Advances in adjunctive pharmacological therapy for percutaneous coronary interventions

All percutaneous interventions disrupt atherosclerotic plaque and denude the endothelium. These processes stimulate both platelet aggregation and the coagulation cascade. Therefore, pharmacological treatment during percutaneous intervention is based on the use of antithrombotic agents. In addition to aspirin, whose benefit has been clearly demonstrated in all forms of ischemic heart disease, clopidogrel, given before and after cardiac catheterization, also reduces the rate of thrombosis after stent placement. Moreover, the introduction of glycoprotein IIb/IIIa inhibitors has improved the results of percutaneous revascularization, especially in high-risk patients. On the other hand, anticoagulants are essential for preventing the acute thrombotic complications that result from the invasive nature of the procedure. Low-molecular-weight heparins, direct thrombin inhibitors (e.g., hirudin and its derivatives), and recently developed pentasaccharides, which inhibit factor X, provide new alternatives to classical unfractionated heparin. These novel compounds lead to fewer hemorrhagic complications than unfractionated heparin and do not require such extensive monitoring. Finally, new antiproliferative agents, such as oral rapamycin, have been introduced to reduce the rate of coronary restenosis during follow-up.     

Medical therapies in pituitary adenomas: Current rationale for the use and future perspectives

Pituitary adenomas (PA) represent in the majority of cases, benign tumors whose treatment currently associate surgery, medical therapies and radiotherapy in a multidisciplinary approach. While trans-sphenoidal surgery remains, except for prolactin-secreting adenomas, the first-line treatment of PA, it can considerably be hampered by the existence of an invasive and/or aggressive tumor for which medical therapies are often requested. In this review, we extensively discuss, both at molecular and clinical levels, the medical therapies currently used and in development in the different phenotypes of pituitary adenomas.     

Current status and perspectives of immune-based therapies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a frequent cancer with a high mortality. For early stage cancer there are potentially curative treatments including local ablation, resection and liver transplantation. However, for more advanced stage disease, there is no optimal treatment available. Even in the case of a “curative” treatment, recurrence or development of a new cancer in the precancerous liver is common. Thus, there is an urgent need for novel and effective (adjuvant) therapies to treat HCC and to prevent recurrence after local treatment in patients with HCC. The unique immune response in the liver favors tolerance, which remains a genuine challenge for conventional immunotherapy in patients with HCC. However, even in this “immunotolerant” organ, spontaneous immune responses against tumor antigens have been detected, although they are insufficient to achieve significant tumor death. Local ablation therapy leads to immunogenic tumor cell death by inducing the release of massive amounts of antigens, which enhances spontaneous immune response. New immune therapies such as dendritic cell vaccination and immune checkpoint inhibition are under investigation. Immunotherapy for cancer has made huge progress in the last few years and clinical trials examining the use of immunotherapy to treat hepatocellular carcinoma have shown some success. In this review, we discuss the current status of and offer some perspectives on immunotherapy for hepatocellular carcinoma, which could change disease progression in the near future.     

Clopidogrel as adjunctive antiplatelet therapy during coronary stenting

OBJECTIVES

We examined the procedural and 30-day clinical outcomes among patients receiving aspirin and either ticlopidine or clopidogrel during coronary stenting.

BACKGROUND

Ticlopidine-plus-aspirin has become standard antiplatelet therapy for the prevention of thrombotic complications after coronary stenting. Clopidogrel has a similar mechanism of action as ticlopidine, but both its efficacy and its safety as a pharmacologic adjunct to coronary stenting have not been well described.

METHODS

This single-center, prospective analysis examined the in-hospital procedural and 30-day clinical outcomes among 875 consecutive patients undergoing coronary stenting who received adjunctive aspirin and either clopidogrel (n = 514; 58.7%) or ticlopidine (n = 361; 41.3%) therapy.

RESULTS

Procedural success rates were similar among the clopidogrel- (99.6%) and ticlopidine-treated patients (99.4%). Subacute stent thrombosis (i.e., >24 h ≤30 days) occurred in one clopidogrel-treated (0.2%) and in one ticlopidine-treated (0.3%) patient (p = 0.99). By 30 days following the index procedure, the combined rates of death, nonfatal myocardial infarction and need for target vessel revascularization were similar among patients who received either clopidogrel (2.1%) or ticlopidine (1.4%; p = 0.57) therapy.

CONCLUSIONS

In this analysis the antiplatelet combination therapy of aspirin-plus-clopidogrel was an effective regimen for preventing thrombotic complications and major adverse cardiovascular events among a broad spectrum of patients undergoing coronary artery stenting.     

Strategies to increase the use of forearm approach during coronary angiography and interventions

The aim of this article is to focus on the utilization of forearm approach for cardiac catheterization in challenging groups of patients. Radial and ulnar approaches have gained significant popularity among the majority of interventional cardiologists. Multiple studies have demonstrated the feasibility, safety and efficacy of forearm route for cardiac catheterization and have highlighted the significant reduction in bleeding complications by avoiding the puncture of the groin. In this review we present the strategies need to be followed in order to apply the forearm approach in challenging group of patients.     

Guiding catheter thrombectomy during percutaneous coronary interventions for acute coronary syndromes.

Despite the advancements in the pharmacological and mechanical treatment of acute coronary syndromes, intracoronary thrombus and distal embolization remain among the major limitations of percutaneous transluminal coronary interventions. We describe three cases in which intragraft or intracoronary thrombus was completely aspirated during PTCI using the guiding catheter. In the first case, a 4-cm-long unfragmented embolized thrombus was effectively and completely aspirated from a saphenous vein graft, with immediate restoration of normal flow. In the second case, multiple fragments of embolized thrombus were aspirated from a large right coronary artery, while in the third case, intragraft thrombus was electively aspirated. In each case, the index lesions were then successfully stented without complications. Cathet. Cardiovasc. Intervent. 49:192-196, 2000.     

Brachytherapy after coronary interventions: current state and future perspectives

Intracoronary brachytherapy is a novel, meanwhile established therapy. It is currently the only interventional procedure which has proven to effectively reduce the restenosis rates after intervention of long and diffuse in-stent restenosis. For this indication, brachytherapy can be regarded as the current treatment of choice. Randomized studies yield promising results for bypass interventions or interventions in small vessels or diabetic patients. These findings may encourage the decision to perform a percutaneous, transluminal intervention in such high-risk patients. In clinical practice, implantation of new stents in combination with brachytherapy procedures should be avoided as far as possible. In any case, the combined antiaggregatory therapy should be conducted sufficiently long to minimize the danger of late stent thrombosis. Under this treatment, the expected thrombosis rates ar within the range of placebo-treated patients. The length of the radiation source should be sufficient to cover the entire interventional injury length to avoid recurrent edge stenosis. De novo lesions are currently not a routine indication for intracoronary brachytherapy. Although intracoronary brachytherapy may effectively reduce restenosis rates in sufficiently irradiated de novo lesion segments, de novo lesions should be treated only within the set-up of controlled studies. The current available data with a follow-up period of up to 5 years show that intracoronary brachytherapy is also in the mid-term a safe and effective therapy for the reduction of restenosis after coronary interventions.     

Sidebranch compromise during percutaneous coronary interventions

Justified concerns exist about coronary balloon angioplasty and stent deployment when a sidebranch is within the vicinity of the interventional site. Assessment of the jeopardized sidebranch for the risk of compromise can be made by evaluating the sidebranch diameter, the myocardial territory supplied, the relationship to the parent vessel lesion and the presence of ostial disease. This can help in the decision-making process of the proposed intervention, allowing a strategy to be pre-planned in the event of sidebranch compromise. Sidebranch compromise associated with flow reduction in a branch vessel that is of medium or large diameter and serving moderate or large territory is often associated with a cardiac enzyme rise. It is now recognized that any cardiac enzyme rise after intervention is associated with increased long-term risk and such compromised sidebranches may be considered for re-opening to help preserve the myocardium. A variety of balloon angioplasty and stenting techniques are described for sidebranch compromise with some short-term success. Long-term outcomes and effect of sidebranch intervention have not yet been fully evaluated.     

Monitoring anticoagulation during percutaneous coronary interventions

Summary Monitoring of the activated clotting time in the interventional catheterization suite is essential to minimize the risk of acute thrombotic occlusion, as well as to minimize the risk of bleeding-related complications postprocedure. Based on the technique used, a Hemochron ACT of >400 seconds or a HemoTec ACT of >300 seconds is associated with a low risk of acute thrombotic occlusion. Avoiding an ACT of >500 seconds should minimize the risk of procedure-related bleeding complications.     

Enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention

Randomized controlled trials of patients with non-ST segment elevation acute coronary syndromes have established the superiority of enoxaparin (versus unfractionated heparin) for reducing adverse ischemic outcomes. Furthermore, adjunctive abciximab therapy during percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. Since algorithms for integrating these pharmacotherapies have not been determined, patients undergoing elective PCI were enrolled into 2 distinct and separate studies conducted by the National Investigators Collaborating on Enoxaparin (NICE) study groups (NICE 1 and NICE 4 studies). Patients in NICE 1 were administered enoxaparin 1.0 mg/kg intravenously (without abciximab) and those enrolled in NICE 4 were administered a reduced dose (0.75 mg/kg) of enoxaparin in combination with standard-dose abciximab intravenously during PCI. Bleeding events and ischemic outcomes assessed in-hospital and at 30-days post-PCI were infrequent with either pharmacologic regimen. In the dose regimens studied, enoxaparin with or without abciximab appears to provide safe and effective anticoagulation during PCI. The combination of reduced-dose enoxaparin and abciximab was associated with a low incidence of adverse outcomes (bleeding or ischemic events). Additional studies may be required to establish the relative safety and efficacy of this new adjunctive pharmacologic strategy when compared with the combination of low-dose, weight-adjusted unfractionated heparin and abciximab.     

切割球囊在冠状动脉介入治疗中的应用

目的　研究切割球囊在冠状动脉介入治疗中的有效性和安全性。方法　22例病人,23支病变冠状动脉,25处病变,其中支架内再狭窄17例、18支血管、18处病变,距前次介入治疗平均(7.6±3.5)个月,使用切割球囊对病变进行扩张,观察扩张效果并进行临床门诊随访。结果　全部病变均取得成功,平均扩张次数(5.2±2.3)次,平均球囊总充盈时间(233.9±94.8)s,平均最大扩张压力(9.4±1.9)大气压,术后血管狭窄程度明显减轻［(89.6±8.7)%vs(17.6±17.1)%,P=0.001］,无严重并发症发生,再狭窄病变中有3处需使用普通球囊补充扩张,1处因原支架出口处撕裂再次置入支架,初次介入治疗者,因明显内膜撕裂或残余狭窄需置入支架者3例。临床随访0.5～20(7.4±6.9)个月,有2例出现心绞痛复发。结论　切割球囊对冠状动脉狭窄尤其是支架内再狭窄是有效、安全的介入治疗方法。     

Cardiologists' use of percutaneous coronary interventions for stable coronary artery disease

BACKGROUND: Percutaneous coronary intervention (PCI) is commonly performed in patients with stable coronary artery disease, despite current evidence suggesting that such patients derive minimal benefit from the procedure. We sought to determine the influences on cardiologists' decision to perform elective PCI in patients with stable coronary artery disease. METHODS: We conducted a qualitative study using 3 focus groups of interventional and noninterventional cardiologists in California. Participants discussed issues surrounding the decision to perform PCI using hypothetical case scenarios. We analyzed the data according to the principles of grounded theory. RESULTS: Despite acknowledging data showing that PCI offers no reduction in the risk of death or myocardial infarction in patients with stable coronary artery disease, cardiologists generally believed that PCI would benefit such patients. Reasons given for performing PCI included belief in the benefits of treating ischemia and the open artery hypothesis, especially with drug-eluting stents; potential regret for not intervening if a cardiac event could be averted; alleviation of patient anxiety; and medicolegal considerations. Participants believed that, in patients undergoing coronary angiography, an "oculostenotic reflex" prevailed and all significant amenable stenoses would receive intervention, even in asymptomatic patients. CONCLUSIONS: The widespread application of PCI in stable coronary artery disease for indications unsupported by evidence may reflect discordance between cardiologists' clinical knowledge and their beliefs about the benefits of PCI. Nonclinical factors appear to have substantial influence on physician decision making. Future studies should focus on the development of methods to help providers more fully incorporate clinical evidence into their medical decision making.     

Anti-angiogenic therapies for metastatic colorectal cancer:Current and future perspectives

Colorectal cancer(CRC)is the fourth most commonly diagnosed cancer and the second leading cause of cancer death in both men and women in the United States,with about 142820 new cases and 50830 deaths expected in 2013.Metastatic disease(mCRC)remains a challenge for oncologists worldwide due to its potential comorbidities.Recently,chemotherapy regimens containing 5-fluorouracil,leucovorin,oxaliplatin and irinotecan combinations are a standard of care in the metastatic disease.Currently,biological therapies involving vascular endothelial growth factor and epidermal growth factor receptor pathways,such as bevacizumab and cetuximab,have emerged as good option for improving mCRC patient survival.Now,aflibercept plus standard chemotherapy has also been approved in second line regimen for mCRC patients.Our review will discuss novel biological drugs and their indications for mCRC patients and will bring future perspectives in this regard.     

Current perspectives on the use of gene therapy for hypertension

Systemic hypertension is a pathophysiological state that is manifested as high blood pressure and is a major risk factor for stroke, ischemic heart disease, peripheral vascular disease, and progressive renal damage. Pulmonary hypertension occurs in 3 distinct forms: primary pulmonary hypertension, pulmonary hypertension of the newborn, or secondary pulmonary hypertension attributable to a variety of lung and cardiovascular diseases. This review discusses the use of gene therapy in the control of systemic and pulmonary hypertension. Overexpression of vasodilator genes as well as antisense knockdown of vasoconstrictor genes has been successfully used in animal models of both forms of hypertension. Furthermore, the use of viral vectors to deliver these constructs has achieved long-term control of hypertension. The successful establishment of gene therapy techniques in the animal models of hypertension coupled with the anticipated advances in the genetic aspects of this disease would make it highly feasible to attempt gene delivery in the control of human hypertension.