Anti PCSK9 Monoclonal Antibody Treatment in Elderly Patients: A Real-world Clinical Experience.

BACKGROUND: The use of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) is emerging for lowering low-density lipoprotein cholesterol (LDL-C). However, real-world data is lacking for their use among elderly patients. OBJECTIVES: To define the characteristics of elderly patients treated with PCSK9 mAbs and to evaluate the efficacy and tolerability compared with younger patients. METHODS: We conducted a retrospective cohort study of elderly patients (≥ 75 years at enrollment) treated with PCSK9 mAbs for primary and secondary cardiovascular prevention. Data were retrieved for demographic and clinical characteristics; indications for treatment; agents and dosages; concomitant lipid lowering treatment; LDL-C levels at baseline, 6, 12 months, and at the end of follow up. Data also included achieving LDL-C target levels and adverse effects. RESULTS: The cohort included 91 elderly patients and 92 younger patients, mean age 75.2 ± 3.76 and 58.9 ± 7.4 years (P < 0.0001). Most patients (82%, 80%) were in high/very high-risk categories. For almost all (98%, 99%), the indication was statin intolerance, with PCSK9 mAb monotherapy the most prevalent regimen. The average follow-up was 38.1 ± 20.5 and 30.9 ± 15.8 months (P = 0.0258). Within 6 months the LDL-C levels were reduced by 57% in the elderly group and by 59% in the control group (P = 0.2371). Only 53% and 57% reached their LDL-C target levels. No clinically significant side effects were documented. CONCLUSIONS: PCSK9 mAbs have similar effects and are well tolerated among elderly patients as in younger patients.

The obesity paradox in patients with acute coronary syndromes over 2 decades - the ACSIS registry 2000-2018.

BACKGROUND: Obesity is a worldwide epidemic which is associated with major cardiovascular (CV) risk factors. Nevertheless, substantial distant data, mostly published more than a decade ago, have demonstrated an obesity paradox, where obese patients generally have a better short- and long-term prognosis than do their leaner counterparts with the same CV profile. Nonetheless, it is not fully elucidated whether the obesity paradox is still relevant in the contemporary cardiology era among patients with acute coronary syndrome (ACS). We aimed to examine temporal trends in the clinical outcomes of ACS patients by their BMI status. METHODS: Data from the ACSIS registry including all patients with calculated BMI data between the years 2002-2018. Patients were stratified by BMI groups to underweight, normal, overweight and obese. Clinical endpoints included 30d major cardiovascular events (MACE), and 1-year mortality. Temporal trends were examined in the late (2010-2018) vs. the early period (2002-2008). Multivariable models examined factors associated with clinical outcomes by BMI status. RESULTS: Among the 13,816 patients from the ACSIS registry with available BMI data, 104 were underweight, 3921 were normal weight, 6224 were overweight and 3567 were obese. 1-year mortality was highest among underweight patients (24.8%), as compared to normal weight patients (10.7%) and lowest among overweight and obese patients (7.1% and 7.5% respectively; p for trend <0.001). 30-day MACE rates followed a similar pattern (24.3% for underweight, 13.6% for normal weight, 11.6% for overweight, and 11.7% for obese; p for trend<0.001). Comparing the 2 time-periods, 30-day MACE was significantly lower in the late period in all BMI groups, but unchanged in patients who were underweight. Similarly, 1-year mortality has decreased in normal weight and obese patients but remained similarly high in underweight patients. CONCLUSIONS: In ACS patients, during 2-decades, 30-day MACE and 1-year mortality were lower among overweight and obese patients compared to underweight and even normal weight patients. Temporal trends revealed that 30-day MACE and 1-year mortality have decreased among all BMI groups other than the underweight ACS patients, among whom the adverse CV rates were consistently high. Our findings suggest that the obesity paradox is still relevant in ACS patients in the current cardiology era.

An unusual case report of transcatheter aortic valve implantation-related actinomycosis endocarditis.

Background: Actinomycosis is a chronic invasive infection caused by Actinomyces species. Actinomycosis endocarditis has been described, yet considered rare. We present the first reported transcatheter aortic valve implantation (TAVI)-related actinomycosis endocarditis. Case summary: A 70-year-old female patient, presented 4 months after TAVI with malaise and vocal-cord paralysis. She underwent computed tomography angiography which demonstrated a 28 mm pseudoaneurysm of the ascending aorta, which compressed the laryngeal nerves. Her condition rapidly deteriorated with cardiogenic shock and required an emergent surgery, which reviled a tamponade with active bleeding, due to an ascending aortic dissection. She underwent aortic valve and ascending aorta replacement. A 2 cm vegetation was found on the TAVI prosthetic valve and sent for cultures, which later revealed an Actinomyces neuii infection. Long-term intravenous ampicillin treatment was given. Discussion: This case describes a patient with endocarditis on TAVI prosthetic valve, with an unusual clinical presentation and rapid deterioration to an emergency intervention. This unique presentation of tumour-like tissue invasion is characteristic of actinomycosis, and should be suspected especially following valve replacement.

The Association between Low Levels of Low Density Lipoprotein Cholesterol and Intracerebral Hemorrhage: Cause for Concern?

Excessive levels of low-density lipoprotein cholesterol (LDL-C) in the blood are a known risk factor for atherosclerosis, and a common target of treatment for primary and secondary prevention of cerebrocardiovascular disease. As lipid lowering agents including statins, ezetimibe and anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have shown good therapeutic results, the guidelines are constantly lowering the "optimal" LDL-C goals. However, old and new data point towards an association between low LDL-C and total cholesterol and intracerebral hemorrhage (ICH). In this review we aimed to shed light on this troubling association and identify the potential risk factors of such a potential adverse reaction. With respect to the data presented, we concluded that in patients with high risk of ICH, a cautious approach and individualized therapy strategy are advised when considering aggressive LDL reduction.

Comparison of Low and Full Dose Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Renal Dysfunction (from a National Registry).

The use of direct oral anticoagulants for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) is robust. However, the efficacy and safety of different dosage in patients with renal dysfunction is still a clinical challenge. We aimed to evaluate the clinical characteristics and outcomes of patients treated with apixaban in its different doses. A multicenter prospective cohort study, where consecutive eligible apixaban or warfarin treated patients with NVAF and renal impairment, were registered. Patients were followed-up for clinical events over a mean period of 1 year. Analyses were performed according to the dose of apixaban given, with consideration to the standard indications for dose reduction. Primary outcome was a composite of 1-year mortality, stroke or systemic embolism, major bleeding and myocardial infarction, while secondary outcomes included those components separated. Among the study population (n = 2,140), risk of composite outcome was significantly lower in the high dose apixaban group (10%, n = 491) than the low dose group (18%, n = 673) and the warfarin group (18%, n = 976) p <0.001. Results of 1-year mortality were similar. Apixaban dosing analysis revealed 65% of patients were appropriately dosed, while 31% were under-dosed and 4% were over-dosed. Furthermore, 53% of patients treated with low dose apixaban were under-dosed. Propensity score analysis revealed that patients who were appropriately treated with low-dose apixaban had a trend towards better composite outcome and mortality than 1:1 matched warfarin treated patients (18% vs 24%, p = 0.09 and 16% vs 23%, p = 0.06, respectively). Overall, appropriately dosed apixaban treated patients at any dose had significantly better outcomes than matched warfarin treated patients (composite outcome probability of 13.1% vs 18.6%, p = 0.007). In conclusion, apixaban at any dose is a reasonable alternative to warfarin in patients with renal impairment, possibly associated with improved outcomes.

Apixaban in Patients with Atrial Fibrillation and Severe Renal Dysfunction: Findings from a National Registry.

BACKGROUND: Real-world information regarding the use of direct oral anticoagulants therapy and the outcome in patients with renal dysfunction is limited. OBJECTIVES: To evaluate the clinical characteristics and outcomes of patients with atrial fibrillation (AF) and severe renal dysfunction who are treated with apixaban. METHODS: A sub-analysis was conducted within a multicenter prospective cohort study. The study included consecutive eligible apixaban- or warfarin-treated patients with non-valvular AF and renal impairment (estimated glomerular filtration rate [eGFR] modification of diet in renal disease [MDRD] < 60 ml/min/BSA) were registered. All patients were prospectively followed for clinical events and over a mean period of 1 year. Our sub-analysis included the patients with 15 < eGFR MDRD < 30 ml/min/BSA. The primary outcomes at 1 year were recorded. They included mortality, stroke or systemic embolism, major bleeding, and myocardial infarction as well as their composite occurrence. RESULTS: The sub-analysis included 155 warfarin-treated patients and 97 apixaban-treated ones. All had 15 < eGFR MDRD < 30 ml/min/BSA. When comparing outcomes for propensity matched groups (n=76 per group) of patients treated by reduced dose apixaban or warfarin, the rates of the 1-year composite endpoint as well as mortality alone were higher among the warfarin group (30 [39.5%] vs. 14 [18.4%], P = 0.007 and 28 [36.8%] vs.12 [15.8%], P = 0.006), respectively. There was no significant difference in the rates of stroke, systemic embolism, or major bleeding. CONCLUSIONS: Apixaban might be a reasonable alternative to warfarin in patients with severe renal impairment.

Thrombin Generation in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The optimal antithrombotic treatment for patients with atrial fibrillation (AF) that undergo percutaneous coronary intervention (PCI) is controversial. Dual therapy (clopidogrel and a direct oral anticoagulant [DOAC]) is safer than triple therapy (warfarin, aspirin, and clopidogrel), while efficacy is unclear. We aimed to evaluate thrombin generation (TG) under dual and triple therapy. METHODS: A noninterventional prospective trial in patients with AF undergoing PCI. Patients received 4 weeks of triple therapy with aspirin, clopidogrel, and a DOAC followed by aspirin withdrawal. TG was measured in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) at 3 five to 21 points, day 1 after PCI (TIME 0), 4 weeks after PCI (TIME 1), and 2 weeks after aspirin withdrawal (TIME 2). RESULTS: Twenty-three patients (18 men, median age 78 years, 83% with acute coronary syndrome) were included. Endogenous thrombin potential (ETP) in PPP was high at TIME 0 compared with TIME 1 (ETP 3,178 ± 248 nM vs. 2,378 ± 222 nM, p = 0.005). These results remained consistent when measured in PRP. No significant difference in ETP was found before (TIME 1) and after aspirin withdrawal (TIME 2) although few patients had high ETP levels after stopping aspirin. CONCLUSIONS: TG potential is high immediately after PCI and decreases 4 weeks after PCI in patients receiving triple therapy. TG remains constant after aspirin withdrawal in most patients, suggesting that after 1 month the antithrombotic effect of dual therapy may be similar to triple therapy.

Prognosis of STEMI Patients with Multi-Vessel Disease Undergoing Culprit-Only PCI without Significant Residual Ischemia on Non-Invasive Stress Testing.

AIMS: In about 50-80% of ST-segment elevation myocardial infarction (STEMI) patients there is significant atherosclerotic disease in other coronary arteries in addition to the culprit vessel. There is substantial controversy as to the optimal revascularization approach in these patients. We sought to compare the outcomes of STEMI patients with multi-vessel disease (MVD) treated with culprit-only primary percutaneous coronary intervention (PPCI) without significant ischemia on subsequent non-invasive testing, to those of STEMI patients with single-vessel disease (SVD). METHODS AND RESULTS: Between 2001-2010, 1,540 consecutive patients treated with primary PCI for STEMI were prospectively observed and entered into a comprehensive clinical database. The primary end point was a composite of major adverse cardiac events (MACE), consisting of mortality, re-infarction and revascularization within 1 and 3 years following PPCI (excluding events occurring during the first 30 days). Patients with cardiogenic shock were excluded. The study included 720 patients with SVD and 185 patients with MVD who underwent culprit-only PPCI and had no residual ischemia on subsequent non-invasive stress testing. Patients with MVD were older, more likely to have hypertension or previous MI and less likely to be smokers and present with anterior MI than patients with SVD. One and 3-year MACE rates were similar between the groups. On cox proportional-hazards regression MVD without residual ischemia was not independently associated with MACE and its components. CONCLUSIONS: STEMI patients with MVD treated with culprit only-PCI without significant residual ischemia on non-invasive stress testing appear to have similar prognosis to STEMI patients with SVD.