Randomized placebo controlled trial evaluating the safety and efficacy of single low-dose intracoronary insulin-like growth factor following percutaneous coronary intervention in acute myocardial infarction (RESUS-AMI).

BACKGROUND: Residual and significant postinfarction left ventricular (LV) dysfunction, despite technically successful percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), remains an important clinical issue. In preclinical models, low-dose insulin-like growth factor 1 (IGF1) has potent cytoprotective and positive cardiac remodeling effects. We studied the safety and efficacy of immediate post-PCI low-dose intracoronary IGF1 infusion in STEMI patients. METHODS: Using a double-blind, placebo-controlled, multidose study design, we randomized 47 STEMI patients with significantly reduced (≤40%) LV ejection fraction (LVEF) after successful PCI to single intracoronary infusion of placebo (n = 15), 1.5 ng IGF1 (n = 16), or 15 ng IGF1 (n = 16). All received optimal medical therapy. Safety end points were freedom from hypoglycemia, hypotension, or significant arrhythmias within 1 hour of therapy. The primary efficacy end point was LVEF, and secondary end points were LV volumes, mass, stroke volume, and infarct size at 2-month follow-up, all assessed by magnetic resonance imaging. Treatment effects were estimated by analysis of covariance adjusted for baseline (24 hours) outcome. RESULTS: No significant differences in safety end points occurred between treatment groups out to 30 days (χ2 test, P value = .77). There were no statistically significant differences in baseline (24 hours post STEMI) clinical characteristics or LVEF among groups. LVEF at 2 months, compared to baseline, increased in all groups, with no statistically significant differences related to treatment assignment. However, compared with placebo or 1.5 ng IGF1, treatment with 15 ng IGF1 was associated with a significant improvement in indexed LV end-diastolic volume (P = .018), LV mass (P = .004), and stroke volume (P = .016). Late gadolinium enhancement (±SD) at 2 months was lower in 15 ng IGF1 (34.5 ± 29.6 g) compared to placebo (49.1 ± 19.3 g) or 1.5 ng IGF1 (47.4 ± 22.4 g) treated patients, although the result was not statistically significant (P = .095). CONCLUSIONS: In this pilot trial, low-dose IGF1, given after optimal mechanical reperfusion in STEMI, is safe but does not improve LVEF. However, there is a signal for a dose-dependent benefit on post-MI remodeling that may warrant further study.

The association of night-time systolic blood pressure with ultrasound markers of subclinical cardiac and vascular disease.

INTRODUCTION: The aim of this study was to examine the association of night-time systolic blood pressure (BP) with subclinical cardiac dysfunction measured by global longitudinal strain (GLS) and subclinical vascular damage measured by carotid intima-media thickness (CIMT) and carotid plaques. METHODS: GLS was measured by speckle-tracking analysis of echocardiogram images. CIMT was measured at the distal 1 cm of the common carotid artery. The presence of carotid plaques was recorded. Philips QLAB cardiac and vascular ultrasound quantification software was used for analysis. The association of night-time systolic BP with GLS, CIMT and carotid plaques was assessed using linear and logistic regression. RESULTS: Fifty (response rate 63%) individuals took part in this study. In univariable models, night-time systolic BP was significantly associated with GLS [ß coefficient 0.85 for every 10 mmHg increase, 95% confidence interval (CI): 0.3-1.4] and carotid plaques (odds ratio 1.9 for every 10 mmHg increase, 95% CI: 1.1-3.2). Univariable analysis of daytime systolic BP did not show any statistically significant associations. In age-adjusted and sex-adjusted models, the association for night-time systolic BP and GLS remained significant (ß coefficient 0.68 for every 10 mmHg increase, 95% CI: 0.1-1.3). The association for carotid plaques was no longer statistically significant. In multivariable models, findings were diminished. DISCUSSION: Our results suggest a trend towards an association between night-time systolic BP and subclinical cardiac and vascular disease. When assessing ambulatory blood pressure monitoring results, the absolute night-time systolic BP seems to be a better prognostic parameter than daytime systolic BP, but ultimately a large randomised controlled trial involving chronotherapy is necessary to fully address this.

Hypertension Prevalence, Awareness, Treatment, and Control: Should 24-Hour Ambulatory Blood Pressure Monitoring be the Tool of Choice?

We aimed to examine hypertension prevalence, awareness, treatment and control in a community sample and investigate the impact of using 24 hour ABPM. Office blood pressure (BP) was taken from the electronic health record. Study BP was measured by standardised methods. Participants were invited to undergo ABPM. Hypertension was defined by accepted thresholds or anti-hypertensive use. Standardised questions assessed awareness and treatment. Control was defined as anti-hypertensive use with BP below normal threshold. There were 931 (45%) participants with office BP, study BP and ABPM. By study BP, hypertension prevalence was 60%, awareness 59%, 60% were treated and 46% controlled. By daytime ABPM threshold, prevalence was 61%, awareness 59%, 59% were treated and 54% controlled. ABPM reclassified 13.5% from normotensive to hypertensive and 14.5% from hypertensive to normotensive. ABPM may not hugely impact population hypertension prevalence but at an individual level it reduces misclassification and facilitates more appropriate management.

Night-time blood pressure and target organ damage: a comparative analysis of absolute blood pressure and dipping status.

BACKGROUND: The prognostic significance of abnormal circadian blood pressure (BP) patterns is well established. Research to date has focused on both nocturnal dipping and absolute night-time BP levels; however, which of these variables should be the primary target for therapy remains unclear. The aim of this study is to determine whether dipping status or absolute night-time BP levels have a stronger association with subclinical target organ damage (TOD). METHODS: The Mitchelstown Cohort was established to examine cardiovascular health in an adult population sample recruited from primary care. Night-time BP was categorized by dipping status. Subclinical TOD was defined as Cornell Product left ventricular hypertrophy (LVH) voltage criteria on ECG and urine albumin : creatinine ratio (ACR) at least 1.1 mg/mmol. Multivariable logistic regression analysis was used to assess the association between night-time BP and TOD. RESULTS: Of 2047 participants, 1207 (response rate 59%), underwent 24-h ambulatory BP monitoring. We excluded 161 studies due to incomplete data. Of 1046 participants, 178 (17%) had evidence of TOD. Each 10-mmHg rise in night-time SBP increased the odds of TOD. Odds ratio (OR) ACR at least 1.1 mg/mmol 1.5 [95% confidence interval (95% CI) 1.2-1.8] and OR LVH 1.4 (95% CI 1.1-1.8). CONCLUSION: Absolute BP level rather than dipping status may be a superior early marker of risk associated with night-time BP. Interventional studies are required to determine whether there is a benefit in specifically targeting absolute night-time BP levels to prevent clinically important outcomes.

Isolated nocturnal hypertension and subclinical target organ damage: a systematic review of the literature.

Isolated nocturnal hypertension (INH) is associated with greater mortality and cardiovascular events. Subclinical target organ damage (TOD) is a prognostic marker for cardiovascular events. Our objective is to systematically summarize evidence on the association between INH and subclinical TOD. Observational population studies were considered. INH was defined as nighttime blood pressure (BP) ⩾120 and/or 70 mm Hg with daytime BP <135/85 mm Hg. We systematically searched Pubmed, EMBASE and the Cochrane Library. Abstracts were reviewed by two assessors. Potentially eligible articles were compared with inclusion criteria. The search yielded 954 titles, 13 abstracts were selected for review and four articles fulfilled inclusion criteria. INH was associated with higher ambulatory arterial stiffness index (0.4 unit vs. 0.35 unit, P<0.05), pulse wave velocity (16.2 m s(-1) vs. 14.7 m s(-1), P<0.05), central (140.4% vs. 134.0%, P<0.05) and peripheral (82.6% vs. 76.5%, P<0.01) augmentation index in a Chinese study. In the same population there was no association with left ventricular hypertrophy documented by electrocardiogram. INH was not associated with increased arterial stiffness or left venticular mass index in a Swedish study. An American study demonstrated higher left ventricular mass (152.46 g vs. 136.16 g, P=0.01) and greater odds of left ventricular hypertrophy (odds ratio 3.03, 95% confidence interval 1.02-9.05) in unadjusted analysis. There was no association with proteinuria. Evidence is inconclusive regarding the association between INH and subclinical TOD. Future research should focus on trying to elucidate the mechanisms that generate INH and contribute to the higher mortality associated with this BP pattern.

Role of Transesophageal Echocardiography Compared to Computed Tomography in Evaluation of Pulmonary Vein Ablation for Atrial Fibrillation (ROTEA study).

BACKGROUND: Computed tomography (CT) is the gold standard for assessing pulmonary vein (PV) anatomy and stenosis after ablation for atrial fibrillation (AF), but radiation exposure can be a concern. Transesophageal echocardiography (TEE) provides anatomic and functional assessment of the PVs, although no study has prospectively compared findings on TEE with those on CT. METHODS: The Role of Transesophageal Echocardiography Compared to Computed Tomography in Evaluation of Pulmonary Vein Ablation for Atrial Fibrillation (ROTEA) study was a prospective, single-blinded observational study of patients with paroxysmal or persistent AF undergoing ablation. TEE and CT were performed immediately before and 3 months after AF ablation. The study included 43 patients (84% men; mean age, 56 ± 11 years). RESULTS: In the preprocedural study, TEE identified 98% of PVs with adequate Doppler measurements obtained. After ablation, no moderate or severe PV stenosis was detected on CT, and a 30% to 50% reduction in luminal diameter was seen in 5% of studied veins. Functional PV stenosis by pulsed-wave Doppler was seen in two veins on TEE. PV diameters decreased after ablation by 0.20 ± 0.03 and 0.22 ± 0.03 cm as measured by CT and TEE, respectively (P < .001). However, TEE underestimated PV ostial dimensions compared with CT, especially for the inferior PVs. Severe spontaneous echo contrast and low left atrial appendage emptying velocities, were identified in 10% of patients in sinus rhythm after ablation. CONCLUSIONS: In the ROTEA study, TEE was feasible in assessing PVs before and after ablation, providing both anatomic and functional information that complemented CT. PV ostial dimensions after ablation can be monitored using either modality, although TEE underestimates PV dimensions, especially for the inferior veins.

Intracavitary course of the right coronary artery: an increasingly recognized anomaly by coronary computed tomography angiography.

Coronary computed tomography angiography is being increasingly used for evaluation of coronary artery anatomy. We present a case report in which coronary computed tomography angiography detected an uncommon intracavitary course of the right coronary artery.

Right ventricular response to intensive medical therapy in advanced decompensated heart failure.

BACKGROUND: Right ventricular (RV) systolic dysfunction is a strong predictor of adverse outcomes in heart failure, yet quantitatively assessing the impact of therapy on this condition is difficult. Our objective was to compare the clinical significance of changes in RV echocardiographic indices in response to intensive medical treatment in patients admitted to the hospital with acute decompensated heart failure (ADHF). METHODS AND RESULTS: Serial comprehensive echocardiography was performed in 62 consecutive patients with ADHF, and adverse events (death, cardiac transplantation, assist device, heart failure rehospitalization) were prospectively documented. RV peak systolic strain was assessed using speckle-tracking longitudinal strain analysis as the average of the basal, mid-, and apical segment of the RV free wall. Other conventional parameters of RV function (RV fractional area change, RV myocardial performance index, tricuspid annular peak systolic excursion, and tissue Doppler peak tricuspid annular systolic velocity) were measured for comparison. In our study cohort [left ventricular ejection fraction, 26+/-10%; cardiac index, 2.0+/-0.6 L/(min . m(2))], overall mean RV peak systolic strain was -14+/-4% at baseline and -15+/-4% at 48 to 72 hours (P=0.27). Among all the RV functional indices measured, only RV peak systolic strain at 48 to 72 hours was associated with adverse events (P=0.02). In particular, improvement in RV peak systolic strain after intensive medical treatment was associated with lower adverse events in this patient population (26% versus 78%; hazard ratio, 0.13; 95% CI, 0.02 to 0.84; P=0.02). CONCLUSION: Dynamic improvement in RV mechanics in response to intensive medical therapy was associated with lower long-term adverse events in patients with ADHF than in patients not showing improvement.

Meta-analysis of diagnostic efficacy of 64-slice computed tomography in the evaluation of coronary in-stent restenosis.

We sought to conduct a meta-analysis using available studies to determine the diagnostic efficacy of 64-slice computed tomography (CT) in evaluation of in-stent restenosis (ISR). Sixty-four-slice CT allows optimal noninvasive assessment of coronary artery disease. However, a variety of artifacts limit evaluation of stented coronary segments. We included studies that used 64-slice CT for evaluation of coronary ISR. We pooled efficacy estimates across studies using random-effects models. We identified 14 studies, which included 895 patients (1,447 stents, mean diameter 3.1 mm). Of these, 1,231 (91.4%) stents were adequately assessed by 64-slice CT. Overall sensitivity was 91% (95% confidence interval [CI] 86 to 94), specificity was 91% (95% CI 89 to 92), positive predictive value (PPV) was 68% (95% CI 63 to 73), and negative predictive value (NPV) was 98% (95% CI 97 to 99). The summary receiver operating characteristic curves graph showed a symmetric area under the curve of 0.96. When nonassessable segments were included, overall sensitivity and specificity decreased to 87% (95% CI 81 to 92) and 84% (95% CI 82 to 87), with a PPV of 53% (95% CI 47 to 59) and an NPV of 97% (95% CI 96 to 98), respectively. In conclusion, 64-slice CT detects (high sensitivity and specificity) or excludes ISR (high NPV) with a high degree of confidence; however, precise quantification of ISR is not accurate (low PPV). Efficacy estimates are even lower when nonassessable segments are included. Hence, at this point, stress imaging remains the most acceptable noninvasive technique for diagnosis of ISR.

Association of total cholesterol/ high-density lipoprotein cholesterol ratio with proximal coronary atherosclerosis detected by multislice computed tomography.

The authors assessed the association between an elevated total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio (> or = 4) and proximal coronary artery disease (CAD), as observed on multislice computed tomography. Coronary multislice computed tomographic angiography (96% on 40- or 64-slice) was performed in 295 individuals (39% women; mean age, 54 +/- 13 years) without documented CAD who were referred for coronary evaluation. Significant CAD was defined as > or = 50% stenosis in the left main, proximal left anterior descending, or > or = 2 epicardial vessels. Proximal plaque was defined as presence of any plaque in left main or proximal left anterior descending vessels. Individuals with an elevated TC/HDL-C ratio vs those without had a higher prevalence of proximal plaque (62% vs 48%, P = .04) and significant CAD (19% vs 9%, P = .009). On multivariate logistic regression analysis, only age, sex, and TC/HDL-C ratio > or = 4 were associated with significant CAD and proximal plaque.

Prognostic utility of 64-slice computed tomography in patients with suspected but no documented coronary artery disease.

AIMS: Although multislice computed tomography (MSCT) detects obstructive coronary artery disease (CAD) with high diagnostic accuracy, there is a paucity of long-term prognostic data. We sought to assess the incremental prognostic value of 64-slice CT in patients with suspected but no documented CAD. METHODS AND RESULTS: Coronary MSCT was performed on 227 individuals (61% men, mean age 54 +/- 12 years, 63% with intermediate pre-test probability) without documented CAD, referred for coronary evaluation. Coronary artery disease by MSCT was categorized as follows: none or mild CAD (<50%, n = 172), > or =50% in one vessel (n = 23), two vessels [or in the proximal left anterior descending (LAD), n = 12], and three vessels (or in two vessels including the proximal LAD or left main, n = 20). Baseline risk factors, length of follow-up, and major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), and coronary revascularization were recorded. Over a mean follow-up of 2.3 +/- 0.8 years, there were 18 MACE [including four hard events (one cardiac death and three MIs)]. Also, patients with one or more vessel obstructive CAD had increased hard events compared with those with less than one-vessel disease (log-rank statistic P-value 0.01). One or more vessel obstructive CAD was a significant predictor of MACE on univariable and multivariable Cox proportional survival analysis [hazard ratios 29.1 (6.7-126.6) and 9.82 (3.58-27.01), respectively, both P < 0.0001]. In 172 patients, with no or mild CAD, there was 99% freedom from MACE during follow-up. CONCLUSION: Multislice computed tomography-classified extent of CAD provides incremental prognostic information in patients with suspected but no documented CAD.

Tissue Doppler imaging in the estimation of intracardiac filling pressure in decompensated patients with advanced systolic heart failure.

BACKGROUND: The ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity (E/Ea) has been correlated with pulmonary capillary wedge pressure (PCWP) in a wide variety of cardiac conditions. The objective of this study was to determine the reliability of mitral E/Ea for predicting PCWP in patients admitted for advanced decompensated heart failure. METHODS AND RESULTS: Prospective consecutive patients with advanced decompensated heart failure (ejection fraction < or =30%, New York Heart Association class III to IV symptoms) underwent simultaneous echocardiographic and hemodynamic evaluation on admission and after 48 hours of intensive medical therapy. A total of 106 patients were included (mean age, 57+/-12 years; ejection fraction, 24+/-8%; PCWP, 21+/-7 mm Hg; mitral E/Ea ratio, 20+/-12). No correlation was found between mitral E/Ea ratio and PCWP, particularly in those with larger left ventricular volumes, more impaired cardiac indexes, and the presence of cardiac resynchronization therapy. Overall, the mitral E/Ea ratio was similar among patients with PCWP >18 and < or =18 mm Hg, and sensitivity and specificity for mitral E/Ea ratio >15 to identify a PCWP >18 mm Hg were 66% and 50%, respectively. Contrary to prior reports, we did not observe any direct association between changes in PCWP and changes in mitral E/Ea ratio. CONCLUSIONS: In decompensated patients with advanced systolic heart failure, tissue Doppler-derived mitral E/Ea ratio may not be as reliable in predicting intracardiac filling pressures, particularly in those with larger LV volumes, more impaired cardiac indices, and the presence of cardiac resynchronization therapy.

Association of coronary atherosclerosis detected by multislice computed tomography and traditional risk-factor assessment.

Framingham risk score is an office-based tool used for long-term coronary heart disease risk stratification. Most acute coronary events occur in association with proximal nonobstructive atherosclerotic plaque. Multislice computed tomography detects both obstructive coronary artery disease (CAD) and proximal atherosclerotic plaque with high accuracy. The association of Framingham risk score with obstructive CAD and proximal atherosclerotic plaque was tested. Coronary multislice computed tomography was performed in 295 patients (61% men, mean age 54 +/- 13 years) without documented CAD referred for evaluation of cardiac symptoms. Framingham risk score was computed and patients were stratified according to 10-year risk (n = 213 [72%] low, n = 74 [25%] intermediate, and n = 8 [3%] high). Obstructive CAD was defined as > or =50% stenosis in > or =1 epicardial coronary artery. Proximal atherosclerotic plaque was defined as calcified or noncalcified plaque in the left main or proximal left anterior descending artery. In the low- and intermediate-Framingham risk score groups, there was a high frequency of proximal atherosclerotic plaque (44% and 75%) and obstructive CAD (16% and 34%), although both findings were more prevalent in the high-Framingham risk score group (63% for atherosclerotic plaque, 88% for obstructive CAD), respectively. Proximal atherosclerotic plaque was noncalcified in approximately 13 of patients. In women (n = 114) and younger (<55 years) patients (n = 148), most (93% and 91%, respectively) had a low Framingham risk score. There were 48 women and 51 younger patients with proximal atherosclerotic plaque, of whom only 40% (in each group) were on statin therapy. In conclusion, of patients with a low and intermediate Framingham risk score, a significant proportion had proximal atherosclerotic plaque or obstructive CAD.

Multidetector computed tomographic angiography in planning of reoperative cardiothoracic surgery.

BACKGROUND: Redo cardiothoracic surgery is associated with increased morbidity and mortality compared with primary operations. Multidetector computed tomographic angiography (MDCTA) delineates the course of previous coronary artery bypass grafts (CABG) and proximity of mediastinal structures to the chest wall. We sought to determine if high-risk preoperative MDCTA findings were associated with greater use of preventive surgical strategies during redo cardiac surgery in patients with prior CABG. METHODS: We studied 167 patients (mean age 69 +/- 9 years, 79% men) with prior CABG, referred for redo cardiac surgery, who underwent contrast-enhanced MDCTA to assess CABG location and mediastinal relationship to chest wall. Preoperative risk was determined. Prevalence of high-risk MDCTA findings, use of preventive surgical strategies, frequency of severe intraoperative bleeding, and postoperative mortality were recorded. RESULTS: Mean risk score was high (7.5 +/- 3). High-risk MDCTA findings included proximity (<1 cm) of right ventricle/aorta to chest wall (24%) or CABG crossing midline in close proximity (<1 cm anteroposteriorly) to sternum (38%). Preventive surgical strategies included surgery cancelled (4%), nonmidline incision (8%), deep hypothermic circulatory arrest (5%), initiation of peripheral cardiopulmonary bypass (11%) and extrathoracic vascular exposure before incision (53%). These strategies were used at a higher frequency in patients with high-risk MDCTA findings versus those without (88% versus 28%, p < 0.0001). Frequency of severe bleeding, graft injuries, and 1-month mortality were 4.4%, 5%, and 2.5%, respectively. CONCLUSIONS: Routine use of preoperative MDCTA to detect high-risk findings has a strong association with adoption of preventive surgical strategies in high-risk patients undergoing redo cardiac surgery.

Long-term outcomes in high-risk symptomatic patients with hypertrophic cardiomyopathy undergoing alcohol septal ablation.

OBJECTIVES: We sought to assess outcomes of alcohol septal ablation (ASA) in high-risk patients. BACKGROUND: Because surgical myectomy is the preferred treatment in patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM) at our institution, we perform ASA in patients who are at high risk for surgery. METHODS: We studied 55 symptomatic HOCM patients (mean age 63 +/- 13 years, 67% women, mean follow-up 8 +/- 1 years), at high risk for surgery (as the result of age/comorbidities) who had ASA between 1997 and 2000. The following were recorded at baseline, 3 months, and 1 year: septal thickness, maximal (resting or provocable) left ventricular outflow tract gradient, Minnesota living with heart failure questionnaire score, and the presence of a permanent pacemaker. All-cause mortality was recorded. RESULTS: No patients died at 48 h, 2 died at 1 year, 7 died at 5 years, and 13 died at 10 years. Only age >65 years at time of ASA predicted long-term mortality (log-rank p = 0.03). Mean maximal left ventricular outflow tract gradient (104 +/- 35 mm Hg vs. 49 +/- 28 mm Hg), septal thickness (2.4 +/- 0.4 cm vs. 1.8 +/- 0.6 cm), and Minnesota living with heart failure score (63 vs. 25) improved at 3 months, compared with baseline (all p < 0.001), with no significant changes at 1 year. New permanent pacemaker was present in 26% of patients. CONCLUSIONS: In symptomatic HOCM patients who are at high risk for surgery, ASA is associated with symptomatic improvement and low short-term mortality; with long-term mortality only associated with older age at time of procedure. In symptomatic HOCM patients at high-risk for surgery, ASA is a viable option.

Platelet response to low-dose enteric-coated aspirin in patients with stable cardiovascular disease.

OBJECTIVES: We investigated whether use of low-dose enteric-coated (EC) aspirin for secondary prevention of cardiovascular events has sufficient bioavailability to achieve complete platelet cyclooxygenase (COX) inhibition in all individuals. BACKGROUND: Aspirin reduces cardiovascular morbidity and mortality in patients with pre-existing vascular disease; however, there is variability in the way individuals respond. Persistent normal platelet function despite therapy, referred to as "aspirin resistance," is associated with an increased risk of major cardiovascular events. METHODS: We studied 131 stable cardiovascular patients between March and September 2002 who were taking 75 mg EC aspirin. Serum thromboxane (TX) B2 levels were assayed as a measure of COX activity. Mean arachidonic acid (AA)-induced platelet aggregation > or =20% was deemed evidence of persistent platelet activity and an incomplete aspirin response. RESULTS: Patients of median age 63 years (61% men) were enrolled. Forty-four percent of patients had elevated serum TX B2 levels (>2.2 ng/ml). Arachidonic acid-induced platelet aggregation occurred more frequently in these patients (21% vs. 3%; p = 0.004). In all cases addition of exogenous aspirin during the assay abolished platelet aggregation. Patient weight and age were significant independent predictors of an incomplete response to EC aspirin (p = 0.025 and p < 0.001, respectively). These patients were also more likely to have a history of myocardial infarction (MI) (p = 0.038). CONCLUSIONS: Many patients who are prescribed low-dose EC aspirin for secondary prevention of cardiovascular events have persistent uninhibited platelet COX activity. Younger and heavier patients and those with a previous MI are most likely to have an inadequate response to treatment.