Early technology review: towards an expedited pathway.

OBJECTIVES: Evidence development for medical devices is often focused on satisfying regulatory requirements with the result that health professional and payer expectations may not be met, despite considerable investment in clinical trials. Early engagement with payers and health professionals could allow companies to understand these expectations and reflect them in clinical study design, increasing chances of positive coverage determination and adoption into clinical practice. METHODS: An example of early engagement through the EXCITE International model using an early technology review (ETR) is described which includes engagement with payers and health professionals to better inform companies to develop data that meet their expectations. ETR is based on an early evidence review, a framework of expectations that guides the process and identified gaps in evidence. The first fourteen ETRs were reviewed for examples of advice to companies that provided additional information from payers and health professionals that was thought likely to impact on downstream outcomes or strategic direction. Given that limitations were imposed by confidentiality, examples were genericized. RESULTS: Advice through early engagement can inform evidence development that coincides with expectations of payers and health professionals through a structured, objective, evidence-based approach. This could reduce the risk of business-related adverse outcomes such as failure to secure a positive coverage determination and/or acceptance by expert health professionals. CONCLUSIONS: Early engagement with key stakeholders exemplified by the ETR approach offers an alternative to the current approach of focusing on regulatory expectations. This could reduce the time to reimbursement and clinical adoption and benefit patient outcomes and/or health system efficiencies.

Long-term outcomes of percutaneous coronary intervention for in-stent restenosis among Medicare beneficiaries.

BACKGROUND: In-stent restenosis (ISR) is highly prevalent and leads to repeat revascularisation. Long-term implications of ISR are poorly understood. AIMS: This study aimed to evaluate the long-term outcomes of patients undergoing percutaneous coronary intervention (PCI) for ISR. METHODS: National Cardiovascular Data Registry CathPCI records for individuals aged ≥65 years undergoing PCI from July 2009 to December 2014 were linked to Medicare claims. Baseline characteristics and long-term rates of death, myocardial infarction (MI), repeat revascularisation including target vessel revascularisation (TVR), and major adverse cardiovascular and cerebrovascular events (MACCE) were compared between ISR PCI versus de novo lesion PCI. RESULTS: Of 653,304 individuals, 10.2% underwent ISR PCI and 89.8% underwent de novo lesion PCI. The median duration of follow-up was 825 days (quartile 1: 352 days-quartile 3: 1,379 days). The frequency of MACCE (55.6% vs 45.0%; p<0.001), all-cause mortality (27.8% vs 25.5%; p<0.001), MI (19.0% vs 12.3%; p<0.001), repeat revascularisation (31.9% vs 18.6%; p<0.001), TVR (22.4% vs 8.0%; p<0.001), and stroke (8.8% vs 8.3%; p=0.005) was higher after ISR PCI. After multivariable adjustment, ISR PCI remained associated with worse long-term outcomes than after de novo lesion PCI (hazard ratio [HR] for MACCE 1.24 [95% CI: 1.22, 1.26], mortality 1.07 [95% CI: 1.05, 1.09], MI 1.44 [95% CI: 1.40, 1.48], repeat revascularisation 1.55 [95% CI: 1.51, 1.59], and TVR 2.50 [95% CI: 2.42, 2.58]). CONCLUSIONS: ISR PCI was common and was associated with a significantly higher risk of recurrent long-term major ischaemic events compared to patients undergoing de novo lesion PCI. There remains a need for new strategies to minimise ISR.

Lipid Management in Patients Presenting With Acute Coronary Syndromes: A Review.

Despite many improvements in its prevention and management, acute coronary syndrome (ACS) remains a major cause of morbidity and mortality in the developed world. Lipid management is an important part of secondary prevention after ACS, but many patients currently remain undertreated and do not attain guideline-recommended levels of low-density lipoprotein cholesterol reduction. This review details the current state of evidence on lipid management in patients presenting with ACS, provides directions for identification of patients who may benefit from early escalation of lipid-lowering therapy, and discusses novel lipid-lowering medication that is currently under investigation in clinical trials. Moreover, a treatment algorithm aimed at attaining guideline-recommended low-density lipoprotein cholesterol levels is proposed. Despite important advances in the initial treatment and secondary prevention of ACS, ≈20% of ACS survivors experience a subsequent ischemic cardiovascular event within 24 months, and 5-year mortality ranges from 19% to 22%. Knowledge of the current state of evidence-based lipid management after ACS is of paramount importance to improve outcomes after ACS.

Echocardiographic assessment of insulin-like growth factor binding protein-7 and early identification of acute heart failure.

AIMS: Concentrations of insulin-like growth factor binding protein-7 (IGFBP7) have been linked to abnormal cardiac structure and function in patients with chronic heart failure (HF), but cardiovascular correlates of the biomarker in patients with more acute presentations are lacking. We aimed to determine the relationship between IGFBP7 concentrations and cardiac structure and to evaluate the impact of IGFBP7 on the diagnosis of acute HF among patients with acute dyspnoea. METHODS AND RESULTS: In this pre-specified subgroup analysis of the International Collaborative of N-terminal pro-B-type Natriuretic Peptide Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department (ICON-RELOADED) study, we included 271 patients with and without acute HF. All patients presented to an emergency department with acute dyspnoea, had blood samples for IGFBP7 measurement, and detailed echocardiographic evaluation. Higher IGFBP7 concentrations were associated with numerous cardiac abnormalities, including increased left atrial volume index (LAVi; r = 0.49, P < 0.001), lower left ventricular ejection fraction (r = -0.27, P < 0.001), lower right ventricular fractional area change (r = -0.31, P < 0.001), and higher tissue Doppler E/e' ratio (r = 0.44, P < 0.001). In multivariable linear regression analyses, increased LAVi (P = 0.01), lower estimated glomerular filtration rate (P = 0.008), higher body mass index (P = 0.001), diabetes (P = 0.009), and higher concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP, P = 0.02) were independently associated with higher IGFBP7 concentrations regardless of other variables. Furthermore, IGFBP7 (odds ratio = 12.08, 95% confidence interval 2.42-60.15, P = 0.02) was found to be independently associated with the diagnosis of acute HF in the multivariable logistic regression analysis. CONCLUSIONS: Among acute dyspnoeic patients with and without acute HF, increased IGFBP7 concentrations are associated with a range of cardiac structure and function abnormalities. Independent association with increased LAVi suggests elevated left ventricular filling pressure is an important trigger for IGFBP7 expression and release. IGFBP7 may enhance the diagnosis of acute HF.

Tailoring Antiplatelet Therapy Intensity to Ischemic and Bleeding Risk.

BACKGROUND: Balancing ischemic and bleeding risk is an evolving framework. METHODS AND RESULTS: Our objectives were to simulate changes in risks for adverse events and event-driven costs with use of ticagrelor or prasugrel versus clopidogrel according to varying levels of ischemic and bleeding risk. Using the validated PARIS risk functions, we estimated 1-year ischemic (myocardial infarction or stent thrombosis) and bleeding (Bleeding Academic Research Consortium types 3 or 5) event rates among PARIS study participants who underwent percutaneous coronary intervention with drug-eluting stent implantation for an acute coronary syndrome and were discharged with aspirin and clopidogrel (n=1497). Simulated changes in adverse events with ticagrelor or prasugrel were calculated by applying treatment effects from randomized trials for a 1-year time horizon. Event costs were estimated using National Inpatient Sample data. Net costs were calculated between antiplatelet therapy groups according to level of ischemic and bleeding risk. After weighting events for quality-of-life impact, we calculated event rates and costs for risk-tailored treatment versus clopidogrel under multiple drug pricing assumptions. One-year rates (per 1000 person-years) for ischemic events were 12.6, 24.1, and 66.1, respectively, among those at low (n=630), intermediate (n=536), and high (n=331) ischemic risk. Analogous bleeding rates were 11.0, 23.9, and 66.2, respectively, among low (n=728), intermediate (n=634), and high (n=135) bleeding risk patients. Mean per event costs were $22 174 (ischemic) and $12 203 (bleeding). When risks for ischemia matched or exceeded bleeding, simulated utility-weighted event rates favored ticagrelor/prasugrel, whereas clopidogrel reduced utility-weighted events when bleeding exceeded ischemic risk. One-year costs were sensitive to drug pricing assumptions, and risk-tailored treatment with either agent progressed from cost incurring to cost saving with increasing generic market share. CONCLUSIONS: Tailoring antiplatelet therapy intensity to patient risk may improve health utility and could produce cost savings in the first year after percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00998127.

Cost Implications of Anticoagulation Strategies After Percutaneous Coronary Intervention Among Patients With Atrial Fibrillation (A PIONEER-AF PCI Analysis).

The PIONEER AF-PCI trial demonstrated that in atrial fibrillation patients who underwent intracoronary stenting, either rivaroxaban 15 mg daily plus P2Y12 inhibitor monotherapy (Group 1) or 2.5 mg rivaroxaban twice daily plus dual antiplatelet therapy (DAPT) (Group 2) was associated with fewer recurrent hospitalizations, primarily for bleeding and cardiovascular events, compared with standard-of-care vitamin K antagonist and DAPT (Group 3). Associated costs are unknown. This study estimates costs associated with rivaroxaban strategies compared with vitamin K antagonist and DAPT. Medication costs were estimated using wholesale acquisition costs, medication discontinuation rates, and costs of monitoring. Using a large US healthcare claims database, the mean adjusted increase in 1-year cost of care for individuals with atrial fibrillation and percutaneous coronary intervention (PCI) rehospitalized for bleeding, cardiovascular, and other events was compared with those not rehospitalized. Using adjudicated rehospitalization rates from PIONEER AF-PCI, cost differences were estimated. Rates of rehospitalization for bleeding were 6.5%, 5.4%, 10.5%, and 20.3%, 20.3%, 28.4% for cardiovascular events in Groups 1, 2, and 3. Medication and monitoring costs were $3,942, $4,115, and $1,703. One-year costs for all recurrent hospitalization costs and/or patient for the groups were $24,535, $20,205, and $29,756. One-year cost increase associated with bleeding rehospitalizations and/or patient was $4,160, $3,212, and $6,876 and was $13,264, $11,545, and $17,220 for cardiovascular rehospitalizations and/or patient. Overall estimated cost per patient was $28,476, $24,320, and $31,458. Compared with warfarin, both rivaroxaban treatment strategies had higher medication costs, but these were more than accounted for by fewer hospitalizations.

Cost implications of intraprocedural thrombotic events and bleeding in percutaneous coronary intervention: Results from the CHAMPION PHOENIX ECONOMICS Study.

BACKGROUND: Despite improvements in percutaneous coronary intervention (PCI), intraprocedural thrombotic events (IPTE) and bleeding complications occur and are prognostically important. These have not been included in prior economic studies. METHODS: PHOENIX ECONOMICS was a substudy of the CHAMPION PHOENIX trial, evaluating cangrelor during PCI. Hospital bills were reviewed from 1,171 patients enrolled at 22 of 63 US sites. Costs were estimated using standard methods including resource-based accounting, hospital billing data, and the Medicare fee schedule. Bleeding and IPTE, defined as abrupt vessel closure (transient or sustained), new/suspected thrombus, new clot on wire/catheter, no reflow, side-branch occlusion, procedural stent thrombosis or urgent need for CABG were identified. Costs were calculated according to whether a complication occurred and type of event. Multivariate analyses were used to estimate the incremental costs of IPTE and postprocedural events. RESULTS: IPTE occurred in 4.3% and were associated with higher catheterization laboratory and overall index hospitalization costs by $2,734 (95%CI $1,117, $4,351; P = 0.001) and $6,354 (95% CI $4,122, $8,586; P < 0.001), respectively. IPTE were associated with MI (35.4% vs. 3.6%; P < 0.001), out-of-laboratory stent thrombosis (4.2% vs. 0.1%; 0 = 0.005), ischemia driven revascularization (12.5% vs. 0.3%; P < 0.001), but not mortality (2.1% vs. 0.2%; P = 0.12) vs. no procedural thrombotic complication. By comparison, ACUITY minor bleeding increased hospitalization cost by $1,416 (95%CI = 312, $2,519; P = 0.012). ACUITY major bleeding increased cost of hospitalization by $7,894 (95%CI $4,154, $11,635; P < 0.001). CONCLUSIONS: IPTE and bleeding complications, though infrequent, are associated with substantial increased cost. These complications should be collected in economic assessments of PCI.

Incidence, Predictors, and Outcomes of Acquired Thrombocytopenia After Percutaneous Coronary Intervention: A Pooled, Patient-Level Analysis of the CHAMPION Trials (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition).

BACKGROUND: The influence of cangrelor on the incidence and outcomes of post-percutaneous coronary intervention (PCI) thrombocytopenia is not defined. We aimed to explore the incidence, predictors, and clinical impact of thrombocytopenia after PCI in cangrelor-treated patients. METHODS AND RESULTS: This was a pooled, patient-level analysis of the CHAMPION trials (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition), which compared cangrelor with clopidogrel for prevention of thrombotic complications during and after PCI. Acquired thrombocytopenia was defined as either a drop in platelet count to <100 000 after PCI or a drop of >50% between baseline and a follow-up. The main efficacy outcome was major adverse cardiac events. The primary safety outcome was noncoronary artery bypass grafting-related Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries-defined severe bleeding at 48 hours. Patients (23 783) were enrolled, and 3009 (12.7%) received a GPI (glycoprotein IIb/IIIa inhibitor). Acquired thrombocytopenia occurred in 200 patients (0.8%). The adjusted rate of major adverse cardiovascular events at 48 hours was significantly higher in patients who developed thrombocytopenia compared with those who did not (odds ratio, 3.00; 95% confidence interval, 1.89-4.69; P<0.001), as was major bleeding (odds ratio, 14.71; 95% confidence interval, 5.96-36.30; P<0.001). GPI use was the strongest independent predictor of acquired thrombocytopenia (odds ratio, 2.93; 95% confidence interval, 2.15-3.97; P<0.0001). There was no difference in the rate of acquired thrombocytopenia in patients randomized to cangrelor or clopidogrel. CONCLUSIONS: Acquired thrombocytopenia after PCI is strongly associated with substantial early morbidity and mortality, as well as major bleeding. GPI use is a significant predictor of thrombocytopenia. Cangrelor is not associated with acquired thrombocytopenia, and its clinical efficacy and safety is consistent irrespective of thrombocytopenia occurrence. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00305162, NCT00385138, and NCT01156571.

Lack of Concordance Between Local Investigators, Angiographic Core Laboratory, and Clinical Event Committee in the Assessment of Stent Thrombosis: Results From the TRACER Angiographic Substudy.

BACKGROUND: Stent thrombosis (ST) is an important end point in cardiovascular clinical trials. Adjudication is traditionally based on clinical event committee (CEC) review of case report forms and source documentation rather than angiograms. However, the degree to which this method of adjudication is concordant with the review of independent angiographic core laboratories (ACLs) has not been studied. This report represents the first assessment of variability between local investigators (LIs), a CEC, and an ACL. METHODS AND RESULTS: Serial angiograms of 329 patients with acute coronary syndrome without ST-segment-elevation who underwent percutaneous coronary intervention at entry in the Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Particpants With Acute Coronary Syndrome (TRACER) and who met criteria for possible ST subsequent to the index event were reviewed by an ACL. The ACL was blinded to the assessment by both LIs and the CEC regarding the presence or absence of ST. CEC adjudication was based on Academic Research Consortium definitions of ST, using case report form data and source documents, including catheterization laboratory reports. The ACL, CEC, and LIs agreed on the presence or absence of ST in 52.9% events (κ=0.32; 95% confidence interval, 0.26-0.39). The ACL and CEC agreed on 82.7% of events (κ=0.57; 95% confidence interval, 0.47-0.67); the ACL and LIs agreed on 61.1% of events (κ=0.25; 95% confidence interval, 0.16-0.34); and the CEC and LIs agreed on 62% of events (κ=0.28; 95% confidence interval, 0.21-0.36). CONCLUSIONS: ST reporting by an ACL, a CEC, and LIs is discordant. The assessment of ST is more often detected by direct review of angiograms by an ACL. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00527943.

Extended-Duration Thromboprophylaxis Among Acute Medically Ill Patients: An Unmet Need.

Acute medical illnesses are associated with a prolonged elevation in inflammatory markers that predisposes patients to thrombosis beyond the duration of their hospital stay. In parallel, both observational and randomized data have demonstrated a rate of postdischarge venous thromboembolic events that often exceeds that observed in the hospital setting. Despite this significant residual risk of venous thromboembolic events following discharge among acute medically ill patients, no therapeutic strategies have been recommended to address this unmet need. Available randomized trials have demonstrated the efficacy of extending the duration of thromboprophylaxis with available anticoagulants; however, the efficacy is offset, at least in part, by an increase in bleeding events. Identification of the optimal therapeutic strategies, treatment duration, and risk assessment tools that reconcile both efficacy and safety of extended-duration thromboprophylaxis among acute medically ill patients is an area of ongoing investigation.

Assessment of the clinical effects of cholesteryl ester transfer protein inhibition with evacetrapib in patients at high-risk for vascular outcomes: Rationale and design of the ACCELERATE trial.

BACKGROUND: Potent pharmacologic inhibition of cholesteryl ester transferase protein by the investigational agent evacetrapib increases high-density lipoprotein cholesterol by 54% to 129%, reduces low-density lipoprotein cholesterol by 14% to 36%, and enhances cellular cholesterol efflux capacity. The ACCELERATE trial examines whether the addition of evacetrapib to standard medical therapy reduces the risk of cardiovascular (CV) morbidity and mortality in patients with high-risk vascular disease. STUDY DESIGN: ACCELERATE is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients qualified for enrollment if they have experienced an acute coronary syndrome within the prior 30 to 365 days, cerebrovascular accident, or transient ischemic attack; if they have peripheral vascular disease; or they have diabetes with coronary artery disease. A total of 12,092 patients were randomized to evacetrapib 130 mg or placebo daily in addition to standard medical therapy. The primary efficacy end point is time to first event of CV death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Treatment will continue until 1,670 patients reached the primary end point; at least 700 patients reach the key secondary efficacy end point of CV death, myocardial infarction, and stroke, and the last patient randomized has been followed up for at least 1.5 years. CONCLUSIONS: ACCELERATE will establish whether the cholesteryl ester transfer protein inhibition by evacetrapib improves CV outcomes in patients with high-risk vascular disease.

Independent data monitoring committees: preparing a path for the future.

Independent data monitoring committees (IDMCs) were introduced to monitor patient safety and study conduct in randomized clinical trials (RCTs), but certain challenges regarding the utilization of IDMCs have developed. First, the roles and responsibilities of IDMCs are expanding, perhaps due to increasing trial complexity and heterogeneity regarding medical, ethical, legal, regulatory, and financial issues. Second, no standard for IDMC operating procedures exists, and there is uncertainty about who should determine standards and whether standards should vary with trial size and design. Third, considerable variability in communication pathways exist across IDMC interfaces with regulatory agencies, academic coordinating centers, and sponsors. Finally, there has been a substantial increase in the number of RCTs using IDMCs, yet there is no set of qualifications to help guide the training and development of the next generation of IDMC members. Recently, an expert panel of representatives from government, industry, and academia assembled at the Duke Clinical Research Institute to address these challenges and to develop recommendations for the future utilization of IDMCs in RCTs.

Angiographic validation of the American College of Cardiology Foundation-the Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies study.

BACKGROUND: The goal of this study was to compare angiographic interpretation of coronary arteriograms by sites in community practice versus those made by a centralized angiographic core laboratory. METHODS AND RESULTS: The study population consisted of 2013 American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR) records with 2- and 3- vessel coronary disease from 54 sites in 2004 to 2007. The primary analysis compared Registry (NCDR)-defined 2- and 3-vessel disease versus those from an angiographic core laboratory analysis. Vessel-level kappa coefficients suggested moderate agreement between NCDR and core laboratory analysis, ranging from kappa=0.39 (95% confidence intervals, 0.32-0.45) for the left anterior descending artery to kappa=0.59 (95% confidence intervals, 0.55-0.64) for the right coronary artery. Overall, 6.3% (n=127 out of 2013) of those patients identified with multivessel disease at NCDR sites had had 0- or 1-vessel disease by core laboratory reading. There was no directional bias with regard to overcall, that is, 12.3% of cases read as 3-vessel disease by the sites were read as <3-vessel disease by the core laboratory, and 13.9% of core laboratory 3-vessel cases were read as <3-vessel by the sites. For a subset of patients with left main coronary disease, registry overcall was not linked to increased rates of mortality or myocardial infarction. CONCLUSIONS: There was only modest agreement between angiographic readings in clinical practice and those from an independent core laboratory. Further study will be needed because the implications for patient management are uncertain.

Cost-Effective Medicines for Stroke Prophylaxis in Patients with Atrial Fibrillation.

Non-valvular atrial fibrillation is the most common arrhythmia encountered in clinical practice and is associated with substantial healthcare costs. The risk of thromboembolic stroke is 3-5 times higher in patients with atrial fibrillation compared with the general population. Until the recent emergence of direct thrombin (factor IIa) and factor Xa inhibitors, antithrombotic therapy for atrial fibrillation was achieved with antiplatelet agents or vitamin K antagonists, which are considered cost-effective strategies when compared to no treatment. Now newer agents, such as the direct thrombin inhibitor dabigatran, can lower thromboembolic events and reduce the risk of fatal and intracerebral hemorrhage compared with warfarin, in addition to eliminating the need for costly therapeutic monitoring. Multiple analyses have shown that dabigatran, when compared with warfarin therapy that achieves a time in therapeutic range (TTR) consistent with previous large-scale trials, is a cost-effective approach to antithrombotic therapy in atrial fibrillation, ranging from $16,385 to $86,000 per quality-adjust life-year (QALY) gained. It has been shown to be especially cost-effective (QALY < $50,000) for high stroke-risk patients, those with a CHADS2 score of > 3 (barring excellent INR control) and for lower-risk patients with a CHADS2 of 2 but concomitant high risk of hemorrhage. In addition, factor Xa inhibitors, such as rivaroxaban (recently approved by the Federal Drug Administration [FDA]) and apixaban, may exhibit the same cost savings as dabigatran in terms of reduction of bleeding and elimination of therapeutic level monitoring costs. Going forward, the use of these agents and their role in thromboembolic stroke prophylaxis will need to be evaluated on a patient-by-patient basis, balancing consideration of the patient?s stroke and bleeding risks, as well as quality of life post-therapy.

Hospitals with and without percutaneous coronary intervention capability: considerations for treating acute coronary syndromes.

The crucial aim in the emergency management of patients presenting with chest pain is the identification of acute coronary syndromes (ACS) and the initiation of appropriate treatment. Institution-specific triage to initial medical or interventional therapies is influenced by the availability of percutaneous coronary intervention (PCI) facilities. Although the use of invasive strategies has increased, most US hospitals do not have PCI facilities. Pharmacological management is an integral part of all treatment strategies, regardless of the availability of interventional capability. Given the growing importance of invasive management strategies, a therapy that is compatible with both medical and invasive therapy options is becoming increasingly important. Aspirin and clopidogrel are recommended for patients with ACS regardless of the conservative or invasive management strategy. With enoxaparin, patients with ACS can seamlessly transition from the medical management phase to the interventional management phase without the need for introducing a second anticoagulant in the cardiac catheterization laboratory. Fondaparinux can be used for patients with ACS treated medically, but should not be used alone during PCI because of the risk of catheter thrombosis. Bivalirudin can be used in non-ST-segment elevation myocardial infarction patients who are managed invasively.

Use of the TIMI frame count in the assessment of coronary artery blood flow and microvascular function over the past 15 years.

Since its introduction, the TIMI frame count method has contributed to the understanding of the pathophysiology of coronary artery disease. In this article, the evolution of the TFC method and its applicability in the assessment of various therapeutic modalities are described.

Trends in quality of care for patients with acute myocardial infarction in the National Registry of Myocardial Infarction from 1990 to 2006.

BACKGROUND: Trends in the use of guideline-based treatment for acute myocardial infarction (AMI) as well as its association with patient outcomes have not been summarized in a large, longitudinal study. Furthermore, it is unknown whether gender-, race-, and age-based care disparities have narrowed over time. METHODS AND RESULTS: Using the National Registry of Myocardial Infarction database, we analyzed 2,515,106 patients with AMI admitted to 2,157 US hospitals between July 1990 and December 2006 to examine trends overall and in select subgroups of guideline-based admission, procedural, and discharge therapy use. The contribution of temporal improvements in acute care therapies to declines in in-hospital mortality was examined using logistic regression analysis. From 1990 to 2006, the use of all acute guideline-recommended therapies administered rose significantly for patients with ST-segment elevation myocardial infarction and patients with non-ST-segment myocardial infarction but remained below 90% for most therapies. Cardiac catheterization and percutaneous coronary intervention use increased in patients with ST-segment elevation myocardial infarction and patients with non-ST-segment myocardial infarction, whereas coronary bypass surgery use declined in both groups. Despite overall care improvements, women, blacks, and patients > or =75 years old were significantly less likely to receive revascularization or discharge lipid-lowering therapy relative to their counterparts. Temporal improvements in acute therapies may account for up to 37% of the annual decline in risk for in-hospital AMI mortality. CONCLUSION: Adherence to American Heart Association/American College of Cardiology practice guidelines has improved care of patients with AMI and is associated with significant reductions in in-hospital mortality rates. However, persistent gaps in overall care as well as care disparities remain and suggest the need for ongoing quality improvement efforts.