Effects of prednisone on biomarkers of tubular damage induced by radiocontrast in interventional cardiology.

BACKGROUND: Contrast-induced nephropathy (CI-AKI) is a complication of diagnostic/therapeutic hemodynamic procedures in cardiology, which may also cause renal cholesterolinic atheroembolism. Despite the severe clinical impact of these complications, there is no optimal therapy for preventing and treating them. We suggest a short course of high-dose steroids as an effective preventive measure. METHODS: Patients at risk of CI-AKI (n = 38) undergoing cardiovascular procedures were assigned 1:1 to 1 of 2 experimental arms (prednisone+hydration vs. hydration alone). Oral prednisone 1 mg/kg was administered 12 hours before, at 6 am on the same day, and 24 hours following the procedure. Serum creatinine was tested immediately before and again 24-48 hours after the procedure; neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), protein and albumin were assayed in spot urine before and 6 hours after the procedure.
 RESULTS: NGAL and KIM-1 tended to rise after the procedure, but to a lesser degree in the prednisone group (delta NGAL: hydration = +128%, prednisone = +46%; p = 0.26; delta KIM-1: hydration = +99%, prednisone = +11%; p = 0.02). Proteinuria and albuminuria decreased significantly in the prednisone group. In 5 patients developing CI-AKI, their delta NGAL and delta KIM-1 did not differ from the values seen in patients without CI-AKI. Hypertension, peripheral arteriopathy and use of low-dose aspirin or diuretics were positive predictors of baseline NGAL, while treatment with calcium channel blockers and statins were negative predictors. Statins were negative predictors of baseline KIM-1. CONCLUSIONS: A short course of prednisone reduces the procedure-induced changes in biomarkers of renal tubular damage. This study suggests that steroids had a tubule-protecting effect.

Three-year follow-up of the MULTIcentre evaluation of Single high-dose Bolus TiRofiban versus Abciximab with Sirolimus-eluting STEnt or Bare-Metal Stent in Acute Myocardial Infarction StudY (MULTISTRATEGY).

BACKGROUND: The Multicentre Evaluation of Single high-dose Bolus TiRofiban versus Abciximab with Sirolimus-eluting Stent or Bare Metal Stent in Acute Myocardial Infarction Study [MULTISTRATEGY]) randomised 745 patients with ST-elevation myocardial infarction to receive high-dose bolus (HDB) tirofiban or abciximab infusion and sirolimus-eluting (SES) or uncoated-stent (BMS) implantation. Tirofiban was non-inferior to abciximab in terms of ST-segment resolution after intervention, whereas 8 month-major adverse cardiac events occurred in 14.5% in the BMS and 7.8% in the SES groups (P = 0.0039), reflecting a reduction of reintervention rates (10.2% vs. 3.2%). A three-year follow-up was performed to extend previous short- to mid-term findings. METHODS AND RESULTS: Complete data at 3 years was available for 736 patients (99%). All-cause mortality was 6.7% in the tirofiban and 7.8% in the abciximab (P = 0.56) and 7.5% in the BMS vs 7.0 in the SES groups, P = 0.79. The composite of all-cause death or MI was identical at 12.9% in tirofiban and abciximab groups, P = 0.99 and it occurred in 13.2% in the BMS vs. 12.6% in the SES groups (P = 0.83). The need for reintervention remained more than twice as common with BMS (13.7%; versus 6.2%, P = 0.0006). The cumulative rate of stent thrombosis (ST) did not differ. This is inspite of a higher very late definite, probable or possible ST thrombosis rate in the SES group. CONCLUSIONS: The 3-year follow-up of MULTISTRATEGY demonstrated comparable outcomes with HDB Tirofiban or abciximab and a sustained efficacy of SES to reduce reintervention with no difference in death, repeat MI or ST.

Persistent coronary no flow after wire insertion is an early and readily available mortality risk factor despite successful mechanical intervention in acute myocardial infarction: a pooled analysis from the STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) trials.

OBJECTIVES: These studies sought to investigate the impact on mortality of coronary flow after passage of the wire through the culprit vessel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical reperfusion. BACKGROUND: Reduced spontaneous coronary flow before percutaneous coronary intervention influences mortality in patients with STEMI. Response to vessel wiring in patients with an occluded coronary artery before intervention might further discriminate outcomes irrespective of pre- and post-intervention coronary flow. METHODS: Data from the STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) trials were pooled: of 919 index procedures, 902 films (98%) were technically adequate for core laboratory TIMI (Thrombolysis In Myocardial Infarction) flow determination. RESULTS: TIMI flow grade 0 was present before percutaneous coronary intervention in 59% of infarct vessels, TIMI flow grade 1 to 2 was found in 21%, whereas the remainder of infarct arteries presented with TIMI flow grade 3. In 49% of patients who showed persistent TIMI flow grade 0 after wire insertion (AWI), mortality was higher at 30 days (5.3%) and 1 year (9.4%) compared with patients in whom TIMI flow grade before percutaneous coronary intervention was either >0 (0.8%; p < 0.003 and 3.6%, p < 0.008) or improved from 0 AWI (1.5%, p < 0.04 and 3.6%, p < 0.02). After correcting for multiple imbalances, including baseline and final flow, persistent TIMI flow grade 0 AWI remained associated at 30 days to 2-fold (risk ratio [RR]: 2.1, 95% confidence interval [CI]: 1.08 to 5.00; p = 0.038) and at 1 year to almost 3-fold increases of mortality (RR: 2.7, 95% CI: 1.3 to 5.6; p = 0.008). CONCLUSIONS: STEMI patients displaying persistent no-flow AWI have a lower survival rate despite an apparently successful mechanical intervention. As an early marker for high residual mortality risk, persistent no-flow AWI may qualify STEMI patients for dedicated pharmacomechanical treatment strategies.

Quinaprilat-eluting stents do not attenuate intimal thickening following stenting in porcine coronary arteries.

OBJECTIVE: Vascular injury increases angiotensin-converting enzyme (ACE) activity in the vessel wall, and experimental evidence suggests that high-dose oral ACE inhibition reduces intimal hyperplasia following balloon angioplasty. Local drug delivery can achieve high local concentrations which may be especially efficacious in inhibiting tissue growth following stent implantation. The aim of this study was to evaluate the angiographic and histomorphologic effects of quinaprilat-eluting stents in normal porcine coronary arteries. METHODS: Ten pigs received phosphorylcholine-coated stents in each of the three major coronary arteries: one loaded with 780 microg quinaprilat, one with the solvent and one non-loaded control. Quantitative angiography was performed before and after stenting and at 4 weeks follow-up. At this time point the stented arteries were also analyzed using histology and morphometry. RESULTS: Repeated measures ANOVA yielded significantly smaller angiographic lumen in both quinaprilat and solvent groups: 2.62+/-0.31 and 2.65+/-0.31 mm, respectively versus control: 2.70+/-0.32 mm at follow-up, p<0.05. Histology confirmed this finding with an increment in intimal area (2.5+/-0.86 mm(2)) and thickness (0.57+/-0.29 mm) in the quinaprilat group; versus solvent (1.98+/-0.57 mm(2) 0.4+/-0.26 mm) and controls (1.92+/-0.50mm(2) and 0.41+/-0.18 mm). CONCLUSION: Quinaprilat-eluting stents do not attenuate neointimal thickening following implantation in normal porcine coronary arteries, but rather show a tendency towards the opposite.

Drug-eluting stent safety: findings from preclinical studies.

After pivotal clinical trials, drug-eluting stents (DES) are now considered the standard of care for the management of acute coronary syndrome. However, late stent thrombosis has emerged as a major concern. Preclinical testing is an important regulatory process that determines the safety and efficacy of devices prior to human clinical trials. Histopathologic analysis following placement of DES has typically been performed in porcine coronary artery models to ensure safety in these devices. The recently issued consensus report from the US FDA, for the approval of DES recommends the use of the porcine model for the safety assessment of these devices in the vascular bed for which they are intended. Other models are also recommended, as vascular responses to stents are much slower in man than in animals, and no animal truly elicits the response seen in humans. The rabbit iliac artery can provide further data, especially regarding endothelialization, which is slower in the rabbit model than in the porcine model. Furthermore, inflammation is not as extensive in the rabbit and may thus be a closer model of humans than the porcine models. The FDA recognizes that it may be more appropriate to test these devices in atherosclerosis. The choice of animal model may mask the serious drawbacks of the devices; therefore, we suggest the use of both models to understand the healing following DES implantation, with emphasis on endothelialization, inflammation and neointimal formation and, whenever possible, to complement the observations in the environment of atherosclerosis.