Statins and Contrast-induced Acute Kidney Injury with Coronary Angiography

BackgroundContrast-induced acute kidney injury is an adverse outcome resulting from radiocontrast medium exposure during coronary angiography and percutaneous coronary intervention.MethodsA systematic search was conducted to retrieve studies that investigated the impact of statin exposure before coronary angiography or percutaneous coronary intervention on the development of contrast-induced acute kidney injury. The primary outcome was the development of contrast-induced acute kidney injury. We separately analyzed statin/placebo comparisons and high-/low-dose statin comparisons.ResultsFifteen randomized controlled trials met inclusion criteria: 11 studies with statin-naïve subjects, 2 studies with chronic statin users, and 2 studies with unspecified prior statin exposure. Statin exposure reduced the risk of contrast-induced acute kidney injury relative to placebo (relative risk [RR] 0.63, P = .01) with a nonsignificant reduction in the need for hemodialysis (RR 0.25, P = .08). This benefit was also observed in high-dose versus low-dose statin trials (RR 0.46, P = .004), in statin-naïve patients (RR 0.53, P <.0001), and with all studied statins. Higher statin exposure reduced contrast-induced acute kidney injury in patients with acute coronary syndromes compared with placebo or low-dose statins (RR 0.49, P <.00001), with no significant benefit among patients undergoing elective procedures (RR 0.86, P = .50). Subgroup analyses confirmed the benefit of statins in patients with diabetes, chronic kidney disease, congestive heart failure, and those receiving >140 mL of contrast dye.ConclusionStatin therapy is effective at reducing the risk of contrast-induced acute kidney injury. It should thus be considered, at least on a short-term basis, for patients at increased risk of this complication.     

泮托拉唑联合吉法酯对经皮冠状动脉介入术后双联抗血小板药物治疗的患者上消化道出血的预防作用研究

目的 探讨泮托拉唑钠肠溶胶囊联合吉法酯片对经皮冠状动脉介入治疗（PCI）术后双联抗血小板药物治疗的患者上消化道出血的预防作用。方法 选取2014年10月-2017年10月在西电集团医院行PCI的患者121例作为研究对象,按照入院先后顺序分为两组。对照组在术后第1天开始口服吉法酯片,100 mg/次,3次/d。观察组在对照组的基础上联合泮托拉唑钠肠溶胶囊,40 mg/d。比较两组患者术后6个月内上消化道出血的发生率、心血管不良事件、消化道不良反应和血小板聚集率。结果 术后6个月观察组患者的上消化道出血发生率显著低于对照组（P<0.05）;心血管不良事件发生率两组比较无统计学差异,观察组消化道不良反应发生率显著低于对照组（P<0.05）。两组患者治疗前后的血小板聚集率相比无统计学差异。结论 泮托拉唑钠肠溶胶囊联合吉法酯片对PCI术后双联抗血小板药物治疗患者上消化道出血具有较好的预防作用,且显著降低消化道不良反应发生率,不增加心血管不良事件发生率,值得临床应用。     

Tamoxifen induces resistance to activated protein C

Introduction

The estrogen antagonist tamoxifen (TAM) increases the thrombotic risk similar to estrogen containing oral contraceptives (OC). In OC users this risk is attributed to alterations of hemostasis resulting in acquired resistance to activated protein C (APC). TAM-induced APC resistance has not been reported yet.

Materials and Methods

Blood samples were collected prospectively from women with breast cancer before (n = 25) and monthly after start of adjuvant TAM treatment (n = 75). APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. To detect increased in vivo APC generation APC plasma levels were measured using a highly sensitive oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were measured additionally.

Results

APC sensitivity decreased by 41% (p = 0.001) compared to baseline after one month of TAM application and remained significantly decreased during the study period. Free protein S increased (p = 0.008) while other analyzed procoagulant factors, inhibitors, and activation markers of coagulation decreased or did not change significantly. In five patients the APC concentration increased to non-physiological levels but an overall significant increase of APC was not observed.

Conclusions

This is the first study showing acquired APC resistance under TAM therapy. Acquired APC resistance might explain the increased thrombotic risk during TAM treatment. Observed changes of hemostasis parameters suggest different determinants of TAM-induced APC resistance than in OC-induced APC resistance. The presence of acquired APC resistance in TAM patients warrants further evaluation if these patients may benefit from antithrombotic prophylaxis in the presence of additional thrombotic risk factors.     

Door-to-balloon: Where do we lose time? Single centre experience in India

Background/AimsTo assess the factors causing delay in attaining DTB time of <90 min.MethodsEighty-five patients who underwent primary PCI from August 2008 to July 2009 were studied. From door-to-balloon, time was divided into 6 stages; any reason for delay was studied.ResultsThe mean DTB time was 80.5 min (SD = 34.4, median time 75 min, range 30–195). DTB time was <90 min in 76.5%, and DTB time >90 min occurred in 23.5%. Mean door to ECG – 6.5 min (SD = 2.7), mean time for the decision of PCI – 7.5 min (SD = 10.5), mean time taken for the patient's consent – 19.6 min (SD = 17.6), for STEMI team activation – 6.7 min (SD = 7.6), average time for financial process – 39.2 min (SD = 22.9). Average time for sheath to balloon – 5.2 min (SD = 1.7). Hospital related delay occurred in 5%, patient related delay in 80%, both together in 15%. 89.5% of patient related delay was due to delay in giving consent and financial reasons. There was no statistically significant delay for patients presented at morning or night and during the weekdays or weekend. Total mortality was 4.7%. Mortality among <90 min was 3.1%, mortality among >90 min was 10% (‘p’ = 0.2).ConclusionsWith effective hospital strategies, the DTB time of 90 min can be achieved in majority of patients. The chief delay in DTB time in this study was due to a delay in obtaining consent and financial reasons.     

Aging might increase myocardial ischemia / reperfusion-induced apoptosis in humans and rats

Previous studies indicated aging results in the significant cardiac function decreasing and myocardial apoptosis increasing in normal humans or rats. Additionally, animal experiments demonstrated aging increased myocardial ischemia / reperfusion (MI/R)-induced apoptosis. However, whether more myocardial apoptosis happen in the old acute myocardial infarction (AMI) patients is unclear. Reperfusion injury-induced apoptosis is an important cause of heart failure. This study determined the effect of aging upon myocardial apoptosis and cardiac function in patients suffering AMI. All enrolled AMI patients received percutaneous coronary intervention therapy. Volunteers and AMI patients were assigned to four groups: adult (age <65, n = 24) volunteers, elderly (age ≥65, n = 21) volunteers, adult (age <65, n = 29) AMI patients, and elderly (age ≥65, n = 36) AMI patients. Blood samples were obtained from all study participants. Plasma apoptotic markers (soluble form of Fas, tumor necrosis factor alpha, and interleukin 6) levels were determined. Cardiac function was evaluated with echocardiogram and Killip class. Due to lack of a direct apoptotic assay method in live human subjects, an additional animal experiment was performed. Both young (2 months) and old (24 months) rats were subjected to 30-min myocardial ischemia and 3 (for TUNEL/caspase activity apoptotic assay) or 24-h (for cardiac function determination) reperfusion. Compared to adult patients, the elderly patients manifested decreased cardiac function and increased plasma apoptotic marker levels significantly. The animal experiment results (cardiac function and plasma apoptotic markers assays) were consistent with the human result data. Animal TUNEL staining and caspase activity measurement revealed a higher myocardial apoptotic ratio in the older rat group. Aging exacerbated MI/R injury in humans and rats. Differential myocardial apoptosis may play a vital role in mediating the observed effects.     

Comparison of benefit and safety between different loading dose of clopidogrel on elderly patients undergoing primary percutaneous cronary intervention for ST-segment elevation myocardial infarction

Background Despite the proven benefit of 600-mg loading dose of clopidogrel in patients with acute ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous cronary intervention (PCI), there is still concern about its benefit and safety on elderly population. Methods Data of 172 consecutive elderly patients (≥75 years) with STEMI who underwent primary PCI at Guangdong Provincial Cardiovascular Institute from January 2008 to December 2011 were retrospectively collected. Patients were divided into 600-mg loading clopidogrel group and 300-mg clopidogrel group accoring to the loading dose of clopidogrel before primary percunaeous coronary intervention(PCI). Enzymatic myocardial infarction size estimated by peak creatine kinase-myocardial band (CK-MB) and patency of the infarct-related artery (IRA) were compared. Thirty-day major adverse cardiac events (MACEs), which consist of death, nonfatal myocardial infarction (MI), nonfatal stroke, target vessel revascularization (TVR) or stent thrombosis (ST) were compared to assess the efficacy of different loading dose. Bleeding information was compared as well to assess the safety of different pretreatment stragety before primary PCI. Results 96 patients were adminstered with 600-mg loading clopidogrel before primary PCI while 76 were administered with 300-mg. Patency of the IRA was significantly higher in patients administered with 600-mg loading clopidogrel therapy as compared with those who received 300-mg loading clopidogrel (94.8% vs. 85.5%, P = 0.038). 600-mg loading dose of clopidogrel was associated with lower incidence of 30-day MACEs compared with 300-mg loading dose of clopidogrel (8.3% vs. 19.7%, P = 0.029) while did not increase the risk of TIMI major (3.1% vs. 3.9%, P = 0.770) and minor bleeding (10.4% vs. 6.6%, P = 0.376). Conclusion 600-mg loading clopidogrel improves final patency of the IRA and clinical outcome as compared with 300-mg loading clopidogrel without increasing bleeding hazard.