Citations

Bridging for antiplatelet therapy remains a subject of debate with data favoring GP blockers but at a risk of bleeding. This Conversation in Cardiology addresses a key and often asked question about use of alternatives to P2Y12 agents in patients requiring surgery within 6 months after drug eluting stent implantation. © 2013 Wiley Periodicals, Inc.

Background— Sex-specific differences affect the evaluation, treatment, and prognosis of coronary artery disease. We tested the hypothesis that long-term outcomes of fractional flow reserve (FFR)–guided percutaneous coronary intervention (PCI) are different between women and men. Methods and Results— Consecutive 1090 patients, referred for PCI and undergoing FFR measurements at the Mayo Clinic between October 2002 and December 2009, were included in this registry study. Clinical events were compared between the sexes during a median follow-up of 50.9 months. Of all patients, women had higher FFR adjusted by visual coronary stenosis than men ( P =0.03). The Kaplan–Meier percent of major adverse cardiac events at 5 years was 35% in women and 38% in men ( P =0.54). Interestingly, in patients undergoing PCI with an FFR <0.75, the incidence of death or myocardial infarction was significantly higher in women than in men (hazard ratio, 2.16; 95% confidence interval, 1.04–4.51; P =0.04). Moreover, compared with patients with FFR >0.80, deferral of PCI for those with FFR between 0.75 and 0.80 was associated with an increased rate of major adverse cardiac events, particularly death or myocardial infarction in women (hazard ratio, 3.25; 95% confidence interval, 1.56–6.74; P =0.002) and revascularization in men (hazard ratio, 2.66; 95% confidence interval, 1.66–4.54; P <0.001). Conclusions— Long-term outcome differs between women and men undergoing FFR-guided PCI. Our data suggest that the sex-based treatment strategy is necessary to further optimize prognosis of patients with coronary artery disease.

Background— High sensitivity C-reactive protein (hsCRP) has been identified as a predictor of adverse cardiovascular outcomes. Whether hsCRP is a useful biomarker for risk stratification in contemporary percutaneous coronary intervention remains unknown. Methods and Results— We conducted a prospective study among 513 patients undergoing non-emergency percutaneous coronary intervention and examined the relationship between pre- and postprocedural hsCRP levels and outcomes. The patients were divided according to the median preprocedural hsCRP level (0.3 mg/dL). Patients with high hsCRP had significantly more adverse clinical characteristics. Preprocedural hsCRP level was an independent predictor of periprocedural myocardial infarction (odds ratio per doubling of hsCRP 1.15 [95% confidence interval, 1.01–1.31]; P =0.038). Unadjusted mortality (29.7% versus 9.9%; P <0.001) and the combined end point of death or myocardial infarction (36.5% versus 16.0%, P <0.001) during a follow-up of 5 years were markedly greater in patients with high preprocedural hsCRP. Similar relationships existed for postprocedural hsCRP. However, after multivariable adjustment, neither preprocedural hsCRP levels (hazard ratio per doubling 0.96 [0.92, 1.00]; P =0.066) nor postprocedural hsCRP levels (hazard ratio 0.98 [0.94, 1.02]; P =0.27) were significantly associated with mortality. Conclusions— High hsCRP is associated with a greater independent risk of periprocedural myocardial infarction, as defined by the universal definition, but is not an independent determinant of mortality after percutaneous coronary intervention. Our findings suggest that routine measurement of hsCRP in patients undergoing percutaneous coronary intervention in contemporary practice is unlikely to be beneficial.

Background —In patients receiving intracoronary stents, stent thrombosis is reduced when ticlopidine therapy is combined with aspirin after the procedure. However, ticlopidine causes neutropenia in 1% of patients when administered for >2 weeks, and little is known about the duration that ticlopidine needs be administered to prevent stent thrombosis. Methods and Results —We analyzed 827 patients undergoing successful stent placement in 1061 coronary segments at Mayo Clinic who were treated between May 1, 1996, and October 31, 1997. Chronic warfarin therapy, cardiogenic shock, and enrollment in research protocols requiring 4 weeks of ticlopidine were exclusion criteria; ticlopidine was discontinued after 14 days in all remaining patients. The mean age of the study population was 64±11 years; 49% had suffered a prior infarction, 20% had undergone coronary artery bypass surgery, and 65% had multivessel disease. The indication for stent placement was dissection or abrupt closure in 31% of patients and suboptimal results from balloon angioplasty in 18%. Placement was elective in 51% of patients, and 10.3% of patients were treated within 12 hours of an acute myocardial infarction. Mean nominal stent size was 3.3±0.5 mm. High-pressure inflations (≥12 atm) were performed in all patients (mean, 17±4 atm). Intravascular ultrasound was used to facilitate stent placement in 8.8% of patients. Abciximab was administered to 38% of patients; 11% of patients who were at increased risk of stent thrombosis were treated with enoxaparin for 10 to 14 days. Adverse cardiovascular events in the 14 days after stent placement occurred in 11 patients (1.3%). Two patients died of nonischemic causes (sepsis and renal failure) in the 15th through 30th days after ticlopidine was stopped. However, there were no cardiovascular deaths, myocardial infarctions, coronary artery bypass operations, or repeat angioplasty procedures between the 15th and 30th days; stent thrombosis did not occur in any patient after ticlopidine had been stopped. No patient developed neutropenia, although 1.8% of the first 489 patients who were closely monitored for side effects from ticlopidine developed side effects requiring its discontinuation, and milder side effects occurred in 4.7%. Conclusions —In patients receiving intracoronary stents, the discontinuation of ticlopidine therapy 14 days after stent placement is associated with a very low frequency of stent thrombosis and other adverse events.

Background —This study applied the New York State conventional coronary angioplasty (PTCA) model of clinical outcomes to evaluate whether it has relevance in the current era of stent implantation. The model was developed in 62 670 patients treated with conventional PTCA from 1991 to 1994 to risk adjust mortality and bypass surgery after PTCA. Since then, stents have become the dominant form of intervention. Whether that model remains relevant is uncertain. Methods and Results —All patients undergoing stenting at the Mayo Clinic from 1995 to 1998 were analyzed for in-hospital mortality, bypass surgery performed after attempted stenting, and longer-term mortality. No patients were excluded. The New York model was used to risk adjust and predict in-hospital and follow-up mortality. There were 3761 patients with 4063 procedural admissions for stenting; 6472 target vessel segments were attempted, and 96.1% of procedures were successful. With the New York multivariable risk factor equation, 79 in-hospital deaths were expected (1.95%); 66 deaths (1.62%) were observed. The New York model risk score in a logistic regression model was the most significant factor associated with in-hospital mortality (OR, 1.86; P <0.001). During a mean follow-up of 1.2±1.0 years, there were 154 deaths. Multivariable analysis documented 6 factors associated with subsequent mortality; New York risk score was the most significant (χ 2 =16.64, P =0.0001). Conclusions —Although the New York mortality model was developed in an era of conventional angioplasty, it remains relevant in patients undergoing stenting. The risk score derived from that model is the variable most significantly associated with not only in-hospital but also longer-term outcome.

Background The use of exercise echocardiography for the diagnosis of coronary artery disease (CAD) has been validated in pilot studies but is not documented in clinical practice and in women comparatively with men. The objectives of this study were to determine the effects of sex and of test verification bias on the diagnostic performance of exercise echocardiography. Methods and Results Three thousand six hundred seventy-nine consecutive patients (1714 women, 1965 men) who underwent an exercise echocardiographic study were studied; the observed sensitivity, specificity, and correct classification rate were calculated among 340 patients (244 men, 96 women) who underwent angiography; to study the effect of test verification bias, sensitivity and specificity were estimated for all patients who underwent exercise echocardiography including those not referred to angiography. In the angiographic group, the prevalence of CAD was 60% in women and 80% in men. The observed sensitivity and specificity of exercise echocardiography was 78% and 44% in men and 79% and 37% in women. After adjustment for test verification bias, the estimated sensitivity was lower in women (32% versus 42% in men), whereas specificity was similar in both sexes. The positive predictive value was lower in women (66%) compared with men (84%). Conclusions In clinical practice, test verification bias results in a lower observed specificity and a higher sensitivity of exercise echocardiography. In women, positive predictive value and adjusted sensitivity are lower compared with that in men.

Background The endothelium modulates vascular tone through release of vasodilating substances, such as endothelium-derived relaxing factors, and vasoconstricting substances, such as endothelin. Endothelin concentrations are elevated in humans with atherosclerosis and in hypercholesterolemic pigs. Furthermore, the endothelium-dependent vasodilator acetylcholine increases endothelin in hypercholesterolemia in association with coronary vasoconstriction. The present study was designed to test the hypotheses that coronary endothelial dysfunction in humans is characterized by enhanced coronary and circulating endothelin and that the vasoconstriction associated with acetylcholine results in further release of coronary endothelin. Methods and Results Coronary and circulating endothelin concentrations were measured at baseline and during intracoronary acetylcholine administration in 20 patients undergoing diagnostic coronary angiography. Patients were divided into two groups on the basis of their response to intracoronary acetylcholine. Group 1 (n=7) demonstrated a normal vasodilatory response, but group 2 (n=13) demonstrated coronary vasoconstriction. Baseline coronary and circulating endothelin concentrations (as determined by coronary sinus and femoral artery measurements, respectively) were higher in patients who responded to acetylcholine with coronary vasoconstriction (group 2) than in group 1 patients (coronary sinus, 15.9±1.0 pg/mL versus 7.1±1.0 pg/mL; femoral, 14.1±0.9 pg/mL versus 6.8±1.0 pg/mL, respectively; P <.01). In response to intracoronary acetylcholine, a further increase in coronary endothelin was observed only in group 2; this increase correlated with changes in coronary artery diameter. Conclusions This study demonstrates that endothelin immunoreactivity is enhanced in the coronary and systemic circulation in humans with coronary endothelial dysfunction. Moreover, acetylcholine further increased coronary endothelin concentration in patients with coronary endothelial dysfunction and was associated with coronary vasoconstriction. These observations strongly support a role for endothelin as an early participant in and marker for coronary endothelial dysfunction in humans.