FRESH –First-in-Class Aminopeptidase-A Inhibitor Firibastat Fails in Resistant Hypertension
- 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.
The Diuretic Comparison Project (DCP): For hypertensive patients already on hydrochlorothiazide, switching to chlorthalidone does not improve outcomes
- 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.
PROMINENT: Pemafibrate reduces triglyceride levels but not cardiovascular events in patients with dyslipidemia and T2DM
- 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.
EPIC-STEMI: Early Routine PCSK-9 Use Added to High Intensity Statin Reduces LDL after Primary PCI for STEMI
- 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.
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
Post-Hoc Analysis of DAPA-HF: Dapagliflozin Use Is Associated With Rapid Reduction of Cardiovascular Death Among Patients With Heart Failure With Reduced Ejection Fraction
A recent study by Dr. David D. Berg, published in JAMA Cardiology, found that the use of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, was associated with reducing the risk of cardiovascular death and heart failure hospitalization, emerging very early after randomization. Of note, patients with a recent history of hospitalization due to heart failure worsening tend to benefit more and experienced greater relative and absolute risk reductions when treated with dapagliflozin. Continue reading
STOP AF First Trial: Cryoballoon Ablation Is Superior to Antiarrhythmic Drug Therapy for the Prevention of Atrial Arrhythmia Recurrence in Patients With Paroxysmal Atrial Fibrillation
A recent trial by Dr. Oussama M. Wazni, published in the New England Journal of Medicine, indicated that in patients with paroxysmal atrial fibrillation, cryoballoon ablation therapy is superior as compared with antiarrhythmic drug therapy, in the prevention of atrial fibrillation recurrence. The study also showed the non-inferiority of this procedure over the drug therapy approach in terms of safety.
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.
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.
EMPEROR-Reduced Trial: Empagliflozin Use Was Associated With a Better Clinical Outcomes Among Patients With Heart Failure and a Reduced Ejection Fraction
A recent study by Dr. Milton Packer, published in Circulation, demonstrated that empagliflozin use has been associated with a reduction in the total number of inpatient and outpatient visits in patients with heart failure and a reduced ejection fraction. These benefits were observed within 12-28 days of treatment initiation and were persisted over the duration of the trial. Continue reading
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.
Meta-Analysis Shows Heparin Administration Decreases the Risk of Venous Thromboembolism Among Ambulatory Patients With Cancer
A recent study by Dr. Holger J Schünemann, published in THE LANCET Haematology, demonstrated that, in patients with solid tumors, venous thromboembolic events can be reduced by administering low-molecular-weight heparin without an increase in the risk of bleeding complications or a change in the survival rate.
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.
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).
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
Study Shows Aortic Valve Replacement Was Associated With Better Outcomes in Patients with Low-Gradient Aortic Stenosis and Preserved Left Ventricular Ejection Fraction Compared With High-Gradient Aortic Stenosis Analysis of PARTNER 2A randomized trial and SAPIEN 3 registry
A recent study by Dr. Salaun, published in Circulation: Cardiovascular Interventions, demonstrated that aortic valve replacement in patients with the low gradient (LG, defined as mean gradient <40 mmHg) severe aortic stenosis (AS) and preserved ejection fraction (EF) has resulted in better outcomes versus in those with the high gradient (HG, defined as a mean transvalvular gradient (MG) ≥ 40 mmHg) AS. Also, the study revealed that patients with classical low flow, low gradient (CLF-LG, defined as MG <40 mmHg and LVEF <50%) AS were at higher risk of death, rehospitalization, or stroke at 2 years.
100,000 Patient Meta-Analysis Shows Carotid Intima-Media Thickness Progression Can Be Used as a Surrogate Marker for Cardiovascular Risk
A recent meta-analysis of clinical trials with more than 100,000 patients has shown that the carotid intima-media thickness (cIMT) progression can be used as a surrogate marker for cardiovascular risk in the clinical trials. The results of this study published in Circulation. According to Dr. Willeit, the assessment of cIMT progression can provide a link for the development and license of new therapies for cardiovascular disease. Continue reading
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.
SASSCAIA Trial Showed No Difference Between Intensified Prasugrel-Based and Standard Clopidogrel-Based Loading Strategies in Terms of Safety and Efficacy in Patients Undergoing Elective Percutaneous Coronary Intervention
A recent study by Dr. Julinda Mehilli, M.D., published in Circulation journal, has shown that in patients undergoing elective percutaneous coronary intervention (PCI), pretreatment strategy with the intensified prasugrel loading does not differ from standard clopidogrel loading dose in terms of Safety and Efficacy. According to the trial, both strategies can be safely applied among patients undergoing elective PCI.
Retrospective Population-Based Cohort Study Showed Increased Mortality of Cardiac Arrest Patients With Non-shockable Rhythm After Application of Targeted Temperature Management
A recent study by Dr. Khan and his colleagues, published in the American Heart Journal, has shown that the application of post-resuscitation targeted temperature management (TTM) or hypothermia protocol was associated with increased mortality in patients with non-shockable associated sudden cardiac arrest (SCA). Additionally, TTM utilization was recognized as an independent predictor of mortality in this specific group after multivariate regression analysis. Continue reading