Michael C. Kim

Impact of the everolimus-eluting stent on stent thrombosis: a meta-analysis of 13 randomized trials

OBJECTIVES We evaluated the impact of the everolimus-eluting stent (EES) on the frequency of stent thrombosis (ST), target vessel revascularization (TVR), myocardial infarction (MI), and cardiac death in randomized controlled trials comparing the EES to non-everolimus-eluting drug-eluting stents (EE-DES). BACKGROUND Whether or not the unique properties of the EES translate into reductions in ST remains unknown. METHODS We searched MEDLINE, Scopus, the Cochrane Library, and Internet sources for articles comparing outcomes between EES and non-EE-DES without language or date restriction. Randomized controlled trials reporting the frequency of ST were included. Variables relating to patient and study characteristics and clinical endpoints were extracted. RESULTS We identified 13 randomized trials (n = 17,101) with a weighted mean follow-up of 21.7 months. Compared with non-EE-DES, the EES significantly reduced ST (relative risk [RR]: 0.55; 95% confidence interval [CI]: 0.38 to 0.78; p = 0.001), TVR (RR: 0.77; 95% CI: 0.64 to 0.92; p = 0.004), and MI (RR: 0.78; 95% CI: 0.64 to 0.96; p = 0.02). There was no difference in cardiac mortality between the groups (RR: 0.92; 95% CI: 0.74 to 1.16; p = 0.38). The treatment effect was consistent by different follow-up times and duration of clopidogrel use. The treatment effects increased with higher baseline risks of the respective control groups with the strongest correlation observed for ST (R(2) = 0.89, p < 0.001). CONCLUSIONS Intracoronary implantation of the EES is associated with highly significant reductions in ST with concordant reductions in TVR and MI compared to non-EE-DES. Whether these effects apply to different patient subgroups and DES types merits further investigation.

Changing outcomes and treatment strategies for wire induced coronary perforations in the era of bivalirudin use.

Objectives: The objective of this study is to analyze the clinical outcomes and treatment strategies of coronary wire perforations (WPs) in the era of heparin use compared to the era of bivalirudin use. Background: Percutaneous coronary intervention (PCI) advances have led to progressive decrease in complications. Therefore, complex coronary lesions such as chronic total occlusions and calcified lesions are being attempted with stiff/hydrophilic wires with resultant higher incidence of coronary WP. Methods: A single‐center retrospective data analysis of coronary perforation (CP) for the last 4 years with review of coronary angiograms was done and WPs were identified. A simple classification scheme based on angiographic appearance of CP was made: Type I (“myocardial stain,” with no frank dye extravasation) and type II (“myocardial fan,” with dye extravasation to pericardial cavity or cardiac chambers). Results: Overall incidence of CP was 0.49% (82/16,859). Of these 50 (61%) were caused by WP; 30 occurred with heparin use (Group A) and 20 with bivalirudin use (Group B). WPs always occurred in type B2/C lesions (100%) and commonly with use of hydrophilic guidewires (70%). Major adverse cardiac events and cardiac tamponade were frequent in group A (50%) and none in group B (0%); P < 0.01. All WP in group B responded to stopping anticoagulation and prolonged balloon inflation, while group A type II perforations frequently required additional interventions (pericardiocentesis, coil embolization). Conclusions: Cardiac tamponade and major adverse cardiac events from WPs were less frequent with bivalirudin use compared to heparin use. This beneficial effect of bivalirudin may be explained on the basis of its short half‐life and reversible thrombin inhibition property. Therefore, bivalirudin may offer a safer alternative for anticoagulation in complex PCI.

Predictors of low clopidogrel adherence following percutaneous coronary intervention.

Few data are available on factors associated with low adherence or early clopidogrel discontinuation after percutaneous coronary intervention (PCI). Patients (n = 284) were evaluated before hospital discharge after PCI to identify factors associated with low adherence to clopidogrel 30 days later. Adherence to daily medications before PCI was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8) and categorized as low (score <6), medium (score 6 to <8), or high (score 8). Low adherence to clopidogrel was defined as MMAS-8 score <6 (n = 21) or having discontinued clopidogrel (n = 11), which was ascertained during a 30-day interview after PCI. At 30 days after PCI, 11% of patients had low adherence to clopidogrel. Odds ratios (95% confidence intervals [CIs]) for low adherence to clopidogrel were 3.78 (1.09 to 13.1), 3.06 (1.36 to 6.87), 2.46 (0.97 to 6.27), and 3.36 (0.99 to 11.4) for patients who before PCI reported taking smaller doses of medication because of cost, had difficulty filling prescriptions, had difficulty reaching their primary physician, and were not comfortable asking their doctor for instructions, respectively. Odds ratios (95% CIs) for low clopidogrel adherence after PCI in patients with medium and low versus high adherence to daily medications before PCI were 6.13 (1.34 to 28.2) and 10.9 (2.46 to 48.7), respectively. The c-statistic associated with MMAS-8 scores before PCI for discriminating low clopidogrel adherence at 30 days after PCI was 0.733 (95% CI 0.650 to 0.852). In conclusion, adherence to daily medications before PCI may be a useful indicator for identifying patients who will have low clopidogrel adherence after PCI.

Outcome of intracoronary stenting after failed maximal medical therapy in patients with symptomatic myocardial bridge

The aim of the present study was to study the outcome of coronary stenting in patients with symptomatic myocardial bridging refractory to standard medical therapy.

Comparison of coronary flow reserve and fractional flow reserve in patients with versus without diabetes mellitus and having elective percutaneous coronary intervention and abciximab therapy (from the PREDICT Trial).

Patients with diabetes mellitus (DM) have poor long-term outcome after percutaneous coronary intervention (PCI) partly because of microvascular disease and distal embolization. Microvascular obstruction can be assessed by measuring coronary flow reserve (CFR). The Prediction of CK-MB RElease During Successful Stenting Correlating with Indicators of Microvascular ObstruCTion (PREDICT) trial compared the CFR in patients with versus without DM during PCI. Patients undergoing elective PCI were prospectively enrolled according to diabetic (n = 36) and nondiabetic (n = 36) status. All patients received drug-eluting stent with abciximab and were followed for 30-day major adverse cardiac events. CFR and FFR (fractional flow reserve) before and after stenting were measured before and after intracoronary adenosine bolus. Procedural success, MB enzyme of creatine-kinase (CK-MB), troponin I, and high-sensitive C-reactive protein elevation, vascular complications, and major adverse cardiac events were not different. FFR before stenting was 0.77 +/- 0.03 in patients with DM versus 0.76 +/- 0.02 in patients without DM (p = 0.69). FFR after stenting was 0.97 +/- 0.03 and 0.99 +/- 0.01 (p = 0.26), respectively. CFR before stenting was 1.36 +/- 0.31 in patients with DM versus 1.49 +/- 0.25 in patients without DM (p = 0.064). However, CFR after stenting was significantly lower in patients with versus without DM (1.89 +/- 0.30 versus 2.44 +/- 0.67, p <0.001, respectively). CFR after stenting only moderately correlated with CK-MB and high-sensitive C-reactive protein after PCI but did not correlate with 30-day major adverse cardiac events. In conclusion, patients with DM have significantly lower CFR after stenting despite equivalent FFR and myonecrosis compared with patients without DM, indicating greater microvascular obstruction after PCI despite abciximab.

Failed repeated thrombolysis requiring left ventricular assist device pump exchange

A 51‐year‐old male with untreated hepatitis C infection, cirrhosis, and dilated cardiomyopathy with a HeartMate II LVAD presented with right heart failure and cardiogenic shock, INR of 7, hemolysis, and renal failure. Acute LVAD thrombosis was suspected. Alteplase was injected into the inflow cannula of the LVAD with little effect. Intravenous alteplase was given but failed to restore an adequate pump output, resulting in the need for emergency pump exchange. The patient had an uncomplicated postoperative recovery and was discharged uneventfully. Inspection of the pump identified a thrombus wedged between the spines of the impeller. Our case highlights the challenges in managing pump thrombosis which is often resistant to thrombolysis and may instead rely upon prompt surgical intervention to be resolved.

Effect of bivalirudin on aortic valve intervention outcomes study: A two-centre registry study comparing bivalirudin and unfractionated heparin in balloon aortic valvuloplasty

AIMS We sought to assess if bivalirudin use during balloon aortic valvuloplasty (BAV) would affect clinical outcomes compared with heparin. METHODS AND RESULTS We compared the outcomes of consecutive patients who underwent elective or urgent BAV with intraprocedural use of bivalirudin or heparin at two high-volume centres. All in-hospital events post BAV were adjudicated by an independent, blinded clinical events committee. Of 427 patients, 223 patients (52.2%) received bivalirudin and 204 (47.8%) received heparin. Compared with patients who received heparin, patients who received bivalirudin had significantly less major bleeding (4.9% vs. 13.2%, p=0.003). Net adverse clinical events (NACE, major bleeding or major adverse cardiovascular events [MACE]) were also reduced (11.2% vs. 20.1%, p=0.01). There was no significant difference in the rates of MACE (mortality, myocardial infarction or stroke, 6.7% vs. 11.3%, p=0.1), or vascular complications (major, 2.7% vs. 2.0%; minor, 4.5% vs. 4.9%; p=0.83). After multivariate analysis controlling for vascular preclosure, the use of bivalirudin remained independently associated with reduced major bleeding (OR 0.37; 95% CI: 0.16 to 0.84; p=0.02) while the association was attenuated in propensity-adjusted analysis (OR 0.44, 95% CI: 0.18 to 1.07, p=0.08). CONCLUSIONS In this registry of patients with severe aortic stenosis, bivalirudin as compared to heparin resulted in improved in-hospital outcomes post BAV in terms of reduced major bleeding, similar MACE and reduced NACE. If verified in a randomised study and extended to the transcatheter aortic valve implantation (TAVI) population, these results might indicate a potential benefit for patients undergoing such procedures.

Thrombolysis In Myocardial Infarction (TIMI) risk score and mortality in patients with advanced chronic kidney disease and on dialysis.

There are limited data on the validity of the Thrombolysis In Myocardial Infarction (TIMI) risk score for unstable angina pectoris (UAP)/non-ST-elevation myocardial infarction in patients with moderate to advanced chronic kidney disease (CKD), including patients using dialysis. Accordingly, we evaluated the prognostic ability of the TIMI risk score in consecutive patients across the entire spectrum of CKD who presented with UAP or non-ST elevation myocardial infarction and underwent percutaneous coronary intervention from July 1, 1999, to June 30, 2007. Patients were categorized by estimated glomerular filtration rate (eGFR) > or = 60 (n = 4,938), 30 to 59 (n = 1,592), and <30 ml/min/1.73 m2 (n = 202) and use of dialysis (n = 208). Hazard ratios of all-cause mortality associated with TIMI risk score levels (0 to 2, 3 to 4, > or = 5) were calculated within each eGFR category. Over a median follow-up of 3.2 years, 813 deaths occurred. For patients with an eGFR > or = 60 ml/min/1.73 m2, race- and gender-adjusted hazard ratios of mortality associated with TIMI risk scores of 3 to 4 and > or = 5 compared with 0 to 2 were 2.92 (95% confidence interval [CI] 1.93 to 4.40) and 4.26 (95% CI 2.82 to 6.43), respectively. Analogous hazard ratios were 1.26 (95% CI 0.80 to 1.98) and 1.77 (95% CI 1.13 to 2.78) for patients with an eGFR of 30 to 59 ml/min/1.73 m2, 2.23 (95% CI 0.71 to 6.94) and 2.83 (95% CI 0.89 to 8.99) for patients with an eGFR <30 ml/min/1.73 m2, and 3.16 (1.33 to 7.48) and 3.67 (95% CI 1.52 to 8.86), respectively, for patients on dialysis. In conclusion, the TIMI risk score for UAP/non-ST elevation myocardial infarction discriminates mortality risk across the full range of CKD, including patients on dialysis.

Relation of high-density lipoprotein cholesterol to mortality after percutaneous coronary interventions in patients with low-density lipoprotein <70 mg/dl.

High-density lipoprotein (HDL) cholesterol level is a strong predictor of morbidity and mortality in the general population. Conflicting data exist on the protective effects of high HDL cholesterol in patients with optimal low-density lipoprotein (LDL) cholesterol levels. To determine the association of high HDL cholesterol with mortality in patients with LDL cholesterol levels <70 mg/dl who undergo percutaneous coronary intervention, 3,616 consecutive patients with LDL cholesterol levels <70 mg/dl who underwent percutaneous coronary intervention from July 1, 1999, to June 1, 2007, were retrospectively analyzed and followed through July 1, 2007. All-cause mortality was identified using the National Death Index. The mortality rates was 34.7, 25.2, 23.7, and 18.8 per 1,000 person-years in patients with HDL cholesterol levels of <40, 40 to 49, 50 to 59, and > or =60 mg/dl, respectively (p for trend <0.001). After multivariate adjustment for demographic characteristics, cigarette smoking, biochemical variables, and co-morbid conditions, the hazard ratios for mortality in patients with HDL cholesterol levels of 40 to 49, 50 to 59, and > or =60 mg/dl, compared with their counterparts with HDL cholesterol levels <40 mg/dl, were 0.68 (95% confidence interval [CI] 0.50 to 0.93), 0.55 (95% CI 0.35 to 0.85), and 0.45 (95% CI 0.27 to 0.74), respectively. For each 1-SD increase in HDL cholesterol level (14 mg/dl), the multivariate-adjusted hazard ratio for all-cause mortality was 0.68 (95% CI 0.58 to 0.79). In conclusion, in patients with LDL cholesterol levels <70 mg/dl who underwent percutaneous coronary intervention, a strong inverse association was present between HDL cholesterol level and all-cause mortality.

Serum creatinine ratio: a novel predictor of mortality after percutaneous coronary intervention in patients with normal and abnormal renal function.

The occurrence of contrast induced nephropathy (CIN) is associated with increased mortality after percutaneous revascularization procedures. However, the exact correlation between various levels of creatinine elevation relative to the baseline and subsequent mortality in patients with chronic renal insufficiency (CRI) is not well established. In addition, the relationship between elevated postprocedural creatinine and ensuing mortality in patients with normal baseline renal function needs to be investigated. Methods: All percutaneous coronary intervention (PCI) patients (n = 12,997) were analyzed for any rise in serum creatinine (SCr): CRI group (BSC ≥ 1.5 mg/dl) (n = 1,853) and normal baseline renal function (NBR BSC < 1.5 mg/dl) group (n = 11,144). Patients in each group were analyzed for any elevation in SCr postprocedure and subdivided based on the SCr ratio [peak SCr/Baseline creatinine (BSC)] of <1.25, 1.25–1.5, and >1.5. The overall incidence of CIN (defined as an increment of 25% over baseline creatinine) was 5.9%: 11.3% in the CRI group versus 5.1% in normal BSC group (P < 0.01). Recursive partitioning and Cox hazard modeling were used to assess significant variables associated with mortality within 1 year. Only serum creatinine ratio (SCrR) > 1.5 correlated with increased mortality in both CRI group as well as normal BSC group. Conclusions: SCrR > 1.5 predicts mortality at 1 year after PCI. The association between SCrR > 1.5 and increased mortality at follow‐up is observed in patients with CRI as well as normal baseline renal function. SCrR may thus serve as a useful clinical tool for risk stratification and prognostication of patients after PCI.