BrigHTN: Baxdrostat, an aldosterone synthase inhibitor, showed dose-related reductions in blood pressure and safely and effectively lowers blood pressure in patients with resistant hypertension

Key Points

  • In a Phase 2 randomized trial, baxdrostat, a highly potent and selective aldosterone synthase inhibitor, had dose-related reductions in blood pressurein patients with resistant hypertension compared to placebo, without any serious adverse events.

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FRESH –First-in-Class Aminopeptidase-A Inhibitor Firibastat Fails in Resistant Hypertension

Key Points

  • Hypertension remains a major public health threat contributing significantly to rates of ischemic heart disease and strokes worldwide despite a wide array of antihypertensives available
  • A new antihypertensive agent, firibastat, is a first-in-class prodrug that acts through the inhibition of amiopeptidase A to block the conversion of angiotensin II to angiotensin III resulting in a decrease in blood pressure
  • Firibastat failed to demonstrate efficacy to decrease blood pressure in patients with difficult-to-treat/resistant hypertension and was associated with allergic skin reactions.

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PRECISION –Dual Endothelin Receptor Antagonist Aprocitentan Superior to Placebo in Resistant Hypertension

Key Points

  • Despite the many drug classes available to treat hypertension, the prevalence of resistant hypertension (hypertension requiring at least 3 blood pressure medications of different classes) points to significant pathways not yet explored or addressed by current therapeutics
  • Dual endothelin receptor antagonist (ERA), aprocitentan, offers a new pathway to the treatment of hypertension, pertinent to those prone to developing resistant hypertension including Black patients, patients with obesity or obstructive sleep apnea
  • Aprocitentan lowered both office and 24-hour ambulatory blood pressures compared to placebo after 4 weeks of treatment, maintaining its effect over 48 weeks. It was, however, associated with fluid retention/edema which was clinically manageable with diuretic therapy.

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RAPID – Self-Administered Etripamil Improves PSVT Conversion to Sinus Rhythm

Key Points

-The RAPID study achieved its primary efficacy endpoint of terminating PSVT with self-administered Etripamil using a symptom-based optimal repeat dosing.

-Pooled analysis with the NODE-301 study showed that self-administered etripamil showed a significant reduction in emergency department utilization and medical intervention.

-This Phase III trial showed a favorable safety and tolerability profile of etripamil consistent with prior etripamil trials.

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NOVA – No significant difference in rate of post-op AF with botulinum toxin vs placebo

Key Points:

-In a Phase II, dose-ranging trial of epicardial fat pad injection of botulinum toxin type A (AGN-151607) there was no significant differences in the rates of post-operative atrial fibrillation (POAF).

-Subgroup analyses suggest a lower rate of POAF and rehospitalization in patients >65 years of age who received the 125 U dose of AGN-151607, and those undergoing isolated CABG.

-The mechanism of POAF within the first 30 days may be related to both direct autonomic influences and decreased inflammation.

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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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PRO-HF Sub-Study:  Routine KCCQ-12 assessments in HF improves accuracy of provider assessment of patient health status.

Key Points

  • Clinicians estimate heart failure (HF) health status using New York Heart Association (NYHA) class; however, this is often discordant with patient-reported symptom burden.
  • The Patient-Reported Outcomes in Heart Failure Clinic (PRO-HF) is a pragmatic, randomized, unblinded trial comparing routine Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) collection prior to outpatient HF clinic visits, which is then shared with the treating clinician, to usual care.
  • The primary objectives in this pre-specified sub study were to determine the effect of this intervention on the accuracy of clinician assessment of patient health status and patient experience.
  • Provider assessment of NYHA class in the KCCQ-12 arm was more accurate, and patients in the KCCQ-12 arm felt their providers better understood their symptoms.
  • Future investigations will determine the effect of routine KCCQ-12 administration on longer term clinical outcomes.

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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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The Diuretic Comparison Project (DCP): For hypertensive patients already on hydrochlorothiazide, switching to chlorthalidone does not improve outcomes

Key Points:

  • Thiazide type diuretics are first-line medications for hypertension (HTN); while chlorthalidone (CTD) has been shown to lower blood pressure to a greater extent than hydrochlorothiazide (HCTZ), whether this translates into improved cardiovascular outcomes is unknown.
  • The DCP trial enrolled Veterans Affairs (VA) patients aged 65 or older currently on HCTZ 25-50mg daily and randomized them to either continue taking HCTZ or to switch to an equivalent dose of CTD.
  • There was no difference between the two groups for the primary composite outcome of time to non-cancer death, stroke, myocardial infarction (MI), urgent revascularization, or heart failure hospitalization.
  • The DCP used a novel pragmatic “point of care” design in which the primary care providers (PCPs) managed the medications, no study staff were present at study sites, and the outcome data was collected passively through the electronic medical record (EMR) or national databases, thereby mitigating the cost of study execution.

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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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Does Loop Diuretic Type Affect Clinical Outcomes in Heart Failure? Furosemide vs. Torsemide Compared in the TRANSFORM-HF Trial

Key points:

  • Loop diuretics are routinely used to manage congestion in heart failure (HF) but have never been directly compared in a large-scale randomized trial.
  • The TRANSFORM-HF trial compared torsemide vs. furosemide for long-term clinical outcomes among patients hospitalized with HF.
  • At median follow up of 17.4 months, there was no significant difference in clinical outcomes (all-cause mortality) between torsemide and furosemide in HF patients.
  • The pragmatic nature of the TRANSFORM-HF study allowed for diverse patient recruitment, high site engagement and clinically generalizable results.

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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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