OPTION –Indobufen is Noninferior to Aspirin After Coronary Drug-Eluting Stent Implantation

Key Points:

  • Indobufen, a platelet aggregation inhibitor, has been shown to be a shorter acting antiplatelet in comparison to aspirin. However, it has not been studied as a component of DAPT in patients requiring stent implantation.
  • In the OPTION study, patients with CAD undergoing stent placement were randomized to either indobufen or aspirin. The primary outcome of interest was a 1-year composite of CV death, nonfatal MI, ischemic stroke, definite or probable stent thrombosis, or BARC type-2, 3, or 5 bleeding
  • Indobufen was found to be non-inferior to aspirin in the primary endpoint.

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PRECISE–A precision diagnostic strategy in patients with suspected CAD improves outcomes

Key Points:

  • There is substantial heterogeneity in the use of different non-invasive and invasive modalities for CAD risk stratification; however, there limited is RCT evidence dictating the optimal strategy.
  • In the PRECISE study, patients with typical or atypical symptoms suggestive of potential CAD were randomized to either a risk-score based, “precision” strategy or usual care. The primary outcome of interest was a 1-year composite of death, nonfatal MI, or a coronary catheterization yielding no obstructive CAD.
  • The precision strategy resulted in a significant 70% reduction in the primary outcome at 1 year compared to usual care.

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RAPCO: Radial artery grafting is superior to both RITA and SVG in patients undergoing CABG

Key Points:

  • Recent guidelines have supported the use of arterial grafts over venous grafts in coronary artery bypass grafting (CABG), but there has yet to be a single randomized trial examining long-term cardiovascular outcomes with these different grafting methods.
  • In the RAPCO study, patients undergoing CABG were randomized to either a) radial artery (RA) grafting versus right internal thoracic artery (RITA) grafting or b) radial artery (RA) grafting versus saphenous vein grafting (SVG). The primary outcome of interest was MACE, a composite of cardiovascular mortality, acute MI, and revascularization.
  • RA grafting was superior to both RITA and SVG grafting over 15 years of follow-up.

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CTS-AMI: Tongxinluo (TXL) improves CV outcomes in acute STEMI

Key Points:

  • Tongxinluo (TXL) is a traditional Chinese medicine with endothelial-protective effects which has been used for angina and stroke prevention in China. It has yet to be tested as a means of improving clinical outcomes in acute STEMI.
  • In the CTS-MI study, patients presenting with STEMI were randomized to either TXL (at randomization, and then continued for a year) or placebo. The primary outcome of interest was 30-day MACCE, a composite of cardiovascular mortality, recurrent MI, stroke, and emergent coronary revascularization. Secondary outcomes included 1-year MACCE as well as the individual components of MACCE, severe MI complications, and adverse events.
  • TXL use resulted in a 36% reduction of MACCE at 30-days and 1-year, as well as reduced severe STEMI complications. TXL use was safe, with no increase in adverse events.

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PROMINENT: Pemafibrate reduces triglyceride levels but not cardiovascular events in patients with dyslipidemia and T2DM

Key Points

  • High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would reduce the incidence of cardiovascular events is not clear.
  • In the PROMINENT study, patients with dyslipidemia and type 2 diabetes mellitus were randomized to a new cholesterol medication, pemafibrate, or placebo, the primary outcome being a clinical composite endpoint of MI, ischemic stroke, coronary revascularization, or CV death.
  • In patients receiving pemafibrate , the incidence of CV events was not lower than those who received placebo, although pemafibrate lowered triglyceride levels, VLDL, and apolipoprotein C-III. There were worrisome adverse events such as an increased risk of venous thromboembolism and renal events in the pemafibrate arm.

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EPIC-STEMI: Early Routine PCSK-9 Use Added to High Intensity Statin Reduces LDL after Primary PCI for STEMI

Key Points:

  • Early high-intensity statin therapy is standard of practice in acute STEMI patients, but this is often insufficient to achieve LDL targets. PCSK-9 therapy has never been tested as routine therapy in STEMI.
  • In the EPIC STEMI trial, routine PCSK-9 initiation in addition to high-intensity statin prior to primary PCI resulted in a 22% LDL reduction at 6 weeks relative to sham, with a higher proportion of patients achieving therapeutic LDL targets.

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Extended outcomes of BEST: No difference in MACE between PCI and CABG in MVD at 12 years, but higher repeat revascularization and spontaneous MI in PCI arm

Key Points:

  • Previous studies have demonstrated the superiority of CABG over PCI in the treatment of multivessel disease; however, most studies were performed without the use of newer second-generation stents.
  • The two-year outcomes of the BEST trial demonstrated superiority of CABG compared to PCI with second-generation everolimus-eluting DES; however, the authors then pursued an extended outcome analysis up to a median follow-up of 11.8 years.
  • There was no difference between PCI and CABG at extended follow-up in the primary outcome composite of all-cause death, MI, and total revascularization. However, the rate of spontaneous MI and repeat revascularization was higher in the PCI arm.
  • IVUS use reduced the incidence of the primary composite amongst patients undergoing PCI.

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Additional background and insight

Presented by Dr. Schuyler Jones, assistant professor of medicine, Duke University, and a member of the Duke Clinical Research Institute in the first Late Breaking Clinical Trial session, “Aspirin Dosing: A patient-centric Trial Assessing the Benefits and Long-term Effectiveness (ADAPTABLE)” asked a key question that many patients and physicians, PAs, and NPs face every day: Is 81 mg or 325 mg of aspirin more effective for secondary prevention for patients with pre-existing or established cardiovascular disease?

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DAPT with Clopidogrel Superior to Ticagrelor one month after PCI: Results from the TALOS-AMI Trial

With the widespread use of second-generation drug eluting stents, it has become more apparent that the risk of stent thrombosis decreases significantly after the first thirty days. The risk of bleeding, on the other hand, increases during that same time period. It has been proposed that de-escalation of potent P2Y12 inhibitors could mitigate that risk of bleeding. Dr. Kiyuk Chang and his co-investigators sought to answer this in the TALOS-AMI trial, the results of which were presented during a late breaking clinical trial session today at the 2021 American College of Cardiology Scientific Sessions. Continue reading

Aspirin Dosing: a Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) trial


  • There was no significant difference in primary composite endpoint of all-cause mortality, hospitalization for myocardial infarction, or hospitalization for stroke in patients with coronary artery disease taking 81 mg versus 325 mg of aspirin every day.
  • There was no significant difference in the safety endpoint of hospitalization for major bleeding with blood product transfusion in patients with coronary artery disease taking 81 mg versus 325 mg of aspirin every day.
  • Conducting pragmatic study in a real world, patient-centric approach will likely continue to emerge as an appealing, cost effective trial design in the field of cardiology.

Cardiovascular disease is costly and a major cause of death worldwide. Aspirin has been the mainstay of treatment in secondary prevention of coronary artery disease for over thirty years. More recently, several analyses have suggested varying doses aspirin (81 mg vs 325 mg) as well as the use of other, newer antiplatelet agents for the treatment of coronary artery disease. Continue reading

PURE Study Finds That Cardiovascular Disease Mortality Is Associated with the Glycemic Index of Foods in the Diet

A recent study by Dr. David J. A. Jenkins, published in the New England Journal Of Medicine, demonstrated that the glycemic index of the diet is directly associated with the risk of cardiovascular disease and death. This study was conducted in multiple countries and the results were similar across various economic and geographic regions. Continue reading

TIPS-3 Trial: The Combination of Polypill and Aspirin Administered to Patients at Intermediate Risk Led to a Lower Incidence of Cardiovascular Events Compared With Double Placebo

A recent trial by Dr. Salim Yusuf, published in The New England Journal of Medicine, indicated that combination therapy with aspirin plus a polypill (consisting of a statin plus three blood-pressure-lowering drugs) can reduce the incidence of cardiovascular events compared with placebo among participants without established cardiovascular disease, but at moderate cardiovascular risk.

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Post-Hoc Analysis of ISCHEMIA Trial: The Choice of Myocardial Infarction Definition Influences Clinical Interpretation of Results

A recent study by Dr. Bernard R. Chaitman, published in Circulation investigated the impact on clinical interpretation of using different definitions for myocardial infarctions in the ISCHEMIA trial.

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DAPA Trial: Prophylactic Defibrillator Implantation After Primary Percutaneous Coronary Intervention Lowers Long Term Mortality in Patients at High Risk of Death

Results of the DAPA trial, published in Circulation: Arrhythmia and Electrophysiology, demonstrated that the use of early prophylactic implantable cardioverter defibrillator (ICD) in high-risk post-primary percutaneous coronary intervention (PCI) patients was associated with lower all-cause and cardiac mortality rates. However, the results of this trial should be interpreted with caution, since the trial was stopped prematurely.

The optimal timing of ICD implantation in STEMI patients treated with primary angioplasty is not identified yet. Previous clinical trials have failed to show the benefit of early ICD implantation (4-60 days) in post-MI patients with a low left ventricular ejection fraction (≤35-40%). The risk of sudden cardiac death (SCD) is high within the post STEMI period.  However, ICD implantation after 40 days may not be indicated due to left ventricular remodeling and a potential increase in LVEF post-primary PCI. The Defibrillator After Primary Angioplasty (DAPA) trial evaluated all-cause and cardiac mortality of patients undergoing early prophylactic ICD implantation after PCI for STEMI. Following a recommendation from the data safety board, the trial was terminated early after just 38% of the planned sample size was enrolled due to slow enrollment.

This multicenter, randomized, controlled trial included patients with STEMI who had undergone primary PCI and met at least one of the following criteria: LVEF<30% within 4 days after admission, primary ventricular fibrillation (VF) within 24 hours (during PCI excluded), signs of heart failure on admission (Killip class ≥ 2), and/or thrombolysis in myocardial infarction (TIMI) flow post PCI < 3. The participants were randomized in a 1:1 ratio to receive either ICD implantation or conventional therapy within 30 to 60 days of the STEMI event. The primary endpoint was all-cause mortality at 3 and 9-years. The secondary endpoints of the study included the incidence of sudden cardiac death (SCD) and hospital admission for sustained ventricular tachyarrhythmias or appropriate ICD therapy.

A total of 266 patients with primary PCI for STEMI were included in the study with 131 patients allocated to the ICD arm and 135 patients assigned to the conventional therapy arm. After 3-years of follow-up, the primary outcome of interest was significantly lower among patients who received ICD implantation (5%) compared to the conventional therapy group (13%) (Hazard ratio (HR):0.37; [95% CI: 0.15-0.95]; p=0.04). This result remained similar at a median of 9-years follow-up (HR: 0.58; [95% CI: 0.37-0.91]; p=0.02). In terms of cardiac mortality, ICD implantation was associated with fewer deaths (11%) compared to the control group (22%) (HR: 0.52; [95% CI: 0.28-0.99]; p=0.04). Although not statistically significant, the incidence of SCD was also lower in the ICD group (3.1%) compared to the control group (5.9%) (HR 0.45; [95% CI 0.14–1.50]; p=0.19).

The results of this study should be interpreted with consideration of the following limitations. First, the premature termination of the study makes it underpowered for analysis. Second, the study used more than one inclusion criteria, so results should be interpreted with consideration of the patient characteristics. The high treatment crossovers (10.2%) within the first 3 years of the study and the lack of information on treatment crossovers between 3 and 9 years are additional limitations of the trial.  Furthermore, while pharmacotherapy of the participants was similar at baseline, there is a lack of data regarding the follow-up medical therapy which may have impacted the mortality rates.

In conclusion, this prematurely terminated trial suggests that early prophylactic ICD implantation may be associated with a better survival rate in patients at high risk of death after primary PCI for STEMI. The results of this trial should be confirmed in future studies.

COACT Trial Shows Immediate Coronary Angiography Does Not Change the 1-Year Clinical Outcomes of Patients After Cardiac Arrest Without ST-Segment Elevation

A trial by Dr. Jorrit S. Lemkes, published in JAMA Cardiology, demonstrated that immediate coronary angiography and percutaneous coronary intervention (PCI) does not improve the 1-year clinical outcomes of patients after successful resuscitation from non-ST segment elevation cardiac arrest. Also, the survival rate was comparable between patients whose angiography was performed immediately (61.4%) versus those whose angiography was delayed (64.0%).

Given the high prevalence of coronary artery disease among patients with cardiac arrest, coronary angiography and PCI should be considered in these patients with suggested evidence of coronary artery involvement. However, the current data regarding the appropriate timing of this intervention is lacking. The interim results of the Coronary Angiography after Cardiac Arrest (COACT) trial failed to find a significant difference between the 90-days clinical outcomes of patients with delayed coronary angiography versus patients with immediate coronary angiography after non-ST segment elevation cardiac arrest. The 1-year follow-up study investigated the long-term clinical outcomes of immediate coronary angiography in these patients.

COACT study, an open-label, multicenter, randomized trial, compared the short-term clinical outcomes of immediate versus delayed coronary angiography in patients resuscitated from cardiac arrest without ST-segment elevation on the electrocardiogram tracing. Briefly, a total of 552 patients with out-of-hospital arrest and no signs of ST-segment elevation myocardial infarction (STEMI) who successfully resuscitated from cardiac arrest were randomized in a 1:1 ratio to undergo immediate (within 2 hours of randomization) or delayed (after neurological recovery or discharge from intensive care unit) coronary angiography. The 1-year endpoints of the study included survival rate, myocardial infarction, repeated revascularization, hospitalization for heart failure, and implantable cardiac defibrillator (ICD) shock since the index hospitalization.

At 1-year follow-up, 94.6% of the participants (n=522) were available for analysis. The recent analysis of the data indicated no significant differences between the two groups. The survival rate was 61.4% and 64.0% in the immediate and delayed coronary angiography group, respectively (odds ratio (OR)=0.90; 95%Confidence Interval (CI):0.63-1.28). Additionally, the endpoints of the interest were equivalent in the 2 groups. For example, the rate of myocardial infarction was 0.8%in the immediate group and 0.4%in the delayed group (OR=1.96; 95%CI: 0.18-21.8). The study also showed that the post-cardiac arrest mortality usually occurs within the first 90 days after the arrest, and the survival rate after this period is relatively favorable.

The trial has some limitations that need to be taken into account. First, the study is not powered for a 1-year analysis. Second, the findings of this study are not generalizable to patients with shock, severe renal dysfunction, or persistent ST-segment elevation due to their exclusion from the trial.

The results of this trial suggest that in patients with out-of-hospital cardiac arrest with no signs of STEMI, the coronary angiography, if necessary, can be delayed until after neurological recovery.

Study Shows the Efficacy of Adding Corticosteroids to Initial Intravenous Immunoglobulin Therapy in the Prevention of Coronary Artery Abnormality Among Patients at High Risk for Kawasaki Disease

A recent study by Dr. Ryusuke Ae, published in the Journal of the American Heart Association, demonstrated the efficacy of combining the initial intravenous immunoglobulin (IVIG) treatment with multiple-dose corticosteroids in the prevention of coronary artery abnormalities in selected patients at high risk for Kawasaki disease. The study showed a reduction in coronary artery abnormalities and treatment failure after applying this treatment strategy.
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PREMIER Trial Shows Incremental Plaque Regression by a Single Lipid Apheresis and Maintained Statin Therapy in ACS Patients Treated With PCI

A recent study by Dr. Banerjee, published in Circulation: Cardiovascular Interventions, demonstrated the efficacy and safety of low-density lipoprotein (LDL) lowering therapy via a single LDL apheresis treatment plus ongoing statin therapy in nonfamilial hyperlipidemia acute coronary syndrome patients treated with the percutaneous coronary intervention (PCI).
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Post Hoc Analyses of GLOBAL LEADERS Trial: Compared with Standard 12-Month Dual Anti-Platelet Therapy, Ticagrelor Monotherapy Reduced the Ischemic and Bleeding Events by up to 8% Following Percutaneous Coronary Intervention

The post hoc analyses of GLOBAL LEADERS study by Dr. Hara, published in Circulation: Cardiovascular Quality and Outcomes reported that in multiple statistical analyses considering the total number and severity of bleeding and ischemic events, ticagrelor monotherapy consistently decreased the risk of these events by 5% to 8% compared to 1-year conventional dual antiplatelet therapy. This analysis supported the beneficial effects of ticagrelor monotherapy after percutaneous coronary intervention. Continue reading

DAPA-HF Trial: Compared to Placebo, Dapagliflozin Was Beneficial in Patients with Heart Failure and Reduced Ejection Fraction Regardless of Background Diuretic Therapy

A recent study by Dr. Alice M. Jackson M.D., published in Circulation journal, showed that the use of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with reduced ejection fraction heart failure (HF) is associated with reduced risk of cardiovascular (CV) death or a worsening HF event, and all-cause death. These effects remained consistent among different subgroups of diuretic therapy. 
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Meta-Analysis of Randomized Trials Shows Early Aspirin Discontinuation with P2y12 Inhibitor Monotherapy Decreases Risks of Major Bleeding After Percutaneous Coronary Intervention

A recent study by Dr. O’Donoghue, published in Circulation, shows that early aspirin discontinuation with continued P2Y12 inhibitor monotherapy, after the percutaneous coronary intervention (PCI),  was associated with a significant reduction in major bleeding compared to dual antiplatelet therapy. This study did not show a significant increase in major adverse cardiovascular events (MACE) after aspirin discontinuation in the participants.
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