hsCRP is a Stronger Predictor of CV Events and Death than LDL-C in High-Risk Patients on Statins

Key Points:

  • Both inflammatory risk and hyperlipidemia and crucial risk factors for MACE in patients at high risk of CVD.
  • In a large collaborative study of patients combining data from the PROMINENT (N = 9,988), REDUCE-IT (N = 8,179) and STRENGTH (N = 13,078) trials, the effect of residual inflammatory risk (as measured by hsCRP) and LDL-C levels on MACE were assessed.
  • Residual inflammatory risk as assessed by hsCRP was a stronger determinant of risk for future cardiovascular events and death than residual cholesterol risk as assessed by LDL-C.

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FREEDOM COVID: Therapeutic dose anticoagulation does not reduce MACE in non-critically ill COVID-19 patients

Key Points:

  • There have been conflicting data on the role and recommended dosage of anticoagulation in non-critically-ill patients with COVID-19.
  • In the open-label FREEDOM COVID study, therapeutic anticoagulation was compared with prophylactic doses of enoxaparin in patients hospitalized for COVID-19. The primary endpoint was a 30-day composite of all-cause mortality, requirement For ICU level-of-care, systemic thromboembolism, or ischemic stroke.
  • Therapeutic anticoagulation did not result in any significant differences in the composite endpoint, but it did result in lower 30-day mortality and endotracheal intubation compared with prophylaxis.

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STELLAR: Sotatercept improves 6MWD in PAH patients and WHO FC II-III

Key Points:

  • Sotatercept is a novel activin signaling inhibitor which was designed to target pulmonary vascular remodeling in PAH.
  • In the STELLAR study, sotatercept was tested against placebo on a background of baseline PAH therapy in adults with WHO II/III PAH. The primary endpoint was change in 6MWD at 16 weeks.
  • Sotatercept resulted in an improvement in 6MWD, PVR, NT-proBNP, and a composite of time to clinical worsening and all-cause mortality at 16 weeks compared to placebo.

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Dapagliflozin Reduces PCWP at Rest and Exercise, Plasma Volume, and Weight in HFpEF patients

Key Points:

  • SGLT2i therapy reduces HF hospitalizations and CV mortality in HFpEF, but the mechanism is not yet clear.
  • In this single-center, double-blinded RCT, patients with HFpEF were randomized to dapagliflozin or placebo and underwent exercise and resting hemodynamics at baseline and at 24 weeks.
  • Dapagliflozin resulted in reduced resting and exercise PCWP, weight, and plasma volume relative to placebo.

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Macitentan/Tadalafil Fixed Dose Combination reduces PVR compared with monotherapy

Key Points:

  • Macitentan and Tadalfil are frequently used in combination for PAH, which opens up the possibility of a fixed-dose combination pill.
  • In the DUE study, macitentan/tadalafil FDC therapy was compared against macitentan and tadalafil monotherapy. The primary outcome was PVR reduction at 16 weeks.
  • M/T FDC resulted in a significant reduction in PVR at 16 weeks compared to either macitentan or tadalfil monotherapy. There was a non-significant trend towards reduction in 6MWD at 16 weeks.

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Black women with TTR V122I variant have higher risk of CVD and all-cause mortality

Key Points:
 The prognostic significance of the V122I variant (associated with wt-ATTR) in Black women has not yet been established.
 A substudy of the WHI aimed to establish the association of the V122I variant with a composite of CVD and all-cause mortality in Black Women.
 The V122I variant was associated with increased composite CVD and all-cause mortality in Black women; this association was particularly significant for women age 60+.

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Elevated hs-cTnL levels precede and predict pre-eclampsia

Key Points:

  • There have been limited data regarding the biomarkers that may predict the development and severity of preeclampsia.
  • hs-cTnI was significantly elevated in pregnant women who would later develop preeclampsia starting at 14 weeks. A cutoff hs-cTnI value of >2.2pg/ml at 14 weeks and >2.6pg/ml at 26 weeks had a combined 100% negative predictive value for predicting severe preeclampsia in women at high a prior risk.

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TRILUMINATE: Tri-Clip reduces tricuspid regurgitation and improves quality of life at one year

Key Points:

  • There have been limited data examining the safety and efficacy of transcatheter tricuspid repair systems.
  • In the TRILUMINATE study, Tri-Clip was compared against medical therapy in patients with severe symptomatic TR.
  • Tri-Clip implantation reduced severity of TR and improved quality of life. Tri-Clip was safe and resulted in only a 1.7% rate of major adverse events.

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FLAME: FlowTriever use for PE associated with decreased in-hospital adverse outcomes

Key Points:

  • Mortality in high-risk PE remains unacceptably high (25%) despite advances in medical and interventional therapies.
  • The FLAME study was a prospective, multi-center non-randomized observational study to describe the outcomes of patients undergoing mechanical thrombectomy and other modern therapies and generate evidence in high-risk PE. The primary outcome was a composite of all-cause mortality, bailout to alternate thrombus removal strategy, clinical deterioration, and major bleeding.
  • Compared with a pre-established performance goal of 32%, patients treated with Flowtriever had a significant reduction in the primary endpoint. There was also significant reduction in in-hospital mortality (1.9% compared to 28.5%). There was no increase in adverse events in the FlowTriever group.
  • Randomized evidence will be required to follow-up this observational study, but FlowTriever appears to be a safe, effective treatment which may reduce mortality in high-risk PE.

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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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ECMO-CS: Early ECMO Does not Improve Outcomes in Severe Cardiogenic Shock

Key Points:

  • ECMO has been used as a salvage strategy in severe cardiogenic shock. However, it is unclear whether immediate ECMO initiation is superior to an initial trial of medical therapy with subsequent MCS utilization as needed if no improvement occurs.
  • In the ECMO-CS study, patients presenting with severe cardiogenic shock (SCAI stage D-E) were randomized to either immediate ECMO or medical therapy (with downstream MCS as needed) The primary outcome of interest was a 30-day composite of death from any cause, resuscitated circulatory arrest, and implementation of any other MCS device.
  • Immediate ECMO initiation was not associated with a significant reduction in the primary outcome relative to medical therapy with downstream as-needed MCS. There was a 40% crossover in the conservative arm to eventual downstream ECMO.

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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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IRONMAN: Intravenous Ferric Derisomaltose did not not meet primary endpoint in HFrEF

Key Points:

  • Iron deficiency is common and a poor prognostic feature in patients with heart failure. However, while iron infusion has improved symptoms in patients with HFrEF, there has been no association with improved “hard” outcomes such as hospitalization or CV death.
  • In the IRONMAN study, patients with HFrEF and iron deficiency were randomized to Intravenous Ferric Derisomaltose (IV FDI) or placebo. The primary outcome of interest was a composite of recurrent HF hospitalizations and CV death.
  • The observed reduction in primary endpoint with Intravenous Ferric Derisomaltose did not reach statistical significance compared to usual care.

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COACH – A Patient-Risk Based Health System Intervention for Acute Heart Failure Care: The Comparison of Outcomes and Access to Care for Heart Failure (COACH) Trial

Key Points:

  • HF patients frequently present to the ED for acute exacerbations, and the decision whether to discharge, observe, or admit these patients can be complex.
  • The COACH trial randomized acute HF patients presenting to the ED to either a standardized clinical risk stratification algorithm (based on the EHMRG30-ST score) with associated rapid outpatient HF clinic or to standard of care.
  • Patients receiving the intervention had reduced 30-day and 20-month composite death and non-elective cardiovascular hospitalizations.

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First-in-Human in vivo Crispr/Cas9 Editing of the TTR Gene by NTLA-2001 in patients with Transthyretin Amyloid Cardiomyopathy

Key Points:

  • Transthyretin Amyloidosis (ATTR) is a highly morbid and often fatal cause of cardiomyopathy. Existing therapies targeting TTR protein reduction have been effective, but have not managed to achieved complete or sustained knockdown of TTR levels.
  • This was a Phase I study of a novel in vivo Crisp/Cas9 editing system (NTLA-2001) to reduce TTR. The primary objective was to assess safety, tolerability and PK and PD, and the secondary objective was to evaluate efficacy on clinical measures of cardiac disease.
  • NTLA-2001 was generally well tolerated, with largely mild-moderate adverse events reported. Patients receiving NTLA-2001 achieved sustained, >90% reduction in TTR up to 4-6 months after infusion.

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RIVARAD: Post-Procedural Rivaroxaban Use After Radial Access for Coronary Procedures Reduces Radial Artery Occlusion at 30 Days

Key Points:

  • Radial artery occlusion (RAO) is the most common complication after radial access for coronary procedures; while routine intra-procedural heparin administration is a protective factor, the role of post-procedural anticoagulation has not been established.
  • In the RIVARAD study, patients undergoing trans-radial access for coronary procedures were randomized to a week of post-procedural rivaroxaban vs no additional treatment. The primary outcome of interest was 30-day incidence of RAO by ultrasound.
  • Patients receiving rivaroxaban experienced a 50% reduction in RAO by ultrasound and a 52% reduction in RAO by palpation compared to the control group. Rivaroxaban use was safe with no increase in overall hemorrhagic complications relative to the control 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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