Scott A. Harding

Prophylaxis of contrast-induced nephropathy in patients undergoing coronary angiography.

Contrast‐induced nephropathy (CIN) is a common complication of cardiac catheterization, reported to result in a 15% incidence of acute renal failure. Convincing evidence supports the prophylactic use of prehydration and low volumes of contrast medium. Recently, the antioxidant acetylcysteine has been shown to have a potential preventive role. The aim of this study was to examine the hypothesis that acetylcysteine prevents CIN. Patients undergoing cardiac catheterization with a serum creatinine ≥ 1.5 mg/dl were prospectively randomized to receive acetylcysteine or placebo. A total of five doses of acetylcysteine 600 mg b.i.d. or placebo was administered, commencing on the day of the procedure. All patients were prehydrated with 0.45% saline and during the catheterization a nonionic low‐osmolality contrast medium was used. Serum creatinine and urea were measured at 24, 48, and 72 hr postprocedure. A total of 43 patients were studied. There was no significant difference between the groups in terms of baseline characteristics, including baseline renal function. No adverse events were experienced with acetylcysteine treatment. Serum creatinine levels at 48 and 72 hr remained largely unchanged in the acetylcysteine group but continued to rise at 48 and 72 hr in the placebo group. By 72 hr, the incidence of CIN, defined as a 25% increase in baseline creatinine, was significantly lower in the acetylcysteine arm compared to placebo (5% for acetylcysteine vs. 32% for placebo; P = 0.046). In patients with mild to moderate renal impairment undergoing cardiac catheterization, prophylactic treatment with oral acetylcysteine reduces the incidence of contrast‐induced nephropathy. Catheter Cardiovasc Interv 2003;60:458–461.

Acute coronary syndrome is a common clinical presentation of in-stent restenosis ☆

Coronary stents have been the major advancement in percutaneous coronary intervention in the last decade and are used in 60% to 80% of patients. However, in-stent restenosis continues to be a problem, occurring in 20% to 30% of cases. The clinical presentation of patients who develop restenosis after stenting has not been well characterized. In this study we compared the clinical presentation of in-stent restenosis with that of restenosis without stenting. Of 739 patients who underwent percutaneous coronary intervention and had repeat catheterization between October 1, 1997, and June 30, 2000, 262 consecutive patients with recurrent ischemia and restenosis were identified: 191 patients with (group A) and 71 without (Group B) stenting. Patients who underwent interventions in bypass grafts and those who developed early acute stent thrombosis were excluded from the study. Recurrent clinical ischemia occurred at a mean of 5.5 months in group A and 6.5 months in group B (p = 0.24). Rest angina (Braunwald class II and III) was more frequent in group A (48% vs 32%, p = 0.032). Acute coronary syndromes, the combination of rest angina, and acute myocardial infarction were also more frequent in group A (68% vs 46%, p = 0.03). Patients in group A were more likely to have angiographically visible thrombus than those in group B (9% vs 0%, p = 0.02). Thus, acute coronary syndromes are a common clinical presentation of restenosis among patients whose follow-up angiogram is obtained for clinical reasons, and occur more frequently in patients with in-stent restenosis than in those with restenosis without stenting.

Flow cytometric analysis of circulating platelet-monocyte aggregates in whole blood: Methodological considerations

Platelet-monocyte aggregates are increasingly being used to quantify platelet activation. The variables that influence platelet-monocyte aggregates have not been well defined. We sought to determine the effect of blood collection, handling and processing techniques on detected levels of platelet-monocyte aggregates using a flow cytometric assay. Whole blood was labelled with anti-CD14-PE and anti-CD42a-FITC. Thereafter, samples were fixed and red cells lysed. Analysis was performed with the flow cytometer initially triggering on light scatter and then on FL-2 to identify CD14-PE positive monocytes. Platelet-monocyte aggregates were defined as monocytes positive for CD42a. The effect of collection, handling and processing techniques on this assay were assessed. Anticoagulation with heparin (20.1 +/- 2.0%), PPACK (16.8 +/- 1.9%), sodium citrate (12.3 +/- 1.6%) and EDTA (9.5 +/- 1.0%) resulted in markedly different levels of platelet-monocyte aggregation (P < 0.0001). Platelet-monocyte aggregation was higher in samples obtained from intravenous cannulae compared to those obtained by venepuncture (20.9 +/- 3.9% vs.13.8 +/- 2.4%, P = 0.03). For every 10 minutes of delay prior to processing platelet-monocyte aggregates increased by 2.8% (P = 0.0001) in PPACK anticoagulated blood and 1.7% (P = 0.01) in citrate anticoagulated blood. Erythrocyte lysis together with fixation does not affect platelet-monocyte aggregation. Platelet-monocyte aggregates remained stable over 24 hours when fixed and stored at 4 degrees C. Multiple handling and processing factors may affect platelet-monocyte aggregation. We recommend the measurement of platelet-monocyte aggregates on samples collected by direct venepuncture, using a direct thrombin inhibitor as the anticoagulant and minimising the time delay before sample fixation.

Adjunctive pharmacotherapy for coronary stenting.

The use of coronary stents improves the outcomes of percutaneous coronary intervention (PCI). This has led to a rapid increase in their use. Coronary stenting is not without problems and is complicated by both early ischemic events and late restenosis. The combination of anticoagulation with unfractionated heparin (UFH) and the use of antiplatelet agents including aspirin, thienopyridines, and glycoprotein IIb/IIIa inhibitors has led to a major reduction in early ischemic events after stenting. Low molecular weight heparin (LMWH) and direct thrombin inhibitors have a number of theoretical advantages over UFH. Their role as an adjunct to coronary stenting is still under investigation. Trials of systemic pharmacotherapy aimed at reducing in-stent restenosis have been consistently disappointing. Preliminary results of stents coated with agents that inhibit neointimal proliferation are extremely promising. The results of ongoing phase III trials of these coated stents are eagerly awaited.

The effect of glycoprotein IIb/IIIa receptor inhibitor on the microcirculation in patients undergoing high-risk coronary stenting; a prospective, randomized study.

AbstractObjectives: We evaluated the effect of the glycoprotein IIb/IIIa inhibitor, tirofiban, on the microcirculation measured by Doppler coronary flow reserve (CFR) in patients undergoing high-risk coronary stenting.nBackground: The mechanisms by which glycoprotein IIb/IIIa inhibitors benefit patients undergoing high-risk angioplasty are not fully understood. This may be due to prevention of distal embolization of the coronary clot at the site of angioplasty.nMethods: Thirty two consecutive patients with acute coronary syndrome within 72 hours or with high-risk angiographic features were randomized into 2 groups. Group A (n = 17) received tirofiban (10 μg/kg bolus followed 0.15 μg/kg/min). Group B (n = 15) received placebo bolus and infusion. Coronary flow reserve was measured by Doppler wire technique at baseline, post balloon angioplasty and post-stenting. Platelet aggregation was measured at baseline, 10 minutes, 6 hours and 12 hours post bolus.nResults: There was no significant difference in CFR between the groups at baseline and after balloon angioplasty. Post-stenting CFR, however, was significantly higher in the group pretreated with tirofiban (2.94 vs. 2.25, p = 0.014). The inhibition of platelet aggregation was 94% at 10 minutes, 97% at 6 hours and 94% at 12 hours in the tirofiban group.nConclusion: In patients undergoing high-risk coronary stenting, tirofiban protects and improves the microcirculation measured by Doppler wire technique. This may be due to prevention of distal embolization of clot by tirofiban and explain the clinical benefit.

The use of mechanical devices as adjuncts to intracoronary stenting.

A number of mechanical adjuncts to intracoronary stenting are now available to the interventional cardiologist. These devices have assisted in the development of a safer and more effective stenting practice. Intravascular ultrasound-guided stenting has been shown to reduce the rate of subacute thrombosis and subsequent restenosis. It allows a greater appreciation of lesion structure and severity so that an appropriate intervention strategy can be devised. Debulking techniques may allow the optimal deployment of stents so that restenosis is reduced; however, the results of large randomized studies are still awaited. The use of thrombectomy and distal embolization protection devices is emerging as a safer alternate to stenting alone in difficult patient subsets, such as those with thrombus-laden lesions and degenerated vein grafts. Doppler and pressure wires may be useful in determining optimal stent deployment and predict subsequent patient outcomes. An understanding of the indications and limitations of these devices is of increasing importance to the interventional cardiologist as the coming decade threatens to yield an impressive array of high-tech innovations.

Triple Therapy Versus Dual Antiplatelet Therapy for Patients with Atrial Fibrillation and Acute Coronary Syndromes: A Systematic Literature Review

Background: Patients with acute coronary syndromes (ACS) and a history of atrial fibril-lation (AF) have indications for both dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC). Triple therapy (TT), the combination of DAPT and OAC, is recommended in guidelines. We examined studies comparing clinical outcomes on DAPT versus TT for patients with AF and ACS. Methods: We searched Medline, Medline pending, EMBASE and Evidence-Based Medicine Re-views databases for studies published between January 2000 to December 2016 in AF patients with ACS that compared DAPT and TT that reported ischaemic and/or bleeding outcomes. Studies that were not purely an AF population were excluded. Results: Ten studies were included in the review, all of which were observational, 8 of which were retrospective. None of the studies detailed the specifics of treatment allocation. All but one were of AF patients with a mix of stable coronary disease and ACS patients. TT was associated with in-creased bleeding when compared to DAPT, with adjusted odds ratios ranging from 1.25 to 6.84. While the largest study reported a reduction in stroke associated with TT (odds ratio 0.67), two other studies reported non-significant increases in stroke with TT. Variable composite ischaemic endpoints were reported, none showing a statistical significant difference between DAPT and TT. Conclusion: In patients with ACS and AF, TT is likely to be associated with increased risk of bleed-ing, without a clear reduction in ischaemic endpoints. The quality of the evidence to support current guidelines for this patient group was generally poor.