Israel Medical Association Journal

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.

Objective: 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.

Conclusion: PCSK9 mAbs have similar effects and are well tolerated among elderly patients as in younger patients.

Background: Statin-induced myalgia is defined as muscle pain without elevation of serum creatine phosphokinase levels and is a well-known complaint among statin users. Chronic pain syndromes affect a high percentage of the population. These pain syndromes may confound the reports of statin-induced myalgia.

Objectives: To compare the occurrence of chronic pain among patients on statin therapy who developed myalgia with those who did not.

Methods: This study included 112 statin-treated patients, who were followed at the lipid center at Sheba Medical Center. Fifty-six patients had a diagnosis of statin-associated muscle symptoms (SAMS) and 56 did not. Verified questionnaires were used to assess the diagnoses of fibromyalgia, pain intensity, functional impairment, anxiety, and depression in the study population.

Results: Patients with statin myalgia were more likely to fulfil the diagnostic criteria for fibromyalgia than patients without statin myalgia (11 [19.6%] vs. 0, respectively). Patients in the SAMS group exhibited higher levels of anxiety and depression compared with the control group. Female sex, higher scores on the Brief Pain Inventory pain intensity scale, and a Hamilton rating scale level indicative of an anxiety disorder were found to be significant predictors for fibromyalgia in patients presenting with statin myalgia.

Conclusions: A significant percentage of patients diagnosed with statin myalgia fulfilled the diagnostic criteria for fibromyalgia depression or anxiety disorder. Detection of these patients and treatment of their primary pain disorders or psychiatric illnesses has the potential to prevent unnecessary cessation of effective statin therapy.

Background: Statins have anti-inflammatory effects that are independent of their lipid-lowering activity.

Objectives: To examine whether prior statins therapy affects the clinical course of the first episode of acute idiopathic pericarditis (AIP) as the 1-year recurrence and length of hospitalization (LOH).

Methods: This retrospective study included 148 subjects with first episode AIP admitted between the years 2015 and 2019. Data were collected from two hospitals in Northern Israel. We divided the patients in into two groups: 117 those without statins use and 31 those with prior statins use. We compared age, sex, co-morbidities, drugs, laboratory data, 1-year recurrence, and LOH.

Results: The mean age of participants was 43.1 ± 19.4 years. Comparisons between subjects without statins and with prior statins use were made according to age (37.5 ± 16.7 years vs. 64.4 ± 12.7 years, P < 0.01), C-reactive protein (50 ± 40 vs. 48 ± 35 mg/dl, P = 0.9), LOH (5.4 ± 2.85 vs. 8.03 ± 4.92 days, P < 0.01), 1-year recurrence of pericarditis (23 vs. 6 cases, P = 0.95), respectively. Multivariate logistic regression analysis revealed that 1-year recurrence (odds ratio [OR] 0.8, 95% confidence interval [95%CI 0 0.6–1.1, P = 0.41), was not associated with prior statin use, while LOH (OR 2.56, 95%CI 2.08–2.75, P = 0.01) was prolonged with prior statins use in patients with first episode of AID.

Conclusions: Prior statins use in patients with the first episode of AIP did not reduce the 1-year recurrence of pericarditis and prolong the LOH.

Background: Statins and selective serotonin reuptake inhibitors (SSRIs) have beneficial effects on health outcomes in the general population. Their effect on survival in debilitated nursing home residents is unknown.

Objectives: To assess the relationships between statins, SSRIs, and survival of nursing home residents.

Methods: Baseline patient characteristics, including chronic medications, were recorded. The association of 5-year survival with different variables was analyzed. A sub-group analysis of survival was performed according to baseline treatment with statins and/or SSRIs.

Results: The study comprised 993 residents from 6 nursing homes. Of them, 285 were males (29%), 750 (75%) were fully dependent, and 243 (25%) were mobile demented. Mean age was 85 ± 7.6 years (range 65–108). After 5 years follow-up, the mortality rate was 81%. Analysis by sub-groups showed longer survival among older adults treated with only statins (hazard ratio [HR] for death 0.68, 95% confidence intervals [95%CI] 0.49–0.94) or only SSRIs (HR 0.6, 95%CI 0.45–0.81), with the longest survival among those taking both statins and SSRIs (HR 0.41, 95%CI 0.25–0.67) and shortest among residents not taking statins or SSRIs (P < 0.001). The survival benefit remained significant after adjusting for age and after conducting a multivariate analysis adjusted for sex, functional status, body mass index, mini-mental state examination, feeding status, arrhythmia, diabetes mellitus, chronic kidney disease, and hemato-oncological diagnosis.

Conclusion: Treatment with statins and/or SSRIs at baseline was associated with longer survival in debilitated nursing home residents and should not be deprived from these patients, if medically indicated. 

Background: The salutary effects of statin therapy in patients with cardiovascular disease (CVD) are well established. Although generally considered safe, statin therapy has been reported to contribute to induction of diabetes mellitus (DM).

Objectives: To assess the risk-benefit of statin therapy, prescribed for the prevention of CVD, in the development of DM.

Methods: In a population-based real-life study, the incidence of DM and CVD were assessed retrospectively among 265,414 subjects aged 40–70 years, 17.9% of whom were treated with statins. Outcomes were evaluated according to retrospectively determined baseline 10 year cardiovascular (CV) mortality risks as defined by the European Systematic COronary Risk Evaluation, statin dose-intensity regimen, and level of drug adherence.

Results: From 2010 to 2014, 5157 (1.9%) new cases of CVD and 11,637 (4.4%) of DM were observed. Low-intensity statin therapy with over 50% adherence was associated with increased DM incidence in patients at low or intermediate baseline CV risk, but not in patients at high CV risk. In patients at low CV risk, no CV protective benefit was obtained. The number needed to harm (NNH; incident DM) for low-intensity dose regimens with above 50% adherence was 40. In patients at intermediate and high CV risk, the number needed to treat was 125 and 29; NNH was 50 and 200, respectively.

Conclusions: Prescribing low-dose statins for primary prevention of CVD is beneficial in patients at high risk and may be detrimental in patients at low CV risk. In patients with intermediate CV risk, our data support current recommendations of individualizing treatment decisions.

Background: While earlier studies indicated that cholesterol levels decrease significantly after an acute myocardial infarction (MI), a more recent study refuted this observation. 

Objectives: To assess changes in plasma lipid levels after onset of acute MI, and determine important predictors of lipid dynamics.

Methods: We prospectively measured lipid levels of patients who presented with an acute MI. Blood samples were drawn on admission to the hospital (day 1), after fasting at least 12 hours overnight (day 2), and on the 4th day of hospitalization (day 4). 

Results: Of 67 acute MI patients, 30 were admitted for ST elevation MI (STEMI) and 37 for non-STEMI. Both total cholesterol and low density lipoprotein cholesterol (LDL-C) levels decreased significantly (by 9%) in the 24 hours after admission and by 13% and 17% respectively on day 4. High density lipoprotein cholesterol (HDL-C) levels as well as triglycerides did not change significantly. Independent predictors of LDL-C decrease were the presence of diabetes mellitus [odds ratio (OR) 6.73, P = 0.01), and elevated cardiac troponin T (cTnT) levels (OR 1.81, P < 0.04).

Conclusions: LDL-C levels decrease significantly after an acute MI. The reduction is correlated with cTnT levels. Diabetes is a strong independent predictor of LDL-C decrease. In acute MI patients only measurements taken within 24 hours of onset should be used to guide selection of lipid-lowering medication.

 

Objectives: To determine if low plasma vitamin D level is a risk factor for MAEs in statin users.

Methods: Plasma levels of 25(OH) vitamin D were measured as part of the routine evaluation of unselected statin-treated patients attending the coronary and lipid clinics at our hospital during the period 2007–2010. Medical data on muscle complaints and statin use were retrieved from the medical files. Creatine kinase (CK) levels were derived from the hospital laboratory database.

Results: The sample included 272 patients (141 men) aged 33–89 years. Mean vitamin D level was 48.04 nmol/L. Levels were higher in men (51.0 ± 20.5 vs. 44.7 ± 18.9 nmol/L, P = 0.001) and were unaffected by age. MAEs were observed in 106 patients (39%): myalgia in 95 (35%) and CK elevation in 20 (7%); 11 patients (4%) had both. There was no difference in plasma vitamin D levels between patients with and without myalgia (46.3 ± 17.7 vs. 48.9 ± 21.0 nmol/L, P = 0.31), with and without CK elevation (50.2 ± 14.6 vs. 47.8 ± 20.3 nmol/L, P = 0.60), or with or without any MAE (50.4 ± 15.0 vs. 47.8 ± 10.2 nmol/L, P = 0.27). These findings were consistent when analyzed by patient gender and presence/absence of coronary artery disease, and when using a lower vitamin D cutoff (< 25 nmol/L).

Conclusions: There is apparently no relationship between plasma vitamin D level and risk of MAEs in statin users.

Background: There is a wide treatment gap between evidence-based guidelines and their implementation in primary care.

Objective: To evaluate the extent to which physicians "literally" follow guidelines for secondary prevention of dyslipidemia and the extent to which they practice "substitute" therapeutic measures.

Methods: We performed a post hoc analysis of data collected in a prospective cluster randomized trial. The participants were 130 primary care physicians treating 7745 patients requiring secondary prevention of dyslipidemia. The outcome measure was physician "literal" adherence or "substitute" adherence. We used logistic regressions to evaluate the effect of various clinical situations on “literal” and “substitute” adherence.

Results: "Literal" adherence was modest for ordering a lipoprotein profile (35.1%) and for pharmacotherapy initiations (26.0%), but rather poor for drug up-titrations (16.1%) and for referrals for specialist consultation (3.8%). In contrast, many physicians opted for "substitute" adherence for up-titrations (75.9%) and referrals for consultation (78.7%). Physicians tended to follow the guidelines “literally” in simple clinical situations (such as the need for lipid screening) but to use "substitute" measures in more complex cases (when dose up-titration or metabolic consultation was required). Most substitute actions were less intense than the actions recommended by the guidelines.

Conclusions: Physicians often do not blindly follow guidelines, but rather evaluate their adequacy for a particular patient and adjust the treatment according to their assessment. We suggest that clinical management be evaluated in a broader sense than strict guideline adherence, which may underestimate physicians' efforts.
 

Pulmonary epithelioid hemangioendothelioma (PEH), previously known as "intravascular bronchoalveolar tumor," is a rare vascular malignancy with an unpredictable prognosis. Treatment can vary from observation in asymptomatic patients to surgery in patients with resectable disease or chemotherapy in patients with disseminated disease. This report describes the clinical, radiological and pathological features of three cases of PEH and a review of the current literature.
 

Background: High sensitivity C-reactive protein, a marker of inflammation, has been proposed to stratify coronary artery disease risk and is lowered by HMG-CoA reductase (statin) therapy. However, the reproducibility of persistently elevated hs-CRP[1] levels and association with other markers of inflammation in patients with stable CAD[2] on aggressive statin therapy is unknown.

Objectives: To determine the reproducibility of hs-CRP levels measured within 2 weeks in patients with documented CAD with stable symptoms and to identify associations with other markers of inflammation.

Methods: Levels of hs-CRP were measured twice within 14 days (7 ± 4) in 23 patients (22 males and 1 female, average age 66 ± 10 years) with stable CAD and hs-CRP ≥ 2.0 mg/L but ≤ 10 mg/L at visit 1. All patients had received statins for cholesterol management (low density lipoprotein-cholesterol 84 ± 25 mg/dl) with no dose change for > 3 months. None had a history or evidence of malignancy, chronic infection or inflammation, or recent trauma. There was no change in medications between visits 1 and 2, and no patient reported a change in symptoms or general health during this interval. White blood cell count and pro- and anti-inflammatory cytokines were measured at both visits.

Results: hs-CRP levels tended to be lower at visit 2 (median 2.4 mg/L, range 0.8–11 mg/L) than at visit 1 (median 3.3 mg/L, range 2.0–9.7 mg/L; P = 0.1793). However, between the two visits hs-CRP levels decreased by more than 1.0 mg/L in 10 patients and increased by more than 1.0 mg/L in 4 patients. Changes in hs-CRP levels were unrelated to changes in levels of white blood cells (P = 0.4353). Of the cytokines tested, only the anti-inflammatory cytokine interleukin-1 receptor antagonist and the pro-inflammatory cytokine interleukin-8 were above lower limits of detection, but there were no correlations between changes in these values and changes in hs-CRP (both P > 0.5).

Conclusions: In stable CAD patients on aggressive statin therapy, hs-CRP levels may fluctuate over brief periods in the absence of changes in health, cardiac symptom status and medications, and without corroboration with other measures of inflammation. Accordingly, elevated hs-CRP levels should be interpreted with caution in this setting.