Faculty Bibliography

Von Willebrand disease (VWD) is an inherited bleeding disorder that often manifests clinically with hemorrhage after invasive procedures. We investigated the association between a diagnosis of VWD and bleeding and thrombotic outcomes following major non-cardiac surgery in a large national database from the United States. Patients age >/=45 years requiring major non-cardiac surgery were identified from Healthcare Cost and Utilization Project's National Inpatient Sample data. Von Willebrand disease, perioperative major adverse cardiovascular events (MACE), thrombotic events, and hemorrhage were defined by ICD9 diagnosis codes. From 2004 to 2013, a total of 10,581,621 hospitalizations for major non-cardiac surgery met study inclusion criteria and VWD was identified in 3765 (0.036%). In adjusted analyses, patients with VWD were significantly more likely to develop post-operative hemorrhage than patients without VWD (5.5 vs. 1.9%, p < 0.001; adjusted OR 3.49, 95% CI 3.03-4.03), but had similar odds of perioperative MACE and thrombotic events. Thus, a diagnosis of VWD was associated with increased risks of bleeding with non-cardiac surgery, without a corresponding reduction in perioperative thrombosis in comparison to patients without VWD. Perioperative management of patients with hereditary bleeding disorders and mitigation of thrombotic risks requires further study.

Background/UNASSIGNED:Venous thromboembolism (VTE) is a common vascular complication of non-cardiac surgery. Methods/UNASSIGNED:We evaluated national trends in perioperative in-hospital VTE incidence, management, and outcomes using a large database of hospital admissions from the United States. Patients aged ≥ 45 years undergoing major non-cardiac surgery from 2005 to 2013 were identified from the National Inpatient Sample. In-hospital perioperative VTE was defined as lower extremity deep vein thrombosis (DVT) or pulmonary embolism (PE), and the incidence was evaluated over time. Multivariable regression models with demographics and comorbidities as covariates were generated to estimate adjusted odds ratios (aOR). Results/UNASSIGNED:Major non-cardiac surgery was performed in 9,431,442 hospitalizations that met inclusion criteria, and perioperative VTE occurred in 99,776 patients (1,057 per 100,000), corresponding to an annual incidence of ≈53,000 after applying sample weights. Over time, perioperative VTE per 100,000 surgeries increased by 135 (95% CI 107 - 163), from 925 in 2005 to 1,060 in 2013 (p for trend <0.001; aOR [for 2013 versus 2005] 1.22, 95% CI 1.19 - 1.26), due to increases in non-fatal VTE rates (from 840 [per 100,000 surgeries] in 2005 to 987 in 2013; p for trend <0.001). Perioperative VTE occurred most frequently in patients undergoing thoracic (2.0%) and vascular surgery (1.8%). Mortality was higher in patients with VTE than those without VTE (aOR 3.12, 95% CI 3.05 - 3.20). Conclusions/UNASSIGNED:Perioperative VTE occurs in approximately 1% of patients ≥45 years undergoing major non-cardiac surgery, with increasing incidence of non-fatal VTE over time.

PURPOSE OF REVIEW: Approximately one-fourth of the adult population is diagnosed with hypertension, which has been associated with increased cardiovascular morbidity and mortality including cardiovascular death, myocardial infarction, heart failure and stroke. Early detection and treatment is a key and can lead to a significant reduction in cardiovascular morbidity and mortality. RECENT FINDINGS: In this review, we discuss the management and treatment strategies in patients with hypertension in the current era. Blood pressure (BP) targets will be reviewed in accordance with the recent literature and current guidelines. There is a controversy about lower BP target in patients with coronary artery disease with some studies showing a J-curve relationship but a recent randomized trial (SPRINT) showing a benefit, albeit with controversy as to how BP was measured in the trial. Nevertheless, lower BP targets come with a price of needing more medication (thus impacting cost and compliance) and increases in medication-related adverse effects. There is a growing recognition that angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium antagonists or thiazide diuretics can be used a first-line therapy for hypertension. Evidence also supports the use of combination drug therapy as opposed to monotherapy for more synergistic effect on lowering of BP, offsetting side effects and for improved adherence to a drug regimen. SUMMARY: Overall, we aim to review BP targets and medical therapies for hypertension in the current era, recognizing varying clinical characteristics such as comorbidities and patient-risk profile.

BACKGROUND: The optimal blood pressure (BP) target has been a matter of debate. The recent SPRINT trial showed significant benefits of a BP target of <120 mm Hg albeit with an increase in serious adverse effects related to low BP. METHODS: PUBMED, EMBASE, and CENTRAL were searched for randomized trials comparing treating to different BP targets. Trial arms were grouped into five systolic BP target categories: 1) <160 mm Hg; 2) <150 mm Hg; 3) <140 mm Hg; 4) <130 mm Hg and 5) <120 mm Hg. Efficacy outcomes of stroke, myocardial infarction, death, cardiovascular death, heart failure and safety outcomes of serious adverse effects were evaluated using a network meta-analysis. RESULTS: Seventeen trials that enrolled 55,163 patients with 204,103 patient-years of follow-up were included. There was a significant decrease in stroke (RR=0.54; 95% CI 0.29-1.00) and myocardial infarction (RR=0.68; 95% CI 0.47-1.00) with systolic BP <120 mm Hg (vs. <160 mm Hg). Sensitivity analysis using achieved systolic BP showed a 72%, 97% and 227% increase in stroke with systolic BP of <140 mm Hg, <150 mm Hg and <160 mm respectively, when compared with systolic BP <120 mm Hg. There was no difference in death, cardiovascular death or heart failure when comparing any of the BP targets. However, the point estimate favored lower BP targets (<120 mm Hg, <130 mm Hg) when compared with higher BP targets (<140 mm Hg or <150 mm Hg). BP targets of <120 mm Hg and <130 mm Hg ranked #1 and #2 respectively, as the most efficacious target. There was a significant increase in serious adverse effects with systolic BP <120 mm Hg vs. <150 mm Hg (RR=1.83; 95% CI 1.05-3.20) or vs. <140 mm Hg (RR=2.12; 95% CI 1.46-3.08). BP targets of <140 mm Hg and <150 mm Hg ranked #1 and #2 respectively, as the safest target for the outcome of serious adverse effects. Cluster plots for combined efficacy and safety showed that a systolic BP target of <130 mm Hg had optimal balance between efficacy and safety. CONCLUSIONS: In patients with hypertension, a systolic BP target of <130 mm Hg achieved optimal balance between efficacy and safety.

BACKGROUND:Gout, hyperuricemia, and cardiovascular disease (CVD) are prevalent conditions in the United States, and while they share common risk factors such as obesity, hypertension, hypercholesterolemia, and type 2 diabetes mellitus, relatively little is known about what patient and disease characteristics may link CVD with hyperuricemia and gout and how the presence of both diseases affects management decisions differently than for patients with gout alone. OBJECTIVE:To identify differences in patient characteristics, patterns of urate-lowering therapy (ULT) use, and gout control in gout patients with and without cardiovascular comorbidity. METHODS:Data were assessed from a survey of U.S. physicians who performed in-depth patient chart audits of their last 5 consecutive adult patients with confirmed gout as determined by the medical record and clinical notes. Comorbidities, gout symptoms, length of current treatment, sociodemographic factors, and physician type were identified from the chart review. Descriptive statistics and logistic regression described differences among patients with and without comorbid CVD and assessed ULT use and gout control. RESULTS:Of the 1,159 patient charts that were reviewed, 738 patients had CVD and gout, and 421 had gout alone. Patients with CVD had longer duration of gout (mean [SD] = 52 [68.2] vs. 34 [47.2] months; P < 0.001) and were more likely to have clinician-reported tophi (28% vs. 15%; P < 0.001), organ/joint damage (19% vs. 9%; P < 0.001), and more flares (2.1% vs. 1.8%; P = 0.017) in the previous 12 months. Time from gout diagnosis to start of ULT was delayed for those with CVD (mean [SD] = 24.3 [56.6] vs. 15.5 [33.2] months; P = 0.023), but these patients were more likely to be receiving ULT (83% vs. 59%; P < 0.001). Gout patients with CVD were more likely to have a variety of additional comorbidities than those without CVD, such as obesity (28% vs. 18%; P < 0.001), diabetes (26% vs. 12%; P < 0.001), osteoarthritis (25% vs. 11%; P < 0.001), chronic kidney disease (17% vs. 5%; P < 0.001), and prostate disease (males, n = 933; 10% vs. 2%; P < 0.001). Gout patients with CVD were more likely to have an emergency department visit (12% vs. 7%; P = 0.003) for gout in the previous 12 months. In patients with CVD, ULT use was associated with better gout control. CONCLUSIONS:Gout patients with CVD were more likely to have additional comorbidities, more gout-related symptoms, and a delay in initiating treatment, which may be associated with the greater severity of disease in these patients. These data suggest that gout patients with CVD may constitute a less healthy group in need of earlier, more aggressive therapy. DISCLOSURES/UNASSIGNED:This study was supported by AstraZeneca. Pillinger reports consultancies at AstraZeneca, SOBI, Crealta/Horizon; investigator-initiated grants from Takeda (closed 2016); and was an investigator on industry-sponsored clinical trials for Takeda. Klein is employed by AstraZeneca. At the time of this study, Baumgartner was employed by Ardea Biosciences, a wholly owned subsidiary of AstraZeneca and owns stock in AstraZeneca. Baumgartner and Morlock are consultants to Ardea Biosciences. Morlock reports consulting fees from Genentech, Ironwood Pharmaceuticals, Astellas, and Abbot Medical Optics outside of this study. Bangalore reports consultancies at Pfizer, Merck, Abbott Vascular, Medicines Company, AstraZeneca, and the National Heart, Lung, and Blood Institute. The authors did not receive any honoraria for this publication. Study concept and design were primarily contributed by Morlock, along with the other authors. Morlock collected the data, and data interpretation was performed by all the authors. All authors equally contributed to preparation and revision of the manuscript. Preliminary results from this study were presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2016; San Francisco, California; April 19-22, 2016.