An adaptation of the diabetes prevention program for use with high-risk, minority patients with type 2 diabetes

PURPOSE: The purpose of this pilot study was to determine the effectiveness of an edited Diabetes Prevention Program (DPP) Lifestyle Resources Core Teaching Plan for managing patients with type 2 diabetes in an urban underserved setting. Modifications were made to attempt to cut to the bare essentials to work within the constrained budgets of safety net providers. The primary aim was to achieve a mean absolute reduction in HbA1c level of 1 percentage point. METHODS: The authors conducted a randomized controlled trial of 9 months' duration for patients with type 2 diabetes with an HbA1c>or=8.0%. A total of 67 patients randomized into usual-care and case management groups were evaluated with an intention-to-treat analysis. A modified DPP workbook was used during 7 monthly visits with a nurse case manager. RESULTS: As compared with the usual-care group, those in the case management group experienced a greater reduction in HbA1c level (-1.87 vs -0.54; P=.011) and weight (-2.47 kg vs +0.88 kg; P=.011). CONCLUSION: Use of an edited version of the DPP workbook in an urban, low-income, minority population with type 2 diabetesproduced a significant absolute reduction in HbA1c percentage and weight.     

Managing high-risk patients with hypertension: focus on the renin-angiotensin system

The goal of treating hypertension has evolved from merely lowering blood pressure to an emphasis on the more important objective of decreasing morbidity and mortality. Recent trials have emphasized, however, that the major benefit in outcome relates to the level of blood pressure achieved. Hypertension associated with other risk factors, such as age, diabetes, nephropathy, and left ventricular hypertrophy, places patients at high risk of myocardial infarction, stroke, renal failure, and cardiovascular death. In numerous studies, reductions in end points were usually achieved with combination therapy. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) reaffirmed the value of diuretics in treating high-risk hypertension and reducing morbidity, but it also confirmed the necessity of combination drug therapy. Agents that block the effects of angiotensin II are an important component of antihypertensive therapy because of their proven ability to lower the incidence of cardiovascular and renal events in high-risk hypertensive patients.     

Long-term efficacy and safety of triple-combination therapy with olmesartan medoxomil and amlodipine besylate and hydrochlorothiazide for hypertension

J Clin Hypertens (Greenwich). 2012;14:149–157. ©2012 Wiley Periodicals, Inc. Most patients with hypertension require combination therapy in order to achieve blood pressure (BP) goals. This 40‐week open‐label extension of the 12‐week double‐blind Tri ple Therapy With Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hyperten si ve Patient s Study (TRINITY) evaluated the efficacy and safety of triple‐combination treatments with olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide (OM/AML/HCTZ) in 2112 participants with moderate to severe hypertension. Following 2 weeks of initial treatment with OM 40/AML 5/HCTZ 12.5 mg, participants not achieving BP goal were titrated to OM 40/AML 5/HCTZ 25 mg or OM 40/AML 10/HCTZ 12.5 mg on a randomized basis. At week 16, participants who did not achieve BP goal were further titrated to OM 40/AML 10/HCTZ 25 mg. At the end of the study, 44.5% to 79.8% of participants reached BP goal and the mean BP decreased from 168.6/100.7 mm Hg (baseline BP at randomization) to 125.0 to 136.8 mm Hg/77.8 to 82.5 mm Hg, depending on treatment. Long‐term treatment with OM/AML/HCTZ was well tolerated and effective with no new safety concerns.     

Extrahepatic metastases occur in a minority of hepatocellular carcinoma patients treated with locoregional therapies: analyzing patterns of progression in 285 patients

Although most cancers are considered predominantly systemic processes, this may not hold true for hepatocellular carcinoma (HCC). The literature regarding patterns of progression of HCC (local versus systemic) has been relatively sparse. Our objectives were to: (1) analyze patterns of progression in HCC patients presenting with intrahepatic disease from initial treatment until death, and (2) identify clinically relevant risk factors for the development of metastases. Over a 9-year period, 285 patients treated with transarterial locoregional therapies underwent scheduled imaging follow-up from treatment until death and were categorized by pattern of progression: (i) intrahepatic (increased tumor enhancement/size, development/progression of vascular invasion, new hepatic lesions) progression or (ii) extrahepatic (adrenal/bone/lung/lymph node) metastases. Uni/multivariate analyses assessing the risk factors for the development of metastases were performed. The median time from last scan to death was 2.4 months (interquartile range: 1.3-4.8 months). The time to development of metastases, vascular invasion, and/or new lesions was 13.8 months (confidence interval: 11.3-17.7 months). Of the 209 patients followed until death, only 50 developed extrahepatic metastases (24%). Multivariate analyses identified age <65 years (P = 0.038), alpha-fetoprotein >200 ng/mL (P = 0.04), and vascular invasion (P = 0.017) as significant predictors of metastases development. CONCLUSION: Knowledge of the risk factors associated with the development of metastases may help guide assessment of patient prognosis. Because 76% of patients presenting with local disease treated with locoregional therapies die without developing extrahepatic metastases, the notion of HCC as a systemic disease, as detected by imaging, may be reconsidered.     

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.     

Usefulness of heart rate to predict cardiac events in treated patients with high-risk systemic hypertension

A high heart rate (HR) predicts future cardiovascular events. We explored the predictive value of HR in patients with high-risk hypertension and examined whether blood pressure reduction modifies this association. The participants were 15,193 patients with hypertension enrolled in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial and followed up for 5 years. The HR was assessed from electrocardiographic recordings obtained annually throughout the study period. The primary end point was the interval to cardiac events. After adjustment for confounders, the hazard ratio of the composite cardiac primary end point for a 10-beats/min of the baseline HR increment was 1.16 (95% confidence interval 1.12 to 1.20). Compared to the lowest HR quintile, the adjusted hazard ratio in the highest quintile was 1.73 (95% confidence interval 1.46 to 2.04). Compared to the pooled lower quintiles of baseline HR, the annual incidence of primary end point in the top baseline quintile was greater in each of the 5 study years (all p <0.05). The adjusted hazard ratio for the primary end point in the highest in-trial HR heart rate quintile versus the lowest quintile was 1.53 (95% confidence interval 1.26 to 1.85). The incidence of primary end points in the highest in-trial HR group compared to the pooled 4 lower quintiles was 53% greater in patients with well-controlled blood pressure (p <0.001) and 34% greater in those with uncontrolled blood pressure (p = 0.002). In conclusion, an increased HR is a long-term predictor of cardiovascular events in patients with high-risk hypertension. This effect was not modified by good blood pressure control. It is not yet known whether a therapeutic reduction of HR would improve cardiovascular prognosis.     

Low plasma adiponectin is associated with coronary artery disease but not with hypertension in high-risk nondiabetic patients

OBJECTIVE: To investigate the association of plasma adiponectin levels with coronary artery disease (CAD), arterial hypertension (HT), and insulin resistance (IR) in nondiabetic Caucasian patients. DESIGN: We measured plasma adiponectin levels, IR (HOMA index), and the CAD atherosclerotic burden (angiography-based modified Duke Index score) in 400 nondiabetic patients undergoing coronary angiography. HT was diagnosed by the European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines or if patients were on antihypertensive treatment. RESULTS: Coronary artery disease was found in 62% of the patients and ruled out in the rest (non-CAD group). Plasma adiponectin levels were inversely related to the CAD score (beta = -0.12, P = 0.029) and predicted the coronary atherosclerotic burden independent of other cardiovascular risk factors. However, they were similar in NT and HT and showed no correlation with blood pressure values. In non-CAD, but not in CAD patients, they were lower in patients with than without IR (8.3 +/- 1.2 vs. 11.3 +/- 1.3, respectively; P = 0.007). CONCLUSIONS: In nondiabetic high-risk Caucasian patients plasma adiponectin levels are inversely related to CAD severity and IR; however, they are not strongly related to blood pressure values.     

Alternative first-line therapies in geriatric hypertension

Between 45 and 60% of elderly persons have mild to moderate hypertension. In those with combined systolic/diastolic hypertension, blood pressure reduction significantly reduces morbidity and mortality. Secondary causes of hypertension, particularly renovascular, should be considered in elderly patients with a recent history of hypertension. Because of their proven efficacy and low cost, low-dose thiazide diuretics remain an important first-line therapy. Angiotensin-converting enzyme (ACE) inhibitors and calcium-channel blocking agents have also been shown to be effective and well-tolerated in the elderly. Increased attention is being paid to adverse drug effects and to the overall effect of antihypertensive therapy on quality of life. ACE inhibitors are particularly attractive in the elderly due to their possibilities in this area. In the elderly, the combination of a low-dose thiazide diuretic with an ACE inhibitor enhances antihypertensive efficacy while blunting the adverse metabolic effects of the diuretic.     

Comparison of efficacy and safety between third-dose triple and third-dose dual antihypertensive combination therapies in patients with hypertension

We compared the efficacy and safety of third-standard-dose triple and third-standard-dose dual antihypertensive combination therapies in patients with mild to moderate hypertension. This was a phase II multicenter, randomized, double-blind, parallel-group trial. After a 4-week placebo run-in period, 245 participants were randomized to the third-dose triple combination (ALC group; amlodipine 1.67 mg + losartan potassium 16.67 mg + chlorthalidone 4.17 mg) or third-dose dual combination (AL group; amlodipine 1.67 mg + losartan potassium 16.67 mg, LC group; losartan potassium 16.67 mg + chlorthalidone 4.17 mg, AC group; amlodipine 1.67 mg + chlorthalidone 4.17 mg) therapy groups and followed up for 8 weeks. The mean systolic blood pressure (BP) reduction was -18.3 ± 13.2, -13.0 ± 13.3, -16.3 ± 12.4, and -13.8 ± 13.2 mmHg in the ALC, AL, LC, and AC groups, respectively. The ALC group showed significant systolic BP reduction compared to the AL and AC groups at weeks 4 (P = .010 and P = .018, respectively) and 8 (P = .017 and P = .036, respectively). At week 4, the proportion of systolic BP responders was significantly higher in the ALC group (42.6%) than in the AL (22.0%), LC (23.3%), and AC (27.1%) groups (P = .013, P = .021, and P = .045, respectively). At week 8, the proportion of systolic and diastolic BP responders was significantly higher in the ALC group (59.7%) than in the AL (39.3%) and AC (42.4%) groups (P = .022 and P = .049, respectively) at week 8. Third-standard-dose triple antihypertensive combination therapy demonstrated early effective BP control compared to third-standard-dose dual combination therapies, without increasing adverse drug reactions in patients with mild-to-moderate hypertension.     

A statewide primary care approach to cardiovascular risk factor control in high-risk diabetic and nondiabetic patients with hypertension

Patients with multiple cardiovascular risk factors benefit from having them all controlled, but this rarely occurs. Fifty-seven primary care providers were enrolled in a program to monitor cardiovascular risk factor control. Data were obtained on 7315 hypertensives. This analysis focuses on 3460 high-risk hypertensives including 2199 with diabetes and 1261 with clinical cardiovascular disease. Blood pressures were <140/90 mm Hg and <130/80 mm Hg in only 44.3% and 20.4% of diabetics and 49.6% and 26.6% nondiabetics, respectively, despite the use of an average of 2.7±1.8 anti-hypertensive medications. Among high-risk dyslipidemic hypertensives, the low-density lipoprotein cholesterol level was <100 mg/dL in only 34% of diabetic and 33% of nondiabetic patients. Among 1696 diabetic hypertensives, the most recent glycosylated hemoglobin value averaged 7.5%, with 46.6% less than 7%. Among 805 diabetic, dyslipidemic hypertensives, all three risk factors were controlled to goal in only 6.6% with higher rates in whites than in African Americans (14.8% vs. 1.6%, p <0.001). An angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or both were prescribed in 89.9% of diabetic and 70.8% of nondiabetic patients, p<0.05. Primary care providers use evidence-based combination therapy in high-risk hypertensive patients with and without diabetes. These findings confirm the low rates of multiple risk factor control and highlight challenges of reaching evidence-based goals in primary care.     

New and future therapies in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is defined as a mean pulmonary artery pressure greater then 25 mm Hg at rest and greater then 30 mm Hg with exercise in association with normal left heart filling pressures. However, many patients with PAH have much higher pulmonary artery pressures, which, untreated, can rapidly result in marked disability, right heart failure, and death. A myriad of recent therapeutic advances have revolutionized the treatment of PAH, significantly impacting both symptoms and survival. This article briefly discusses some of the medication classes currently approved to treat patients with PAH and reviews novel therapies in the context of recent clinical trials. Also examined here are the rationale and data available for the role of combination therapy in the treatment of PAH. The article closes with speculation on new directions in the therapeutic management of this life-threatening disease.     

Assessment and management of hypertension in patients with type 2 diabetes

Background: Hypertension is a major risk factor for adverse outcomes in type 2 diabetes and an important target for intervention. Despite this, the management of blood pressure (BP) remains suboptimal, particularly in patients at increased risk for cardiovascular and chronic kidney disease. The aim of this study was to estimate the frequency of hypertension and its management in consecutive clinic‐based samples of patients with type 2 diabetes in Australian primary care. Methods: BP levels and antihypertensive management strategies were compared in patients with type 2 diabetes recruited as part of the Developing Education on Microalbuminuria for Awareness of reNal and cardiovascular risk in Diabetes (DEMAND) study in 2003 (n = 1831) and the National Evaluation of the Frequency of Renal impairment cO‐existing with Non‐insulin‐dependent diabetes (NEFRON) study in 2005 (n = 3893). Systolic BP levels and the use of antihypertensive therapies were examined in patients with and without chronic kidney disease. Results: The patient characteristics in both studies were similar in that more than 80% of patients in both studies were hypertensive. Systolic BP targets of ≤130 mmHg were achieved in approximately half of all treated patients in both studies. However, the use of antihypertensive therapy either alone or in combination increased from 70.4% in DEMAND to 79.5% in NEFRON 2 years later (P < 0.001). Despite this, antihypertensive therapy continued to be underutilized in high‐risk groups, including in those with established chronic kidney disease. Conclusion: The DEMAND and NEFRON studies both show that BP control is achievable in Australian general practice, with more than half of all patients seeing their general practitioners achieving a target systolic BP ≤130 mmHg. However, more needs to be done to further reduce BP levels, particularly in patients at high risk of adverse outcomes.