Rihal, Charanjit S.

Background— Existing models for outcome after percutaneous coronary interventions (PCIs) lack assessment of long-term prognosis. Our goal was to derive 1- and 5-year mortality and mortality/myocardial infarction (MI) risk models for PCI outcomes from simple, easily obtainable clinical and laboratory variables. Methods and Results— Using the Mayo Clinic registry, we analyzed long-term mortality and mortality/MI following PCIs on 9165 unique patients from January 1, 2001, through December 31, 2007. Cox proportional hazards regression was used to model the calculated risk score and major procedural complications. A total of 1243 patients died, and 696 had MI. Separate risk models derived from clinical, procedural, and laboratory characteristics were made for mortality and mortality/MI. Older age, comorbid conditions, low ejection fraction, acute MI, history of smoking, heart failure, hyperlipidemia, 3-vessel disease, procedural failure, ventricular arrhythmia during PCI, and low medication score were predictors of long-term mortality and mortality/MI. Simple integer scores stratified patients into low, moderate, high, and very high risk for subsequent events. Models had adequate goodness of fit, and areas under the receiver operating characteristic curve were 0.786 and 0.728 for mortality and mortality/MI, respectively, indicating good overall discrimination. Bootstrap analysis indicated that the model was not overfit to the available data set. Conclusions— Easily obtainable variables can be combined into a convenient risk scoring system at the time of patient dismissal following PCI to accurately predict long-term mortality and mortality/MI. This model may be useful for providing patients with individualized, evidence-based estimates of long-term risk.

Background— Endothelin (ET-1) is one of the most potent vasoconstrictors and plays a seminal role in the pathogenesis of atherosclerosis. The present study was designed to test the hypothesis that long-term treatment with an endothelin-A (ET A ) receptor antagonist improves coronary endothelial function in patients with early coronary atherosclerosis. Methods and Results— Forty-seven patients with multiple cardiovascular risk factors, nonobstructive coronary artery disease, and coronary endothelial dysfunction were randomized in a double-blind manner to either the ET A receptor antagonist atrasentan (10 mg) or placebo for 6 months. Coronary endothelium-dependent vasodilation was examined by infusing acetylcholine (10 −6 to 10 −4 mol/L) in the left anterior descending coronary artery. N G -monomethyl- l -arginine was administered to a subgroup of patients. Endothelium-independent coronary flow reserve was examined by use of intracoronary adenosine and nitroglycerin. Baseline characteristics and incidence of adverse effects were similar between the 2 groups. There was a significant improvement in percent change of coronary blood flow in response to acetylcholine at 6 months from baseline in the atrasentan group compared with the placebo group (39.67%, 95% confidence interval 23.23% to 68.21%, versus −2.22%, 95% confidence interval −27.37% to 15.28%; P <0.001). No significant difference in the percent change of coronary artery diameter or change in coronary flow reserve was demonstrated. Coronary blood flow, coronary artery diameter, and the effect of N G -monomethyl- l -arginine were similar between the groups at baseline and at 6 months. Conclusions— This study demonstrates that 6-month treatment with atrasentan improves coronary microvascular endothelial function and supports the role of the endogenous endothelin system in the regulation of endothelial function in early atherosclerosis in humans. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00271492.

Background— Contrast-induced nephropathy (CIN) is associated with significant morbidity and mortality. The objective of our meta-analysis was to assess the efficacy of iodixanol compared with low-osmolar contrast media (LOCM) for prevention of CIN. Methods and Results— We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and internet sources of cardiology trial results for individual and relevant reviews of randomized, controlled trials, for the terms contrast media, contrast nephropathy, renal failure, iodixanol, Visipaque, and low-osmolar contrast media. All studies reported an incidence rate of CIN for each study group; there was no restriction on the definition of CIN. There were no restrictions on journal type or patient population. Overall, 36 trials were identified for analysis of aggregated summary data on 7166 patients; 3672 patients received iodixanol and 3494 patients received LOCM. Overall, iodixanol showed no statistically significant reduction in CIN incidence below that observed with heterogeneous comparator agents ( P =0.11). Analysis of patient subgroups revealed that there was a significant benefit of iodixanol when compared with iohexol alone (odds ratio, 0.25; 95% confidence interval, 0.11 to 0.55; P <0.001) but not when compared with LOCM other than iohexol or with other ionic dimers or among patients receiving intra-arterial contrast injections or among patients undergoing coronary angiography with or without percutaneous intervention. Conclusions— Analysis of aggregated summary data from multiple randomized, controlled trials of iodixanol against diverse LOCMs for heterogeneous procedures and definitions of CIN show an iodixanol-associated reduction that is suggestive but statistically nonsignificant.

Background— Circadian rhythms with regard to time of symptom onset for patients with acute myocardial infarction have been observed, although their relationship to outcomes has been debated. We evaluated these rhythms in patients with ST-elevation myocardial infarction as a function of the 24-hour circadian cycle. Methods and Results— The relationship between onset of symptoms during the 24-hour circadian cycle and prehospital delays from symptom onset to hospital arrival, timeliness of reperfusion, and in-hospital death was assessed in 2143 patients with ST-elevation myocardial infarction presenting from 2004–2008 at 1 of 3 tertiary-care healthcare ST-elevation myocardial infarction systems. There was a significant association between time of onset and the circadian cycle, with the greatest percentage (39%) of patients experiencing onset between 8 am and 3 pm ( P <0.001). Time of onset was associated with prehospital delay and timeliness of reperfusion. Patients with onset from 12 am to 5:59 am had median prehospital delays of 121 minutes versus 70 minutes from 12 pm to 5:59 pm ( P <0.001). Patients with onset time from 12 am to 5:59 am had median door-to-balloon times of 75 minutes versus 60 minutes from 6 am to 11:59 am ( P <0.001). Using multivariable modeling to control for baseline patient characteristics, prehospital delay, and timeliness of reperfusion, there was no significant association between time of symptom onset with in-hospital death. Conclusions— Patients with ST-elevation myocardial infarction exhibit significant circadian patterns in symptom onset, prehospital delay, and timeliness of reperfusion. Patients who develop symptoms from 12 am to 5:59 am present with longer prehospital delays and have longer door-to-balloon times. After multivariable adjustment, there was no significant association between circadian patterns of time of onset and in-hospital death.

Background The American College of Cardiology released a scientific advisory that included a recommendation to delay elective of noncardiac surgery (NCS) for 1 yr after percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). Methods This single-center, retrospective study examined the risk for complications of NCS performed within 2 yr after DES placement and examined whether this risk changed based on the time between procedures. The primary endpoint was major adverse cardiac events (MACEs) during the hospitalization for NCS. Bleeding events were analyzed as a secondary endpoint. Results From April 22, 2003, to December 31, 2006, a total of 520 patients underwent NCS within 2 yr after PCI with a DES at Mayo Clinic. The majority, 84%, of the DES placed were Cypher stents. The frequency of MACE was not found to be significantly associated with the time between PCI and NCS (rate of MACEs 6.4, 5.7, 5.9, and 3.3% at 0-90, 91-180, 181-365, and 366-730 days after PCI with DES, respectively; P = 0.727 for comparison across groups). Characteristics found to be associated with MACEs in univariate analysis were advanced age (P = 0.031), emergent NCS (P = 0.006), shock at time of PCI (P = 0.035), previous history of myocardial infarction (P = 0.046), and continuation of a thienopyridine (ticlopidine or clopidogrel) into the preoperative period (P = 0.040). The rate of transfusion did not seem to be associated with antiplatelet therapy use. Conclusions The risk of MACEs with NCS after DES placement was not significantly associated with time from stenting to surgery, but observed rates of MACEs were lowest after 1 yr.

Background The duration of time that elective noncardiac surgery (NCS) should be delayed after percutaneous coronary intervention (PCI) with bare metal stents (BMSs) is unknown. Methods This large, single-center, retrospective study examined the relation between complication rate in patients with BMSs undergoing NCS and the duration of time between PCI and NCS. Primary endpoints included in-hospital major adverse cardiac events (death, myocardial infarction, stent thrombosis, or repeat revascularization with either coronary artery bypass grafting or PCI of the target vessel) and bleeding events. The relation between the events and the timing of noncardiac surgery after PCI with BMS was assessed using univariate analysis and multiple logistic regression. Results From January 1, 1990, to January 1, 2005, a total of 899 patients were identified. The frequency of major adverse cardiac events was 10.5% when NCS was performed less than 30 days after PCI with BMS, 3.8% when NCS was performed between 31 and 90 days after PCI with BMS, and 2.8% when NCS was performed more than 90 days after PCI with BMS. In univariate and multivariate analyses, a shorter time interval between PCI with BMS and noncardiac surgery was significantly associated with increased incidence of major adverse cardiac events (univariate: P < 0.001; odds ratio = 4.0; 95% confidence interval, 2.0-8.3; multivariate: P = 0.006; odds ratio = 3.2; 95% confidence interval, 1.5-6.9). Bleeding events were not associated with time between PCI with BMS and NCS or with the use of antiplatelet therapy in the week before NCS. Conclusions The incidence of major adverse cardiac events is lowest when NCS is performed at least 90 days after PCI with BMS.

Background— The economic outcomes of clinical management strategies are important in assessing their value to patients. Methods and Results— Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized patients with type 2 diabetes mellitus and angiographically documented, stable coronary disease to strategies of (1) prompt revascularization versus medical therapy with delayed revascularization as needed to relieve symptoms and (2) insulin sensitization versus insulin provision. Before randomization, the physician declared whether coronary artery bypass grafting or percutaneous coronary intervention would be used if the patient were assigned to revascularization. We followed 2005 patients for medical utilization and costs and assessed the cost-effectiveness of these management strategies. Medical costs were higher for revascularization than medical therapy, with a significant interaction with the intended method of revascularization ( P <0.0001). In the coronary artery bypass grafting stratum, 4-year costs were $80 900 for revascularization versus $60 600 for medical therapy ( P <0.0001). In the percutaneous coronary intervention stratum, costs were $73 400 for revascularization versus $67 800 for medical therapy ( P <0.02). Costs also were higher for insulin sensitization ($71 300) versus insulin provision ($70 200). Other factors that significantly ( P <0.05) and independently increased cost included insulin use and dose at baseline, female sex, white race, body mass index ≥30, and albuminuria. Cost-effectiveness based on 4-year data favored the strategy of medical therapy over prompt revascularization and the strategy of insulin provision over insulin sensitization. Lifetime projections of cost-effectiveness showed that medical therapy was cost-effective compared with revascularization in the percutaneous coronary intervention stratum ($600 per life-year added) with high confidence. Lifetime projections suggest that revascularization may be cost-effective in the coronary artery bypass grafting stratum ($47 000 per life-year added) but with lower confidence. Conclusions— Prompt coronary revascularization significantly increases costs among patients with type 2 diabetes mellitus and stable coronary disease. The strategy of medical therapy (with delayed revascularization as needed) appears to be cost-effective compared with the strategy of prompt coronary revascularization among patients identified a priori as suitable for percutaneous coronary intervention. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00006305.