The researchers found that the number of patients with suspected PE in whom imaging can be withheld has increased, because of use of an age-adjusted D-dimer threshold. D-dimer is a sensitive marker for VTE. Furthermore, the Pulmonary Embolism Rule-Out Criteria safely exclude PE without imaging when the pretest probability is low.

In fact, the authors found that imaging can be excluded in 29 percent of patients with suspected deep vein thrombosis (DVT) and in 28 percent of those with suspected pulmonary embolism (PE) by using diagnostic algorithms including pretest probability assessment and D-dimer testing. For the remaining patients, compression ultrasonography or computed tomography pulmonary angiography (CTPA) is necessary to determine the presence of VTE.

The YEARS diagnostic algorithm – aimed at simplifying the diagnosis of suspected PE – includes the presence of clinical signs of DVT, presence of hemoptysis, determination of PE to be the most likely diagnosis and D-dimer level at two different thresholds. PE is excluded if none of these criteria are present and the D-dimer level is <1,000 ng/mL or if there are one more of these criteria present and the D-dimer level is <500 ng/mL. However, the evidence is limited and the authors state further validation is needed before YEARS is used in clinical practice.

Other diagnostic advances include emergency physicians performing prompt compression ultrasonography of the proximal veins having a good overall diagnostic accuracy, with the caveat of operator experience. Magnetic resonance veno-graphy may have a role in specific populations where compression ultrasonography is not feasible, e.g., morbidly obese patients.

Ventilation/perfusion (V/Q) SPECT is an emerging technology with potential diagnostic accuracy similar with CT angiography in acute PE without using intravenous contrast, but requires further validation and is not ready for routine clinical practice yet.

Among the therapeutic advances is the finding that direct oral anticoagulants (DOACs) are noninferior to vitamin K antagonists (VKAs) for prevention of recurrent VTE in all-comers. However, VKAs are preferred in patients with severe renal impairment or there are significant drug-drug interactions with DOACs.

In patients with noncancer-provoked VTE, anticoagulation is recommended for three months. In patients with cancer-associated VTE, anticoagulation may be given until the cancer is cured. The DOACs edoxaban or rivaroxaban are noninferior to low-molecular weight heparin in cancer patients.

New reversal agents for DOACs are now approved (idarucizumab for dabigatran; andexanet-alfa for apixaban and rivaroxaban). However, cessation of therapy and supportive care may be sufficient in most bleeding events with DOACs. Currently there is insufficient evidence to support the use of DOACs in patients with antiphospholipid syndrome, heparin-induced thrombocytopenia or venous thrombosis at unusual sites, such as splanchnic vein thrombosis.

Recurrent VTE prevention management after an unprovoked first VTE differs by gender. First, unprovoked VTE in men warrants indefinite anticoagulation in low bleeding risk scenarios. Serially measured D-dimer levels and HERDOO2 clinical decision rule can guide discontinuation of extended anticoagulation in women.

For patients with isolated distal DVT, ultrasound surveillance only to monitor thrombus extension is preferred over anticoagulation, according to the 2016 American College of Chest Physicians guidelines. Compression stockings are not recommended to treat DVT, but may be used when acute or chronic symptoms are present.

The authors write that the lack of a bleeding risk score that has been prospectively validated in a management study remains an important knowledge gap in making decisions regarding anticoagulation treatment in unprovoked VTE. Bleeding risk assessment should be improved in the future to tailor individual treatment strategies.

Tritschler T, Kraaijpoel N, Le Gal G, Wells PS. JAMA 2018;320:1583-94.

<<< Return to Top

A total of 29,069 patients (mean age 62 years, 28 percent women) were included, and 5,751 events were identified over 95,576 person-years. Associations of baseline and on-statin treatment lipoprotein(a) with cardiovascular disease risk were approximately linear, with increased risk at lipoprotein(a) values of ≥30 mg/dL for baseline lipoprotein(a) and ≥50 mg/dL for on-statin lipoprotein(a).

Initiation of statin therapy reduced LDL-C (mean change –39 percent) without a significant change in lipoprotein(a). Compared with baseline lipoprotein(a) <15 mg/dL, the risk of events increased as the lipoprotein(a) level increased, with an age- and sex-adjusted hazard ratio (HR) of 1.04, 1.11 and 1.30 for the 15 to <30 mg/dL, 30 to <50 mg/dL and ≥50 mg/dL groups, respectively.

For patients on statin therapy, the HRs were 0.94, 1.06 and 1.43, respectively, vs. <15 mg/dL. HRs were nearly identical after further adjustment for previous cardiovascular disease, diabetes, smoking, systolic blood pressure, LDL-C and HDL-C.

The authors conclude these findings suggest a need for evaluating drugs that can specifically lower lipoprotein(a) and may also reduce residual cardiovascular risk independent of statin treatment. Further, these data provide a rationale for testing the lipoprotein(a) lowering hypothesis in cardiovascular disease outcomes trials.

Willeit P, Ridker PM, Nestel PJ, et al. Lancet 2018;392:1311-20.

<<< Return to Top

Mandy Geserick, MSc, et al., found that a majority of the adolescents with normal weight had always had a normal weight throughout childhood. A majority of the adolescents who were obese had a normal weight as infants, but were overweight or obese by the time they were five years old. Among these children, the BMI standard-deviation score further increased with age. Almost 90 percent of the children who were obese at three years of age were overweight or obese in adolescence.

Among the adolescents who were obese, the greatest acceleration in annual BMI increments had occurred between two and six years of age, with a further rise in BMI percentile thereafter. High acceleration in annual BMI increments during the preschool years (but not during the school years) was associated with a risk of overweight or obesity in adolescence that was 1.4-times as high as the risk among children who had had a stable BMI.

The rate of overweight or obesity in adolescence was higher among children who had been large for gestational age at birth (43.7 percent) than among those who had been at an appropriate weight for gestational age (28.4 percent) or small for gestational age (27.2 percent), which corresponded to a risk of adolescent obesity that was 1.55-times as high among those who had been large for gestational age as among the other groups.

"A practical clinical implication of our study results would be surveillance for BMI acceleration, which should be recognized before six years of age, even in the absence of obesity," the authors write. "The tracking of growth and weight patterns, particularly in children with predisposing factors (e.g., maternal overweight or large-for-gestational-age status at birth), may help to identify children at increased risk and prompt early intervention even before overweight is evident. It is therefore important for health care professionals, educational staff, and parents to become more sensitive to this critical time period."

Geserick M, Vogel M, Gausche R, et al. N Engl J Med 2018;379:1303-12.

<<< Return to Top

The current analysis assessed outcomes stratified by baseline estimated glomerular filtration rate (eGFR; <60 vs. ≥60 ml/min/1.73 m2) and baseline albuminuria. Overall, 2,158 and 7,182 patients had baseline eGFR <60 or >60 ml/min/1.73 m2, respectively.

The primary outcome (composite of cardiovascular death, nonfatal myocardial infarction [MI] or nonfatal stroke) and secondary outcomes (including all-cause mortality and individual components of the primary composite outcome) were analyzed using Cox regression.

The primary composite outcome occurred in a lower proportion of patients taking liraglutide than placebo for both eGFR groups. Among patients with an eGFR <60 ml/min/1.73 m2, the rates were 15.4 vs. 21.4 percent, respectively, and among patients with an eGFR >60 ml/min/1.73 m2 the rates were 12.3 vs. 13.0 percent.

Risk reduction for the primary composite cardiovascular outcome with liraglutide was greater in patients with eGFR <60 ml/min/1.73 m2 (hazard ratio [HR], 0.69; 95 percent confidence interval [95 percent CI], 0.57-0.85) vs. eGFR ≥60 ml/min/1.73 m2 (HR, 0.94; 95 percent CI, 0.83-1.07; interaction p=0.01).

No consistent effect for modification with liraglutide was seen across finer eGFR subgroups (interaction p=0.13) and when analyzing eGFR as a continuous variable (interaction p=0.61). Risk reductions in patients with eGFR <60 vs. ≥60 ml/min/1.73 m2 were: nonfatal MI, HR, 0.74 vs. HR, 0.93; nonfatal stroke, HR, 0.51 vs. HR, 1.07; CV death, HR, 0.67 vs. HR, 0.84; all-cause mortality, HR, 0.74 vs. 0.90.

Risk reduction for the primary composite cardiovascular outcome was not different for those with vs. without baseline albuminuria (HR, 0.83 vs. HR, 0.92; interaction p=0.36). "These findings are important given that evidence consistently shows that patients with diabetes and low eGFR and/or elevated albuminuria experience substantially greater cardiovascular morbidity and mortality than those with diabetes and normal eGFR and albuminuria," the authors write.

Mann JF, Fonseca V, Mosenzon O, et al. Circulation 2018; Oct 3:[Epub ahead of print].

<<< Return to Top