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Effect of a Home-Based Exercise Intervention of Wearable Technology and Telephone Coaching on Walking Performance in Peripheral Artery Disease

Question  Among patients with lower-extremity peripheral artery disease (PAD), does a home-based exercise intervention that consists of a wearable activity monitor and telephone coaching improve walking performance?

Findings  In this randomized clinical trial of 200 participants with PAD, a wearable activity monitor combined with telephone coaching did not significantly improve 6-minute walk distance at 9 months (5.5 m in the intervention group vs 14.4 m in the usual care group).

Meaning  These results do not support home-based exercise interventions of wearable devices combined with telephone coaching to improve walking performance in patients with PAD.

Reference: JAMA. 2018;319(16):1665-1676.

Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes

Question  How do sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors compare in reducing mortality and cardiovascular events in patients with type 2 diabetes?

Findings  In this network meta-analysis that includes 236 trials with 176 310 participants, the use of SGLT-2 inhibitors or GLP-1 agonists was significantly associated with lower all-cause mortality compared with the control groups (placebo or no treatment) (hazard ratio [HR], 0.80, and HR, 0.88, respectively) and with DPP-4 inhibitors (HR, 0.78, and HR, 0.86, respectively).

Meaning  In patients with type 2 diabetes, the use of SGLT-2 inhibitors or GLP-1 agonists was associated with better mortality outcomes than DPP-4 inhibitors.

Reference: JAMA. 2018;319(15):1580-1591.

Association Between Baseline LDL-C Level and Total and Cardiovascular Mortality After LDL-C Lowering

Question  Does the magnitude of reductions in total and cardiovascular mortality after low-density lipoprotein cholesterol (LDL-C) lowering depend on the baseline LDL-C level?

Findings  In this meta-analysis of 34 randomized clinical trials that included 270 288 participants, more intensive LDL-C–lowering therapy was associated with a progressive reduction in total mortality with higher baseline LDL-C levels (rate ratio, 0.91 for each 40-mg/dL increase in baseline level); however, this relationship was not present with baseline LDL-C levels less than 100 mg/dL. There was a similar relationship for cardiovascular mortality.

Meaning  The greatest benefit from LDL-C–lowering therapy may occur for patients with baseline LDL-C levels of 100 mg/dL or greater.

Reference: JAMA. 2018;319(15):1566-1579.

Association of Inhaled Corticosteroids and Long-Acting β-Agonists as Controller and Quick Relief Therapy With Exacerbations and Symptom Control in Persistent Asthma

Question  What is the efficacy associated with using inhaled corticosteroids and long-acting β-agonists (LABAs) together as both the controller and the quick relief therapy termed single maintenance and reliever therapy(SMART) in patients with persistent asthma?

Findings  In this meta-analysis that included 22 524 patients aged 12 years or older and 341 children aged 4 to 11 years with persistent asthma, SMART was associated with a significantly lower risk of asthma exacerbations compared with a higher dose of inhaled corticosteroids and LABA as controller therapy, absolute risk difference, −2.8% for the older age group and −12.0% for the younger age group, although less robust data were available for this group.

Meaning  SMART was associated with better clinical outcomes than conventional approaches in patients with persistent asthma.

Reference: JAMA. 2018;319(14):1485-1496.

Association of Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists With Asthma Control in Patients With Uncontrolled, Persistent Asthma

Question  What is the efficacy associated with long-acting muscarinic antagonists (LAMAs) as add-on therapy to inhaled corticosteroids in patients with uncontrolled, persistent asthma?

Findings  In this meta-analysis that included 15 randomized clinical trials with 7122 participants 12 years or older with uncontrolled, persistent asthma, LAMA vs placebo as an add-on therapy to inhaled corticosteroids was associated with a lower risk of exacerbations requiring systemic corticosteroids (risk difference, −1.8).

Meaning  LAMA use was associated with better clinical outcomes than placebo in patients with uncontrolled, persistent asthma.

Reference: JAMA. 2018;319(14):1473-1484.

Relationship between Clinic and Ambulatory Blood-Pressure Measurements and Mortality


Evidence for the influence of ambulatory blood pressure on prognosis derives mainly from population-based studies and a few relatively small clinical investigations. This study examined the associations of blood pressure measured in the clinic (clinic blood pressure) and 24-hour ambulatory blood pressure with all-cause and cardiovascular mortality in a large cohort of patients in primary care.


We analyzed data from a registry-based, multicenter, national cohort that included 63,910 adults recruited from 2004 through 2014 in Spain. Clinic and 24-hour ambulatory blood-pressure data were examined in the following categories: sustained hypertension (elevated clinic and elevated 24-hour ambulatory blood pressure), “white-coat” hypertension (elevated clinic and normal 24-hour ambulatory blood pressure), masked hypertension (normal clinic and elevated 24-hour ambulatory blood pressure), and normotension (normal clinic and normal 24-hour ambulatory blood pressure). Analyses were conducted with Cox regression models, adjusted for clinic and 24-hour ambulatory blood pressures and for confounders.


During a median follow-up of 4.7 years, 3808 patients died from any cause, and 1295 of these patients died from cardiovascular causes. In a model that included both 24-hour and clinic measurements, 24-hour systolic pressure was more strongly associated with all-cause mortality (hazard ratio, 1.58 per 1-SD increase in pressure; 95% confidence interval [CI], 1.56 to 1.60, after adjustment for clinic blood pressure) than the clinic systolic pressure (hazard ratio, 1.02; 95% CI, 1.00 to 1.04, after adjustment for 24-hour blood pressure). Corresponding hazard ratios per 1-SD increase in pressure were 1.55 (95% CI, 1.53 to 1.57, after adjustment for clinic and daytime blood pressures) for nighttime ambulatory systolic pressure and 1.54 (95% CI, 1.52 to 1.56, after adjustment for clinic and nighttime blood pressures) for daytime ambulatory systolic pressure. These relationships were consistent across subgroups of age, sex, and status with respect to obesity, diabetes, cardiovascular disease, and antihypertensive treatment. Masked hypertension was more strongly associated with all-cause mortality (hazard ratio, 2.83; 95% CI, 2.12 to 3.79) than sustained hypertension (hazard ratio, 1.80; 95% CI, 1.41 to 2.31) or white-coat hypertension (hazard ratio, 1.79; 95% CI, 1.38 to 2.32). Results for cardiovascular mortality were similar to those for all-cause mortality.


Ambulatory blood-pressure measurements were a stronger predictor of all-cause and cardiovascular mortality than clinic blood-pressure measurements. White-coat hypertension was not benign, and masked hypertension was associated with a greater risk of death than sustained hypertension. (Funded by the Spanish Society of Hypertension and others.)

Reference: N Engl J Med 2018; 378:1509-1520

Change in Overweight from Childhood to Early Adulthood and Risk of Type 2 Diabetes


Childhood overweight is associated with an increased risk of type 2 diabetes in adulthood. We investigated whether remission of overweight before early adulthood reduces this risk.


We conducted a study involving 62,565 Danish men whose weights and heights had been measured at 7 and 13 years of age and in early adulthood (17 to 26 years of age). Overweight was defined in accordance with Centers for Disease Control and Prevention criteria. Data on type 2 diabetes status (at age ≥30 years, 6710 persons) were obtained from a national health registry.


Overweight at 7 years of age (3373 of 62,565 men; 5.4%), 13 years of age (3418 of 62,565; 5.5%), or early adulthood (5108 of 62,565; 8.2%) was positively associated with the risk of type 2 diabetes; associations were stronger at older ages at overweight and at younger ages at diagnosis of type 2 diabetes. Men who had had remission of overweight before the age of 13 years had a risk of having type 2 diabetes diagnosed at 30 to 60 years of age that was similar to that among men who had never been overweight (hazard ratio, 0.96; 95% confidence interval [CI], 0.75 to 1.21). As compared with men who had never been overweight, men who had been overweight at 7 and 13 years of age but not during early adulthood had a higher risk of type 2 diabetes (hazard ratio, 1.47; 95% CI, 1.10 to 1.98), but their risk was lower than that among men with persistent overweight (hazard ratio [persistently overweight vs. never overweight], 4.14; 95% CI, 3.57 to 4.79). An increase in body-mass index between 7 years of age and early adulthood was associated with an increased risk of type 2 diabetes, even among men whose weight had been normal at 7 years of age.


Childhood overweight at 7 years of age was associated with increased risks of adult type 2 diabetes only if it continued until puberty or later ages. (Funded by the European Union.)