Controversies in the Use of Omega-3 Fatty Acids to Prevent Atherosclerosis.

PURPOSE OF REVIEW: We discuss current controversies in the clinical use of omega-3 fatty acids (FA), primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and examine discrepancies between recent trials. Furthermore, we discuss potential side effects reported in these studies and the role of mixed omega-3 FA dietary supplements and concerns about their use. RECENT FINDINGS: REDUCE-IT showed that addition of icosapent ethyl, a highly purified form of EPA, can reduce risk of cardiovascular events among statin-treated individuals with high triglycerides. Additional supportive evidence for EPA has come from other trials and meta-analyses of omega-3 FA therapy. In contrast, trials of mixed EPA/DHA products have consistently failed to improve cardiovascular outcomes. Discrepancies in results reported in RCTs could be explained by differences in omega-3 FA products, dosing, study populations, and study designs including the placebo control formulation. Evidence obtained from highly purified forms should not be extrapolated to other mixed formulations, including "over-the-counter" omega-3 supplements. Targeting TG-rich lipoproteins represents a new frontier for mitigating ASCVD risk. Clinical and basic research evidence suggests that the use of omega-3 FA, specifically EPA, appears to slow atherosclerosis by reducing triglyceride-rich lipoproteins and/or inflammation, therefore addressing residual risk of clinical ASCVD.

Regression of human coronary artery plaque is associated with a high ratio of (18-hydroxy-eicosapentaenoic acid + resolvin E1) to leukotriene B4.

Inflammation in arterial walls leads to coronary artery disease (CAD). We previously reported that a high omega-3 fatty index was associated with prevention of progression of coronary atherosclerosis, a disease of chronic inflammation in the arterial wall. However, the mechanism of such benefit is unclear. The two main omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are precursors of specialized pro-resolving lipid mediators (SPMs)-resolvins and maresins-which actively resolve chronic inflammation. To explore whether SPMs are associated with coronary plaque progression, levels of SPMs and proinflammatory mediators (leukotriene B4 [LTB4 ] and prostaglandins) were measured using liquid chromatography-tandem mass spectrometry in 31 statin-treated patients with stable CAD randomized to either EPA and DHA, 3.36 g daily, or no EPA/DHA (control). Coronary plaque volume was measured by coronary computed tomographic angiography at baseline and at 30-month follow-up. Higher plasma levels of EPA+DHA were associated with significantly increased levels of two SPMs-resolvin E1 and maresin 1-and 18-hydroxy-eicosapentaenoic acid (HEPE), the precursor of resolvin E1. Those with low plasma EPA+DHA levels had a low (18-HEPE+resolvin E1)/LTB4 ratio and significant plaque progression. Those with high plasma EPA+DHA levels had either low (18-HEPE+resolvin E1)/LTB4 ratios with significant plaque progression or high (18-HEPE+resolvin E1)/LTB4 ratios with significant plaque regression. These findings suggest that an imbalance between pro-resolving and proinflammatory lipid mediators is associated with plaque progression and potentially mediates the beneficial effects of EPA and DHA in CAD patients.

THE ABCDE'S OF PRIMARY PREVENTION OF CARDIOVASCULAR DISEASE.

The growing burden of obesity, smoking, elevated cholesterol, diabetes, hypertension, sedentary lifestyle, and unhealthy dietary habits fuels cardiovascular disease. In 2015, the rates of cardiovascular disease in the United States rose for the first time after decades of steady decline. To combat this rising trend, there is a great need to emphasize primary cardiovascular prevention. In this review, we provide a summary of the current primary prevention recommendations using a simplified ABCDE approach. The aim is to help clinicians utilize an easy-to-use, structured approach to primary atherosclerotic cardiovascular disease prevention.

The Effect of Eicosapentaenoic and Docosahexaenoic Acid Supplementation on Coronary Artery Calcium Progression in Subjects With Diabetes and Coronary Artery Disease: A Secondary Analysis of a Randomized Trial.

Higher coronary artery calcium (CAC) scores and progression of CAC are associated with higher mortality. We previously reported that subjects with coronary artery disease randomly allocated to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation or none had similar significant increases in CAC score over 30 months. Whether these findings are influenced by diabetes status is unknown. A total of 242 subjects with coronary artery disease who were on statin therapy were randomly allocated to to 1.86 g EPA and 1.5 g DHA daily or none (control). The CAC score was measured at baseline and 30-month follow-up using noncontrast, cardiac computed tomography. A significant interaction term between diabetes status and treatment arm was noted in the prediction of the CAC score (p <0.001). A total of 176 subjects (85.8% men) had no diabetes and 66 subjects (80.3% men) had diabetes. The mean age was 62.9 ± 7.9 versus 63.2 ± 7.1 years, respectively. The mean low-density lipoprotein cholesterol and median triglyceride levels were not significantly different between those without and with diabetes: 77.7 ± 25.9 versus 77.1 ± 30.2 mg/100 ml, respectively, and 117.0 (78.0 to 158.0) versus 119.0 (84.5 to 201.5) mg/100 ml, respectively. Subjects with diabetes on EPA+DHA had a greater increase in CAC score than subjects with diabetes in the control group (median 380.7 vs 183.5, respectively, p = 0.021). In contrast, no difference occurred between the EPA+DHA and control groups in subjects without diabetes (175.7 vs 201.1, respectively, p = 0.41). In conclusion, EPA+DHA supplementation was associated with greater CAC progression in subjects with diabetes than subjects with diabetes in the control group over a 30-month period; whether this indicates progression of the disease burden or plaque stabilization requires further study.

Cardiovascular Outcomes Among Patients with Acute Coronary Syndromes and Diabetes: Results from ACS QUIK Trial in India.

Background: Despite cardiovascular disease being the leading cause of death in India, limited data exist regarding the factors associated with outcomes in patients with diabetes who suffer acute myocardial infarction (AMI). Methods: We examined 21,374 patients with AMI enrolled in the ACS QUIK trial. We compared in-hospital and 30-day major adverse cardiac events including death, re-infarction, stroke, or major bleeding in those with and without diabetes. The associations between diabetes and cardiac outcomes were adjusted for presentation and in-hospital management using logistic regression. Results: Mean ± SD age was 60.1 ± 12.0 years, 24.3% were females, and 44.4% had diabetes. Those with diabetes were more likely to be older, female, hypertensive, and have higher Killip class but less likely to present with STEMI. Patients with diabetes had longer symptoms onset-to-arrival (median 225 vs 290 min; P < 0.001) and, in case of STEMI, longer door-to-balloon times (median, 75 vs 91 min; P < 0.001). Diabetes was independently associated with higher in-hospital death (adjusted odds ratio [aOR], 1.46; 95% CI, 1.12-1.89), in-hospital reinfarction (aOR, 1.52; 95% CI, 1.15-2.02), 30-day MACE (aOR, 1.33; 95% CI, 1.14-1.55) and 30-day death (aOR, 1.40; 95%CI, 1.16-1.69) but not 30-day stroke or 30-day major bleeding. Conclusion: Among patients presenting with AMI in Kerala, India, a considerable proportion has diabetes and are at increased risk for in-hospital and 30-day adverse cardiovascular outcomes. Increased awareness of the increased cardiovascular risk and attention to the implementation of established cardiovascular therapies are indicated for patients with diabetes in lower-middle-income countries who develop AMI. Clinical Trial registration: ClinicalTrials.gov Unique identifier: NCT02256658.

Regression of Coronary Fatty Plaque and Risk of Cardiac Events According to Blood Pressure Status: Data From a Randomized Trial of Eicosapentaenoic Acid and Docosahexaenoic Acid in Patients With Coronary Artery Disease.

Background Residual risk of cardiovascular events and plaque progression remains despite reduction in low-density lipoprotein cholesterol. Factors contributing to residual risk remain unclear. The authors examined the role of eicosapentaenoic acid and docosahexaenoic acid in coronary plaque regression and its predictors. Methods and Results A total of 240 patients with stable coronary artery disease were randomized to eicosapentaenoic acid plus docosahexaenoic acid (3.36 g/d) or none for 30 months. Patients were stratified by regression or progression of coronary fatty plaque measured by coronary computed tomographic angiography. Cardiac events were ascertained. The mean±SD age was 63.0±7.7 years, mean low-density lipoprotein cholesterol level was <2.07 mmol/L, and median triglyceride level was <1.38 mmol/L. Regressors had a 14.9% reduction in triglycerides that correlated with fatty plaque regression (r=0.135; P=0.036). Compared with regressors, progressors had higher cardiac events (5% vs 22.3%, respectively; P<0.001) and a 2.89-fold increased risk of cardiac events (95% CI, 1.1-8.0; P=0.034). Baseline non-high-density lipoprotein cholesterol level <2.59 mmol/L (100 mg/dL) and systolic blood pressure <125 mm Hg were significant independent predictors of fatty plaque regression. Normotensive patients taking eicosapentaenoic acid plus docosahexaenoic acid had regression of noncalcified coronary plaque that correlated with triglyceride reduction (r=0.35; P=0.034) and a significant decrease in neutrophil/lymphocyte ratio. In contrast, hypertensive patients had no change in noncalcified coronary plaque or neutrophil/lymphocyte ratio. Conclusions Triglyceride reduction, systolic blood pressure <125 mm Hg, and non-high-density lipoprotein cholesterol <2.59 mmol/L were associated with coronary plaque regression and reduced cardiac events. Normotensive patients had greater benefit than hypertensive patients potentially due to lower levels of inflammation. Future studies should examine the role of inflammation in plaque regression. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01624727.

The role of coronary artery calcium in allocating pharmacotherapy for primary prevention of cardiovascular disease: The ABCs of CAC.

Determining optimal candidates for the numerous potential pharmacotherapies for primary prevention of atherosclerotic cardiovascular disease remains challenging. Selective use of coronary artery calcium (CAC) scoring is recommended by the 2018 and 2019 American Heart Association/American College of Cardiology Cholesterol and Primary Prevention Guidelines as a tool for refining cardiovascular disease risk assessment. A growing body of research shows that CAC has potential value in allocation of primary prevention aspirin, determining blood pressure targets and treatment intensity, the intensity of cholesterol management, and use of the more expensive medications for type 2 diabetes. We also review the literature regarding very elevated CAC scores greater than 400 or 1000 and how these scores appear to confer a risk for cardiovascular disease on par with secondary prevention cohorts.

Omega-3 fatty acids, subclinical atherosclerosis, and cardiovascular events: Implications for primary prevention.

BACKGROUND AND AIMS: High-dose eicosapentaenoic acid (EPA) therapy was beneficial in high-risk patients without clinical cardiovascular disease (CVD). Whether higher plasma levels of EPA and docosahexaenoic acid (DHA) have similar benefits in those without subclinical CVD is unclear. We aim to evaluate the interplay between plasma omega-3 fatty acids and coronary artery calcium (CAC) in relation to CVD events. METHODS: We examined 6568 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with plasma EPA and DHA levels and CAC measured at baseline. The primary outcome was incident CVD events (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Hazard ratios for the primary outcome were adjusted for potential confounder using Cox regression. RESULTS: Mean ± SD age was 62.1 ± 10.2 years and 52.9% were females. The median follow-up time was 15.6 years. Higher loge(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.94) and loge(DHA) (aHR = 0.79; 95% CI, 0.66-0.96) were independently associated with fewer CVD events. The difference in absolute CVD event rates between lowest vs. highest EPA tertile increased at higher CAC levels. The adjusted HR for highest vs. lowest EPA tertile within CAC = 0 was 1.02 (95% CI, 0.72-1.46), CAC = 1-99 was 0.71 (95% CI, 0.51-0.99), and CAC≥100 was 0.67 (95% CI, 0.52-0.84). A similar association was seen in tertiles of DHA by CAC category. CONCLUSIONS: In an ethnically diverse population free of clinical CVD, higher plasma omega-3 fatty acid levels were associated with fewer long-term CVD events. The absolute decrease in CVD events with higher omega-3 fatty acid levels was more apparent at higher CAC scores.

Association Between Omega-3 Fatty Acid Levels and Aortic Valve Calcium (from the Multi-Ethnic Study of Atherosclerosis).

Calcific aortic valve disease, a condition of chronic inflammation, is associated with increased cardiovascular events and all-cause mortality. Omega-3 fatty acids (O3FAs) reduce both acute and chronic inflammation, but their associations with aortic valve calcium (AVC) have not been studied. The Multi-Ethnic Study of Atherosclerosis is a prospective cohort study of 6,814 adults without clinical cardiovascular disease. Plasma fatty acid levels and cardiac computed tomography (CT) scans were performed at baseline, and CT scans were performed at subsequent clinical visits over a median 9-year period. We assessed whether plasma levels of O3FAs and their species correlate with the presence, severity, and progression of AVC measured by CT in Multi-Ethnic Study of Atherosclerosis. The mean age of the 6,510 included participants with baseline fatty acid levels, AVC, and covariate data was 62.1 ± 10.2 years, and 47.1% of the participants were male. Race distribution was 38.6% White, 27.2% Black, 22.1% Hispanic/Latino, and 12.1% Chinese. Among the 6,510 participants, 5,884 had a subsequent CT scan, and 3,304 had a third CT scan with AVC measurements. At baseline, 862 participants (13.2%) had prevalent AVC (Agatston score >0), and were more likely to be of older age, male, of the White race, have a lower education level, and have co-morbidities that are associated with a higher risk for AVC. Plasma tertiles of eicosapentaenoic acid, docosahexaenoic acid, and total O3FA were not associated with prevalent AVC at baseline, incident AVC, or change in AVC. In conclusion, plasma levels of O3FAs in subjects not routinely supplemented with O3FAs are not useful for predicting the presence or development of AVC. Whether high plasma O3FA levels, achievable by high-dose O3FA over-the-counter supplementation or pharmacotherapy, is associated with AVC requires further investigation.

Update on the omega-3 fatty acid trial landscape: A narrative review with implications for primary prevention.

Residual risk mediated by hypertriglyceridemia among statin-treated individuals is an important clinical and public health challenge. Niacin, fibrates and omega-3 FA are three classes of non-statin agents with demonstrated TG-lowering effects. Randomized controlled trials of niacin and fibrates have been consistently negative, but the trial landscape for two key sources of omega-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is more complex. Clinical trials evaluating omega-3 FA can be differentiated into those that studied mixed formulations (EPA + DHA) and those that studied EPA alone. Those assessing the impact of mixed formulations have not consistently demonstrated CVD risk reduction, whereas trials of EPA alone have been successful. Two recent trials of mixed formulations - STRENGTH (Long-Term Outcomes Study to Assess Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia) and OMEMI (Omega-3 fatty acids in Elderly patients with Myocardial Infarction) - studied contemporarily treated patients with mixed EPA + DHA formulations at higher doses than before and showed no benefit, thus adding valuable information to our overall understanding of this evolving therapeutic class. In this review, we contextualize the findings of STRENGTH and OMEMI within the existing omega-3 FA clinical trial landscape and look ahead to how future trials can inform existing knowledge gaps, particularly with regards to the applicability of these agents within the primary prevention realm.

Sex disparities in the presentation, management and outcomes of patients with acute coronary syndrome: insights from the ACS QUIK trial.

AIMS: Our aim was to explore sex differences and inequalities in terms of medical management and cardiovascular disease (CVD) outcomes in a low/middle-income country (LMIC), where reports are scarce. METHODS: We examined sex differences in presentation, management and clinical outcomes in 21 374 patients presenting with acute coronary syndrome (ACS) in Kerala, India enrolled in the Acute Coronary Syndrome Quality Improvement in Kerala trial. The main outcomes were the rates of in-hospital and 30-day major adverse cardiovascular events (MACEs) defined as composite of death, reinfarction, stroke and major bleeding. We fitted log Poisson multivariate random effects models to obtain the relative risks comparing women with men, and adjusted for clustering by centre and for age, CVD risk factors and cardiac presentation. RESULTS: A total of 5191 (24.3%) patients were women. Compared with men, women presenting with ACS were older (65±12 vs 58±12 years; p<0.001), more likely to have hypertension and diabetes. They also had longer symptom onset to hospital presentation time (median, 300 vs 238 min; p<0.001) and were less likely to receive primary percutaneous coronary intervention for ST-elevation myocardial infarction (45.9% vs 49.8% of men, p<0.001). After adjustment, women were more likely to experience in-hospital (adjusted relative risk (RR)=1.53; 95% CI 1.32 to 1.77; p<0.001) and 30-day MACE (adjusted RR=1.39; 95% CI 1.23 to 1.57, p<0.001). CONCLUSION: Women presenting with ACS in Kerala, India had greater burden of CVD risk factors, including hypertension and diabetes mellitus, longer delays in presentation, and were less likely to receive guideline-directed management. Women also had worse in-hospital and 30-day outcomes. Further efforts are needed to understand and reduce cardiovascular care disparities between men and women in LMICs.

Association Between Omega-3 Fatty Acid Levels and Risk for Incident Major Bleeding Events and Atrial Fibrillation: MESA.

Background Randomized trials of pharmacologic strength omega-3 fatty acid (n3-FA)-based therapies suggest a dose-dependent cardiovascular benefit. Whether blood n3-FA levels also mediate safety signals observed in these trials, such as increased bleeding and atrial fibrillation (AF), remains uncertain. We hypothesized that higher baseline n3-FA levels would be associated with incident bleeding and AF events in MESA (Multi-Ethnic Study of Atherosclerosis), which included a population free of clinical cardiovascular disease at baseline. Methods and Results We examined the association between baseline plasma n3-FA levels (expressed as percent mass of total fatty acid) with incident bleeding and AF in MESA, an ongoing prospective cohort study. Bleeding events were identified from review of hospitalization International Classification of Diseases, Ninth Revision (ICD-9), and International Classification of Diseases, Tenth Revision (ICD-10), codes, and AF from participant report, discharge diagnoses, Medicare claims data, and study ECGs performed at MESA visit 5. Separate multivariable Cox proportional hazard modeling was used to estimate hazard ratios of the association of continuous n3-FA (log eicosapentaenoic acid [EPA], log docosahexaenoic acid [DHA], log [EPA+DHA]) and incident hospitalized bleeding events and AF. Among 6546 participants, the mean age was 62.1 years and 53% were women. For incident bleeding, consistent statistically significant associations with lower rates were seen with increasing levels of EPA and EPA+DHA in unadjusted and adjusted models including medications that modulate bleeding risk (aspirin, NSAIDS, corticosteroids, and proton pump inhibitors). For incident AF, a significant association with lower rates was seen with increasing levels of DHA, but not for EPA or EPA+DHA. Conclusions In MESA, higher plasma levels of n3-FA (EPA and EPA+DHA, but not DHA) were associated with significantly fewer hospitalized bleeding events, and higher DHA levels (but not EPA or EPA+DHA) with fewer incident AF events.

Clinical characteristics and outcomes of young adults with first myocardial infarction: Results from Gulf COAST.

INTRODUCTION: Limited data exists on the risk factor profile and outcomes of young patients suffering their first acute myocardial infarction (AMI). METHODS: We examined 1562 Gulf-Arabs without prior cardiovascular disease presenting with first AMI enrolled in the Gulf COAST prospective cohort. Clinical characteristics were compared in patients ≤50 years of age (young) vs. >50 years (older). Associations between age group and in-hospital adverse events (re-infarction, heart failure, cardiogenic shock, cardiac arrest, stroke, and in-hospital death) or post-discharge mortality were estimated using logistic regression. RESULTS: Young patients represented 26.1% (n = 407) of first AMI cases and were more likely to be men (82.8% vs. 66.5%), current smokers (49.9% vs 19.0%), obese (38.3% vs 28.0%), and have family history of premature coronary artery disease (21.4% vs 10.4%) compared with older patients (all P < 0.001). Young patients were more likely to receive ß-blockers (83.0% vs 74.4%; P < 0.001), clopidogrel (82.3% vs 76.0%; P = 0.009) and primary reperfusion therapy (85.6% vs. 75.6%; P = 0.003). Young adults had lower in-hospital death (adjusted odds ratio [aOR] = 0.37; 95%CI = 0.16-0.86) or any in-hospital adverse cardiovascular events (aOR = 0.53; 95%CI = 0.34-0.83). Young adults had lower likelihood of cumulative death at 12-month post-discharge (aOR = 0.34; 95%CI = 0.19-0.59) after adjusting for potential confounders. CONCLUSION: Young patients with first AMI were more likely to be obese, smokers and have family history of premature coronary artery disease compared to older adults. Young patients were more likely to receive guideline-proven therapies and have better in-hospital and post-discharge mortality. These data highlight important age-related care gaps in patients suffering AMI for the first time.

Summarizing 2019 in Cardiovascular Prevention Using the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease's 'ABC's Approach.

In 2019, Preventive Cardiology welcomed many exciting discoveries that improve our ability to reduce the burden of cardiovascular disease (CVD) nationwide. Not only did 2019 further clarify how various environmental exposures and innate and acquired risk factors contribute to the development of CVD, but it also provided new guidelines and therapeutics to more effectively manage existing CVD. Cardiovascular disease prevention requires the prioritization of early and effective detection of CVD in order to implement aggressive lifestyle and pharmacologic therapies, which can slow, halt, or even reverse the progression of the disease. To help streamline and simplify the process of CVD prevention, The Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease has historically adopted an 'ABC' approach, which focuses on optimizing individual CVD risk through lifestyle, behavioral, and pharmacologic interventions. Given the practice changing research and innovation from the past year, this article intends to summarize the Ciccarone Center's key takeaways from CVD prevention in 2019 utilizing our expanded 'ABC' approach.

Inflammation and cardiovascular disease: From mechanisms to therapeutics.

Inflammation constitutes a complex, highly conserved cascade of molecular and cellular events. Inflammation has been labeled as "the fire within," is highly regulated, and is critical to host defense and tissue repair. In general, inflammation is beneficial and has evolved to promote survival. However, inflammation can also be maladaptive when chronically activated and sustained, leading to progressive tissue injury and reduced survival. Examples of a maladaptive response include rheumatologic disease and atherosclerosis. Despite evidence gathered by Virchow over 100 years ago showing that inflammatory white cells play a role in atherogenesis, atherosclerosis was until recently viewed as a disease of passive cholesterol accumulation in the subendothelial space. This view has been supplanted by considerable basic scientific and clinical evidence demonstrating that every step of atherogenesis, from the development of endothelial cell dysfunction to foam cell formation, plaque formation and progression, and ultimately plaque rupture stemming from architectural instability, is driven by the cytokines, interleukins, and cellular constituents of the inflammatory response. Herein we provide an overview of the role of inflammation in atherosclerotic cardiovascular disease, discuss the predictive value of various biomarkers involved in inflammation, and summarize recent clinical trials that evaluated the capacity of various pharmacologic interventions to attenuate the intensity of inflammation and impact risk for acute cardiovascular events.

Efficacy and Safety of Pharmacoinvasive Strategy Compared to Primary Percutaneous Coronary Intervention in the Management of ST-Segment Elevation Myocardial Infarction: A Prospective Country-Wide Registry.

Background: A pharmacoinvasive reperfusion strategy is recommended for ST-elevation myocardial infarction (STEMI) patients when primary percutaneous coronary intervention (PCI) cannot be achieved in a timely fashion. This is based on a limited number of trials. The effectiveness of this strategy in the real-world is unclear. Objectives: To compare the effectiveness of pharmacoinvasive strategy versus primary PCI using a nationwide prospective registry of STEMI patients. Methods: We examined 936 STEMI patients from the reperfusion in ST-elevation myocardial infarction in Kuwait (REPERFUSE Kuwait) registry who underwent either primary PCI or pharmacoinvasive reperfusion. A composite outcome was measured based on death, congestive heart failure, reinfarction or stroke prospectively ascertained during hospital stay and up to one-year follow-up. The association between reperfusion strategy and the composite outcome was assessed using multivariate regression and Poisson proportional hazard model. Results: Compared to the pharmacoinvasive group, those undergoing primary PCI had higher Killip class on presentation and required more blood transfusions during hospitalization. There was no significant difference between primary PCI and pharmacoinvasive strategy with regards to the incidence of the composite outcome during the in-hospital period (RR = 1.0; 95% CI 0.98-1.02; p = 0.96) after adjustment for possible confounders. Over one-year follow-up, the survival of the two groups was not different (p = 0.66). The incidence of major bleeding was similar in both groups. Conclusion: STEMI patients treated with a pharmacoinvasive strategy have comparable outcomes to those treated with primary PCI with no increased risk of major bleeding. These real-world data support the use of a pharmacoinvasive strategy when primary PCI cannot be achieved in a timely fashion.

Evaluation and Management of Patients With Stable Angina: Beyond the Ischemia Paradigm: JACC State-of-the-Art Review.

Coronary heart disease is a chronic, systemic disease with a wide range of associated symptoms, clinical outcomes, and health care expenditure. Adverse events from coronary heart disease can be mitigated or avoided with lifestyle and risk factor modifications, and medical therapy. These measures are effective in slowing the progression of atherosclerotic disease and in reducing the risk of thrombosis in the setting of plaque disruptions. With increasing effectiveness of prevention and medical therapy, the role of coronary artery revascularization has decreased and is largely confined to subgroups of patients with unacceptable angina, severe left ventricular systolic dysfunction, or high-risk coronary anatomy. There is a compelling need to allocate resources appropriately to improve prevention. Herein, we review the scientific evidence in support of medical therapy and revascularization for the management of patients with stable coronary heart disease and discuss implications for the evaluation of patients with stable angina and public policy.