Recent Papers in Cardiology

Javad Tafreshi, Pharm.D., BCPS-AQ Cardiology, F.A.H.A. Professor and Chair, Department of Pharmacy Practice

Director, PGY2 Cardiology Pharmacy Residency Program

Loma Linda University School of Pharmacy

Thursday 10/27/2016

• I have no conflicts of interest to disclose

Disclosure

•To evaluate recent published papers in cardiology

•To apply the findings of these studies to clinical practice

Learning Objectives

Studies

•Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE)

•Nitrate’s Effect on Activity Tolerance in Heart Failure with Preserved Ejection Fraction (NEAT-HFpEF)

•Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure (ATMOSPHERE)

•Acute Stroke or Transient IschaemicAttack Treated with Aspirin or Ticagrelorand Patient Outcomes (SOCRATES)

•Ventricular Tachycardia Ablation in Ischemic Heart Disease (VANISH)

•Acute Medically Ill VTE Prevention with Extended Duration Betrixaban (APEX)

•Alberta Vascular Risk Reduction Community Pharmacy Project (RxEACH)

•Dual Antiplatelet Therapy (DAPT)

COURAGE

Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial

N Engl J Med 2007;356:1503-16.

COURAGE, Cont.

Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial

N Engl J Med 2015;373:1937-46.

COURAGE, Cont.

•Between June 1999 and January 2004, 2287 patients with stable ischemic heart disease were randomly assigned to an initial management strategy of optimal medical therapy alone (medical-therapy group) or optimal medical therapy plus PCI (PCI group)

•COURAGE 2007 reported outcomes for up to 7 years

•COURAGE 2015 reported the rate of survival among patients who were followed for up to 15 years after initial enrolment in the trial

COURAGE, Cont.

•All patients had chronic stable angina

•Cardiac risk factor goals included LDL, BP, smoking, exercise, nutrition, and weight control

•PCI was performed according to the judgement of the operator and prevailing best practice• DES was used in about 3% of patients

COURAGE, Cont.

•COURAGE 2007 “As an initial management strategy in patients with stable CAD, PCI did not reduce the risk of death, MI, or other major CV events when added to optimal medical therapy.”

COURAGE, Cont.

•COURAGE 2015 “During an extended follow-up of up to 15 years, we did not find a difference in survival between an initial strategy of PCI plus medical therapy and medical therapy alone in patients with stable ischemic heart disease.”

•Comments:• Stable, non-ACS patients

• 70% had LDL<85 mg/dL

• 65%-94% had BP<130/85 mm Hg

• 45% of DM had A1C<7%

• rate of adherence to diet and exercise (no change in BMI)

• rate of smoking cessation

• ~ 95% were receiving ASA

• 85% were male and 86% were white, many at VA sites

COURAGE, Cont.

NEAT-HFpEF

Nitrate’s Effect on Activity Tolerance in Heart Failure with Preserved Ejection Fraction (NEAT-HFpEF) Trial

N Engl J Med 2015;373:2314-24.

NEAT-HFpEF, Cont.

•Nitrates are prescribed to enhance activity tolerance in patients with heart failure and a preserved EF

•The effect of isosorbide mononitrate or placebo on daily activity was compared

•The primary end point was a comparison of average daily accelerometer units during the period in which patients were receiving the 120-mg dose of isosorbide mononitrate as compared with placebo

NEAT-HFpEF, Cont.

•Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP)

NEAT-HFpEF, Cont.

•110 patients with HFpEF were assigned to a 6-week dose-escalation regimen of ISMN from 30 - 120 mg daily

•Daily activity level was quantified as the average daily accelerometer units during the 120-mg phase, assessed by patient-worn accelerometers• Accelerometers provide continuous assessment of physical

activity during daily life and may more accurately reflect the effect of therapy on functional status

NEAT-HFpEF, Cont.

•The accelerometers measure movement

•Patients were supplied with a belt outfitted with two kinetic activity monitors containing high-sensitivity, triaxis accelerometers

•Patients were instructed to wear the accelerometers 24 hours per day except while bathing or swimming

NEAT-HFpEF, Cont.

•“Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did patients who received placebo.”

•Comments•Unlike HFpEF, in HFrEF, long-acting nitrates may improve activity tolerance

•~ 15-50% of patients with HFpEF are treated with nitrates

• ISDN decreased BP

•More discontinuation in patients receiving ISDN

•Pathophysiology: In HFpEF increased ventricular systolic and vascular stiffness, autonomic dysfunction, chronotropic incompetence, and altered baroreflex sensitivity are common and may limit hemodynamic benefits of nitrates

NEAT-HFpEF, Cont.

ATMOSPHERE

Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure (ATMOSPHERE) Trial

N Engl J Med 2016;374:1521-32.

ATMOSPHERE, Cont.

•ACE inhibitor enalapril was compared with the renin inhibitor aliskiren and with the combination of the two treatments in patients with HFrEF

•Patients were assigned to three groups to receive 1. enalapril 5-10 mg BID, 2. aliskiren (Rasilez®, Tekturna®) 300 mg daily, or 3. combination therapy

ATMOSPHERE, Cont.

•The primary composite outcome was death from cardiovascular causes or hospitalization for heart failure

•The secondary outcomes were the change from baseline to 12 months in the clinical summary score

ATMOSPHERE, Cont.

ATMOSPHERE, Cont.

ATMOSPHERE, Cont.

•For safety outcomes, compared to the enalapril group, the combination-therapy group had a significantly higher risk of hypotensive symptoms, elevated SCr level, and elevated potassium level

ATMOSPHERE, Cont.

•“In patients with chronic heart failure, the addition of aliskiren to enalapril led to more adverse events without an increase in benefit. Noninferiority was not shown for aliskiren as compared with enalapril.”

ATMOSPHERE, Cont.

•Comments• In HFrEF: ACEI’s , ARB’s , [ACEI’s + ARB’s] maybe? (Class IIb),

[ACEI’s + ARB’s + AA’s] , aliskiren as a substitute for ACEI’s

• No worse outcomes in DM patients

• “… these findings suggest that there is a therapeutic ceiling for blockade of the renin-angiotensin system beyond which there is little or no additional efficacy and only more adverse effects.”?

• “These findings also argue against the suggestion that the benefit of sacubitril-valsartan over enalapril could be due to more intense blockade of the renin-angiotensin system”?

SOCRATES

Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) Trial

N Engl J Med 2016;375:35-43.

SOCRATES, Cont.

•An international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk TIA who had not received IV or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset to receive either ticagrelor (Brilinta®) or ASA

SOCRATES, Cont.

•Ticagrelor 180 mg loading dose on day 1 followed by 90 mg BID or ASA 300 mg on day 1 followed by 100 mg daily

•The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days

•The secondary endpoint was the time to ischemic stroke

SOCRATES, Cont.

SOCRATES, Cont.

•Permanent discontinuation occurred in 17.5% of patients in the ticagrelor group versus 14.7% for ASA

•Dyspnea and bleeding events were the most frequent factors, with rates of discontinuation due to dyspnea in the ticagrelor and ASA groups of 1.4% and 0.3%, respectively, and rates of discontinuation due to any bleeding of 1.3% and 0.6%

SOCRATES, Cont.

•“In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days.”

SOCRATES, Cont.

•Comments• There was no evidence of a higher risk of major or intracranial

hemorrhage with ticagrelor than with ASA, but there were more instances of dyspnea and minor bleeding in the ticagrelor group

• AHA/ASA guidelines: ASA monotherapy or the combination of aspirin 25 mg and extended-release dipyridamole (Aggrenox®) 200 mg twice daily is indicated as initial therapy after TIA or ischemic stroke for prevention of future stroke. Clopidogrel monotherapy is a reasonable option for secondary prevention of stroke in place of ASA or combination ASA/dipyridamole

VANISH

Ventricular Tachycardia Ablation versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease (VANISH) Trial

N Engl J Med 2016;375:111-21.

VANISH, Cont.

•A multicenter, randomized, controlled trial involving patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia (VT) despite the use of antiarrhythmic drugs

•Patients were randomly assigned to receive either catheter ablation (ablation group) with continuation of baseline antiarrhythmic medications or escalated antiarrhythmic drug therapy (escalated-therapy group)• Funding was provided by the Canadian Institutes of Health

Research, St. Jude Medical, and Biosense Webster

VANISH, Cont.

•In cardiac catheter ablation, electrodes at the catheter tips transmit energy to destroy the ectopic foci and block the electrical pathway that is causing arrhythmia

VANISH, Cont.

•In the escalated therapy group, amiodarone was initiated if another agent had been used previously

•The dose of amiodarone was increased if it had been less than 300 mg per day or mexiletine was added if the dose was already at least 300 mg per day

•Amiodarone loading dose was 400 mg BID for two weeks followed by 400 mg daily for one week

•Mexiletine was added at a dose of 200 mg TID

VANISH, Cont.

•The primary outcome was a composite of death, three or more documented episodes of VT within 24 hours (VT storm), or appropriate ICD shock

VANISH, Cont.

VANISH, Cont.

VANISH, Cont.

•In the escalated-therapy group, 3 deaths were attributed to AAD therapy, 2 from pulmonary toxicity and 1 from hepatic dysfunction

•Hepatic dysfunction was more frequent as was tremor or ataxia and drug side effects leading to therapy changes

•In the escalated therapy group, treatment-related adverse events were more frequent and occurred in more patients

VANISH, Cont.

•There were more frequent procedural complications among patients in the ablation group than among those in the escalated-therapy group, including major bleeding, vascular injury, cardiac perforation, and heart block

VANISH, Cont.

•“In patients with ischemic cardiomyopathy and an ICD who had VT despite antiarrhythmic drug therapy, there was a significantly lower rate of the composite primary outcome of death, VT storm, or appropriate ICD shock among patients undergoing catheter ablation than among those receiving an escalation in antiarrhythmic drug therapy.”

VANISH, Cont.

•“Consensus statements and guidelines recommend the use of catheter ablation when AAD therapy does not prevent recurrent VT. However, these recommendations have been based largely on expert opinion and nonrandomized case series. This trial provides evidence that catheter ablation should be preferred over escalation of AAD therapy for the reduction of recurrent VT in this population.”

APEX

Acute Medically Ill VTE (Venous Thromboembolism) Prevention with Extended Duration Betrixaban (APEX) Trial

N Engl J Med 2016;375:534-44.

APEX, Cont.

•Betrixaban is an investigational oral direct factor Xa inhibitor• By Portola® Pharmaceuticals Inc (South San Francisco, CA) under

license from Takeda, formerly known as Millennium Pharmaceuticals

•Direct factor Xa inhibitors on the market are rivaroxaban (Xarelto®), apixaban (Eliquis®), and edoxaban (Savaysa®)

•It has undergone trials for VTE and also prevention of stroke following AF (EXPLORE-Xa study)

APEX, Cont.

•Portola is also developing andexanet alfa (AndexXa™), as a universal reversal agent for patients anticoagulated with oral or injectable factor Xa inhibitors

•In August 2016, FDA requested additional information regarding its manufacturing also additional data for inclusion of the anticoagulants edoxaban and enoxaparin in the label prior to its potential approval

APEX, Cont.

•Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban for 35 to 42 days

APEX, Cont.

•Patients were eligible if they were 40 years of age or older, had been hospitalized for less than 96 hours for a specified acute medical illness (HF, respiratory failure, infectious diseases, rheumatic disease, or ischemic stroke), and had reduced mobility and specific risk factors for VTE

APEX, Cont.

•Analysis was performed in three cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort)

•The primary efficacy outcome was a composite of asymptomatic proximal DVT and symptomatic VTE• The statistical analysis plan specified that if the between-group

difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory

•The principal safety outcome was major bleeding

APEX, Cont.

APEX, Cont.

APEX, Cont.

•“Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts.”

RxEACH

The Alberta Vascular Risk Reduction Community Pharmacy (RxEACH) Project

J Am Coll Cardiol 2016;67:2846-54.

RxEACH, Cont.

•The study evaluated the effectiveness of a community pharmacy-based case finding and intervention on CV risk

•Study was a randomized trial conducted in 56 community pharmacies in Alberta Canada

RxEACH, Cont.

•Participants were recruited by their pharmacists, who enrolled adults at high risk for CVD• CKD, atherosclerotic vascular disease, stroke, TIA, CAD, PAD,

Framingham risk score >20%, plus at least 1 uncontrolled risk factor of HTN, LDL-C, HbA1C, or smoking

•Patients were randomized to usual care (usual pharmacist care with no specific intervention) or intervention, comprising an MTM review from their pharmacist and CVD risk assessment and education

RxEACH, Cont.

•Pharmacists in Alberta can bill the provincial health plan for providing such services

•Pharmacists also have a broad scope of practice that includes independent prescribing and ability to order laboratory tests

•Pharmacists prescribed medications and ordered tests as per their scope of practice to achieve treatment targets

•Subjects received monthly follow-up visits for 3 months

RxEACH, Cont.

•Pharmacist training was based on current Canadian guidelines

•The research team developed an online training program that was reviewed internally and externally for content validity

•The training program was hosted online at the Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta server, and provided at face-to-face regional meetings

RxEACH, Cont.

•The training program included modules on case finding, CV risk calculation, and patient communication of CV risk, CKD, HTN, dyslipidemia, DM, smoking cessation, diet and lifestyle management, and documentation of care plans for remuneration by Alberta Health

•A hotline was made available for participating pharmacists to connect them with experts in CV risk reduction and study procedures

RxEACH, Cont.

•The primary outcome was difference in change in estimated CVD risk between groups at 3 months

•CVD risk was estimated using the greater of the Framingham, International, or United Kingdom Prospective Diabetes Study risk scores

•The primary outcome was difference in change in estimated CVD risk between groups at 3 months

RxEACH, Cont.

RxEACH, Cont.

RxEACH, Cont.

•“The RxEACH study was the first large randomized trial of CVD risk reduction by community pharmacists, demonstrating a significant reduction in risk for CVD events. Engagement of community pharmacists with an expanded scope of practice could have significant public health implications.”

•Comments•Opportunities

•Abundance of published studies on pharmacist’s inpatient and outpatient impact

•Reimbursement

•Training

•U.S. versus other systems

RxEACH, Cont.

•Dual Antiplatelet Therapy (DAPT) studies• N Engl J Med 2014;371:2155-66.

• JAMA 2015;313(11):1121-21.

• J Am Coll Cardiol Intv 2016;9:138-47.

• JAMA 2016;315(16):1735-49.

• Eur Heart J 2016;37:390-9.

•JAMA Cardiology Clinical Guidelines Synopsis: Focused Update on Duration of Dual Antiplatelet Therapy for Patients With CAD. JAMA Cardiol 2016;1(6):733-4.

DAPT

•“1. Patients with stable ischemic heart disease (SIHD) treated with DAPT should be given clopidogrel for at least 1 month after implantation of a bare-metal stent (class of recommendation, I; level of evidence, A [high-quality, randomized data]) and for at least 6 months after implantation of a drug-eluting stent (DES) (class of recommendation, I; level of evidence, B-R [moderate-quality randomized data]).”

DAPT, Cont.

•“2. Continuation of DAPT with clopidogrel for longer than 1 month after implantation of a bare-metal stent and for longer than 6 months after implantation of a DES may be reasonable for patients with SIHD who are not at high risk of bleeding and who tolerated DAPT without a bleeding complication (class of recommendation, IIb; level of evidence, A [high-quality randomized data]).”

DAPT, Cont.

•“3. Continuation of DAPT for longer than 12 months may be reasonable for patients with acute coronary syndrome (ACS) who are not at high risk of bleeding, who tolerated DAPT without a bleeding complication, and who have a coronary stent implanted, or are treated with medical therapy only (no revascularization or fibrinolytic agents), or have ST-elevation myocardial infarction (MI) and are treated with fibrinolytic therapy (class of recommendation, IIb; level of evidence, A [high-quality randomized data]).”

DAPT, Cont.

•“…Individualization of therapy based on balancing the expected benefits and harms is central to deciding the duration of DAPT. The focused update included a summary of factors associated with ischemic risk (eg, extensive coronary atherosclerosis, or treatment of bifurcations or stent restenosis) or bleeding risk (oral anticoagulant therapy, low body weight, or anemia), as well as a new decision tool, the DAPT Score, that may help predict the expected benefit or risk of continued DAPT…”

DAPT, Cont.

DAPT, Cont.

•“…For patients receiving DAPT for 1 year without significant bleeding or ischemic events, a score of 2 or higher indicates a favorable benefit to risk ratio for continuing DAPT beyond 1 year, and a score of less than 2 indicates an unfavorable benefit to risk ratio...”

•“…The focused update does not recommend routine use of platelet function testing or genotyping to guide clinical decisions…”

DAPT, Cont.

Yeh RW, et al. Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention. JAMA 2016;315(16):1735-49.

•ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease. Pooling Project of 19 Cohort Studies. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCe): JAMA Intern Med 2016;176(8):1155-66. “On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.”

Other Interesting Readings

•Oral fluoroquinolone use and serious arrhythmia: bi-national cohort study. BMJ 2016;352:i843. “Contrary to previous reports, oral fluoroquinolone treatment was not associated with an increased risk of serious arrhythmia in the general adult populations of Denmark and Sweden. Given the statistical power of the study, even small increases in relative and absolute risk could be ruled out. Since ciprofloxacin was the most commonly used fluoroquinolone in our study, we cannot exclude that intraclass differences influence the risk of serious arrhythmia associated with other less frequently used fluoroquinolones.”

Other Readings, Cont.

•Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet 2016;387:435-43. “Intensive blood pressure lowering provided greater vascular protection than standard regimens. In high-risk patients, there are additional benefits from more intensive blood pressure lowering, including for those with systolic blood pressure below 140 mmHg. The net absolute benefits of intensive blood pressure lowering in high-risk individuals are large.”

Other Readings, Cont.

•Sotalol versus Amiodarone in Treatment of Atrial Fibrillation. J Atr Fibrillation 2016;8(5):6-13. “In summary, sotalol and amiodarone are equally effective in AF conversion and maintenance of NSR post-cardiac surgery.”

Other Readings, Cont.

•Outcomes in patients treated with ticagrelor or clopidogrelafter acute myocardial infarction: experiences from Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry. doi:10.1093/eurheartj/ehw284. “Ticagrelor vs. clopidogrelpost-ACS was associated with a lower risk of death, MI, or stroke, as well as death alone. Risk of bleeding was higher with ticagrelor. These real-world outcomes are consistent with randomized trial results.”

Other Readings, Cont.

•Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease. The Norwegian Coronary Stent Trial (NORSTENT). DOI: 10.1056/NEJMoa1607991. “In patients undergoing PCI, there were no significant differences between those receiving drug-eluting stents and those receiving bare-metal stents in the composite outcome of death from any cause and nonfatal spontaneous myocardial infarction. Rates of repeat revascularization were lower in the group receiving drug eluting stents.”

Other Readings, Cont.

•Apixaban Plus Mono Versus Dual Antiplatelet Therapy in Acute Coronary Syndromes. Insights From the APPRAISE-2 Trial. Apixaban for Prevention of Acute Ischemic Events 2 (APPRAISE-2) Trial. J Am Coll Cardiol 2015;66:777-87. “Post-ACS treatment with apixaban versus placebo showed no efficacy, but it increased bleeding regardless of concomitant therapy with aspirin alone or aspirin plus clopidogrel.”• Post-hoc analysis of APPRAISE-2 Trial. N Engl J Med 2011;365:699-708.

• APPRAISE-1 Trial. Circulation 2009;119:2877-85.

Other Readings, Cont.

•Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. The Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors (ANNEXA-4) study. NEJM DOI: 10.1056/NEJMoa1607887. “On the basis of a descriptive preliminary analysis, an initial bolus and subsequent 2-hour infusion of andexanet substantially reduced anti-factor Xa activity in patients with acute major bleeding associated with factor Xa inhibitors, with effective hemostasis occurring in 79%.”

Other Readings, Cont.

•Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors Apixaban (ANNEXA-A) and Rivaroxaban (ANNEXA-R) Trial. N Engl J Med 2015;373:2413-24. “Andexanet reversed the anticoagulant activity of apixaban and rivaroxaban in older healthy participants within minutes after administration and for the duration of infusion, without evidence of clinical toxic effects.

Other Readings, Cont.

•Edoxaban versus enoxaparin-warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial. Lancet http://dx.doi.org/10.1016/S0140-6736(16)31474-X. “ENSURE-AF is the largest prospective randomised clinical trial of anticoagulation for cardioversion of patients with non-valvular atrial fibrillation. Rates of major and clinically relevant non-major bleeding and thromboembolism were low in the two treatment groups.”

Other Readings, Cont.

1. According to the COURAGE Trial, in patients with stable CAD, those treated with PCI plus medical therapy showed a significant survival benefits compared to patients treated with medical therapy alone.A. True B. False

2. According to the ATMOSPHERE Trial, in patients with chronic HF, the addition of aliskiren to enalapril resulted in less adverse events and more benefits.A. True B. False

3. According to the SOCRATES Trial, in patients with acute ischemic stroke an TIA, ticagrelor was found to be superior to ASA. A. True B. False

Test Questions

•COURAGE Trial. Boden WE, et al. Optimal Medical Therapy with or without PCI for Stable Coronary Disease. N Engl J Med 2007;356:1503-16.

•COURAGE Trial. Sedlis SP, et al. Effect of PCI on Long-Term Survival in Patients with Stable Ischemic Heart Disease. N Engl J Med 2015;373:1937-46.

•NEAT-HFpEF Trial. Redfield MM, et al. Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction. N Engl J Med 2015;373:2314-24.

•ATMOSPHERE Trial. McMurray JJV, et al. Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure. N Engl J Med 2016;374:1521-32.

•SOCRATES Trial. Johnston SC, et al. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. N Engl J Med 2016;375:35-43.

•VANISH Trial. Sapp JL, et al. Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs. N Engl J Med 2016;375:111-21.

•APEX Trial. Cohen AT, et al. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. N Engl J Med 2016;375:534-44.

•RxEACH Trial. Tsuyuki RT, et al. The Effectiveness of Pharmacist Interventions on Cardiovascular Risk. The Multicenter Randomized Controlled RxEACH Trial. J Am Coll Cardiol 2016;67:2846-54.

•DAPT studies: N Engl J Med 2014;371:2155-66., JAMA 2015;313(11):1121-21., J Am Coll Cardiol Intv 2016;9:138-47., JAMA 2016;315(16):1735-49., Eur Heart J 2016;37:390-9.

• JAMA Cardiology Clinical Guidelines Synopsis: Focused Update on Duration of Dual Antiplatelet Therapy for Patients With CAD. JAMA Cardiol2016;1(6):733-4.

References

1. Write down the course code. Space has been provided in the daily program-at-a-glance sections of your program book.

2. To claim credit: Go to www.cshp.org/cpe before December 1, 2016.

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