Andrew O. Maree

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 &bgr;-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 ≤30 minutes: adjusted OR=0.78; 95% CI, 0.65 to 0.92; door-to-balloon time ≤90 minutes: adjusted OR=0.87; 95% CI, 0.79 to 0.95). Women also experienced lower use of cardiac catheterization and revascularization procedures after AMI. Conclusions— Overall, no sex differences in in-hospital mortality rates after AMI were observed after multivariable adjustment. However, women with STEMI had higher adjusted mortality rates than men. The underuse of evidence-based treatments and delayed reperfusion among women represent potential opportunities for reducing sex disparities in care and outcome after AMI.

Variable Platelet Response to Aspirin and Clopidogrel in Atherothrombotic Disease

Humans require rapidly responding, tightly regulated hemostasis because of their closed high-pressure circulatory system. Minor variation in response may predispose to pathological bleeding or thrombosis. In the appropriate setting, pharmacological intervention with antiplatelet therapy stabilizes the atherothrombotic phenotype, though with concomitant hemorrhagic risk. Populations with favorable risk–benefit ratios for acetylsalicylic acid (aspirin) and clopidogrel therapy have nevertheless been defined in major clinical trials. Treatment benefit is established for secondary prevention of cardiovascular and cerebrovascular events, management of acute coronary syndromes, and as an adjunct to percutaneous and surgical revascularization. There is evidence, however, that not all individuals respond comparably to antiplatelet drugs and hence the concept of aspirin and clopidogrel “resistance” has arisen. The term is misleading though because there are many determinants of failure to respond to treatment. Consistent levels of platelet inhibition are required to deliver effective therapy. Adverse consequences of variable response are particularly apparent when antiplatelet drugs are used as an adjunct to coronary revascularization. During percutaneous coronary intervention (PCI), atherosclerotic plaque is invariably disrupted, thrombosis occurs, and endothelial healing is delayed. Intensive periprocedural platelet inhibition minimizes morbidity and mortality, whereas persistence of a prothrombotic environment necessitates chronic antiplatelet therapy. Failure to provide adequate platelet inhibition in all individuals can result in stent thrombosis, myocardial infarction, and death.1,2 Platelet inhibition with aspirin at the time of coronary artery bypass graft surgery also provides benefit. Yet aggressive therapy with aspirin and clopidogrel combined may increase perioperative bleeding in some cases.3 These contrasting clinical problems underlie the need for a tailored approach to therapy and illustrate the requirement for consistent levels of platelet inhibition and a means to confirm individual response. Platelets adhere to sites of vascular injury; however, endothelial disruption is not a prerequisite. Atherosclerotic lesions are associated with impaired endothelial function and hence are …

Cyclooxygenase-1 haplotype modulates platelet response to aspirin

Summary.  Background: Aspirin (acetylsalicylic acid) irreversibly inhibits platelet cyclooxygenase (COX)‐1, the enzyme that converts arachidonic acid (AA) to the potent platelet agonist thromboxane (TX) A2. Despite clear benefit from aspirin in patients with cardiovascular disease (CAD), evidence of heterogeneity in the way individuals respond has given rise to the concept of ‘aspirin resistance.’Aims: To evaluate the hypothesis that incomplete suppression of platelet COX as a consequence of variation in the COX‐1 gene may affect aspirin response and thus contribute to aspirin resistance. Patients and methods: Aspirin response, determined by serum TXB2 levels and AA‐induced platelet aggregation, was prospectively studied in patients (n = 144) with stable CAD taking aspirin (75–300 mg). Patients were genotyped for five single nucleotide polymorphisms in COX‐1 [A‐842G, C22T (R8W), G128A (Q41Q), C644A (G213G) and C714A (L237M)]. Haplotype frequencies and effect of haplotype on two platelet phenotypes were estimated by maximum likelihood. The four most common haplotypes were considered separately and less common haplotypes pooled. Results: COX‐1 haplotype was significantly associated with aspirin response determined by AA‐induced platelet aggregation (P = 0.004; 4 d.f.). Serum TXB2 generation was also related to genotype (P = 0.02; 4 d.f.). Conclusion: Genetic variability in COX‐1 appears to modulate both AA‐induced platelet aggregation and thromboxane generation. Heterogeneity in the way patients respond to aspirin may in part reflect variation in COX‐1 genotype.

Longest available clinical outcomes after drug-eluting stent implantation for unprotected left main coronary artery disease: the DELFT (Drug Eluting stent for LeFT main) Registry.

OBJECTIVES The purpose of this study was to investigate the long-term safety and efficacy of percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation for unprotected left main coronary artery (ULMCA) disease. BACKGROUND Long-term clinical outcomes after DES implantation for ULMCA disease have not yet been ascertained. METHODS From April 2002 to April 2004, 358 consecutive patients who underwent PCI with DES implantation for de novo lesions on ULMCA were retrospectively selected and analyzed in 7 European and U.S. tertiary care centers. No patients were excluded from the analysis, and all patients had a minimum follow-up of 3 years. RESULTS Technical success rate was 100%. Procedural success rate was 89.6%. After 3 years, major adverse cardiovascular events (MACE)-free survival in the whole population was 73.5%. According to the Academic Research Consortium definitions, cardiac death occurred in 9.2% of patients, and reinfarction, target lesion revascularization (TLR), and target vessel revascularization (TVR) occurred in 8.6%, 5.8%, and 14.2% of patients, respectively. Definite stent thrombosis occurred in 2 patients (specifically at 0 and 439 days). In elective patients, the 3-year MACE-free survival was 74.2%, with mortality, reinfarction, TLR, and TVR rates of 6.2%, 8.3%, 6.6%, and 16%, respectively. In the emergent group the 3-year MACE-free survival was 68.2%, with mortality, reinfarction, TLR, and TVR rates of 21.4%, 10%, 2.8%, and 7.1%, respectively. CONCLUSIONS Routine DES implantation in ULMCA disease seems encouraging, with favorable long-term clinical results.

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 TXB2 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.

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 ≤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.

Identification of serum endoglin as a novel prognostic marker after acute myocardial infarction.

Endoglin is a proliferation‐associated and hypoxia‐inducible protein expressed in endothelial cells. The levels of soluble circulating endoglin and their prognostic significance in patients with acute myocardial infarction (AMI) are not known. In this observational prospective study serum endoglin levels were measured by ELISA in 183 AMI patients upon admission to hospital and 48 hrs later and in 72 healthy controls. Endoglin levels in AMI patients on admission were significantly lower than in healthy controls (4.25 ± 0.99 ng/ml versus 4.59 ± 0.87 ng/ml; P= 0.013), and decreased further in the first 48 hours (3.65 ± 0.76 ng/ml, P < 0.001). Upon follow‐up (median 319 days), patients who died had a significantly greater decrease in serum endoglin level over the first 48 hrs than those who survived (1.03 ± 0.91 versus 0.54 ± 0.55 ng/ml; P= 0.025). Endoglin decrease was an independent predictor of short‐term (30 days) (hazard ratio 2.33;95% CI = 1.27–4.23; P= 0.006) cardiovascular mortality, and also predicts overall cardiovascular mortality during the follow‐up (median 319 days) in AMI patients (hazard ratio 2.13;95% CI = 1.20–3.78; P= 0.01). In conclusion, early changes in serum endoglin may predict mortality after AMI.

Predicting Success and Long-Term Outcomes of Percutaneous Mitral Valvuloplasty: A Multifactorial Score

BACKGROUND Percutaneous mitral valvuloplasty (PMV) success depends on appropriate patient selection. A multifactorial score derived from clinical, anatomic/echocardiographic, and hemodynamic variables would predict procedural success and clinical outcome. METHODS Demographic data, echocardiographic parameters (including echocardiographic score), and procedure-related variables were recorded in 1085 consecutive PMVs. Long-term clinical follow-up (death, mitral valve replacement, redo PMV) was performed. Multivariate regression analysis of the first 800 procedures was performed to identify independent predictors of procedural success. Significant variables were formulated into a risk score and validated prospectively. RESULTS Six independent predictors of PMV success were identified: age less than 55 years, New York Heart Association classes I and II, pre-PMV mitral area of 1 cm(2) or greater, pre-PMV mitral regurgitation grade less than 2, echocardiographic score of 8 or greater, and male sex. A score was constructed from the arithmetic sum of variables present per patient. Procedural success rates increased incrementally with increasing score (0% for 0/6, 39.7% for 1/6, 54.4% for 2/6, 77.3% for 3/6, 85.7% for 4/6, 95% for 5/6, and 100% for 6/6; P < .001). In a validation cohort (n = 285 procedures), the multifactorial score remained a significant predictor of PMV success (P < .001). Comparison between the new score and the echocardiographic score confirmed that the new index was more sensitive and specific (P < .001). This new score also predicts long-term outcomes (P < .001). CONCLUSION Clinical, anatomic, and hemodynamic variables predict PMV success and clinical outcome and may be formulated in a scoring system that would help to identify the best candidates for PMV.

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

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.

External iliac artery endofibrosis in an amateur runner: hemodynamic, angiographic, histopathological evaluation and percutaneous revascularization:

We describe a case of external iliac artery endofibrosis in an amateur competitive runner. The diagnosis was made by a combination of hemodynamic, angiographic and histopathological assessment and percutaneous revascularization was performed using a balloon expandable stent.