Herbert D. Aronow

Effect of lipid-lowering therapy on early mortality after acute coronary syndromes: an observational study

BACKGROUND Lipid-lowering agents are known to reduce long-term mortality in patients with stable coronary disease or significant risk factors. However, the effect of lipid-lowering therapy on short-term mortality immediately after an acute coronary syndrome has not been determined. We did an observational study using data from two randomised trials to investigate this issue. METHODS We used data from the GUSTO IIb and PURSUIT trials to compare all-cause mortality among patients with acute coronary syndromes who were discharged on lipid-lowering agents (n=3653) with those who were not (n=17,156). A propensity analysis was done to adjust for presumed selection biases in the prescription of lipid-lowering agents. FINDINGS Lipid-lowering therapy was associated with a smaller proportion of deaths at 30 days (17 [0.5%] vs 179 [1.0%], hazard ratio 0.44 [95% CI 0.27-0.73], p=0.001) and at 6 months (63 [1.7%] vs 605 [3.5%], 0.48 [0.37-0.63], p<0.0001). After adjustment for the propensity to be prescribed lipid-lowering agents and other potential confounders, prescription of a lipid-lowering agent at discharge remained associated with a reduced risk of death at 6 months (0.67 [0.48-0.95], p=0.023). INTERPRETATION Prescription of a lipid-lowering drug at hospital discharge was independently associated with reduced short-term mortality among patients after an acute coronary syndrome.

Age and Outcomes After Carotid Stenting and Endarterectomy The Carotid Revascularization Endarterectomy Versus Stenting Trial

Background and Purpose— High stroke event rates among carotid artery stenting (CAS)-treated patients in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) lead-in registry generated an a priori hypothesis that age may modify the relative efficacy of CAS versus carotid endarterectomy (CEA). In the primary CREST report, we previously noted significant effect modification by age. Here we extend this investigation by examining the relative efficacy of the components of the primary end point, the treatment-specific impact of age, and contributors to the increasing risk in CAS-treated patients at older ages. Methods— Among 2502 CREST patients with high-grade carotid stenosis, proportional hazards models were used to examine the impact of age on the CAS-to-CEA relative efficacy, and the impact of age on risk within CAS-treated and CEA-treated patients. Results— Age acted as a treatment effect modifier for the primary end point (P interaction=0.02), with the efficacy of CAS and CEA approximately equal at age 70 years. For CAS, risk for the primary end point increased with age (P<0.0001) by 1.77-times (95% confidence interval, 1.38–2.28) per 10-year increment; however, there was no evidence of increased risk for CEA-treated patients (P=0.27). Stroke events were the primary contributor to the overall effect modification (P interaction=0.033), with equal risk at ≈64 years. The treatment-by-age interaction for CAS and CEA was not altered by symptomatic status (P=0.96) or by sex (P=0.45). Conclusions— Outcomes after CAS versus CEA were related to patient age, attributable to increasing risk for stroke after CAS at older ages. Patient age should be an important consideration when choosing between the 2 procedures for treating carotid stenosis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

Health-Related Quality of Life after Carotid Stenting versus Carotid Endarterectomy: Results from CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial)

OBJECTIVES The purpose of this study was to compare health-related quality of life (HRQOL) outcomes in patients treated with carotid artery stenting (CAS) versus carotid endarterectomy (CEA). BACKGROUND In CREST (Carotid Revascularization Endarterectomy versus Stenting Trial), the largest randomized trial of carotid revascularization to date, there was no significant difference in the primary composite endpoint, but rates of stroke and myocardial infarction (MI) differed between CAS and CEA. To help guide individualized clinical decision making, we compared HRQOL among patients enrolled in the CREST study. We also performed exploratory analyses to evaluate the association between periprocedural complications and HRQOL. METHODS We measured HRQOL at baseline, and after 2 weeks, 1 month, and 1 year among 2,502 patients randomly assigned to either CAS or CEA in the CREST study. The HRQOL was assessed using the Medical Outcomes Study Short-Form 36 (SF-36) and 6 disease-specific scales designed to study HRQOL in patients undergoing carotid revascularization. RESULTS At both 2 weeks and 1 month, CAS patients had better outcomes for multiple components of the SF-36, with large differences for role physical function, pain, and the physical component summary scale (all p < 0.01). On the disease-specific scales, CAS patients reported less difficulty with driving, eating/swallowing, neck pain, and headaches but more difficulty with walking and leg pain (all p < 0.05). However, by 1 year, there were no differences in any HRQOL measure between CAS and CEA. In the exploratory analyses, periprocedural stroke was associated with poorer 1-year HRQOL across all SF-36 domains, but periprocedural MI or cranial nerve palsy were not. CONCLUSIONS Among patients undergoing carotid revascularization, CAS is associated with better HRQOL during the early recovery period as compared with CEA-particularly with regard to physical limitations and pain-but these differences diminish over time and are not evident after 1 year. Although CAS and CEA are associated with similar overall HRQOL at 1 year, event-specific analyses confirm that stroke has a greater and more sustained impact on HRQOL than MI. (Carotid Revascularization Endarterectomy versus Stenting Trial [CREST]; NCT00004732)

Bleeding risk associated with 1 year of dual antiplatelet therapy after percutaneous coronary intervention: Insights from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial

BACKGROUND The optimal duration of dual antiplatelet therapy after percutaneous coronary intervention (PCI) is unknown. Incremental reductions in the risk of major adverse cardiovascular events may be partially offset by an increased incidence of bleeding in the months after a PCI. METHODS We examined the incidence, severity, and predictors of bleeding associated with 1 year of dual antiplatelet therapy after PCI among 1,816 patients in the Clopidogrel for the Reduction of Event During Observation (CREDO) trial. We also compared bleeding in patients who received dual antiplatelet therapy for 1 year to those who did so for only 4 weeks. Bleeding was categorized as major or minor using the modified Thrombolysis In Myocardial Infarction (TIMI) Study Group criteria. RESULTS Major or minor bleeding occurred in 146 patients during 1 year of follow-up. More than 80% of bleeding events were periprocedural. Multivariable predictors of any bleeding included increasing age and coronary artery bypass. Any (major or minor) bleeding occurred in 71 (8.1%) and 77 (8.9%), major bleeding in 34 (3.9%) and 49 (5.6%), and minor bleeding in 37 (4.2%) and 29 (3.3%) of placebo- and clopidogrel-treated patients, respectively; these differences were not significant. However, major gastrointestinal bleeding occurred in significantly more clopidogrel- than placebo-treated patients (13 [1.4%] vs 3 [0.3%] [P = .011]). CONCLUSIONS Adding clopidogrel to aspirin beyond 4 weeks post PCI is not associated with a significant increase in the overall rate of major or minor bleeding, although it is associated with an increase in major gastrointestinal bleeding in the year after a PCI.

The changing definition of contrast-induced nephropathy and its clinical implications: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2)

BACKGROUND The traditional definition of contrast-induced nephropathy (CIN) has been an absolute rise of serum creatinine (Cr) of ≥0.5 mg/dL, although most recent clinical trials have included a ≥25% increase from baseline Cr. The clinical implication of this definition change remains unknown. METHODS AND RESULTS We compared the association of the two definitions with risk of death or need for dialysis among 58,957 patients undergoing percutaneous coronary intervention in 2007 to 2008 in a large collaborative registry. Patients with a preexisting history of renal failure requiring dialysis were excluded. Contrast-induced nephropathy as defined by a rise in Cr ≥0.5 mg/dL (CIN(Traditional)) developed in 1,601, whereas CIN defined either as Cr ≥0.5 mg/dL or ≥25% increase in baseline Cr (CIN(New)) developed in 4,308 patients. Patients meeting the definition of CIN(New) but not CIN(Traditional) were classified as CIN(Incremental) (n = 2,707). Compared with CIN(New), CIN(Traditional) was more commonly seen in patients with abnormal renal function, which was more likely to develop in patients with normal renal function at baseline. Compared with CIN(Incremental), patients meeting the definition of CIN(Traditional) were more likely to die (16.7% vs 1.7%) and require in-hospital dialysis (9.8% vs 0%). CONCLUSIONS Our data suggest that the traditional definition of CIN (a rise in Cr of ≥0.5 mg/dL) in patients undergoing PCI is superior to ≥25% increase in Cr at identifying patients at greater risk for adverse renal and cardiac events.

Long-term Care After Percutaneous Coronary Intervention: Focus on the Role of Antiplatelet Therapy

Arterial wall injury caused by percutaneous coronary intervention (PCI) triggers transient platelet activation and mural thrombosis; these effects are superimposed on the preexisting platelet hyperreactivity associated with underlying atherothrombosis. Platelet activation has been implicated in the major complications of PCI: acute and subacute thrombosis and restenosis. Antithrombotic and anticoagulant therapy minimizes thrombotic complications after PCI. Aspirin plus a thienopyridine (ticlopidine or clopidogrel) is more effective than aspirin plus heparin and extended warfarin therapy in preventing periprocedural ischemic events and subsequent stent thrombosis and results in less major and minor bleeding. Dual antiplatelet therapy with aspirin and clopidogrel (the preferred thienopyridine because of its superior hematologic safety) is recommended for at least 4 weeks to prevent subacute stent thrombosis with bare-metal stents and 3 to 6 months to prevent late-stent thrombosis with drug-eluting stents. Coronary atherothrombosis is a diffuse vascular disease, and reduction of the risk of future ischemic events requires strategies that extend beyond the focal treatment of stenotic lesions. Optimal long-term care after PCI requires aggressive systemic pharmacotherapy (antiplatelet agents, statins, beta-blockers, and angiotensin-converting enzyme Inhibitors) in conjunction with therapeutic lifestyle changes (smoking cessation, weight reduction, dietary measures, and exercise). In this context, dual antiplatelet therapy (aspirin plus clopidogrel) is recommended for at least 12 months after PCI for prophylaxis of future atherothrombotic events.

Switching from atorvastatin to simvastatin in patients at high cardiovascular risk: effects on low-density lipoprotein cholesterol.

Since generic simvastatin became available in the United States in 2006, approximately one million patients have switched from atorvastatin to simvastatin. We examined the association between switching from atorvastatin to simvastatin and changes in low-density lipoprotein cholesterol (LDL-C) levels in clinical practice. We compared atorvastatin-treated patients at high cardiovascular risk who switched to simvastatin between June 2006 and July 2007 with randomly selected matched patients who remained on atorvastatin and evaluated changes in LDL-C and percentage of patients reaching LDL-C less than 100 mg/dL. Of patients who switched from atorvastatin to simvastatin, the majority were excluded as a result of lack of LDL-C measurements, leaving 383 patients in the analysis. Among these, 122 (31.9%) switched to a simvastatin dose that was less than therapeutically equivalent to their prior atorvastatin dose. Compared with control subjects, switched patients were less likely to reach an LDL-C less than 100 mg/dL (68.4% versus 74.0%; odds ratio, 0.76; 95% confidence interval, 0.59-0.99; P = 0.041) and had higher measured LDL-C (91.4 versus 87.2 mg/dL; P = 0.009). Switched patients who were not prescribed a higher milligram dose of simvastatin were significantly less likely to reach an LDL-C less than 100 mg/dL (62.3% versus 74.0%; odds ratio, 0.55; 95% confidence interval, 0.36-0.84; P = 0.006) and had higher LDL-C (95.1 versus 87.2 mg/dL; P = 0.002) than control subjects. A large proportion of patients who switch from atorvastatin to simvastatin are prescribed doses that are not therapeutically equivalent, and these patients were significantly less likely to meet LDL-C treatment goals compared with patients who remained on atorvastatin.

Leukocyte Count Predicts Microembolic Doppler Signals During Carotid Stenting A Link Between Inflammation and Embolization

Background and Purpose— Protected stenting has emerged as a safe and effective alternative to endarterectomy for the treatment of carotid stenosis in patients at high operative risk. Distal microembolization occurs invariably during carotid stenting. Little is known about the relationship between systemic inflammation and embolization during carotid stenting. Methods— We examined 43 consecutive patients who underwent carotid stenting with simultaneous transcranial Doppler (TCD) monitoring of the ipsilateral middle cerebral artery. Embolization was quantified by measuring microembolic signals (MES) on TCD. Preprocedure leukocyte counts were related to MES. Results— In unadjusted analyses, preprocedure leukocyte count was positively correlated with total procedural MES (r2= 0.16; P=0.008). After considering age, gender, comorbidities, concomitant medical therapies, and the use of emboli prevention devices, increasing leukocyte count (&bgr;=35 for each 1000/&mgr;L increment; P=0.018) remained a significant and independent predictor of embolization (model-adjusted r2=0.365; P=0.0005). Conclusions— Increasing preprocedure leukocyte count independently predicted more frequent MES during carotid stenting. These data suggest that systemic inflammation may influence the degree of procedural embolization.

Molecular and pathologic characterization of an AIDS-related body cavity-based lymphoma, including ultrastructural demonstration of human herpesvirus-8: A case report

Body cavity-based lymphoma, also known as primary effusion lymphoma, is a newly recognized acquired immunodeficiency syndrome (AIDS)-related lymphoma that has been linked to the Kaposis sarcoma-associated herpesvirus (KSHV/HHV-8). To date, direct visualization of the virus in a clinical sample has not been demonstrated. We have performed an extensive clinical, histologic, immunophenotypic, ultrastructural, and molecular genetic correlative study on multiple tissue samples obtained premortem and at autopsy from an patient with AIDS with Kaposis sarcoma and body cavity-based lymphomas. We demonstrate the presence of human herpesvirus-8 in a primary clinical sample at the ultrastructural and molecular level, as well as document multiple lymphomatous tumor masses at autopsy.

The Quality and Impact of Risk Factor Control in Patients With Stable Claudication Presenting for Peripheral Vascular Interventions

Background—Peripheral arterial disease is a manifestation of systemic atherosclerosis and is predictive of future cardiovascular events. Clinical trial data have demonstrated that medical therapy can attenuate cardiovascular morbidity and mortality in patients with peripheral arterial disease. The utilization and impact of recommended medical therapy in a contemporary population of patients who undergo percutaneous interventions for lifestyle-limiting peripheral arterial disease is unknown. Methods and Results—Using the Blue Cross Blue Shield of Michigan Cardiovascular Consortium Peripheral Vascular Intervention (BMC2 PVI) database, we identified 1357 peripheral vascular intervention encounters between January 2007 and December 2009 for the purpose of treating claudication. Before the intervention, 85% of these patients used aspirin, 76% used statin, 65% abstained from smoking, and 47% did all 3. There was no difference in cardiovascular events among those taking an aspirin and a statin on admission and those who were not. However, in both an unadjusted and a multivariable analysis, the odds of an adverse peripheral vascular outcome (repeat peripheral intervention, amputation, or limb salvage surgery) within 6 months decreased by more than half in patients receiving aspirin and statin therapy before peripheral vascular intervention as compared with those who received neither (odds ratio, 0.45; 95% CI, 0.29–0.71). Conclusions—The fundamental elements of medical therapy in patients with lifestyle-limiting claudication are often underutilized before referral for revascularization. Appropriate medical therapy before percutaneous revascularization is associated with fewer peripheral vascular events at 6 months.