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Biomedical subjects

Cindy L Grines

Publications and source records attributed to Cindy L Grines.

At least 19 recordsLinked to original sources
PubMed2003

Benefits and risks of abciximab use in primary angioplasty for acute myocardial infarction: the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial.

BACKGROUND: Trials of platelet glycoprotein IIb/IIIa inhibitors as adjuncts to primary percutaneous coronary intervention for acute myocardial infarction (MI) have shown improved early clinical and angiographic outcomes with treatment. However, variations in trial designs, modest sample sizes, and limited long-term follow-up have precluded these studies from being definitive. METHODS AND RESULTS: As a prespecified secondary analysis of the CADILLAC trial, we compared early and late outcomes by abciximab assignment among 2082 patients randomized in an open-label, 2x2 factorial-design trial of primary stenting versus angioplasty and abciximab treatment (n=1052) versus no abciximab treatment (n=1030). Baseline characteristics were balanced between groups. Abciximab treatment was associated with a significant reduction in the composite end point of death, MI, ischemia-driven target-vessel revascularization (TVR), or disabling stroke at 30 days (4.6% versus 7.0%; relative risk, 0.65; 95% CI, 0.46 to 0.93; P=0.01). Subacute thrombosis also was significantly reduced with abciximab treatment. At 12 months, however, rates of the composite end point did not differ significantly (18.4% for controls versus 16.9% for abciximab-treated patients; relative risk, 0.92; 95% CI, 0.76 to 1.10; P=0.29), reflecting a decrease in the relative difference in TVR rates (ie, no effect of abciximab on reducing restenosis). In an angiographic substudy (n=656), myocardial salvage, restenosis, and infarct-artery reocclusion at 7 months were unaffected by abciximab treatment. There was no significant interaction between stenting and abciximab treatment. CONCLUSIONS: Adjunctive abciximab treatment during primary percutaneous coronary intervention significantly enhanced 30-day event-free survival, predominantly by reducing ischemia-driven TVR. Abciximab treatment did not affect the composite end point at 1 year, reflecting a lack of effect on restenosis.

Abciximab↗
PubMed2003

Percutaneous coronary interventions in octogenarians. glycoprotein IIb/IIIa receptor inhibitors' safety profile.

OBJECTIVES: This study was designed to evaluate the safety profile of glycoprotein IIb/IIIa receptor inhibitors (GPI) in octogenarians undergoing percutaneous coronary intervention (PCI). BACKGROUND: Patients > or =80 years old constitute the fastest growing segment of the U.S. population and have a high prevalence of coronary artery disease. Few data exist regarding the use of GPI during PCI in octogenarians, as these patients have been excluded from randomized clinical trials of GPI. METHODS: Consecutive patients > or =80 years old undergoing PCI between January 1998 and June 2001 were evaluated for clinical outcomes and bleeding complications. RESULTS: One thousand three hundred and ninety two of 14,308 patients (9.7%) undergoing PCI were > or =80 years old. Of these, 459 of 1,392 (33%) of the patients were treated with GPI. Octogenarians treated with GPI were more likely to present with acute coronary syndrome or infarction, receive stents, require an intra-aortic balloon pump, or undergo multi-vessel PCI. Glycoprotein receptor inhibitor use was associated with a higher rate of bleeding, but the transfusion rate was similar to that in patients who did not receive GPI (9.8% vs. 8.6%, p = NS). No cases of intracranial hemorrhage were observed. By multivariate analysis, GPI treatment was associated with longer hospitalization but did not independently predict the need for transfusion or affect mortality. CONCLUSIONS: Octogenarians have a high incidence of bleeding and need for transfusion after PCI. Although the use of GPI was associated with more access and non-access site bleeding and longer hospital stay, GPI treatment does not significantly increase the risk of transfusion or intracranial hemorrhage in this non-randomized cohort.

Abciximab↗
PubMed2003

Coronary plaque morphology and frequency of ulceration distant from culprit lesions in patients with unstable and stable presentation.

OBJECTIVE: Intravascular ultrasound studies describe ruptured coronary plaques at sites remote from the culprit lesion in patients with acute myocardial infarction (MI), suggesting multifocal plaque vulnerability. However, the role of intravascular ultrasound in the diagnosis of lesion vulnerability before rupture is unclear. METHODS AND RESULTS: We compared morphology and frequency of ulceration of additional plaques proximal to the culprit lesion in 105 patients treated with emergent stenting during an evolving, acute MI in the CADILLAC study and 92 patients with stable/subacute presentation who underwent elective stenting. Additional plaques proximal to the culprit lesion were found in 52 (50%) and 54 (59%) patients in the acute MI and stable/subacute group, respectively. The prevalence of ulceration was significantly higher in the acute MI than in the stable/subacute group (19% versus 4%; P=0.014). However, there was no significant difference in other morphological lesion characteristics. CONCLUSIONS: Additional plaques are frequently found adjacent to the culprit lesions in patients undergoing percutaneous coronary intervention independent of clinical presentation. The increased prevalence of plaque ulceration but otherwise similar morphology of additional lesions in patients with acute MI versus stable/subacute presentation demonstrates the limitations of imaging in the assessment of plaque vulnerability.

Angina Pectoris↗
PubMed2003

Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials.

BACKGROUND: Many trials have been done to compare primary percutaneous transluminal coronary angioplasty (PTCA) with thrombolytic therapy for acute ST-segment elevation myocardial infarction (AMI). Our aim was to look at the combined results of these trials and to ascertain which reperfusion therapy is most effective. METHODS: We did a search of published work and identified 23 trials, which together randomly assigned 7739 thrombolytic-eligible patients with ST-segment elevation AMI to primary PTCA (n=3872) or thrombolytic therapy (n=3867). Streptokinase was used in eight trials (n=1837), and fibrin-specific agents in 15 (n=5902). Most patients who received thrombolytic therapy (76%, n=2939) received a fibrin-specific agent. Stents were used in 12 trials, and platelet glycoprotein IIb/IIIa inhibitors were used in eight. We identified short-term and long-term clinical outcomes of death, non-fatal reinfarction, and stroke, and did subgroup analyses to assess the effect of type of thrombolytic agent used and the strategy of emergent hospital transfer for primary PTCA. All analyses were done with and without inclusion of the SHOCK trial data. FINDINGS: Primary PTCA was better than thrombolytic therapy at reducing overall short-term death (7% [n=270] vs 9% [360]; p=0.0002), death excluding the SHOCK trial data (5% [199] vs 7% [276]; p=0.0003), non-fatal reinfarction (3% [80] vs 7% [222]; p<0.0001), stroke (1% [30] vs 2% [64]; p=0.0004), and the combined endpoint of death, non-fatal reinfarction, and stroke (8% [253] vs 14% [442]; p<0.0001). The results seen with primary PTCA remained better than those seen with thrombolytic therapy during long-term follow-up, and were independent of both the type of thrombolytic agent used, and whether or not the patient was transferred for primary PTCA. INTERPRETATION: Primary PTCA is more effective than thrombolytic therapy for the treatment of ST-segment elevation AMI.

Angioplasty, Balloon, Coronary↗
PubMed2003

Impact of angina class on inhibition of platelet aggregation following clopidogrel loading in patients undergoing coronary intervention: do we need more aggressive dosing regimens in unstable angina?

Pretreatment with thienopyridines has been shown to improve clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). We determine the impact of angina class on inhibition of platelet aggregation (IPA) following clopidogrel loading. Seventy-two patients (mean age, 64 +/- 11 years; 76% male) were pretreated with 450 mg of clopidogrel at least 3 hr prior to PCI. All patients received ASA 325 mg prior to the procedure. Patients were classified into two groups according to angina class: group 1 = stable angina or Braunwald class 1 unstable angina (UA; n = 33); group 2 = Braunwald class 2 or 3 UA (n = 39). IPA was measured prior to PCI, with the Ichor point-of-care platelet analyzer (Helena Laboratories, Beaumont, TX), using 20 microM of ADP. Group 2 patients were more likely to have prior MI (54% vs. 27%; P = 0.023), prior CABG (33% vs. 5%; P = 0.046), and received IV heparin (64% vs. 27%; P = 0.0018). Mean IPA was significantly lower in group 2 compared to group 1 (19% +/- 22% vs. 32% +/- 22%; P = 0.004). In multivariate analysis, higher angina class was independently associated with lower IPA (P = 0.018). Patients with UA undergoing PCI have a lower IPA following clopidogrel loading with 450 mg. This may indicate the possibility of clopidogrel resistance in such patients.

Angina, Unstable↗
PubMed2003

Percutaneous intervention of unprotected left main coronary artery.

Successful percutaneous intervention of unprotected left main coronary artery (LMCA) in lieu of surgical revascularization represents the next wave of challenges that the field of interventional cardiology will try to overcome. Significant LMCA stenosis, commonly secondary to atherosclerosis, is seen in about 4-10% of cases presenting to the cardiac catheterization laboratory. Currently, the vast majority of these patients undergo surgical revascularization unless there are prohibitive reasons for surgical revascularization. Several challenges of percutaneous revascularization have been overcome with stents, intravascular brachytherapy, and other technical improvements. Yet, several remaining limitations of percutaneous intervention, such as in-stent restenosis, have to be improved further before randomized clinical trials of surgical and percutaneous revascularization of unprotected LMCA disease can be contemplated to establish a new standard of care.

Arteries↗
PubMed2002

Diagnosis, management, and clinical outcome of cardiac tamponade complicating percutaneous coronary intervention.

Cardiac tamponade is an uncommon but life-threatening complication of percutaneous coronary intervention (PCI). The purpose of the present study was to characterize the incidence, management, and clinical outcome associated with this complication. We analyzed a prospective database of 25,697 PCIs performed at William Beaumont Hospital (Royal Oak, Michigan) between October 1993 and December 2000. Cardiac tamponade was observed in 31 of 25,697 PCI procedures (0.12%). Cardiac tamponade was diagnosed in the catheterization laboratory in 17 of 31 patients (55%), and 14 patients (45%) had a delayed presentation (mean time from PCI 4.4 hours). Cardiac tamponade was twice as frequent after use of atheroablative devices compared with percutaneous transluminal coronary angioplasty and stenting (0.26% vs 0.11%, p <0.05). All patients with immediate cardiac tamponade had coronary artery perforation. In 11 of 14 patients with delayed tamponade (79%), no actual site of perforation could be identified. A moderate or large pericardial effusion was observed in 20 patients, and 9 had small effusions without typical echocardiographic features of tamponade. Pericardiocentesis was performed in 30 patients; 19 patients (61%) were treated successfully with aspiration alone, but 12 patients (39%) required further emergency surgical intervention. In-hospital complications included death (42%), emergency surgery (39%), myocardial infarction (29%), and transfusion (65%). Cardiac tamponade is an uncommon but important complication of PCI and is associated with high mortality and morbidity. Most cases are recognized in the catheterization laboratory, but delayed cardiac tamponade may occur and must be considered as a cause of late hypotension after PCI.

Aged↗
PubMed2002

Impact of different platelet glycoprotein IIb/IIIa receptor inhibitors among diabetic patients undergoing percutaneous coronary intervention: : Do Tirofiban and ReoPro Give Similar Efficacy Outcomes Trial (TARGET) 1-year follow-up.

BACKGROUND: The platelet glycoprotein IIb/IIIa receptor inhibitor abciximab, a monoclonal antibody, has been shown to improve early and late outcomes among diabetic patients undergoing percutaneous coronary intervention (PCI). It is unknown whether small-molecule agents confer similar benefits. METHODS AND RESULTS: In 18 countries, 4809 patients undergoing PCI with stent implantation were randomized to tirofiban or abciximab. At the time of enrollment, patients were stratified according to diabetes status. As compared with non-diabetic patients, patients with diabetes (n=1117) showed similar 30-day ischemic outcomes, an increased incidence of any target vessel revascularization (TVR) at 6 months (10.3% versus 7.8%; P= 0.008), and a trend toward higher 1-year mortality (2.5% versus 1.6%; P=0.056). Among diabetic patients randomized to tirofiban (n=560), the incidence of death, myocardial infarction (MI), or urgent TVR at 30 days was 6.2%, and among those randomized to abciximab (n=557) it was 5.4% (hazard ratio [HR] 1.16; P=0.540). At 6 months, the composite of death, MI, or any TVR occurred in 15.7% and in 16.9% of tirofiban and abciximab patients, respectively (HR 0.93; P=0.610). Any TVR occurred in 9.5% and 11.1%, respectively (HR 0.84; P= 0.366). The 1-year mortality was 2.1% in the tirofiban group and 2.9% in the abciximab group (HR 0.74; P= 0.436). CONCLUSIONS: Among diabetic patients undergoing PCI, tirofiban and abciximab were associated with comparable event rates, including similar rates of 6-month TVR and 1-year mortality. These findings suggest that the non-glycoprotein IIb/IIIa properties of abciximab do not translate into a discernible long-term clinical benefit among diabetic patients.

Abciximab↗
PubMed2002

A randomized trial of transfer for primary angioplasty versus on-site thrombolysis in patients with high-risk myocardial infarction: the Air Primary Angioplasty in Myocardial Infarction study.

OBJECTIVES: The Air Primary Angioplasty in Myocardial Infarction (PAMI) study was designed to determine the best reperfusion strategy for patients with high-risk acute myocardial infarction (AMI) at hospitals without percutaneous transluminal coronary angioplasty (PTCA) capability. BACKGROUND: Previous studies have suggested that high-risk patients have better outcomes with primary PTCA than with thrombolytic therapy. It is unknown whether this advantage would be lost if the patient had to be transferred for PTCA, and reperfusion was delayed. METHODS: Patients with high-risk AMI (age >70 years, anterior MI, Killip class II/III, heart rate >100 beats/min or systolic BP <100 mm Hg) who were eligible for thrombolytic therapy were randomized to either transfer for primary PTCA or on-site thrombolysis. RESULTS: One hundred thirty-eight patients were randomized before the study ended (71 to transfer for PTCA and 67 to thrombolysis). The time from arrival to treatment was delayed in the transfer group (155 vs. 51 min, p < 0.0001), largely due to the initiation of transfer (43 min) and transport time (26 min). Patients randomized to transfer had a reduced hospital stay (6.1 +/- 4.3 vs. 7.5 +/- 4.3 days, p = 0.015) and less ischemia (12.7% vs. 31.8%, p = 0.007). At 30 days, a 38% reduction in major adverse cardiac events was observed for the transfer group; however, because of the inability to recruit the necessary sample size, this did not achieve statistical significance (8.4% vs. 13.6%, p = 0.331). CONCLUSIONS: Patients with high-risk AMI at hospitals without a catheterization laboratory may have an improved outcome when transferred for primary PTCA versus on-site thrombolysis; however, this will require further study. The marked delay in the transfer process suggests a role for triaging patients directly to specialized heart-attack centers.

Aged↗
PubMed2002

Impact of clinical syndrome acuity on the differential response to 2 glycoprotein IIb/IIIa inhibitors in patients undergoing coronary stenting: the TARGET Trial.

BACKGROUND: Although glycoprotein IIb/IIIa inhibitors have been shown to reduce periprocedural and late ischemic events in patients undergoing stent implantation, the relative safety and efficacy of different agents in this class is less established. Also unknown is whether the acuity of the presenting clinical syndrome, which may affect the degree of platelet inhibition required or achieved, influences the response to different antiplatelet agents. METHODS AND RESULTS: A prospective, multicenter, double-blind, randomized trial was performed in which 4809 patients undergoing planned stenting were randomized to receive abciximab or tirofiban. In patients with acute coronary syndromes (ACS; n=3025), abciximab resulted in lower rates of myocardial infarction at 30 days (5.8% versus 8.5%; P=0.004) and 6 months (7.2% versus 9.8%; P=0.013), although 6-month mortality rates were identical (1.39% in both groups; P=0.99). Conversely, in patients without ACS (n=1784), myocardial infarction rates were not significantly lower with tirofiban, survival was similar, and target vessel revascularization was reduced, which translated into a trend toward enhanced 6-month event-free survival with tirofiban (89.7% versus 86.6%; P=0.056). CONCLUSIONS: In patients with ACS undergoing stent implantation, abciximab use compared with tirofiban results in greater suppression of periprocedural myonecrosis, although a survival benefit has not been demonstrated. Patients with stable coronary syndromes may have equivalent or better outcomes with tirofiban relative to abciximab, with fewer adverse hematologic and hemorrhagic events. These data raise important issues regarding the relative pharmacodynamic inhibition of platelet function required in varying clinical scenarios and have important implications for the cost-effective utilization of glycoprotein IIb/IIIa inhibitors.

Abciximab↗
PubMed2002

Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction.

BACKGROUND: As compared with thrombolytic therapy, primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction reduces the rates of death, reinfarction, and stroke, but recurrent ischemia, restenosis, and reocclusion of the infarct-related artery remain problematic. When used in combination with PTCA, coronary stenting and platelet glycoprotein IIb/IIIa inhibitors may further improve outcomes. METHODS: Using a 2-by-2 factorial design, we randomly assigned 2082 patients with acute myocardial infarction to undergo PTCA alone (518 patients), PTCA plus abciximab therapy (528), stenting alone with the MultiLink stent (512), or stenting plus abciximab therapy (524). RESULTS: Normal flow was restored in the target vessel in 94.5 to 96.9 percent of patients and did not vary according to the reperfusion strategy. At six months, the primary end point - a composite of death, reinfarction, disabling stroke, and ischemia-driven revascularization of the target vessel - had occurred in 20.0 percent of patients after PTCA, 16.5 percent after PTCA plus abciximab, 11.5 percent after stenting, and 10.2 percent after stenting plus abciximab (P<0.001). There were no significant differences among the groups in the rates of death, stroke, or reinfarction; the difference in the incidence of the primary end point was due entirely to differences in the rates of target-vessel revascularization (ranging from 15.7 percent after PTCA to 5.2 percent after stenting plus abciximab, P<0.001). The rate of angiographically established restenosis was 40.8 percent after PTCA and 22.2 percent after stenting (P<0.001), and the respective rates of reocclusion of the infarcted-related artery were 11.3 percent and 5.7 percent (P=0.01), both independent of abciximab use. CONCLUSIONS: At experienced centers, stent implantation (with or without abciximab therapy) should be considered the routine reperfusion strategy.

Abciximab↗
PubMed2002

Angiogenic Gene Therapy (AGENT) trial in patients with stable angina pectoris.

BACKGROUND: The angiogenic response to myocardial ischemia can be augmented in animal models by gene transfer with the use of a replication defective adenovirus (Ad) containing a human fibroblast growth factor (FGF) gene. METHODS AND RESULTS: The objectives of the Angiogenic GENe Therapy (AGENT) trial were to evaluate the safety and anti-ischemic effects of 5 ascending doses of Ad5-FGF4 in patients with angina and to select potentially safe and effective doses for subsequent study. Seventy-nine patients with chronic stable angina Canadian Cardiovascular Society class 2 or 3 underwent double-blind randomization (1:3) to placebo (n=19) or Ad5-FGF4 (n=60). Safety evaluations were performed at each visit and exercise treadmill testing (ETT) at baseline and at 4 and 12 weeks. Single intracoronary administration of Ad5-FGF4 seemed to be safe and well tolerated with no immediate adverse events. Fever of <1-day duration occurred in 3 patients in the highest-dose group. Transient, asymptomatic elevations in liver enzymes occurred in 2 patients in lower-dose groups. Serious adverse events during follow-up (mean, 311 days) were not different between placebo and Ad5-FGF4. Overall, patients who received Ad5-FGF4 tended to have greater improvements in exercise time at 4 weeks (1.3 versus 0.7 minutes, P=NS, n=79). A protocol-specified, subgroup analysis showed the greatest improvement in patients with baseline ETT < or =10 minutes (1.6 versus 0.6 minutes, P=0.01, n=50). CONCLUSIONS: Results show evidence of favorable anti-ischemic effects with Ad5-FGF4 compared with placebo, and it appears to be safe. Angiogenic gene transfer with Ad5-FGF4 shows promise as a new therapeutic approach to the treatment of angina pectoris.

Adenoviridae↗