Ron Waksman

The potential clinical utility of intravascular ultrasound guidance in patients undergoing percutaneous coronary intervention with drug-eluting stents

AIMSnTo assess the impact on clinical outcomes of intravascular ultrasound (IVUS) guidance during drug-eluting stent (DES) implantation. IVUS guidance during percutaneous coronary intervention (PCI) has been demonstrated to be useful in optimizing stent deployment. However, it is not proved that routine use of IVUS guidance with DES implantation can prevent stent thrombosis or restenosis.nnnMETHODS AND RESULTSnThe clinical outcomes of 884 patients undergoing IVUS-guided intracoronary DES implantation from April 2003 to May 2006 were compared with the outcomes of a propensity-score matched population undergoing DES implantation with angiographic guidance alone. The primary endpoint of the study was definite stent thrombosis at 12 months. The secondary endpoint was major adverse cardiac events (MACE). After propensity-score matching, the two groups were well matched for clinical and angiographic characteristics. Patients undergoing IVUS-guided DES implantation underwent less direct stenting, more post-dilation, and had greater cutting balloon and rotational atherectomy use. At 30 days and at 12 months, a higher rate of definite stent thrombosis was seen in the No IVUS group (0.5 vs. 1.4%; P = 0.046) and (0.7 vs. 2.0%; P = 0.014), respectively. There were no major differences in late stent thrombosis and MACE (14.5 vs. 16.2%; P = 0.33) at 12 month follow-up between the groups. Rates of death and Q-wave myocardial infarction were similar, and there was no significant difference between groups in target vessel revascularization. However, a trend was seen in favour of the IVUS group in target lesion revascularization (5.1 vs. 7.2%; P = 0.07). IVUS guidance was an independent predictor of freedom from cumulative stent thrombosis at 12 months (adjusted HR 0.5, CI 0.1-0.8; P = 0.02).nnnCONCLUSIONnIVUS guidance during DES implantation has the potential to influence treatment strategy and reduce both DES thrombosis and the need for repeat revascularization.

Impact of “Nuisance” Bleeding on Clopidogrel Compliance in Patients Undergoing Intracoronary Drug-Eluting Stent Implantation

Premature cessation of clopidogrel is a strong risk factor for drug-eluting stent thrombosis in patients undergoing percutaneous coronary intervention. The impact that superficial or nuisance bleeding may have on clopidogrel compliance has not been described. The study population consisted of 2,360 unselected patients undergoing successful drug-eluting stent implantation. Nuisance bleeding, defined as easy bruising, bleeding from small cuts, petechia, and ecchymosis, was assessed during routine clinical follow-up. Internal and alarming bleeding was recorded. Cessation of clopidogrel as a consequence of such bleeding was then assessed. Study population characteristics were 66.1% men, mean age 64.5 +/- 11.8 years, diabetes mellitus in 31.1%, smoking in 18.5%, systemic hypertension in 81.8%, dyslipidemia in 87.9%, history of coronary artery disease in 49.1%, chronic renal insufficiency in 8.7%, and acute myocardial infarction in 10.8%. A total of 837 patients reported bleeding events (incidence 32.4%) of which 85.7% were nuisance, 13.6% were internal, and 0.7% were alarming. Rate of clopidogrel discontinuation as a result of bleeding in the nuisance bleeding group was 11.1%. In conclusion, superficial or nuisance bleeding is common in patients taking dual antiplatelet therapy after percutaneous coronary intervention. Overall, 11.1% of patients with nuisance bleeding discontinued clopidogrel. Greater education and follow-up in this patient subset may lead to improved compliance with clopidogrel therapy.

Temporal relation between Clopidogrel cessation and stent thrombosis after drug-eluting stent implantation.

The risk of late thrombotic events and the need for prolonged dual antiplatelet therapy detract from the clinical advantage offered by drug-eluting stents (DESs). Short-term studies have shown premature clopidogrel cessation to be a strong predictor of stent thrombosis (ST) after DES implantation. Data pertaining to the utility of clopidogrel therapy and its optimal duration to prevent late ST remain limited. The study population consisted of 2,889 patients who underwent unrestricted intracoronary DES implantation from April 2003 to January 2007 for whom clopidogrel compliance data were available. Definite ST proved by angiography or autopsy within 12 months of the index procedure occurred in 61 patients. Comparisons of clinical and procedural characteristics in addition to outcomes (death and Q-wave myocardial infarction) were made between the ST and no-ST (2,828 patients) groups. Clopidogrel compliance was assessed at all follow-up time points. For patients in the ST group, clopidogrel compliance status for the remaining study period was defined as that at the time of ST. Logistic regression analysis was performed at 30 days, 6 months, and 12 months to identify independent predictors of cumulative ST. Patients with ST were more likely to have previous congestive heart failure and worse left ventricular ejection fraction. ST was associated with significantly higher mortality at 12 months (23.5% vs 3.2%, p <0.001). Clopidogrel compliance was 80.2% in the overall population and 73.8% in patients presenting with ST (82.6% in patients presenting with early ST and 43.8% in those with late ST). By logistic regression analysis, clopidogrel cessation was an independent predictor of cumulative ST at 30 days and 6 months but not at 12 months. In conclusion, high rates of clopidogrel compliance can be achieved in contemporary practice. Clopidogrel cessation by 12 months is no longer predictive of ST, thus suggesting the optimal duration of therapy for the prevention of ST to be 6 to 12 months.

Impact of “Off-Label” Utilization of Drug-Eluting Stents on Clinical Outcomes in Patients Undergoing Percutaneous Coronary Intervention

The utilization of drug-eluting stents (DES) in real world practice has deviated from Food and Drug Administration-approved indications. Safety concerns have arisen from recent reports that suggested increased mortality and nonfatal myocardial infarction (MI) with DES usage. Little is known about the clinical outcomes of patients undergoing intracoronary DES implantation for unapproved indications as a group compared with outcomes after bare metal stent (BMS) placement. The clinical outcomes of 546 patients undergoing DES implantation for >or=1 non-Food and Drug Administration-approved (off label) indication since the approval of the device were assessed. The group was then matched by propensity score with 546 patients receiving BMSs prior to DES approval for the same indications. The primary endpoint was major adverse cardiac events (cardiac death, nonfatal Q-wave myocardial infarction [MI], and target vessel revascularization) at 12 months. Baseline clinical and angiographic characteristics were well matched between BMS and DES groups. The use of debulking devices was higher in the BMS group. Patients in the BMS group were more likely to be treated with larger diameter and shorter stents. There was no significant difference in the rate of in-hospital and 30-day adverse cardiac events. At 12 months, the primary endpoint of major adverse cardiac events was significantly reduced in the DES group (23.6% vs 16.7%, p=0.004), driven by reductions in the need for repeat revascularization (target lesion revascularization: 16.4% vs 7.8%, p<0.001; target vessel revascularization: 20.2% vs 13.1%, p=0.003). There was no significant difference in freedom from cardiac death or nonfatal Q-wave MI between groups (p=0.27). In conclusion, the utilization of DES for non-Food and Drug Administration-approved indications proved to be efficacious and safe when compared with a BMS cohort matched by propensity score. The advantage for DES was driven by reductions in repeat revascularization. Off-label DES use was not associated with increased rates of cardiac death and nonfatal MI at 12 months.

Requirement for Emergent Coronary Artery Bypass Surgery Following Percutaneous Coronary Intervention in the Stent Era

Performance of percutaneous coronary intervention (PCI) at centers without cardiothoracic surgery is a contentious issue. Although this practice allows greater access to care, there are safety concerns. The aim was to assess the requirement for emergent coronary artery bypass grafting (CABG) after PCI and characterize patients at highest risk using independent predictors. The study population consisted of 21,957 unselected patients who underwent PCI from August 1994 (Food and Drug Administration stent approval) to January 2008 at a single medical center. Patients requiring emergent CABG (defined as within 24 hours of the index procedure) were identified. Logistic regression analysis was performed to assess for independent correlates of emergent CABG. Emergent CABG was required in 90 patients (cumulative incidence 0.41%). Indications for CABG included triple-vessel disease, dissection, acute closure, perforation, and failure to cross. These patients had significantly higher in-hospital cardiac death rates (7.8% vs 0.7%; p <0.01) and higher rates of Q-wave myocardial infarction, neurologic events, and renal insufficiency. Independent correlates of emergent CABG after PCI were acute ST-segment elevation myocardial infarction presentation, cardiogenic shock, triple-vessel disease, and type C lesion. Risk assessment based on these predictors identified 0.3% of the patient population to have a 9.3% cumulative incidence of emergent CABG. In conclusion, the need for emergent CABG after PCI in the stent era was low and was associated with poor in-hospital outcomes. Risk was nonuniform, with 0.3% of the study population, characterized by acute presentation and complex coronary disease, at heightened risk of emergent surgery.

Incidence, Predictors, and Outcomes of Post-Percutaneous Coronary Intervention Nephropathy in Patients With Diabetes Mellitus and Normal Baseline Serum Creatinine Levels

Diabetes mellitus is an independent predictor of nephropathy after percutaneous coronary intervention (PCI). The outcomes of patients with diabetes with normal baseline serum creatinine who undergo PCI remain underevaluated. The aim of the present study was to assess the incidence, outcomes, and correlates of post-PCI nephropathy in this subset. The study cohort consisted of 570 patients with diabetes with normal serum creatinine (< or =1.3 mg/dl) who underwent PCI from August 2004 to December 2006. Patients aged >75 years and those presenting with either acute myocardial infarctions or cardiogenic shock were excluded. Post-PCI nephropathy was defined as a > or =25% increase in baseline creatinine. The study end points were post-PCI nephropathy and major adverse cardiac events at 6 months. Logistic regression was performed to identify independent predictors. Post-PCI nephropathy occurred in 70 patients (incidence 12.3%). These patients were more likely to be women (55.7% vs 35.5%, p = 0.001) and to have histories of congestive heart failure (24.2% vs 14.7%, p = 0.048). Entry-site complications (hematoma, pseudoaneurysm) and the need for blood transfusion (16.7% vs 1.7%, p <0.001) were more common in this group. In-hospital mortality (8.6% vs 0.2%, p <0.001) and length of stay (4.51 +/- 5.2 vs 2.23 +/- 2.9 days, p <0.001) were significantly higher in the group with post-PCI nephropathy. No study patient required dialysis. At 6 months, major adverse cardiac events were markedly higher in patients with post-PCI nephropathy (21.4% vs 6.0%, p <0.001), driven by death and revascularization. Independent predictors of post-PCI nephropathy were lower body mass index and blood transfusion. Post-PCI nephropathy independently predicted major adverse cardiac events (hazard ratio 4.3, 95% confidence interval 2.1 to 8.6, p <0.001). In conclusion, post-PCI nephropathy occurred in 12.3% of patients with diabetes with normal baseline serum creatinine and carried a significant detrimental impact on prognosis. The requirement for blood transfusions was the strongest correlate identified.

Comparison between sirolimus- and paclitaxel-eluting stents in complex patient and lesions subsets.

Background: Sirolimus‐eluting stents (SES) and paclitaxel‐eluting stents (PES) both significantly reduce the need for repeat intervention compared to bare metal stents. Studies comparing the clinical outcomes of these stents in noncomplex subsets of patients and lesions demonstrate a similar safety and efficacy profile. The data for more complex subsets of patients and lesions remains conflicting. This study aimed to compare SES with PES in a selected population with a broad range of complex features. Methods and Results: The patient population consisted of 1,591 consecutive patients with complex features undergoing drug‐eluting stent (DES) implantation. In the SES group there were 1,095 patients (1,653 lesions) and in the PES group 496 patients (802 lesions). In‐hospital, 30‐day, and 12‐month clinical outcomes were compared between groups. No discernable difference in major adverse cardiac events (MACE) between SES and PES was detected at intermediate and longer‐term follow‐up (SES 22.4% vs. PES 20.5% at 12 months; P = 0.407). A trend toward increased angiographically documented stent thrombosis was observed in the SES group at both 3 and 12 months (SES 2.2% vs. PES 0.8% at 12 months; P = 0.051). When adopting the more inclusive definition of probable stent thrombosis, this trend was no longer seen. After adjusting for baseline differences between the two groups, there still remained no difference in MACE between SES and PES (HR 1.051 [CI 0.826–1.339] P = 0.685). The trend toward increased angiographically documented stent thrombosis in the SES group remained after adjustment for baseline differences (HR 2.836 [CI 0.968–8.311] P = 0.057). Conclusions: In a selected population with complex disease the rate of MACE was comparable between SES and PES, with higher overall rates of thrombosis and MACE compared to a noncomplex population. Thus, the focus should be directed to prevent late complications in this complex subset regardless of stent type selection.

Pharmacology in the catheterization laboratory

Ron Waksman, Andrew E. Ajani. 0.0 Elective PCI. 0.1 Optimal antithrombotic therapy. 0.1.1 Unfractionated heparin and ACT monitoring. 0.1.2 Alternative to unfractionated heparin. 0.1.2.1 LMWH. 0.1.2.2 direct thrombin inhibitor (bivarlirudin). 0.1.2.3 direct Xa antagonist (fondaparinux). 0.2 Optimal antiplatelet therapy. 0.2.1 Dual aspirin and thienopyridine therapy. - pre-treatment and dose. 0.2.2 When to use GP2B3A inhibitor and which one to use. - abciximab, tirofiban, eptifibatide. 0.2.3 Duration of Antiplatelet therapy with drug-eluting vs. bare-metal stents. 1.0 High risk PCI. 1.1 ACS (non ST elevation). 1.1.1 Upstream GP2B3A inhibitors. 1.1.2 Timing, loading dose and duration of clopidogrel therapy. 1.2 Diabetes mellitus. 1.2.1 Peri-procedural management. 1.3 Renal dysfunction. 1.3.1 Renal protective agents. - IV hydration, N-acetylcysteine, bicarbonate, fenoldopam. - Timing, route of administration and duration. 1.3.2 Radiocontrast induced nephropathy. 1.3.2.1 Ideal contrast agent. 1.3.3 Additional risk with other medications. - ACE inhibitors, NSAIDS, hypotensive medications (e.g. nitrates, BBlockers). 1.4 Cardiogenic shock. 1.4.1 Inotropic support. - adrenaline, noradrenaline, dopamine, dobutamine, milrinone, levosimendan, metaraminol. - summary of when to use which agent (ref. ACC/AHA STEMI guidelines). 1.4.2 Anticoagulation support for mechanical devices. - IABP, LVAD, Tandem Heart, Impaler etc. 2.0 Acute STEMI PCI. 2.1 Primary. - summary of optimal anticoagulation, GP2B3A, antiplatelet therapy (aspirin, clopidogrel). 2.2 Rescue. - summary of optimal anticoagulation, GP2B3A, antiplatelet therapy (aspirin, clopidogrel). 2.3 Facilitated. - summary of optimal anticoagulation, GP2B3A and lytic combinations in recent trials. 2.4 Adjunctive therapies. 2.4.1 GIK (glucose-insulin-potassium). 2.4.2 Complement inhibitor (Pexiluzimab). 2.4.3 Intracoronary vs. intravenous GP2B3A inhibitor. 2.4.4 High dose tirofiban. (Standard dose GP2B3A inhibitors for STEMI discussed in 2.1 and 2.2). 3.0 Optimal thrombolytic therapy (as primary therapy for STEMI). - alteplase, reteplase, streptokinase, or tenecteplase. 4.0 Special considerations in PCI. 4.1 Coronary spasm. 4.2 No reflow phenomenon. - IV GTN, GP2B3A inhibitor, nitroprusside, adenosine, verapamil, nicorandil. 4.3 Agents to optimise access of radial artery approach (i.e. nitrates, verapamil). 4.4 Arrhythmia Management. 4.4.1 Tachyarrhythmias management. - IV lignocaine, amiodarone, etc. 4.4.2 Bradyarrhythmias management. - IV atropine, adrenalin, indications for temporary pacing wire. 4.5 Coronary perforations. 4.5.1 Reversal of anticoagulation. - protamine. 4.5.2 Platelet and transfusion of blood products. 4.6 Oral anticoagulation issues in PCI. 4.6.1 Management of patients on anticoagulation undergoing diagnostic catheterisation and PCI. - prosthetic heart valves, AF and other indications. - use of UFH and LMWH as bridging therapy. - when to restart oral anticoagulation post procedure. 4.6.2 Indications for anticoagulation post PCI. - LV thrombus. - large anterior myocardial infarction. - triple (aspirin, clopidogrel and warfarin) vs. dual therapy. 4.7 Role of Antibiotic prophylaxis in PCI. 5.0 Post procedural pharmacotherapy. 5.1 Role of statins, beta-blocker, ACE inhibitors, aldosterone antagonist (epleronone). 5.1.1 ACS (include STEMI/NSTEMI). 5.1.2 Elective PCI. 6.0 Special considerations with antiplatelet therapy. 6.1 Antiplatelet therapy resistance: definition, diagnosis and clinical implications. 6.2 Potential drug-drug interactions. 6.2.1 Clopidogrel and statins. 6.2.2 Aspirin and ibuprofen. 6.2.3 COX-2 inhibitors in patients with coronary artery disease. 6.3 Clopidogrel use in patients requiring CABGS. 6.4 Thrombocytopenia post PCI. 6.4.1 HITTS. 6.4.2 GP2B3A risk. 6.5 Novel antiplatelet therapy. - Prasugrel etc. 7.0 Pharmacotherapy for in-stent restenosis. 7.1 Drug-eluting stents. 7.1.1 Sirolimus. 7.1.2 Paclitaxel. 7.1.3 Other agents (ABT-578). 7.1.4 Oral agents to prevent ISR (Oral Sirolimus, Glitazones). 8.0 Novel pharmacotherapy and PCI. APPENDIX. - Listing of generic drug names in alphabetical order with 1 page summary sheet on each drug. o Indications and contraindications. o Dose and formulations. o Adverse reactions. o Drug interactions