: We performed a pooled analysis of individual patient data from seven randomized trials that compared DESs (i.e., sirolimus- or paclitaxel-eluting stents) with bare-metal stents (BMSs) in patients with STEMI. The analysis involved 389 patients with diabetes mellitus from a total of 2476 patients. The outcomes of interest were target-lesion revascularization, stent thrombosis, death and the composite endpoint of death or recurrent myocardial infarction during a follow-up of 12-24 months. RESULTS: Overall, 206 diabetic patients received a DES and 183, a BMS. The risk of target-lesion revascularization was significantly lower in patients treated with a DES compared to those treated with a BMS (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.23-0.88; P=.02). There was no significant difference in the risk of stent thrombosis between those treated with a DES or a BMS (HR 0.33, 95% CI 0.09-1.13; P=.08). Similarly, the risk of the combined endpoint of death or myocardial infarction was not significantly different between patients treated with a DES or a BMS (HR 0.64, 95% CI 0.36-1.13; P=.12). CONCLUSIONS: Compared with BMSs, DES use improved clinical outcomes in diabetic patients undergoing primary angioplasty for STEMI: the need for reintervention was reduced, with no increase in mortality or myocardial infarction

Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension

BACKGROUND: Excessive diastolic left ventricular stiffness is an important contributor to heart failure in patients with diabetes mellitus. Diabetes is presumed to increase stiffness through myocardial deposition of collagen and advanced glycation end products (AGEs). Cardiomyocyte resting tension also elevates stiffness, especially in heart failure with normal left ventricular ejection fraction (LVEF). The contribution to diastolic stiffness of fibrosis, AGEs, and cardiomyocyte resting tension was assessed in diabetic heart failure patients with normal or reduced LVEF. METHODS AND RESULTS: Left ventricular endomyocardial biopsy samples were procured in 28 patients with normal LVEF and 36 patients with reduced LVEF, all without coronary artery disease. Sixteen patients with normal LVEF and 10 with reduced LVEF had diabetes mellitus. Biopsy samples were used for quantification of collagen and AGEs and for isolation of cardiomyocytes to measure resting tension. Diabetic heart failure patients had higher diastolic left ventricular stiffness irrespective of LVEF. Diabetes mellitus increased the myocardial collagen volume fraction only in patients with reduced LVEF (from 14.6+/-1.0% to 22.4+/-2.2%, P<0.001) and increased cardiomyocyte resting tension only in patients with normal LVEF (from 5.1+/-0.7 to 8.5+/-0.9 kN/m2, P=0.006). Diabetes increased myocardial AGE deposition in patients with reduced LVEF (from 8.8+/-2.5 to 24.1+/-3.8 score/mm2; P=0.005) and less so in patients with normal LVEF (from 8.2+/-2.5 to 15.7+/-2.7 score/mm2, P=NS). CONCLUSIONS: Mechanisms responsible for the increased diastolic stiffness of the diabetic heart differ in heart failure with reduced and normal LVEF: Fibrosis and AGEs are more important when LVEF is reduced, whereas cardiomyocyte resting tension is more important when LVEF is normal