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: 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: 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.
 

Epidemiologic data demonstrate a long-linear realationship between low density lipoprotein-cholesterol levels and risk of coronary heart disease.

Background: Hypertension is considered resistant if blood pressure cannot be reduced to <140/90 mmHg with an appropriate triple-drug regimen, including an oral diuretic, with all agents administered at maximal dosages. This definition has evolved with the development of new therapies and evidence-based data supporting treatment to lower BP[1] goals.

Objective: To assess whether vitamin C and atorvastatin improve endothelial function and blood pressure control in subjects with resistant arterial hypertension and dyslipidemia.

Methods: Forty-eight hyperlipidemic subjects with RH[2] (office systolic BP >140 mmHg and/or office diastolic BP >90 mm/Hg notwithstanding antihypertensive treatment with three medications in maximal doses) were randomized into three groups to receive additional medication for 8 weeks. Group VTC (n = 17) – mean 24 hour SBP[3] 150.6 ± 5.2 mmHg, DBP[4] 86.1 ± 3.3 mmHg, low density lipoprotein 158.1 ± 24.5 mg/dl) – received vitamin C 500 mg per day; Group ATR (n = 15) – mean 24 hour SBP 153.1 ± 4.8 mmHg, DBP 87.1 ± 6.7 mmHg, LDL[5] 162.6 ± 13.6 mg/dl) – received atorvastatin 20 mg/day; and Group PLA (n = 16) – mean 24 hour SBP 151.1 ± 7.4 mmHg, DBP 84.8 ± 5.9 mmHg, LDL 156.7 ± 26.1 mg/dl – received a placebo. High resolution ultrasound was used to calculate brachial artery flow-mediated dilation, and 24 hour ambulatory BP monitoring was performed at study entry and after 8 weeks.

Results: In the ATR group there were significant reductions of SBP (DSBP1-2: 13.7 ± 5.6 mmHg, P < 0.001), DBP (DDBP1-2: 7.8 ± 5.7 mmHg, P < 0.01), LDL (DLDL1-2: 67.7 ± 28.3 mg/dl, P < 0.001) and improvement of brachial artery FMD[6] (DFMD2-1: 4.2 ± 2.6%). No significant changes in BP, LDL and FMD were observed in the other two groups.

Conclusions: In subjects with RH and dyslipidemia, atorvastatin 20 mg/day compared to vitamin C 500 mg/day may help to achieve better BP control and improve endothelial function in a finite period. A larger trial is needed to assess the drug's efficacy in this population for longer periods.

Background: Elevated fibrinogen levels are considered a risk factor for the development of atherosclerosis and might be used as a predictor of risk for the development of atherothrombotic events. Several studies have reached equivocal conclusions regarding the effect of statins on fibrinogen.

Objectives: To evaluate the effect of atorvastatin on plasma fibrinogen levels in patients with severe hypercholesterolemia and no other risk factors.

Methods: Twenty-two patients with low density lipoprotein-cholesterol levels above 170 mg/dl (4.40 mmol/L) and with no other risk factors were included in the study. None of the patients had ever received hypolipidemic medication. Patients were followed for 24 weeks (6 office visits 4 weeks apart). During office visits, lipid profile, complete blood count, fibrinogen and C-reactive protein levels were measured.

Results: After 24 weeks of follow-up, total cholesterol decreased by 33% (287 ± 10 to 192 ± 8 mg/dl, P < 0.001), LDL-C[1] by 45% (198 ± 8 to 111 ± 7 mg/dl, P < 0.001) and triglycerides by 21% (189 ± 26 to 138 ± 15 mg/dl, P <0.001). Fibrinogen levels dropped by 18% (355 ± 26 to 275 ± 7 mg/dl, P = 0.01). CRP[2] levels decreased from 0.51 ± 0.15 to 0.28 ± 0.10 mg/dl, but the difference was not statistically significant (P = 0.09). High density lipoprotein, hemoglobin, white blood cell and platelet counts did not change.

Conclusions: We found that atorvastatin reduces plasma fibrinogen in patients with hypercholesterolemia.

Background: The implementation of treatment guidelines is lacking worldwide.

Objectives: To examine whether follow-up in a specialized lipid clinic improves the achievement rate of the treatment guidelines, as formulated by the National Cholesterol Education Program and the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Methods: The study group included patients who were referred to the lipid clinic because of hyperlipidemia. At each of five visits over a 12 month period, lipid levels, liver and creatine kinase levels, body mass index, and adherence to diet and medications were measured, and achievement of the NCEP[1] target level was assessed.

Results: A total of 1,133 patients (mean age 61.3 years, 60% males) were studied. Additional risk factors for atherosclerosis included hypertension (41%), type II diabetes mellitus (21%), smoking (17%), and a positive family history of coronary artery disease (32%). All patients had evidence of atherosclerotic vascular disease (coronary, cerebrovascular or peripheral vascular diseases). The low density lipoprotein target of <100 mg was present in only 22% of patients before enrollment, with improvement of up to 57% after the follow-up period. During follow-up, blood pressure control was improved (from 38% at the time of referral to 88% after 12 months, P < 0.001), as was glycemic control in diabetic patients (HgA₁C improved from 8.2% to 7.1% after 12 months, P < 0.001). Improved risk factor control was due to increased compliance to medication treatment (from 66% at enrollment to more than 90% after 12 months), as well as careful attention to risk factor management that translated into a change in the treatment profile during the follow-up. There was an increase in the use of the following medications: aspirin from 68% to 96%, statins from 42% to 88%, beta blockers from 20% to 40%, and angiotensin-converting enzyme inhibitors from 28% to 42%; while calcium channel blocker use decreased from 40% to 30% in patients during follow-up.

Conclusion: Follow-up of patients in a specialized clinic enhances the achievement of LDL[2]-cholesterol treatment goals as well as other risk factor treatment goals, due to increased patient compliance and increased use of medications.

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