Hospitalization For Acute Coronary Syndrome Research Articles

Incidence of death and recurring acute coronary syndrome after stopping clopidogrel therapy in a large commercially-insured population in the US

Background/objective:Guidelines support clopidogrel therapy in medically-treated or percutaneous coronary intervention (PCI) patients after hospitalization for acute coronary syndrome (ACS). However, clopidogrel discontinuation has been associated with increased short-term risks. This study evaluated the risk of adverse outcomes (AOs), defined as death or recurrent ACS, after clopidogrel discontinuation in a managed-care population.Methods:ACS patients (n = 7625) with ≥1 clopidogrel pharmacy claim from 2001 to 2006 and no AO before discontinuing clopidogrel were identified from administrative claims data. AO occurrences were recorded at 90-day intervals following clopidogrel discontinuation.Results:The mean (SD) duration of clopidogrel therapy for medically-treated, bare metal stent (BMS) and drug eluting stent (DES) patients was 349.2 (393.1) days, 235.6 (383.0) days, and 280.2 (227.1) days, respectively. Among medically-treated patients, Poisson regression analysis showed a 2.19 times higher AO risk (p < 0.01), a 1.63 times greater risk among BMS patients (p < 0.01), and a 1.56 times greater risk for DES patients (p ≥ 0.05) during days 0–90 versus days 91–180 after clopidogrel discontinuation. Sensitivity analysis showed that medically-treated, BMS and DES patients with ≤90 days of clopidogrel therapy had 2.13, 1.68 and 2.40 times higher AO risk, respectively, during days 0–90 versus 91–180 after discontinuation. No significant elevated AO risk was observed after discontinuation in patients on clopidogrel for 91–270 days. Limitations included those associated with the use of administration claims date, the absence of clinical data and lack of knowledge of aspirin use.Conclusions:Patients who discontinued clopidogrel therapy were at high risk of death or recurrent ACS during the first 90 days. AO risks following discontinuation appeared elevated in patients with ≤90 days of clopidogrel therapy versus those with >90 days of treatment.

Acute Coronary Syndrome Pathways

Changes in public policy, population demographics, and market dynamics are spurring innovative approaches to value-based care. Annually, hospitalizations for Acute Coronary Syndromes (ACS) account for a substantial proportion of healthcare expenditures in the United States. Vanderbilt University Medical Center has developed a framework to deliver comprehensive care incorporating inpatient and outpatient care teams for patients with ACS under an episode-based, bundled reimbursement model for a term of 6 months. As such, a value-oriented pathway was created with the goals of (1) optimizing patient outcomes following ACS; (2) minimizing complications from the treatment of ACS; and (3) reducing costs of healthcare related to the treatment of ACS. In a tertiary care academic medical system receiving patients from multiple facilities involving multiple providers, standardization of care by using practice guidelines and evidence-based data coupled with a robust computerized provider order entry system provides a unique opportunity to produce a "best practice" algorithm for treating patients presenting with ACS. Presented in this study are in-hospital and postdischarge care pathways for treating a diverse group of patients presenting with ACS to our institution.

The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: Rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH)

The aim of this study was to test the hypothesis that patients with atherosclerotic cardiovascular (CV) disease optimally treated on a statin but with residual atherogenic dyslipidemia (low high-density lipoprotein cholesterol [HDL-C] and high triglycerides) will benefit from addition of niacin with fewer CV events compared with placebo. Statin monotherapy trials have found 25%-35% CV risk reduction relative to placebo, leaving significant residual risk. Patients with atherogenic dyslipidemia have substantially increased CV risk. Participants were men and women with established CV disease and atherogenic dyslipidemia. Lipid entry criteria varied by gender and statin dose at screening. All participants received simvastatin (or simvastatin plus ezetimibe) at a dose sufficient to maintain low-density lipoprotein cholesterol (LDL-C) 40-80 mg/dL (1.03-2.07 mmol/L). Participants were randomized to extended-release niacin or matching placebo. The primary end point was time to occurrence of the first of the following: coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebral revascularization. This event-driven trial will have 85% power to show a 25% reduction in primary event frequency after 850 patients have experienced a primary outcome event. AIM-HIGH completed enrollment in April 2010. Follow-up is expected to continue through 2012. AIM-HIGH was designed to determine whether treating residual dyslipidemia with niacin further reduces cardiovascular events in patients with CV disease on a statin at target levels of low-density lipoprotein cholesterol.

The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: Baseline characteristics of study participants. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH) trial

The study aims to report the baseline characteristics of the fully randomized AIM-HIGH study population. Residual risk persists despite aggressive low-density lipoprotein cholesterol (LDL-C) reduction in patients with atherosclerotic cardiovascular (CV) disease, many of whom have atherogenic dyslipidemia (low levels of high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, and small dense LDL particles). All study participants had established CV disease and atherogenic dyslipidemia. Participants received simvastatin (or simvastatin plus ezetimibe) at a dose sufficient to maintain LDL-C at 40 - 80 mg/dL (1.03-2.07 mmol/L) and were randomized to receive extended-release niacin or matching placebo. The primary end point is time to the first occurrence of coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome or symptom-driven coronary or cerebral revascularization with average follow-up of 4.1 years. Between 2006 and 2010, 8,162 individuals signed consent to be screened, 4,275 began study drug run-in, and 3,414 were randomized to treatment. Mean age at entry was 64 ± 9 years, 85% were men, and 92% were white. As expected, risk factors were prevalent with 34% having diabetes; 71%, hypertension; and 81%, metabolic syndrome. Most participants had coronary artery disease (92%), whereas 11% had peripheral arterial disease; and 12%, cerebrovascular disease. Previous coronary revascularization occurred in 82%, and 54% reported a prior myocardial infarction. Among participants on a statin at entry (94%), mean baseline LDL-C was 71 mg/dL (1.84 mmol/L); mean HDL-C, 34.9 mg/dL (0.90 mmol/L); and median triglycerides, 161 mg/dL (1.82 mmol/L). AIM-HIGH enrolled a high-risk group of patients with established atherosclerotic CV disease and atherogenic dyslipidemia. This study should determine whether there is incremental clinical benefit of niacin in reducing cardiovascular events in patients who have attained optimal on-treatment levels of LDL-C with a statin.

On Arrival High Blood Glucose Level is Associated With Detrimental and Fatal Hospitalization Outcomes for Acute Coronary Syndrome.

BackgroundHigh blood glucose level is frequently encountered in acute coronary syndrome. We investigated the effects of high blood glucose measured on arrival on hospitalization adverse events in acute coronary syndrome. Our study patients were Javanese in ethnicity, which constitute half of population in Indonesia. We hypothesized that elevated blood glucose has detrimental effects on hospitalization for acute coronary syndrome.MethodsWe designed an observasional cohort study and recruited 148 consecutive patients with acute coronary syndrome. Venous blood was collected on hospital arrival. High blood glucose level was determined as plasma glucose > 140 mg/dL. Adverse hospitalization events were recorded, i.e. mortality, acute heart failure, cardiogenic shock and heart rhythm disorders. Echocardiography examination was performed to determine left ventricular function.ResultsThe prevalence of on arrival high blood glucose among Javanese patients with acute coronary syndrome was considerably high (36%). On arrival high blood glucose was associated with acute heart failure (P < 0.001) and shock cardiogenic (P = 0.02). Heart rhythm disorders were higher in high blood glucose patients (P = 0.004). Left ventricular dysfunction was more prevalent in high blood glucose patients (P = 0.001) and ejection fraction was lower (P = 0.001). On arrival high blood glucose was independently associated with hospitalization adverse events (adjusted odds ratio = 2.3, 95% confidence interval: 1.1-4.9, P = 0.03) and hospital mortality (adjusted odds ratio = 6.9, 95% confidence interval: 1.2-38.6, P = 0.03).ConclusionsOur study suggests that on arrival high blood glucose among Javanese patients with acute coronary syndrome is considerably high and is associated with detrimental and fatal hospitalization outcomes.

Non-ST-Segment Elevation Acute Coronary Syndrome

Of the nearly 1.4 million hospitalizations for acute coronary syndromes in 2006, approximately two-thirds were for unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI). Given the high risk for in-hospital ischemic events and late mortality in patients with UA/NSTEMI, it is critical to accurately and rapidly diagnose these patients, stratify their level of risk, and provide appropriate pharmacologic and nonpharmacologic treatment that maximizes anti-ischemic benefit and minimizes risk of bleeding. Appropriate in-hospital care following intervention is critical for optimizing both short- and long-term outcomes. However, evidence suggests that up to 26% of opportunities to provide guidelines-recommended care are missed. Nurses can play a critical role in ensuring that patients receive guidelines-based care. This review examines the most recent recommendations for the diagnosis and pharmacologic management of patients with UA/NSTEMI and discusses ways in which nursing staff can contribute to minimizing patient risk and optimizing patient benefit.

Acute coronary syndrome and cerebral arterial gas embolism in a scuba diver

Pulmonary barotrauma is a rare but feared complication of scuba diving, with around 30% mortality. We report an uncommon case of pulmonary barotrauma complicated by arterial gas embolism with both coronary and neurological ischemic injuries after scuba diving. A 46-year-old-man was admitted to our hospital for acute coronary syndrome and stroke following a scuba dive. After hyperbaric oxygen therapy, the patient recovered fully with a subsequent normal coronary angiogram. Myocardial ischemia can be a complication of scuba diving, but does not always reveal significant obstructive coronary artery disease.

Prevalence of Stroke/Transient Ischemic Attack Among Patients with Acute Coronary Syndromes in a Real-World Setting

Background: Atherothrombosis is a systemic disease that may manifest as acute ischemic events in multiple vascular beds. Patients who have experienced an atherothrombosis-related ischemic event in 1 vascular bed are at risk for developing ischemic events in other vascular beds. Antiplatelet therapy demands an understanding of the balance between arterial thrombosis benefit and adverse event risk. Clinical trials indicate that dual antiplatelet therapy with aspirin and the newer thienopyridines increases the risk of bleeding in patients with acute coronary syndromes (ACS) with prior cerebrovascular events. Informed clinical decision making requires a better understanding of the real-world prevalence of cerebrovascular events. Objective and Purpose: To estimate the prevalence of stroke and/or transient ischemic attack (TIA) among patients with ACS within US health plan populations. Methods: A retrospective, observational cohort study was conducted of patients with ACS in 5 health care claims databases. The index event was defined as the first documented inpatient health care claim for myocardial infarction or unstable angina. Patients with ≥ 12 months of pre-index medical care encounter information were included. Stroke/TIA was identified by the first health care claim for these conditions any time prior to or within 90 days following the index ACS event. Results: Across all databases, between 3.8% and 15.7% of patients with ACS had prior stroke/TIA and between 3.4% and 11.7% of patients with ACS with no history of cerebrovascular events had documented stroke/TIA following the index ACS hospitalization. Conclusion: Despite important differences between the various database populations, there is a high prevalence of documented stroke/TIA in patients with ACS both prior to and following the ACS event. These real-world findings, set within the context of the increased bleeding risk observed with the newer thienopyridines, are important considerations when selecting antiplatelet therapy for patients with ACS.

Evaluation of Global Registry of Acute Cardiac Events and Thrombolysis in Myocardial Infarction scores in patients with suspected acute coronary syndrome

Purposes We aimed to evaluate the Global Registry of Acute Cardiac Events (GRACE) and Thrombolysis in Myocardial Infarction (TIMI) scores in patients with suspected but not proven acute coronary syndrome (ACS). Basic procedures We conducted a secondary analysis of data from the RATPAC trial. Standardized data were collected from 2263 patients presenting to 6 emergency departments with suspected but not proven ACS. Patients were followed up by record review and postal questionnaire at 30 and 90 days after recruitment to identify major adverse events, defined as death, emergency revascularization, life-threatening arrhythmia, hospitalization for ACS, or nonfatal acute myocardial infarction (AMI). Main findings Data were available for 2243 patients (mean age, 54.5 years; 58% male). The major adverse event rate was 43 (2%) of 2243 after 30 days and 62 (3%) of 2243 after 90 days. The c statistics for 30-day events were 0.717 (95% confidence interval [CI], 0.698-0.735) for GRACE and 0.682 (95% CI, 0.662-0.701) for TIMI. The corresponding 90-day c statistics were 0.726 (95% CI, 0.707-0.745) for GRACE and 0.693 (95% CI, 0.674-0.712) for TIMI. The c statistic for patient age alone was 0.656 for 30-day events and 0.689 for 90-day events. Principal conclusions The GRACE and TIMI scores are little better than age alone as predictors of major adverse events in patients with suspected but not proven ACS, and thus add little to prognostic assessment of such patients.

Clinical Pathways for Acute Coronary Syndromes in China

Clinical pathways have been shown to be effective in improving quality of care for patients admitted to hospital for acute coronary syndromes (ACS) in high-income countries. However, their utility has not formally been evaluated in low- or middle-income countries. The Clinical Pathways for Acute Coronary Syndromes in China program is a 7-year study with the overall goal of reducing evidence-practice gaps in the management of patients admitted to hospitals in China with suspected ACS. The program comprises 2 phases: a prospective survey of current management of ACS patients to identify the areas that evidence-based patient care can be potentially improved, and a quality care initiative to maximize the use of evidence-based investigations and treatments for ACS patients in China. In this article, we outline the details of the study protocol, including key aspects of the development, implementation, and evaluation of the quality improvement initiative (clinical pathway) for management of patients with suspected ACS.

Letter by Violi et al Regarding Article, “Association of Cyclooxygenase-1–Dependent and –Independent Platelet Function Assays With Adverse Clinical Outcomes in Aspirin-Treated Patients Presenting for Cardiac Catheterization”

To the Editor: In a prospective study performed in 700 patients undergoing percutaneous coronary intervention, Frelinger et al1 demonstrated that patients who had serum thromboxane B2 (TxB2) >3.1 ng/mL were at higher risk of major cardiovascular outcomes, including myocardial infarction, stroke, cardiovascular death, and hospitalization for revascularization or acute coronary syndrome. Among the 562 patients followed up for ≈2 years, 45 patients (8%) reported TxB2 values >3.1 ng/mL, which were suggested to reflect incomplete cyclooxygenase-1 (COX-1) inhibition. …

Impact of Fine and Ultrafine Particles on Emergency Hospital Admissions for Cardiac and Respiratory Diseases

Little is known about the short-term effects of ultrafine particles. We evaluated the effect of particulate matter with an aerodynamic diameter <or=10 microm (PM10), <or=2.5 microm (PM2.5), and ultrafine particles on emergency hospital admissions in Rome 2001-2005. We studied residents aged >or=35 years hospitalized for acute coronary syndrome, heart failure, lower respiratory tract infections, and chronic obstructive pulmonary disease (COPD). Information was available for factors indicating vulnerability, such as age and previous admissions for COPD. Particulate matter data were collected daily at one central fixed monitor. A case-crossover analysis was performed using a time-stratified approach. We estimated percent increases in risk per 14 microg/m PM10, per 10 microg/m PM2.5, and per 9392 particles/mL. An immediate impact (lag 0) of PM2.5 on hospitalizations for acute coronary syndrome (2.3% [95% confidence interval = 0.5% to 4.2%]) and heart failure (2.4% [0.3% to 4.5%]) was found, whereas the effect on lower respiratory tract infections (2.8% [0.5% to 5.2%]) was delayed (lag 2). Particle number concentration showed an association only with admissions for heart failure (lag 0-5; 2.4% [0.2% to 4.7%]) and COPD (lag 0; 1.6% [0.0% to 3.2%]). The effects were generally stronger in the elderly and during winter. There was no clear effect modification with previous COPD. We found sizeable acute health effects of fine and ultrafine particles. Although differential reliability in exposure assessment, in particular of ultrafine particles, precludes a firm conclusion, the study indicates that particulate matter of different sizes tends to have diverse outcomes, with dissimilar latency between exposure and health response.

The information and support needs of Faroese women hospitalised with an acute coronary syndrome

The aim of this study was to describe the information and support needs of Faroese women after their hospitalisation for acute coronary syndrome. The Faroe Islands are located between Iceland and Norway. There are no published studies examining recovery for women following an acute cardiac event. Coronary heart disease remains the greatest killer of women worldwide, including on the Faroe Islands. Describing women's experiences of their recovery processes following acute coronary syndrome can enable timely information and support for the women who are affected. It is important that this information is tailored to the cultural context of women. This qualitative study used a descriptive-exploratory approach. Data were obtained by semi-structured interviews with participants three to four weeks after hospital discharge for their first acute coronary syndrome event. Eight women aged from 48-70 years diagnosed with acute coronary syndrome participated in the research. Two key themes emerged from the data: (1) 'Discharged home, now what?': illustrated the difficulties experienced by these women following discharge and (2) risk factor management and lifestyle adjustments: related to perceptions relating to risk, loss, recovery and support. The findings from this study highlight these women had minimal understanding of the risks and management of heart disease. Participants revealed their in-hospital and postdischarge information and support needs were generally unmet. The experience of Faroese women parallels those of women in other published studies. Nurses are well placed in healthcare to facilitate individualised support and information requirements to this clinical group. Assessing information and support needs of women is of primary importance in preparing for discharge following acute coronary syndrome.

Secular trends in acute coronary syndrome hospitalization from 1994 to 2005

Acute coronary syndrome (ACS) is one of the most frequent reasons for hospitalization worldwide. Although substantial advances have been made in the prevention and treatment of coronary artery disease, their impact on the rates of ACS hospitalization is unclear. Data from the Canadian Institute for Health Information Discharge Abstract Database were used to estimate secular trends in ACS hospitalization. A total of 1.3 million ACS hospitalizations in Canada from April 1, 1994, to March 31, 2006, were examined. Overall hospitalization rates were standardized for age and sex using 1991 Canadian census data, and hospitalization rates were also stratified by age group, sex and Canadian province to assess trends in each subgroup. The Canadian age- and sex-standardized ACS hospitalization rate was 508 per 100,000 persons in 1994, and 317 per 100,000 persons in 2005 - a relative reduction of 37.8% and an average annual relative reduction of 3.9% per year. Declines in ACS hospitalization rates were observed among men (annual relative reduction 3.9%, relative reduction 39.0%) and women (annual relative reduction 3.8%, relative reduction 35.8%). Declining trends were also observed among patients of different age groups and among patients hospitalized across all Canadian provinces. Over the past decade, a substantial decline in ACS hospitalization rates occurred, which has not been previously observed. This finding is likely due to improvements in primary and secondary prevention of coronary artery disease. The present study's data should provide important insights and guidance for future health care planning in Canada.

Air Quality and Cardiovascular Health

Ambient particulate matter has been associated consistently with an increased risk for mortality largely due to cardiovascular diseases.1 Although the relative risk estimates from epidemiological studies are small, they apply to almost the entire population of the United States. Consequently, exposure to ambient particles produces considerable burden of disease, and its mitigation offers the benefit of improving life expectancy.2 Articles see pp 941 and 949 Over the past decade, research has substantiated the understanding of the pathophysiological mechanisms linking ambient particles to the cardiovascular system3,4 once it was noted that ambient air pollution elicits systemic inflammatory responses in the general population.5 An update of the American Heart Association statement on air pollution and cardiovascular disease3 is under way. Mechanisms considered for active and secondhand smoke as well as ambient air pollution are strikingly similar.4,6,7 They include progression of atherosclerotic plaques to vulnerable forms, prothrombotic states, endothelial dysfunction, and altered autonomic nervous system control (Figure). Increased systemic oxidative stress is considered the key mechanism responsible for most of these pathophysiological changes. Increased risks for cardiovascular disease in general and coronary artery disease in particular have been documented for active and secondhand smoke as well as ambient particulate matter. Deep venous thrombosis has been added to this list recently.8 Figure. Overview on pathomechanism linking ambient air pollution,4 secondhand smoke,7 and active smoking to acute coronary syndromes. Nevertheless, the public health relevance of particulate matter in the light of the smoking literature remains hotly debated. Smokers are exposed to considerably higher cumulative doses of particulate matter than the general nonsmoking population. Mortality due to low doses of ambient particles may be considered counterintuitive compared with doses of particles tolerated by smoking individuals. A systematic assessment of the exposure-response function ranging from low doses of inhaled particles …

Exposure to tricyclic antidepressants is associated with an increased risk of incident CHD events in a population-based study

The purpose of this study was to assess the association between antidepressant use and incident coronary heart disease (CHD) events in a sample of individuals without known baseline heart disease. We studied a group of 970 randomly selected community-dwelling adults in the 1995 Nova Scotia Health Survey, who were followed for up to 10 years. Antidepressant usage was classified according to class. Primary outcomes were acute coronary syndrome hospitalizations or cardiac death, determined by centralized, standardized ratings. During a follow-up period of 10 years, there were 147 incident CHD events (139 acute coronary syndromes and 8 cardiac deaths) during the 8129 person-years of observation (incidence rate = 18.1 events/1000 person-years). In a model controlling for age, sex, Framingham risk score, time to last annual exam, aspirin exposure, and depressive symptoms, an increased risk of CHD events was associated with tricyclic antidepressant exposure (adjusted hazard ratio, 2.10; 95% confidence interval, 1.09-4.06; p = 0.027). In this prospective population-based study, exposure to tricyclic antidepressants was associated with higher risk of first CHD events.

Clinical Summaries

Clinical Summaries

Incidence and Prognostic Significance of Thrombocytopenia Developed During Acute Coronary Syndrome in Contemporary Clinical Practice

Prior studies examining thrombocytopenia among patients with acute coronary syndromes (ACS) evaluated highly selected patients in a clinical trial setting using varying definitions of thrombocytopenia. The incidence, severity, and prognostic significance of acquired thrombocytopenia during ACS in community practice have not been well defined. We examined 36 182 patients with non-ST-segment elevation ACS enrolled at 379 US hospitals participating in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) quality improvement initiative between June 2004 and December 2006. Patients with baseline platelet counts <150x10(9)/L were excluded. Overall, 4697 patients (13%) developed new thrombocytopenia, defined as nadir platelet count <150x10(9)/L (referenced lower limit of normal), during their ACS hospitalization. Risks of in-hospital mortality and bleeding correlated directly with severity of thrombocytopenia; even mild thrombocytopenia (nadir 100 to 149x10(9)/L) was associated with increased risks of mortality (adjusted odds ratio [OR], 2.01; 95% CI, 1.69 to 2.38) and bleeding (adjusted OR, 3.76; 95% CI, 3.43 to 4.12). Each 10% drop in platelet count was associated with increased mortality and bleeding risks (adjusted ORs, 1.39 [95% CI, 1.33 to 1.46] and 1.89 [95% CI, 1.83 to 1.95], respectively). A >/=50% drop in platelet count was associated with higher risk of adverse outcomes regardless of the nadir count. A novel combined definition of acquired thrombocytopenia-nadir <150x10(9)/L or platelet count drop >or=50%-identifies a population of ACS patients at higher risk of mortality and major bleeding (adjusted ORs, 2.58 [95% CI, 2.23 to 2.98] and 4.32 [95% CI, 3.97 to 4.70], respectively). Thrombocytopenia, a common complication of ACS, is associated with increased mortality and bleeding risks. Even mild thrombocytopenia or a platelet count drop >/=50% in the setting of normal nadir values is clinically significant. Application of a combined definition for thrombocytopenia using both absolute and relative thresholds permits increased sensitivity for patients at high risk of adverse outcomes.

Impact of Optimal Medical Therapy With or Without Percutaneous Coronary Intervention on Long-Term Cardiovascular End Points in Patients With Stable Coronary Artery Disease (from the COURAGE Trial)

The main results of the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial revealed no significant differences in the primary end point of all-cause mortality or nonfatal myocardial infarction [MI] or major secondary end points (composites of death/MI/stroke; hospitalization for acute coronary syndromes [ACSs]) during a median 4.6-year follow-up in 2,287 patients with stable coronary artery disease randomized to optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI). We sought to assess the impact of PCI when added to OMT on major prespecified tertiary cardiovascular outcomes (time to first event), namely cardiac death and composites of cardiac death/MI, cardiac death/MI/hospitalization for ACS, cardiac death/MI/stroke, MI/stroke, or cardiac death/MI/ACS/stroke, during study follow-up. There were no significant differences between treatment arms for the composite of cardiac death or MI (15% in PCI + OMT group vs 14.2% in OMT group, hazard ratio 1.07, 95% confidence interval 0.86 to 1.33, p = 0.62) or in any of the major prespecified composite cardiovascular events during long-term follow-up, even after excluding periprocedural MI as an outcome of interest. Overall, cause-specific cardiovascular outcomes paralleled closely the primary and secondary composite outcomes of the trial as a whole. In conclusion, compared with an initial management strategy of OMT alone, addition of PCI did not decrease the incidence of major cardiovascular outcomes including cardiac death or the composite of cardiac death/MI/ACS/stroke in patients with stable coronary artery disease.

Risk of Adverse Outcomes Associated With Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Acute Coronary Syndrome

Prior mechanistic studies reported that omeprazole decreases the platelet inhibitory effects of clopidogrel, yet the clinical significance of these findings is not clear. To assess outcomes of patients taking clopidogrel with or without a proton pump inhibitor (PPI) after hospitalization for acute coronary syndrome (ACS). Retrospective cohort study of 8205 patients with ACS taking clopidogrel after discharge from 127 Veterans Affairs hospitals between October 1, 2003, and January 31, 2006. Vital status information was available for all patients through September 30, 2006. All-cause mortality or rehospitalization for ACS. Of 8205 patients taking clopidogrel after discharge, 63.9% (n = 5244) were prescribed PPI at discharge, during follow-up, or both and 36.1% (n = 2961) were not prescribed PPI. Death or rehospitalization for ACS occurred in 20.8% (n = 615) of patients taking clopidogrel without PPI and 29.8% (n = 1561) of patients taking clopidogrel plus PPI. In multivariable analyses, use of clopidogrel plus PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without PPI (adjusted odds ratio [AOR], 1.25; 95% confidence interval [CI], 1.11-1.41). Among patients taking clopidogrel after hospital discharge and prescribed PPI at any point during follow-up (n = 5244), periods of use of clopidogrel plus PPI (compared with periods of use of clopidogrel without PPI) were associated with a higher risk of death or rehospitalization for ACS (adjusted hazard ratio, 1.27; 95% CI, 1.10-1.46). In analyses of secondary outcomes, patients taking clopidogrel plus PPI had a higher risk of hospitalizations for recurrent ACS compared with patients taking clopidogrel without PPI (14.6% vs 6.9%; AOR, 1.86 [95% CI, 1.57-2.20]) and revascularization procedures (15.5% vs 11.9%; AOR, 1.49 [95% CI, 1.30-1.71]), but not for all-cause mortality (19.9% vs 16.6%; AOR, 0.91 [95% CI, 0.80-1.05]). The association between use of clopidogrel plus PPI and increased risk of adverse outcomes also was consistent using a nested case-control study design (AOR, 1.32; 95% CI, 1.14-1.54). In addition, use of PPI without clopidogrel was not associated with death or rehospitalization for ACS among patients not taking clopidogrel after hospital discharge (n = 6450) (AOR, 0.98; 95% CI, 0.85-1.13). Concomitant use of clopidogrel and PPI after hospital discharge for ACS was associated with an increased risk of adverse outcomes than use of clopidogrel without PPI, suggesting that use of PPI may be associated with attenuation of benefits of clopidogrel after ACS.