Deciding on anticoagulating the oldest old with atrial fibrillation: insights from cost-effectiveness analysis

OBJECTIVES: To better understand the tradeoffs between the efficacy of anticoagulation with warfarin and its side effects in the oldest old with nonrheumatic atrial fibrillation (AF). DESIGN: Cost-effectiveness analysis. SETTING: Published literature, including meta-analyses when available, and web-based sources. PARTICIPANTS: Those aged 65 to 100 with AF. INTERVENTION: Anticoagulation with warfarin. MEASUREMENTS: Quality-adjusted life expectancy and cost. RESULTS: Anticoagulation is not effective in persons with AF who do not have other risk factors, even in the oldest old. The best argument for its use (prolongation of life at an acceptable cost) can be made in those at major risk for stroke because of previous stroke or transient ischemic attack, diabetes mellitus, and hypertension, but poor quality of life before anticoagulation and comorbidities that carry their own risks of dying diminish benefits. The decision to anticoagulate the oldest old with AF must take into consideration the risk of hemorrhagic stroke and of death from hemorrhagic stroke that existed before anticoagulation, the increased risk of hemorrhagic stroke and of death from hemorrhagic stroke while anticoagulated, and the efficacy of anticoagulation. Cost-effectiveness is also influenced by the cost of warfarin, the risk of major extracranial bleeding, the risk (natural and anticoagulated) of death from hemorrhagic stroke, the rate of ischemic stroke, the cost of major extracranial bleeding and hemorrhagic strokes, the cost of nursing home care, and the fraction of patients with stroke who need nursing home care. CONCLUSION: There is no compelling evidence to date that anticoagulation prolongs quality-adjusted life expectancy in the oldest old with nonrheumatic AF. More studies that better estimate the risk of intracranial bleeding with and without anticoagulation in the oldest old are needed before recommendations can be made. The oldest old who are most likely to benefit are those who have a high risk of stroke secondary to risk factors other than age alone, although quality of life and life expectancy related to these risk factors limit obtained benefit. Recommendations that all older persons with AF should be anticoagulated are premature.     

Association between lifetime risk of atrial fibrillation and mortality in the oldest old

Background

Age is the strongest predictor of atrial fibrillation (AF), yet little is known about AF incidence in the oldest old.

Hypothesis

AF incidence declines after age 90 years, and morbidity is compressed into a brief period at the end of life.

Methods

In this retrospective, longitudinal cohort study of patients (born 1905–1935), we examined cumulative lifetime incidence of AF and its impact on mortality. Data included records from 1 062 610 octogenarians, 317 161 nonagenarians, and 3572 centenarians. Kaplan–Meier curves were used to estimate cumulative incidence of AF by age group, incidence rates were compared using log‐rank tests, and Cox proportional hazards model was used to estimate unadjusted hazard ratios. The primary outcome was AF incidence at age > 80 years; the secondary outcome was mortality.

Results

The cumulative AF incidence rate was 5.0% in octogenarians, 5.4% in nonagenarians, and 2.3% in centenarians. Octogenarians and nonagenarians had a higher risk of AF incidence compared to centenarians (adjusted hazard ratio 8.74, 95% confidence interval [CI]: 6.31–12.04; and 2.98, 95% CI: 2.17–4.1, respectively). The lowest hazard ratio for mortality in patients with AF compared to those without was 2.3 (95% CI: 2.3–2.4) in patients who were on antiplatelet and anticoagulant medication and had a score of 0 on the Elixhauser comorbidity index score.

Conclusions

Although AF incidence increased with age, being a centenarian was associated with reduced incidence and compression of morbidity. Patients with AF had a higher adjusted mortality rate. However, data suggest that a regimen of anticoagulants and antiplatelets may reduce risk of mortality in patients over 80 with an AF diagnosis.     

Between Scylla and Charybdis: antithrombotic therapy in hematopoietic progenitor cell transplant patients

Patients who undergo hematopoietic progenitor cell transplant may require antithrombotic therapy for a variety of reasons-history of vascular events or developing new ones during therapy. For patients with arterial disease, use of antiplatelet therapy is based on acuity. For primary prevention of an arterial event, aspirin can be withheld at the start of transplant. On the other hand, in the face of a patient experiencing an acute myocardial infarction, aspirin should be given, no matter what the degree of thrombocytopenia is. Patients with cardiac 'hardware'-stents and mechanical valves-pose difficult issues because as higher risk patients (especially patients with recent implantation of a drug eluting stent) they require more aggressive anticoagulation, even in the face of severe thrombocytopenia. Anticoagulation with heparin is dependent on the platelet count with full dose recommended for a platelet count over 50 × 10(9)/L and prophylactic dosing with platelets in the 20-50 × 10(9)/L range. If the patient develops a distal venous thrombosis, then simple observation can be used, but more proximal thrombosis or pulmonary embolism requires consideration of anticoagulation. Central venous catheter thrombosis is best treated by line removal, as the risk of bleeding is high if the device is left in. The advent of new anticoagulants with minimal drug and food interactions may offer better choices for therapy for these difficult patients. This is also an area in which clinical trials would be helpful to clarify the treatment choices.     

Left atrial function and mortality in the oldest old

Background

Previous studies demonstrated that left atrium (LA) size is associated with mortality in an elderly population. It remains unclear whether indices of LA function including reservoir, conduit, or booster elements of LA function provide incremental prognostic information.

Hypothesis

Echocardiographic measures of the various parameters of LA function would predict 5‐year mortality in a community‐dwelling population of 85 to 86 year olds independently of LA volume.

Methods

Subjects ages 85 to 86 years old underwent home echocardiography. LA volumes were assessed by the biplane Simpson's method from apical views using measurements of phasic volumes and functions of the LA, including LA expansion index. LA passive and active emptying fractions were assessed. Survival status at 5‐year follow‐up was assessed.

Results

Two hundred eighty‐two subjects were included, of whom 87 (31%) had died at follow‐up. Survival of the subjects in the lowest quartile of the LA expansion index as well as LA active filling index was significantly lower. When measurements of LA volume index were added to the model, the relationship between survival and indices of LA function remained significant.

Conclusions

This study demonstrated that elderly subjects aged 85 to 86 years with significantly impaired LA function had increased 5‐year mortality independently of indices of LA volume.

     

Between Scylla and Charybdis:The role of the human immune system in the pathogenesis of hepatitis C

Hepatitis C virus(HCV)frequently elicits only mild immune responses so that it can often establish chronic infection.In this case HCV antigens persist and continue to stimulate the immune system.Antigen persistence then leads to profound changes in the infected host’s immune responsiveness,and eventually contributes to the pathology of chronic hepatitis.This topic highlight summarizes changes associated with chronic hepatitis C concerning innate immunity(interferons,natural killer cells),adaptive immune responses(immunoglobulins,T cells,and mechanisms of immune regulation(regulatory T cells).Our overview clarifies that a strong anti-HCV immune response is frequently associated with acute severe tissue damage.In chronic hepatitis C,however,the effector arms of the immune system either become refractory to activation or take over regulatory functions.Taken together these changes in immunity may lead to persistent liver damage and cirrhosis.Consequently,effector arms of the immune system will not only be considered with respect to antiviral defence but also as pivotal mechanisms of inflammation,necrosis and progression to cirrhosis.Thus,avoiding Scylla-a strong,sustained antiviral immune response with inital tissue damage-takes the infected host to virus-triggered immunopathology,which ultimately leads to cirrhosis and liver cancerthe realm of Charybdis.     

Elevated lipoprotein(a) and familial hypercholesterolemia in the coronary care unit: Between Scylla and Charybdis

Background

Elevated lipoprotein(a) (Lp[a]) and familial hypercholesterolemia (FH) are inherited lipid disorders. Their frequencies, coexistence, and associations with premature coronary artery disease (CAD) in patients admitted to the coronary care unit (CCU) remain to be defined.

Hypothesis

Elevated Lp(a) and FH are commonly encountered among CCU patients and independently associated with increased premature CAD risk.

Methods

Plasma Lp(a) concentrations were measured in consecutive patients admitted to the CCU with an acute coronary syndrome (ACS) or prior history of CAD for 6.5 months. Elevated Lp(a) was defined as concentrations ≥0.5 g/L. Patients with LDL‐C ≥ 5 mmol/L exhibited phenotypic FH. Premature CAD was diagnosed in those age < 60 years, and the relationship between this and elevated Lp(a) and FH was determined by logistic regression.

Results

316 patients were screened; 163 (51.6%) had premature CAD. Overall, elevated Lp(a) and FH were identified in 27.0% and 11.6% of patients, respectively. Both disorders were detected in 4.4% of individuals. Elevated Lp(a) (32.0% vs 22.2%; P = 0.019) and FH phenotype (15.5% vs 8.0%; P = 0.052) were more common with premature vs nonpremature CAD. Elevated Lp(a) alone conferred a 1.9‐fold, FH alone a 3.2‐fold, and the combination a 5.3‐fold increased risk of premature CAD (P = 0.005).

Conclusions

Elevated Lp(a) and phenotypic FH were commonly encountered and more frequent with premature CAD. The combination of both disorders is especially associated with increased CAD risk. Patients admitted to the CCU with ACS or previously documented CAD should be routinely screened for elevated Lp(a) and FH.     

Vitamin C neglect in hemodialysis: sailing between Scylla and Charybdis

In our efforts to meet the vitamin C requirements of dialysis patients we confront a medical dilemma--do we allow the patient to become depleted of vitamin C, with the accompanying hematological and other consequences (Scylla), or do we provide for adequate tissue levels of vitamin C, which has been thought to carry the risk of oxalosis (Charybdis). Many practitioners are certain that either one outcome (deficiency) or the other (oxalic acid toxicity) is inevitable, and much like Odysseus, no safe course is to be found. The recent accumulating evidence that vitamin C improves the management of anemia in dialysis patients compels us to find a safe passage through this dilemma. The serious vitamin C deficiency seen in many patients may also contribute to poor oral health and chronic fatigue. The evidence for oxalosis from vitamin C supplements stems from hemodialysis as practiced 20 years ago. Investigators using this therapy are not observing systemic oxalosis, and the most current data support the conclusion that vitamin C therapy is safe for dialysis patients. The question will be resolved by controlled trials that address both vitamin C effectiveness and safety.     

老年心房颤动患者的华法林抗凝治疗

脑卒中是严重威胁我国老年人群健康的主要疾病之一,规范的抗凝治疗可以显著减少与心房颤动(房颤)相关的心源性脑卒中的发生率。现对老年房颤患者的华法林抗凝治疗的有关问题作一阐述。1老年房颤的流行病学房颤是最常见的心律失常。在美国,约有230万房颤患者,每年因房颤住院的患