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Safety of bivalirudin in primary percutaneous coronary intervention following thrombolytic therapy
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Abstracts / Cardiovascular Revascularization Medicine 12 (2011) e1–e46
Conclusion: In view of infrequent major ischemic complications with contemporary PCI, emerging data appear to support selective GPI administration (to patients at high ischemic risk and low bleeding propensity) and more abbreviated GPI administration. These strategies, along with other strategies to reduce bleeding, should be subject to highquality RCTs. doi:10.1016/j.carrev.2011.04.306
Discrepancy between long-term clinical events and the level of platelet aggregation post-PCI: is it the drug or the test? Ayman Magd a, Mohamad Sobhy b, Nereen Okasha a, Mounir Osman a, Hany Ragy a, Yasser Abdelgelil a a Azhar University, Cairo, Egypt b Alexandria University, Cairo, Egypt Background: Late DES thrombosis has emerged as an important issue. At present, light transmission aggregometry (LTA) remains the gold standard for determining adequate platelet inhibition for DES patients on clopidogrel. However, multiple studies have shown considerable interpatient variability response with poor correlation to subsequent clinical events. Moreover, little data exist regarding the long-term inhibition of patients initially inhibited and compliant with clopidogrel. The aim of this study is to determine the long-term effect of clopidogrel on platelets by serial LTA in patients showing an initial adequate response. Methods: Ninety-two patients with an initial adequate response to clopidogrel by LTA were included in this study. Serial LTA studies were performed at 2 weeks, 3 months and 6 months postprocedure. The primary endpoint was clinical events at 6 months. Results: The mean age was 61 years, 39 were diabetic and 12 had renal dysfunction. All patients had an initial loading dose of 600 mg clopidogrel preprocedure. Fifty-two patients were on 75 mg and 42 were on 150 mg clopidogrel at 2 weeks and continued on their dose at the end of the study. All were also on 75 mg ASA. All patients were compliant with study medication for the duration of the study. At 2 weeks, all were adequately inhibited on clopidogrel;, however, at 3 months, only 46/92 (50%) were adequately inhibited (Pb.01). The platelet aggregation response range was 5%–82% (mean=56%). At 6 months, only 51/92 (55%) remained adequately inhibited (range=15%–79%, mean=51%, Pb.01). There were no adverse clinical events detected at 6 months. Conclusion: In this small initial study, nearly 50% of patients with an initial adequate platelet inhibition by LTA on clopidogrel/ASA therapy were not adequately inhibited at 3 and 6 months. Thus, perhaps intermittent reloading may be required .The absence of any adverse clinical events implies either that clopidogrel works by other unmeasurable mechanisms or a deficiency in the technique of LTA. doi:10.1016/j.carrev.2011.04.307
Platelet aggregation response to 150-mg maintenance dose of clopidogrel compared to the conventional dose of 75 mg for patients scheduled for elective PCI. Six-month follow-up study Ahmed Mowafy Cairo University, Cairo, Egypt Aim: Our prospective in this study to test whether increase in the clopidogrel maintenance dose results in increased platelet inhibition that may be reflected in decreasing major adverse cardiac effects after PCI. Introduction: Dual-antiplatelet therapy consisting of aspirin and clopidogrel is currently the therapy of choice to prevent thrombosis after percutaneous coronary intervention (PCI). A considerable interindividual variability in response to clopidogrel has been observed after administration of loading doses of clopidogrel. In a significant proportion of patients (10%– 30%), no or little inhibition of platelet aggregation is achieved with the
currently used dosing regimens. Some authors suggest that the antiplatelet effect achieved with the currently recommended maintenance dose can be augmented. In fact, administration of a 150-mg daily maintenance dose is now broadly discussed and occasionally used in clinical practice. Methods and results: Sixty-two patients after pretreatment with 600-mg loading dose of Plavix and after successful elective PCI were included in the trial. They were allocated to receive one of two clopidogrel daily maintenance doses (75 or 150 mg) for 30 days in a nonrandomized manner. Platelet function was evaluated 30 days after the intervention with the impact R device that measures the surface coverage (SC%) and average particle size (AS Um2) as reflection of platelet adhesion and aggregation. SC% after 30 days was 2.4±0.52 and AS was 23.9±3.5 in pts treated with 150 mg/day, whereas it was 3.6±0.88 and AS was 33.8+4.2 in pts treated with 75 mg/day, with P values of SC=.02 and AS=.7. Conclusion: The main message of our study was to demonstrate that doubling of the conventional maintenance dose of clopidogrel may be an option to improve platelet inhibition that might lead to decreased thrombotic complication after PCI. This study shows that administration of 150-mg daily maintenance dose of clopidogrel results in more intense inhibition of platelet function when compared with administration of the currently recommended daily maintenance dose of 75 mg. The intensified clopidogrel effect of the high oral maintenance dose used in this trial has the potential to further reduce the incidence of ischemic events after PCI. Recently, it was shown that the 150-mg daily maintenance dose is also more effective than the 75-mg daily maintenance dose in diabetic patients with a suboptimal response to clopidogrel. doi:10.1016/j.carrev.2011.04.308
Safety of bivalirudin in primary percutaneous coronary intervention following thrombolytic therapy Gabriel L. Sardi, Michael A. Gaglia Jr., Manuel A. Gonzalez, Gabriel Maluenda, Ana Laynez-Carnicero, Rafael Romaguera, Michael Mahmoudi, Kohei Wakabayashi, Itsik Ben-Dor, Rebecca Torguson, William O. Suddath, Augusto D. Pichard, Lowell F. Satler, Ron Waksman Washington Hospital Center, Washington, DC, USA Background: Thrombolytic therapy is still used for patients presenting with ST-elevation myocardial infarction. The safety and efficacy of bivalirudin (BIV) for primary percutaneous coronary intervention (PCI) in these patients have not been established. This study aimed to compare the safety of BIV vs. unfractionated heparin (UFH) in patients undergoing primary PCI following initial management with thrombolytic therapy. Methods: A series of 104 consecutive patients treated with primary PCI, who received full-dose thrombolytic therapy within 6 h prior to the intervention, was identified and retrospectively analyzed. The use of intraprocedural UFH and BIV was compared for in-hospital bleeding and ischemic events. Results: This series includes 47 patients (45%) treated with BIV and 57 patients (55%) treated with UFH. The baseline characteristics were
Table 1 Comparison of bivalirudin and UFH: basic demographics, adjunctive therapy and in-hospital outcomes
Age (years) Male (%) Low-molecular-weight heparin (%) Intraprocedural IIb/IIIa Inhibitor (%) Preload with clopidogrel (%) TIMI major bleed (%) TIMI minor bleed (%) CVA/TIA (%) Death (%)
Bivalirudin
Heparin
P value
56.6 ±14.7 83.0 42.6 0.0 56.5 4.3 2.1 0.0 2.1
55.4 ±10.8 86.0 21.4 31.6 28.1 3.5 7.0 3.5 5.3
.636 .647 .021 b.001 .003 1.0 .375 .5 .625
Abstracts / Cardiovascular Revascularization Medicine 12 (2011) e1–e46 similar in both groups. Patients on BIV more frequently received lowmolecular-weight heparin and were more frequently preloaded with clopidogrel. Intraprocedural glycoprotein IIb/IIIa inhibitors were used only in UFH patients. Incidence of TIMI major bleeding was similar. Other bleeding events and ischemic endpoints were more frequent in patients treated with UFH, but results did not reach statistical significance (Table 1). Conclusions: During primary PCI, use of BIV after initial management with thrombolytics appears as safe as UFH. A randomized trial addressing safety and outcomes of BIV after lytic therapy is warranted.
doi:10.1016/j.carrev.2011.04.309
Ranolazine for the treatment of refractory angina in a veterans population Ronald Shane Greene a, Robert M. Rangel b, Krystal L. Edwards a, Lisa M. Chastain a, Sara D. Brouse a, Carlos A. Alvarez a, Laura J. Collins c, Emmanouil S. Brilakis c, Subhash Banerjee c a VA North Texas Health Care System and Texas Tech University Health Sciences Center School of Pharmacy, Dallas, TX, USA b Presbyterian Medical Group, Albuquerque, NM, USA c VA North Texas Health Care System and University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA Introduction: Pivotal ranolazine trials did not include patients with refractory angina on optimal antianginal medications. The purpose of this study was to evaluate the efficacy and safety of ranolazine for the treatment of angina refractory to maximal medical treatment in a veterans population. Hypothesis: We hypothesized that ranolazine would decrease the number of weekly self-reported angina episodes and sublingual nitroglycerin tablet utilization as compared to baseline. Methods: The study was a retrospective cohort of patients experiencing three or more angina episodes per week despite treatment with maximally tolerated antianginal therapy (beta-blockers, long-acting dihydropyridine calcium channel blockers and long-acting nitrates). We assessed change in the number of self-reported weekly angina episodes and of sublingual nitroglycerin utilization. Change in the QTc interval was evaluated as a safety endpoint. All comparisons were made from baseline to endpoint using a Wilcoxon signed rank test for paired data. Results: A total of 18 subjects were enrolled. All subjects were white males with a median age of 66.0 years. At study end, a significant decrease in angina episodes and sublingual nitroglycerin doses per week was observed (Table 1). Of the 18 subjects enrolled, 44% had complete resolution of angina episodes. There was no significant change in the QTc interval. Conclusion: Addition of ranolazine to maximally tolerated antianginal therapy significantly decreased both angina episodes and sublingual
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nitroglycerin utilization. Ranolazine may provide a safe and effective treatment option for refractory angina in a veterans population. doi:10.1016/j.carrev.2011.04.310
Percutaneous valve intervention Procedural and postoperative outcomes following balloon aortic valvuloplasty in severe aortic stenosis patients with left ventricular ejection fractions b20% Christopher Pedersen a, Mary Dang b, Irvin Goldenberg b, Dean Krueger a, Michael Mooney a, Timothy D. Henry a, Robert S. Schwartz a a Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN, USA b Twin Cities Heart Foundation, Minneapolis, MN, USA Background: Severe aortic stenosis (AS) patients with left ventricular ejection fraction (LVEF) b20% are currently excluded from transcatheter aortic valve implant trials and are believed to be at higher risk for balloon aortic valvuloplasty (BAV). Methods: Our BAV database, including 260 consecutive patients extending from 2005 to 2010, was reviewed for patients with LVEF b20%. A total of 16 patients were identified. Demographics, hemodynamics, procedural technique and outcom es were analyzed. All patients underwent BAV by retrograde technique using standard noncompliant aortic balloons while at rapid ventricular pacing at 180–220 beats/min. Intravenous inotropes and vasopressors were used to maintain systolic blood pressures N90 mmHg. Results: Patients had a mean age of 83.1±10.5 years. The mean STS score was 18.6%±10.5%. Three patients were on intravenous inotropes prior to arrival at the catheterization laboratory. Predilatation mean arterial pressure was 85±12.1 mmHg, mean pulmonary wedge pressure was 25.7±5.9 mmHg and cardiac index was 1.7±0.4 L/min/m2. An average of 3±1 balloon inflations was performed. Twelve patients (75%) required periprocedural inotropic-vasopressor support. Emergent IABP placement was required in two patients, one of which also required intubation. The procedural mortality was 0%. In-hospital and 6-month mortalities were 18% and 44%, respectively. Eight patients (50%) demonstrated an improved LVEF to ≥20% (mean 26%) on predischarge echocardiography. Pre- and postop echocardiographic findings are listed in the Table 1. Table 1 Echocardiographic findings N=16
Mean valve gradient (mmHg)
Valve area (cm2)
Left ventricular ejection fraction (%)
Pre-BAV Post-BAV
34±12 23±11
0.63±0.21 1.09±0.64
17±3 23±11
Abstracts / Cardiovascular Revascularization Medicine 12 (2011) e1–e46
Conclusion: In view of infrequent major ischemic complications with contemporary PCI, emerging data appear to support selective GPI administration (to patients at high ischemic risk and low bleeding propensity) and more abbreviated GPI administration. These strategies, along with other strategies to reduce bleeding, should be subject to highquality RCTs. doi:10.1016/j.carrev.2011.04.306
Discrepancy between long-term clinical events and the level of platelet aggregation post-PCI: is it the drug or the test? Ayman Magd a, Mohamad Sobhy b, Nereen Okasha a, Mounir Osman a, Hany Ragy a, Yasser Abdelgelil a a Azhar University, Cairo, Egypt b Alexandria University, Cairo, Egypt Background: Late DES thrombosis has emerged as an important issue. At present, light transmission aggregometry (LTA) remains the gold standard for determining adequate platelet inhibition for DES patients on clopidogrel. However, multiple studies have shown considerable interpatient variability response with poor correlation to subsequent clinical events. Moreover, little data exist regarding the long-term inhibition of patients initially inhibited and compliant with clopidogrel. The aim of this study is to determine the long-term effect of clopidogrel on platelets by serial LTA in patients showing an initial adequate response. Methods: Ninety-two patients with an initial adequate response to clopidogrel by LTA were included in this study. Serial LTA studies were performed at 2 weeks, 3 months and 6 months postprocedure. The primary endpoint was clinical events at 6 months. Results: The mean age was 61 years, 39 were diabetic and 12 had renal dysfunction. All patients had an initial loading dose of 600 mg clopidogrel preprocedure. Fifty-two patients were on 75 mg and 42 were on 150 mg clopidogrel at 2 weeks and continued on their dose at the end of the study. All were also on 75 mg ASA. All patients were compliant with study medication for the duration of the study. At 2 weeks, all were adequately inhibited on clopidogrel;, however, at 3 months, only 46/92 (50%) were adequately inhibited (Pb.01). The platelet aggregation response range was 5%–82% (mean=56%). At 6 months, only 51/92 (55%) remained adequately inhibited (range=15%–79%, mean=51%, Pb.01). There were no adverse clinical events detected at 6 months. Conclusion: In this small initial study, nearly 50% of patients with an initial adequate platelet inhibition by LTA on clopidogrel/ASA therapy were not adequately inhibited at 3 and 6 months. Thus, perhaps intermittent reloading may be required .The absence of any adverse clinical events implies either that clopidogrel works by other unmeasurable mechanisms or a deficiency in the technique of LTA. doi:10.1016/j.carrev.2011.04.307
Platelet aggregation response to 150-mg maintenance dose of clopidogrel compared to the conventional dose of 75 mg for patients scheduled for elective PCI. Six-month follow-up study Ahmed Mowafy Cairo University, Cairo, Egypt Aim: Our prospective in this study to test whether increase in the clopidogrel maintenance dose results in increased platelet inhibition that may be reflected in decreasing major adverse cardiac effects after PCI. Introduction: Dual-antiplatelet therapy consisting of aspirin and clopidogrel is currently the therapy of choice to prevent thrombosis after percutaneous coronary intervention (PCI). A considerable interindividual variability in response to clopidogrel has been observed after administration of loading doses of clopidogrel. In a significant proportion of patients (10%– 30%), no or little inhibition of platelet aggregation is achieved with the
currently used dosing regimens. Some authors suggest that the antiplatelet effect achieved with the currently recommended maintenance dose can be augmented. In fact, administration of a 150-mg daily maintenance dose is now broadly discussed and occasionally used in clinical practice. Methods and results: Sixty-two patients after pretreatment with 600-mg loading dose of Plavix and after successful elective PCI were included in the trial. They were allocated to receive one of two clopidogrel daily maintenance doses (75 or 150 mg) for 30 days in a nonrandomized manner. Platelet function was evaluated 30 days after the intervention with the impact R device that measures the surface coverage (SC%) and average particle size (AS Um2) as reflection of platelet adhesion and aggregation. SC% after 30 days was 2.4±0.52 and AS was 23.9±3.5 in pts treated with 150 mg/day, whereas it was 3.6±0.88 and AS was 33.8+4.2 in pts treated with 75 mg/day, with P values of SC=.02 and AS=.7. Conclusion: The main message of our study was to demonstrate that doubling of the conventional maintenance dose of clopidogrel may be an option to improve platelet inhibition that might lead to decreased thrombotic complication after PCI. This study shows that administration of 150-mg daily maintenance dose of clopidogrel results in more intense inhibition of platelet function when compared with administration of the currently recommended daily maintenance dose of 75 mg. The intensified clopidogrel effect of the high oral maintenance dose used in this trial has the potential to further reduce the incidence of ischemic events after PCI. Recently, it was shown that the 150-mg daily maintenance dose is also more effective than the 75-mg daily maintenance dose in diabetic patients with a suboptimal response to clopidogrel. doi:10.1016/j.carrev.2011.04.308
Safety of bivalirudin in primary percutaneous coronary intervention following thrombolytic therapy Gabriel L. Sardi, Michael A. Gaglia Jr., Manuel A. Gonzalez, Gabriel Maluenda, Ana Laynez-Carnicero, Rafael Romaguera, Michael Mahmoudi, Kohei Wakabayashi, Itsik Ben-Dor, Rebecca Torguson, William O. Suddath, Augusto D. Pichard, Lowell F. Satler, Ron Waksman Washington Hospital Center, Washington, DC, USA Background: Thrombolytic therapy is still used for patients presenting with ST-elevation myocardial infarction. The safety and efficacy of bivalirudin (BIV) for primary percutaneous coronary intervention (PCI) in these patients have not been established. This study aimed to compare the safety of BIV vs. unfractionated heparin (UFH) in patients undergoing primary PCI following initial management with thrombolytic therapy. Methods: A series of 104 consecutive patients treated with primary PCI, who received full-dose thrombolytic therapy within 6 h prior to the intervention, was identified and retrospectively analyzed. The use of intraprocedural UFH and BIV was compared for in-hospital bleeding and ischemic events. Results: This series includes 47 patients (45%) treated with BIV and 57 patients (55%) treated with UFH. The baseline characteristics were
Table 1 Comparison of bivalirudin and UFH: basic demographics, adjunctive therapy and in-hospital outcomes
Age (years) Male (%) Low-molecular-weight heparin (%) Intraprocedural IIb/IIIa Inhibitor (%) Preload with clopidogrel (%) TIMI major bleed (%) TIMI minor bleed (%) CVA/TIA (%) Death (%)
Bivalirudin
Heparin
P value
56.6 ±14.7 83.0 42.6 0.0 56.5 4.3 2.1 0.0 2.1
55.4 ±10.8 86.0 21.4 31.6 28.1 3.5 7.0 3.5 5.3
.636 .647 .021 b.001 .003 1.0 .375 .5 .625
Abstracts / Cardiovascular Revascularization Medicine 12 (2011) e1–e46 similar in both groups. Patients on BIV more frequently received lowmolecular-weight heparin and were more frequently preloaded with clopidogrel. Intraprocedural glycoprotein IIb/IIIa inhibitors were used only in UFH patients. Incidence of TIMI major bleeding was similar. Other bleeding events and ischemic endpoints were more frequent in patients treated with UFH, but results did not reach statistical significance (Table 1). Conclusions: During primary PCI, use of BIV after initial management with thrombolytics appears as safe as UFH. A randomized trial addressing safety and outcomes of BIV after lytic therapy is warranted.
doi:10.1016/j.carrev.2011.04.309
Ranolazine for the treatment of refractory angina in a veterans population Ronald Shane Greene a, Robert M. Rangel b, Krystal L. Edwards a, Lisa M. Chastain a, Sara D. Brouse a, Carlos A. Alvarez a, Laura J. Collins c, Emmanouil S. Brilakis c, Subhash Banerjee c a VA North Texas Health Care System and Texas Tech University Health Sciences Center School of Pharmacy, Dallas, TX, USA b Presbyterian Medical Group, Albuquerque, NM, USA c VA North Texas Health Care System and University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA Introduction: Pivotal ranolazine trials did not include patients with refractory angina on optimal antianginal medications. The purpose of this study was to evaluate the efficacy and safety of ranolazine for the treatment of angina refractory to maximal medical treatment in a veterans population. Hypothesis: We hypothesized that ranolazine would decrease the number of weekly self-reported angina episodes and sublingual nitroglycerin tablet utilization as compared to baseline. Methods: The study was a retrospective cohort of patients experiencing three or more angina episodes per week despite treatment with maximally tolerated antianginal therapy (beta-blockers, long-acting dihydropyridine calcium channel blockers and long-acting nitrates). We assessed change in the number of self-reported weekly angina episodes and of sublingual nitroglycerin utilization. Change in the QTc interval was evaluated as a safety endpoint. All comparisons were made from baseline to endpoint using a Wilcoxon signed rank test for paired data. Results: A total of 18 subjects were enrolled. All subjects were white males with a median age of 66.0 years. At study end, a significant decrease in angina episodes and sublingual nitroglycerin doses per week was observed (Table 1). Of the 18 subjects enrolled, 44% had complete resolution of angina episodes. There was no significant change in the QTc interval. Conclusion: Addition of ranolazine to maximally tolerated antianginal therapy significantly decreased both angina episodes and sublingual
e25
nitroglycerin utilization. Ranolazine may provide a safe and effective treatment option for refractory angina in a veterans population. doi:10.1016/j.carrev.2011.04.310
Percutaneous valve intervention Procedural and postoperative outcomes following balloon aortic valvuloplasty in severe aortic stenosis patients with left ventricular ejection fractions b20% Christopher Pedersen a, Mary Dang b, Irvin Goldenberg b, Dean Krueger a, Michael Mooney a, Timothy D. Henry a, Robert S. Schwartz a a Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN, USA b Twin Cities Heart Foundation, Minneapolis, MN, USA Background: Severe aortic stenosis (AS) patients with left ventricular ejection fraction (LVEF) b20% are currently excluded from transcatheter aortic valve implant trials and are believed to be at higher risk for balloon aortic valvuloplasty (BAV). Methods: Our BAV database, including 260 consecutive patients extending from 2005 to 2010, was reviewed for patients with LVEF b20%. A total of 16 patients were identified. Demographics, hemodynamics, procedural technique and outcom es were analyzed. All patients underwent BAV by retrograde technique using standard noncompliant aortic balloons while at rapid ventricular pacing at 180–220 beats/min. Intravenous inotropes and vasopressors were used to maintain systolic blood pressures N90 mmHg. Results: Patients had a mean age of 83.1±10.5 years. The mean STS score was 18.6%±10.5%. Three patients were on intravenous inotropes prior to arrival at the catheterization laboratory. Predilatation mean arterial pressure was 85±12.1 mmHg, mean pulmonary wedge pressure was 25.7±5.9 mmHg and cardiac index was 1.7±0.4 L/min/m2. An average of 3±1 balloon inflations was performed. Twelve patients (75%) required periprocedural inotropic-vasopressor support. Emergent IABP placement was required in two patients, one of which also required intubation. The procedural mortality was 0%. In-hospital and 6-month mortalities were 18% and 44%, respectively. Eight patients (50%) demonstrated an improved LVEF to ≥20% (mean 26%) on predischarge echocardiography. Pre- and postop echocardiographic findings are listed in the Table 1. Table 1 Echocardiographic findings N=16
Mean valve gradient (mmHg)
Valve area (cm2)
Left ventricular ejection fraction (%)
Pre-BAV Post-BAV
34±12 23±11
0.63±0.21 1.09±0.64
17±3 23±11