Real-World Experience With Antiplatelet Agents After Percutaneous Coronary Intervention in Patients With an Indication for an Oral Anticoagulant.

ABSTRACT: Patients undergoing percutaneous coronary intervention (PCI) with a clinical indication for oral anticoagulation (OAC) in addition to antiplatelet therapy (APT) necessitate rigorous evaluation of bleeding and ischemic risk to guide therapy. The optimal OAC/APT drug combination and duration of treatment is not known. This study aimed to evaluate the incidence of patients undergoing PCI with an OAC indication and the rationale for post-PCI combined OAC/APT selection in clinical practice. Consecutive patients undergoing PCI with an indication for combined OAC/APT were included in a 12-month retrospective case series. Patient demographics, clinical characteristics, prescribed OAC/APT regimens, and rationale for drug selection were reviewed. PCI was performed in 1650 patients during the study period, with an indication for OAC/APT in 133 (8.1%). A combination of aspirin, P2Y12 inhibitor, and OAC was the most frequently prescribed regime on discharge (n = 103, 81%). Dual antiplatelet therapy (DAPT) in combination with OAC was continued for a mean duration of 6.4 ± 4.4 weeks (range 3-52 weeks) before one antiplatelet was discontinued. There was no significant difference between the mean CHA2DS2-VASc or HAS-BLED score of patients with atrial fibrillation discharged on OAC/DAPT compared with alternate combinations (DAPT alone or OAC/single APT), 3.6 ± 1.3 versus 3.8 ± 1, P = 0.37 and 2.04 ± 0.7 versus 2.05 ± 1.0, P = 0.98, respectively. This case series identifies high variability in OAC/APT treatment duration and limited application of risk scoring systems and high-risk PCI characteristics in the selection of OAC/APT regimens. A more systematic patient assessment is needed to help standardize OAC/APT prescribing for this important patient cohort.

Significance of the learning curve in left atrial appendage occlusion with two different devices.

OBJECTIVE: To evaluate the impact of learning on outcome with use of two different left atrial appendage (LAA) occlusion devices. BACKGROUND: Two self-expanding devices, the Watchman and the Amplatzer Cardiac Plug (ACP), have been used for LAA occlusion in the last few years. It has been demonstrated that complications associated with implantation decrease in frequency with operator experience. However, the role of operator experience has not been compared across the two device types. METHODS: The study comprises 31 consecutive patients who underwent LAA occlusion. We compare the first 10 patients in whom an ACP was implanted with the subsequent eleven patients who underwent ACP implantation and with 10 cases where a Watcthman device was implanted. The composite safety end point comprised procedure-related events and excessive bleeding events. We also performed 3 months echocardiographic and clinical follow-up. RESULTS: There were not significant differences in the basal clinical and echocardiographical characteristics across the three groups. Cardiac complications only occurred in the ACP initial experience group (9% vs. 0% vs. 0% P = 0.04). Echocardiographic and clinical follow-up at 3 months was completed in all patients. No significant residual leak was detected. One patient in the ACP initial experience group developed a thrombus on the device. One patient in ACP late experience presented an ischemic stroke. CONCLUSIONS: Complications associated with LAA occlusion cluster early in the peri-procedural period and significantly decrease in frequency with operator experience. Initial experience gained with one of device may improve outcome with use of alternative LAA occlusion devices.

Difference in outcome among women and men after percutaneous mitral valvuloplasty.

OBJECTIVE: To analyze the differences in anatomical, clinical and echocardiographic characteristics of women and men undergoing PMV and to evaluate the relationship between sex, PMV success, and immediate and long-term clinical outcome. BACKGROUND: Rheumatic mitral stenosis (MS) is predominantly a disease of middle-aged women. Percutaneous mitral valvuloplasty (PMV) has become the standard of care for suitable patients. However little is known about the relationship between sex, PMV success, and procedural outcome. METHODS AND RESULTS: We evaluated measures of procedural success and clinical outcome in consecutive patients (839 women and 176 men) who underwent PMV. Despite a lower baseline echocardiographic score (7.47 ± 2.15 vs. 8.02 ± 2.18, P = 0.002), women were less likely to achieve PMV success (69% vs. 83%, adjusted OR 0.44, 95% CI 0.27-0.74, P = 0.002), and had a smaller post-procedural MV area (1.86 ± 0.7 vs. 2.07 ± 0.7 cm(2), P < 0.001). Overall procedural and in-hospital complication rates did not differ significantly between women and men. However, women were significantly more likely to develop severe MR immediately post PMV (adjusted OR 2.41, 95% CI 1.0-5.83, P = 0.05) and to undergo MV surgery (adjusted HR 1.54, 95% CI 1.03-2.3, P = 0.037) after a median follow-up of 3.1 years. CONCLUSIONS: Compared to men, women with rheumatic MS who undergo PMV are less likely to have a successful outcome and more likely to require MV surgery on long-term follow-up despite more favorable baseline MV anatomy.

A case report of ventricular septal defect complicating transcatheter aortic valve implant for aortic regurgitation: novel complication and technical considerations.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has proven efficacy in the treatment of aortic stenosis (AS). Understandably, there is increasing enthusiasm for its use to treat aortic regurgitation (AR). However, there are significant anatomical differences between AS and AR which make TAVI for AR more complex. CASE SUMMARY: We present the case of technically challenging TAVI for severe AR, which was complicated by a traumatic ventricular septal defect (VSD) that required percutaneous closure. To our knowledge, this is the first published case of VSD post-TAVI for AR. DISCUSSION: This unanticipated complication highlights anatomical differences between TAVI use in AS and AR. Lack of aortic valve calcification and excessive annular compliance made stable deployment of a self-expanding valve extremely challenging. Despite device oversizing, repeated embolization of the prosthesis into the left ventricular outflow tract traumatized the interventricular septum.

Sex differences in medical care and early death after acute myocardial infarction.

BACKGROUND: Women receive less evidence-based medical care than men and have higher rates of death after acute myocardial infarction (AMI). It is unclear whether efforts undertaken to improve AMI care have mitigated these sex disparities in the current era. METHODS AND RESULTS: Using the Get With the Guidelines-Coronary Artery Disease database, we examined sex differences in care processes and in-hospital death among 78 254 patients with AMI in 420 US hospitals from 2001 to 2006. Women were older, had more comorbidities, less often presented with ST-elevation myocardial infarction (STEMI), and had higher unadjusted in-hospital death (8.2% versus 5.7%; P<0.0001) than men. After multivariable adjustment, sex differences in in-hospital mortality rates were no longer observed in the overall AMI cohort (adjusted odds ratio [OR]=1.04; 95% CI, 0.99 to 1.10) but persisted among STEMI patients (10.2% versus 5.5%; P<0.0001; adjusted OR=1.12; 95% CI, 1.02 to 1.23). Compared with men, women were less likely to receive early aspirin treatment (adjusted OR=0.86; 95% CI, 0.81 to 0.90), early beta-blocker treatment (adjusted OR=0.90; 95% CI, 0.86 to 0.93), reperfusion therapy (adjusted OR=0.75; 95% CI, 0.70 to 0.80), or timely reperfusion (door-to-needle time

Impact of time of presentation on the care and outcomes of acute myocardial infarction.

BACKGROUND: Prior studies have demonstrated an inconsistent association between patients' arrival time for acute myocardial infarction (AMI) and their subsequent medical care and outcomes. METHODS AND RESULTS: Using a contemporary national clinical registry, we examined differences in medical care and in-hospital mortality among AMI patients admitted during regular hours (weekdays 7 am to 7 pm) versus off-hours (weekends, holidays, and 7 pm to 7 am weeknights). The study cohort included 62,814 AMI patients from the Get With the Guidelines-Coronary Artery Disease database admitted to 379 hospitals throughout the United States from July 2000 through September 2005. Overall, 33 982 (54.1%) patients arrived during off-hours. Compared with those arriving during regular hours, eligible off-hour patients were slightly less likely to receive primary percutaneous coronary intervention (adjusted odds ratio [OR], 0.93; 95% confidence interval [CI], 0.89 to 0.98), had longer door-to-balloon times (median, 110 versus 85 minutes; P<0.0001), and were less likely to achieve door-to-balloon < or = 90 minutes (adjusted OR, 0.34; 95% CI, 0.29 to 0.39). Arrival during off-hours was associated with slightly lower overall revascularization rates (adjusted OR, 0.94; 95% CI, 0.90 to 0.97). No measurable differences, however, were found in in-hospital mortality between regular hours and off-hours in the overall AMI, ST-elevated MI, and non-ST-elevated MI cohorts (adjusted OR, 0.99; 95% CI, 0.93 to 1.06; adjusted OR, 1.05; 95% CI, 0.94 to 1.18; and adjusted OR, 0.97; 95% CI, 0.90 to 1.04, respectively). Similar observations were made across most age and sex subgroups and with an alternative definition for arrival time (weekends/holidays versus weekdays). CONCLUSIONS: Despite slightly fewer primary percutaneous coronary interventions and overall revascularizations and significantly longer door-to-balloon times, patients presenting with AMI during off-hours had in-hospital mortality similar to those presenting during regular hours.

Retrograde versus antegrade percutaneous aortic balloon valvuloplasty: immediate, short- and long-term outcome at 2 years.

BACKGROUND: The short- and long-term vascular risks and hemodynamic benefits of antegrade versus retrograde percutaneous aortic balloon valvuloplasty (PAV) have not been clearly established. With the advent of percutaneous aortic valve replacement strategies, more valvuloplasties are being performed. The antegrade approach may reduce vascular complications, particularly in patients with peripheral vascular disease (PVD). Comparing the clinical efficacy and complications of each technique is warranted. METHODS: A cohort of 157 consecutive patients undergoing PAV between 2000 and 2006 were included in the study. Of these, 46 (29%) patients underwent antegrade PAV and 111 (71%) retrograde PAV. Choice of vascular approach (antegrade or retrograde) were determined by operator preference. The rate of death, nonfatal vascular complications, and 2-year survival was explored. RESULTS: The mean age of the study population was 79 years. Patients undergoing antegrade PAV were more likely hypertensive (56% vs. 39%, P = 0.001) with PVD (41% vs. 18%, P = 0.004). Nevertheless, logistic Euroscores were no different between the groups (antegrade 18% vs. retrograde 14%; P = 0.30). Baseline and postprocedural valve areas were also similar. However, patients undergoing antegrade PAV had significantly fewer vascular complications (2% vs. 19%; P = 0.005). Two-year follow-up revealed no significant difference in death (antegrade 81% vs. retrograde 69%; P = 0.16), stroke, congestive heart failure, and surgical aortic valve replacement. CONCLUSIONS: The hemodynamic benefit of PAV occurs regardless of the selected vascular approach. The antegrade technique results in significantly fewer vascular complications and similar long-term outcomes. Antegrade PAV is feasible and safe, particularly in patients with PVD.

Impact of concomitant aortic regurgitation on percutaneous mitral valvuloplasty: Immediate results, short-term, and long-term outcome.

BACKGROUND: The aim of the study is to examine the effect of concomitant aortic regurgitation (AR) on percutaneous mitral valvuloplasty (PMV) procedural success, short-term, and long-term clinical outcome. No large-scale study has explored the impact of coexistent AR on PMV procedural success and outcome. METHODS: Demographic, echocardiographic, and procedure-related variables were recorded in 644 consecutive patients undergoing 676 PMV at a single center. Mortality, aortic valve surgery (replacement or repair) (AVR), mitral valve surgery (MVR), and redo PMV were recorded during follow-up. RESULTS: Of the 676 procedures performed, 361 (53.4%) had no AR, 287 (42.5%) mild AR, and 28 (4.1%) moderate AR. There were no differences between groups in the preprocedure characteristics, procedural success, or in the incidence of inhospital adverse events. At a median follow-up of 4.11 years, there was no difference in the overall survival rate (P = .22), MVR rate (P = .69), or redo PMV incidence (P = .33). The rate of AVR was higher in the moderate AR group (0.9% vs 1.9% vs 13%, P = .003). Mean time to AVR was 4.5 years and did not differ significantly between patients with no AR, mild AR, or moderate AR (2.9 +/- 2.1 vs 5.7 +/- 3.6 vs 4.1 +/- 2.5 years, P = .46). CONCLUSIONS: Concomitant AR at the time of PMV does not influence procedural success and is not associated with inferior outcome. A minority of patients with MS and moderate AR who undergo PMV will require subsequent AVR on long-term follow-up. Thus, patients with rheumatic MS and mild to moderate AR remain good candidates for PMV.

Effect of enteric coating on antiplatelet activity of low-dose aspirin in healthy volunteers.

BACKGROUND AND PURPOSE: Aspirin resistance may be relatively common and associated with adverse outcome. Meta-analysis has clearly shown that 75 mg plain aspirin is the lowest effective dose; however, it is not known whether the recent increased use of enteric-coated aspirin could account for aspirin resistance. This study was designed to determine whether enteric-coated aspirin is as effective as plain aspirin in healthy volunteers. METHODS: Seventy-one healthy volunteers were enrolled in 3 separate bioequivalence studies. Using a crossover design, each volunteer took 2 different aspirin preparations. Five aspirin preparations were evaluated, 3 different enteric-coated 75-mg aspirins, dispersible aspirin 75 mg and asasantin (25-mg standard release aspirin plus 200-mg modified-release dipyridamole given twice daily). Serum thromboxane (TX) B2 levels and arachidonic acid-induced platelet aggregation were measured before and after 14 days of treatment. RESULTS: All other aspirin preparations tested were inferior to dispersible aspirin (P<0.001) in their effect on serum TXB(2) level. Treatment failure (<95% inhibition serum TXB2 formation) occurred in 14 subjects, none of whom were taking dispersible aspirin. Mean weight for those demonstrating treatment failure was greater than those with complete TXB2 (>99%) inhibition (P<0.001). Using logistic regression analysis an 80-kg subject had a 20% probability of treatment failure. Asasantin was the most potent preparation in terms of inhibition of platelet aggregation. CONCLUSIONS: Equivalent doses of the enteric-coated aspirin were not as effective as plain aspirin. Lower bioavailability of these preparations and poor absorption from the higher pH environment of the small intestine may result in inadequate platelet inhibition, particularly in heavier subjects.

Newer pharmacotherapy in patients undergoing percutaneous coronary interventions: a guide for pharmacists and other health care professionals.

Significant advances in pharmacotherapy for patients undergoing percutaneous coronary intervention (PCI) have occurred during the past decade, including the introduction and approval of new antithrombin and antiplatelet therapies, as well as modifications in dosing, administration, and/or duration of older pharmacotherapy regimens. Also, off-label (i.e., not approved by the United States Food and Drug Administration) use of certain agents has become common. Given the novel nature of these agents and the nuances of therapy, the pharmacist and other health care professionals should play an integral role in collaboration with interventional cardiologists in development of hospital protocols, determination of appropriate agent selection, assessment of patient renal function and hematologic status, dosing, and monitoring for adverse effects. In this guide, the newer antiplatelet and antithrombin drugs that may be used during PCI are reviewed, and recommendations regarding the proper administration of these agents are provided.

Renal insufficiency, bleeding and prescription of discharge medication in patients undergoing percutaneous coronary intervention in the National Heart, Lung, and Blood Institute (NHLBI) Dynamic Registry.

AIMS: To establish the relationship between renal insufficiency, bleeding and prescription of cardiovascular medication. METHODS AND RESULTS: This was a prospective, multi-center, cohort study of consecutive patients undergoing PCI during three NHLBI Dynamic Registry recruitment waves. Major and minor bleeding, access site bleeding and rates of prescription of cardiovascular medication at discharge were determined based on estimated glomerular filtration rate (eGFR). Renal insufficiency was an independent predictor of major adverse cardiovascular events (MACE). Bleeding events and access site bleeding requiring transfusion were significantly associated with degrees of renal insufficiency (p<0.001). There was an incremental decline in prescription of cardiovascular medication at discharge proportionate to the degree of renal impairment (aspirin, thienopyridine, statin, coumadin (overall p<0.001), beta blocker (overall p=0.003), ACE inhibitor (overall p=0.02). Bleeders were less likely to be discharged on a thienopyridine (95.4% versus 89.9% for bleeding, p<0.001 and 95.3% versus 87.9% for access site bleeding, p=0.005), but not aspirin (96.3% versus 96.2%, p=0.97 and 96.3% versus 93.6%, p=0.29 respectively). Failure to prescribe anti-platelet therapy at discharge was strongly associated with increased MACE at one year. CONCLUSIONS: Renal insufficiency is associated with bleeding in patients undergoing PCI. Patients with renal insufficiency are less likely to receive recommended discharge pharmacotherapy.

Point-of-care platelet function testing predicts bleeding in patients exposed to clopidogrel undergoing coronary artery bypass grafting: Verify pre-op TIMI 45--a pilot study.

BACKGROUND: Guidelines recommend delaying coronary artery bypass grafting (CABG) for 5 days after discontinuing clopidogrel. However, platelet function may recover quicker in certain individuals. HYPOTHESIS: We hypothesized that perioperative measurement of platelet function with a point-of-care P2Y12 inhibitor assay could predict bleeding during CABG in patients exposed to clopidogrel. METHODS: Verify Pre-Op TIMI 45 was a prospective pilot study of 39 patients on clopidogrel who subsequently underwent CABG. Preoperative on-treatment platelet reactivity was assessed with VerifyNow P2Y12 Reaction Units (PRU), with higher PRU indicating more reactive platelets. Outcomes were stratified by PRU quartiles, as well as prespecified cutpoints for the lowest quartile (PRU 173), a cutpoint for major bleeding determined by the Youden index using receiver operator curve analysis (PRU 207), and clopidogrel resistance (PRU 230). RESULTS: Patients in higher PRU quartiles experienced smaller decreases in hemoglobin and hematocrit (P < 0.05 for all comparisons), less major bleeding (P = 0.021), and less major or minor bleeding (P = 0.003). Patients above the PRU 207 and 230 cutpoints had less chest-tube output (P = 0.041 and P = 0.012, respectively), less major bleeding (P = 0.005 and P = 0.036, respectively), and less major or minor bleeding (P = 0.013 and P < 0.001, respectively). By receiver operator curve analysis, preoperative PRU ≤ 207 discriminated between patients with and without major bleeding during surgery (area under the curve: 0.76, 95% confidence interval: 0.59-0.94, P = 0.018). CONCLUSIONS: In this pilot study, we found that point-of-care platelet function assessment could predict bleeding in patients recently exposed to clopidogrel undergoing CABG.

Aspirin and coronary artery disease.

Coronary atherosclerosis (CAD), a chronic inflammatory disorder, arises when genetic susceptibility, intercurrent conditions such as diabetes and hypertension and environmental factors interact. Although CAD can remain stable for many years, thrombus formation at sites of plaque rupture may lead to unstable angina (UA) or myocardial infarction (MI). Already recognised as the central component of coronary thrombosis, platelets, through their interaction with monocytes and endothelial cells, may also be involved at the earliest stages of atheromatous plaque evolution. Aspirin, the prototype antiplatelet agent, covalently and irreversibly inhibits cyclooxygenase (COX) and thus inhibits platelet thromboxane (TX) A(2) biosynthesis. Anti-oxidant properties and the ability to modulate transcription of immunologically important genes have also been attributed to aspirin. Non-selective COX inhibition, however, predisposes to bleeding, predominantly secondary to dosedependent gastro-intestinal toxicity. The emerging concept of "aspirin resistance" coincides with the development of alternative antiplatelet therapy and point-of-care platelet function assays. Though variable aspirin pharmacokinetics may explain many cases, heritable factors, inducible platelet COX expression and isoprostane formation may also contribute. In future, risk factor screening and point-of-care platelet function assay may identify vulnerable patients who would benefit from additional or alternate antiplatelet therapy.

Effect of elevated pulmonary vascular resistance on outcomes after percutaneous mitral valvuloplasty.

Patients with mitral stenosis with severe pulmonary hypertension constitute a high-risk subset for surgical commissurotomy or valve replacement. The aim of the present study was to examine the effect of elevated pulmonary vascular resistance (PVR) on percutaneous mitral valvuloplasty (PMV) procedural success, short- and long-term clinical outcomes (i.e., mortality, mitral valve surgery, and redo PMV) in 926 patients. Of the 926 patients, 263 (28.4%) had PVR ≥4 Woods units (WU) and 663 (71.6%) had PVR <4 WU. Patients with PVR ≥4 WU were older and more symptomatic and had worse valve morphology for PMV. The patients with PVR ≥4 WU also had lower PMV procedural success than those with PVR <4 WU (78.2% vs 85.6%, p = 0.006). However, after multivariate adjustment, PVR was no longer an independent predictor of PMV success nor an independent predictor of the combined end point at a median follow-up of 3.2 years. In conclusion, elevated PVR at PMV is not an independent predictor of procedural success or long-term outcomes. Therefore, appropriately selected patients with rheumatic mitral stenosis might benefit from PMV, even in the presence of elevated preprocedural PVR.