Randomized study of antihypertensive efficacy and safety of combination aliskiren/valsartan vs valsartan monotherapy in hypertensive participants with type 2 diabetes mellitus.

In this double-blind study, 1143 hypertensive participants with type 2 diabetes and stage 1 or 2 chronic kidney disease (CKD) were randomized to receive combination aliskiren/valsartan 150/160 mg or valsartan 160 mg monotherapy for 2 weeks, with force-titration to 300/320 mg and 320 mg, respectively, for another 6 weeks. Ambulatory blood pressure (ABP), the primary outcome, was available for 665 participants. Reductions from baseline to week 8 in 24-hour ABP were -14.1/-8.7 mm Hg with aliskiren/valsartan vs -10.2/-6.3 mm Hg with valsartan (P<.001). Adverse events were reported in 202 participants (35.2%) taking aliskiren/valsartan and 182 participants (32.2%) taking valsartan. No participant had blood urea nitrogen values>40 mg/dL or serum creatinine values>2.0 mg/dL. There were no confirmed cases of serum potassium values≥6.0 mEq/L. Combination aliskiren/valsartan has additive effects on blood pressure reduction and tolerability similar to valsartan in hypertensive/diabetic participants with early-stage (stages 1 and 2) CKD.

Economic burden of gouty arthritis attacks for employees with frequent and infrequent attacks.

The objective of this study was to compare episode-related and annual costs and work absence days for employees with <3 versus ≥ 3 annual gout attacks. Human Capital Management Services data (2009-2010) from adult employees with gout (International Classification of Diseases, Ninth Revision code 274.x) and ≥ 12 months of medical and pharmacy benefits were studied. Outcomes of interest included medical and drug costs, number of emergency department and urgent care visits, number of inpatient days, short- and long-term disability, sick leave, workers' compensation costs, and work absence days. An algorithm based on diagnosis code and antigout medication use identified acute gout treatment episodes. Multivariate analysis compared annual and pre-episode vs. during-episode outcomes for employees with ≥ 3 vs. <3 gout annual attacks. Of 3361 employees with gout, 76 had ≥ 3 attacks; these employees had higher short-term disability costs ($1663 vs. $643, P=0.06) and days (11.68 versus 4.61, P<0.05), more emergency room visits (0.55 vs. 0.23, P<0.0001), and urgent care visits (0.07 vs. 0.04, P<0.01), and lower pharmacy costs ($1677 vs. $1108, P<0.0001) than those with <3 attacks. Medical costs both before ($203 higher) and during attacks ($136 higher) were significantly higher for those with ≥ 3 attacks than for those with <3 attacks. Additionally, a quadratic increasing relationship was found between number of attacks and cost. Frequency of acute gout attacks (≥ 3 episodes per year) among employees with gout was associated with greater short-term disability cost, absence days, and emergency department and urgent care visits, and trends toward higher overall costs.

The effect of gout on health-related quality of life, work productivity, resource use and clinical outcomes among patients with hypertension.

Although gout has been found to be associated with health-related quality of life (HRQoL), few studies have examined the burden of gout in the presence of concomitant cardiometabolic conditions. The present study evaluated the effect of gout on HRQoL and work productivity among patients with hypertension. Data from the 2010 National Health and Wellness Survey were obtained for respondents ≥18 years of age who had self-reported, physician-diagnosed hypertension or blood pressure levels ≥140/90 mmHg (≥130/80 mmHg for those with physician-diagnosed diabetes or chronic kidney disease). Bivariate analysis was used to evaluate differences between patients with and without self-reported comorbid gout. Generalized linear models were used to evaluate differences in productivity (using the Work Productivity and Activity Impairment scale) and HRQoL (using the physical component summary [PCS], mental component summary and health utilities from the SF-12v2 health survey). As uric acid levels may influence other organ systems, core modeling did not include comorbidities other than osteoarthritis and depression as covariates. Sensitivity analyses were controlled for the Charlson comorbidity index. A total of 22,686 patients with self-reported hypertension met study eligibility requirements. Of these, 4.51% reported having gout. These patients were older, more likely to be male and have insurance through Veteran Affairs (all p-values < 0.05). Patients with comorbid gout reported lower levels of mental component summary scores (47.25 vs 48.93), PCS scores (39.06 vs 43.78) and health utilities (0.68 vs 0.73; all p-values < 0.05). For both PCS and health utilities, differences between groups exceeded clinically meaningful cutoffs. Sensitivity analyses conducted on PCS and health utilities uncovered slightly smaller, but statistically significant and clinically meaningful, effects (p-values < 0.05). The effect of gout on overall work impairment (23.33 vs 17.40% with and without comorbid gout, respectively) remained after controlling for the Charlson comorbidity index. Significantly greater impairment in daily activities (38.96 vs 28.32%; p < 0.05) was also observed among patients with comorbid gout. Results demonstrate that gout has significant and clinically meaningful impact on work productivity, physical HRQoL and utilities independent of other health conditions.

Comparison of patient characteristics and gout-related health-care resource utilization and costs in patients with frequent versus infrequent gouty arthritis attacks.

OBJECTIVE: To examine the association between frequent gouty arthritis and the presence of absolute/relative contraindications to gout therapies, and health-care expenditure associated with frequent gouty arthritis. METHODS: This retrospective study used administrative claims to identify patients with gouty arthritis between 1 July 2005 and 30 June 2010. Patients with ≥3 yearly gouty arthritis attacks (frequent gout) were matched 1:2 to patients with <3 yearly attacks (infrequent gout). Absolute and relative contraindications to gout medications were evaluated based on product labelling. Negative binomial regression and generalized linear models with logarithmic transformation were used for multivariate analysis of overall and gout-related health-care use and cost. RESULTS: Mean patient age was 58 years (n = 15 669) and 77% were men. Compared with patients with infrequent gout, those with frequent gout had higher rates of absolute/relative contraindications to NSAIDs (91.5% vs 78.7%, P < 0.0001), corticosteroids (96.4% vs 87.3%, P < 0.0001), allopurinol (51.0% vs 41.2%, P < 0.0001) and probenecid (13.4% vs 9.4%, P < 0.0001). Mean gout-related costs were $889 for frequent gout vs $210 for infrequent gout (P < 0.0001) and all-cause direct costs were $10 913 for frequent vs $10 685 for infrequent gout (P = ns). Mean all-cause outpatient visits among patients with comorbidities compared with those without were 25.8 vs 11.8 among frequent and 19.7 vs 9.0 among infrequent (both P < 0.001) groups. Gout-related costs were higher among frequent gout patients with comorbidities than those without comorbidities ($886 vs $513, P = 0.03). CONCLUSION: Patients with frequent gouty arthritis are likely to have absolute and/or relative contraindications to gout medications and higher gout-related treatment costs.

Comparison of the effects of aliskiren/valsartan in combination versus valsartan alone in patients with stage 2 hypertension.

The extent to which the combination of a renin inhibitor with an angiotensin receptor blocker (ARB) lowers clinic and ambulatory blood pressure (BP) versus an ARB alone in stage 2 hypertension is not well known. Hence, we performed an 8-week, randomized, double-blind study in 451 patients with stage 2 hypertension to compare the efficacy of the combination of aliskiren/valsartan 300/320 mg versus valsartan 320 mg. The primary endpoint was change in seated systolic BP from baseline to week 8 analyzed on the intent-to-treat (ITT) population using the last-observation-carried-forward (LOCF) approach; patients completing the entire treatment period (per-protocol completers) were similarly analyzed. For the predefined primary analysis, systolic BP reductions for aliskiren/valsartan (n = 230) and valsartan (n = 217) were -22.1 and -20.5 mm Hg, respectively (P = .295). In per-protocol completers, aliskiren/valsartan (n = 201) lowered BP significantly greater than valsartan (n = 196); -23.7 mm Hg versus -20.3 mm Hg, respectively (P = .028). Although limited by a small sample size (n = 76) using ambulatory BP monitoring, aliskiren/valsartan lowered the 24-hour BP significantly more than valsartan alone (-14.6/-9.0 mm Hg versus -5.9/-4.2 mm Hg; P < .01). Safety and tolerability were similar for the two treatment groups. These data demonstrate the importance of multiple modalities to assess BP changes in clinical trials of antihypertensive therapies, particularly in stage 2 hypertension.

Effects of high- and low-sodium diets on ambulatory blood pressure in patients with hypertension receiving aliskiren.

Dietary sodium reduction and, as necessary, pharmacologic treatment are recommended for hypertension management. This prospective, randomized, open-label, blinded-end point, multicenter, crossover study investigated the effect of dietary sodium intake on mean ambulatory systolic blood pressure (maSBP) in patients with hypertension receiving aliskiren 300 mg once daily. Following a 2- to 4-week washout period, patients were randomized to a high- (≥ 200 mmol/d) or low- (≤ 100 mmol/d) sodium diet and were started on aliskiren, 300 mg/d. After 4 weeks, patients were crossed over to the alternate diet for an additional 4 weeks. The primary efficacy variable was change in maSBP between diets. During treatment with aliskiren, maSBP was significantly lower with the low-sodium diet compared with the high-sodium diet (least squares mean difference, 9.4 mm Hg; 95% CI, 7.5-11.4; P < .0001). The percentage of patients achieving a maSBP response to aliskiren (<130 mm Hg or a ≥ 20-mm Hg reduction from baseline) was greater with the low- (76.5%) versus the high-sodium diet (42.6%; P < .0001). Overall, 40.9% patients had ≥ 1 adverse event and the rates were similar between groups. In this study, aliskiren was well tolerated and a low-sodium diet accentuated its antihypertensive effect.