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.

Treatment with Anti-PCSK9 Monoclonal Ab: Experience from a Lipid Clinic in Israel.

BACKGROUND: There is an increasing use of anti-protein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs); however, real-world data is lacking. OBJECTIVES: To define the demographic and clinical characteristics of patients treated with anti-PCSK9 mAbs. To evaluate efficacy, tolerability, and differences between the approved agents. METHODS: A retrospective cohort study was conducted of patients treated at the lipid clinic at Rabin Medical Center (Beilinson Campus), Israel, from January 2016 to December 2019. Data from electronic records were evaluated for demographic and clinical characteristics, indication for use, response of lowering low-density lipoprotein cholesterol (LDL-C)/non-high-density lipoprotein cholesterol (non-HDL-C) levels and reaching target levels, side effects, tolerability, differences between the agents, and doses. RESULTS: The study cohort included 115 patients. Two-thirds (n=75) were at high cardiovascular risk, the rest at very high risk (n=40). The major indication for treatment was statin intolerance (n=97, 84%). Most patients (n=102, 88%) were treated by anti-PCSK9 mAbs agents only. LDL-C and non-HDL-C levels were decreased by 47% and 39%, respectively (156 + 49 to 81 + 39 and 192 + 53 to 116 + 42 mg/dl), within 6 months and remained stable. Two-thirds (n=76) of the patients reached their lipid target levels. No clinically significant differences were observed between the agents in efficacy or tolerability. CONCLUSIONS: In a real-world setting, anti-PCSK9 mAbs are used primarily as a single agent in high-risk and very high-risk cardiovascular populations with statin intolerance. They are well tolerated and effective in reduction of LDL-C levels. Further studies are needed to clarify comparisons between agents and doses.

Eyeball Test for the Assessment of Frailty in Elderly Patients With Cardiovascular Disease: A Prospective Study.

Frailty has been associated with poor outcomes in patients with cardiovascular diseases (CVDs). We aimed to assess the accuracy of the Eyeball test for frailty assessment in elderly patients with CVD. This is a prospective study including stable patients ≥75 years old who were followed-up in a cardiology clinic. Frailty assessment was performed separately through the Eyeball test and the Fried test in a blinded way. Cardiologists were asked to rate the frailty status of participants based on their routine clinical assessment and grade frailty on a Fried-type scale (1 to 5, with frailty defined as a score ≥3). Each patient then underwent formal frailty assessment using the Fried test. Included were 300 consecutive patients with a mean age of 81 ± 6 years. Frailty was diagnosed in 109 (36%) and 125 patients (41%) according to the Fried and Eyeball tests, respectively. The Eyeball test demonstrated 86% sensitivity and 82% specificity for the diagnosis of frailty. A receiver operating characteristics curve analysis demonstrated an area under the curve of 0.82 for the diagnosis of frailty. The Eyeball test demonstrated a very high negative predictive value of 90% and a modest positive predictive value of 73% for frailty assessment. Similar results were observed after subgroup analysis according to age and gender. In conclusion, the Eyeball test is an accurate method to rule out frailty in elderly patients with CVD. However, when frailty is suspected based on the Eyeball test, a formal tool such as the Fried test should be used to confirm the diagnosis.

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.