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.

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.

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.

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.

Impact of pre- and postprocedural mitral regurgitation on outcomes after percutaneous mitral valvuloplasty for mitral stenosis.

Percutaneous mitral valvuloplasty (PMV) is an effective therapy in patients with significant mitral stenosis. Few studies have examined the effect of mitral regurgitation (MR), a frequent periprocedural finding, on PMV outcomes. We examined the effects of pre- and postprocedural MR after PMV. Contrast left ventriculography was performed before and after PMV, and the MR severity was assessed using Sellers' classification. Clinical, hemodynamic, and morphologic variables were collected for all patients. Consecutive patients (n = 876) undergoing a first PMV procedure at a single tertiary center were evaluated. An increasing preprocedural MR severity was associated with reduced PMV success (no MR, 75%; 1+ MR, 65%; 2+ MR, 44%; p <0.0001), increased in-hospital mortality (0.6% vs 2.8% vs 4.9%, respectively; p = 0.007), and other complications. Increasing grades of pre- and postprocedural MR predicted, independently and in a grade-dependent manner, the composite outcome of mortality, mitral valve surgery, or redo PMV (preprocedural MR >or=1+, relative risk [RR] 1.4, 95% confidence interval [CI] 1.2 to 1.8; preprocedural MR >or=2+, RR 1.6, 95% CI 1.1 to 2.4; postprocedural MR >or=1+, RR 1.6, 95% CI 1.2 to 2.0; postprocedural MR >or=2+, RR 2.2, 95% CI 1.7 to 2.7; and postprocedural MR >or=3+, RR 4.6, 95% CI 3.4 to 6.2, respectively). In conclusion, increasing pre- and postprocedural MR grades independently predicted the long-term clinical outcomes after PMV. Patients with moderate preprocedural MR, in particular, appeared to have suboptimal short- and long-term outcomes, necessitating careful monitoring and early referral for mitral valve surgery, when appropriate.

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.

Growth arrest specific gene (GAS) 6 modulates platelet thrombus formation and vascular wall homeostasis and represents an attractive drug target.

GAS6, the product of growth arrest specific (GAS) gene 6 is a ligand for the tyrosine protein kinase receptors Axl, Tyro3 and Mer whose signaling has been implicated in cell growth, survival, adhesion and migration. Although a secreted human vitamin K-dependent protein with close structural similarity with protein S, GAS6 does not exhibit anticoagulant properties but rather may be an important regulator of vascular homeostasis and platelet signaling. GAS6 signals via its receptor tyrosine kinases and appears to modulate platelet outside-in signaling via GP alpha(IIb)beta(III), playing a key role in the perpetuation of platelet aggregates and clot retraction. GAS6 is also implicated in foam cell formation and neointimal proliferation in response to vascular injury. Thus GAS6 acts at key points in the pathophysiology of atherosclerosis and thrombosis; two processes implicated in most acute cardiovascular pathology. Inhibition of GAS6 or its receptors may provide antithrombotic activity in the absence of increased bleeding and thus presents an attractive drug target. GAS6 signaling may be modulated through direct antibody inhibition, blockade of its receptors or GAS6 trapping. However, ubiquitous expression of GAS6 and its receptors and the diverse biological effects of the pathway may make selective drug targeting difficult.

Late loss of early benefit from drug-eluting stents when compared with bare-metal stents and coronary artery bypass surgery: 3 years follow-up of the ERACI III registry.

AIMS: Long-term benefit from coronary revascularization with drug-eluting stents (DES) relative to bare metal stents (BMS) and coronary artery bypass grafting (CABG) has not been established. One year follow-up of the ERACI III registry study showed better outcome with DES. To compare major adverse cardiac and cerebrovascular event (MACCE) rates in patients with multivessel cardiovascular disease (CVD) who received DES with those patients treated with BMS or CABG in the ERACI II trial. METHODS AND RESULTS: Patients with multivessel CVD who met the ERACI II trial, clinical and angiographic inclusion criteria were treated with DES and enrolled in the ERACI III registry. The primary endpoint was 3-year MACCE. ERACI III-DES patients (n = 225) were compared with the BMS (n = 225) and CABG (n = 225) arms of ERACI II. Patients treated with DES were older, more often smokers, more often high risk by euroSCORE and less frequently had unstable angina. They also had higher incidence of type C lesions and received more stents than the BMS-treated cohort. Three year MACCE was lower in ERACI III-DES (22.7%) than in ERACI II-BMS (29.8%, P = 0.015), mainly reflecting less target vessel revascularization (14.2 vs. 24.4%, P = 0.009). MACCE rates at 3 years were similar in DES and CABG-treated patients (22.7%, P = 1.0), in contrast to results at 1 year (12 vs. 19.6%, P = 0.038). MACCE rates in ERACI III-DES were higher in diabetics (RR 0.81, 0.66-0.99; P = 0.018). Death or non-fatal MI at 3 years trended higher in the DES (10.2%) than BMS cohort (6.2%, P = 0.08) and lower than in CABG patients (15.1%, P = 0.07). Sub-acute late-stent thrombosis (LST) (>30 days) occurred in nine DES patients and no BMS patients (P = 0.008). CONCLUSION: In patients with multivessel CVD, the initial advantage for PCI with DES over CABG observed at 1 year was not apparent by 3 years. Furthermore, despite continued lower incidence of MACCE, initial advantage over BMS appeared to decrease with time. LST occurred more frequent in DES-treated patients.