The combination of amlodipine and angiotensin receptor blocker or diuretics in high-risk hypertensive patients: rationale, design and baseline characteristics

The Chinese Hypertension Intervention Efficacy Study (CHIEF) is a multi-centre randomized controlled clinical trial comparing the effects of amlodipine+angiotensin II receptor blocker and amlodipine+diuretics on the incidence of cardiovascular events, represented as a composite of non-fatal stroke, non-fatal myocardial infarction and cardiovascular death events in high-risk Chinese hypertensive patients. The study also evaluates the long-term effects of lipid-lowering treatment and lifestyle modification. From October 2007 to October 2008, 13 542 patients were enrolled into the study in 180 centres in China. Patients will be followed up for 4 years. There was no difference in baseline characteristics between the two blood pressure arms

The potential savings of using thiazides as the first choice antihypertensive drug: cost-minimisation analysis

BACKGROUND: All clinical practice guidelines recommend thiazides as a first-choice drug for the management of uncomplicated hypertension. Thiazides are also the lowest priced antihypertensive drugs. Despite this, the use of thiazides is much lower than that of other drug-classes. We wanted to estimate the potential for savings if thiazides were used as the first choice drug for the management of uncomplicated hypertension. METHODS: For six countries (Canada, France, Germany, Norway, the UK and the US) we estimated the number of people that are being treated for hypertension, and the proportion of them that are suitable candidates for thiazide-therapy. By comparing this estimate with thiazide prescribing, we calculated the number of people that could switch from more expensive medication to thiazides. This enabled us to estimate the potential drug-cost savings. The analysis was based on findings from epidemiological studies and drug trials, and data on sales and prescribing provided by IMS for the year 2000. RESULTS: For Canada, France, Germany, Norway, the UK and the US the estimated potential annual savings were US$13.8 million, US$37.4 million, US$72.2 million, US$10.7 million, US$119.7 million and US$433.6 million, respectively. CONCLUSIONS: Millions of dollars could be saved each year if thiazides were prescribed for hypertension in place of more expensive drugs. Our calculations are based on conservative assumptions. The potential for savings is likely considerably higher and may be more than US$1 billion per year in the US

Informative noncompliance in endpoint trials

Noncompliance with study medications is an important issue in the design of endpoint clinical trials. Including noncompliant patient data in an intention-to-treat analysis could seriously decrease study power. Standard methods for calculating sample size account for noncompliance, but all assume that noncompliance is noninformative, i.e., that the risk of discontinuation is independent of the risk of experiencing a study endpoint. Using data from several published clinical trials (OPTIMAAL, LIFE, RENAAL, SOLVD-Prevention and SOLVD-Treatment), we demonstrate that this assumption is often untrue, and we discuss the effect of informative noncompliance on power and sample size

Evaluation of a community pharmacy-based intervention for improving patient adherence to antihypertensives: a randomised controlled trial

BackgroundThe majority of patients using antihypertensive medications fail to achieve their recommended target blood pressure. Poor daily adherence with medication regimens and a lack of persistence with medication use are two of the major reasons for failure to reach target blood pressure. There is no single intervention to improve adherence with antihypertensives that is consistently effective. Community pharmacists are in an ideal position to promote adherence to chronic medications. This study aims to test a specific intervention package that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications - Hypertension Adherence Program in Pharmacy (HAPPY).Methods/DesignThe HAPPY trial is a multi-centre prospective randomised controlled trial. Fifty-six pharmacies have been recruited from three Australian states. To identify potential patients, a software application (MedeMine CVD) extracted data from a community pharmacy dispensing software system (FRED Dispense&reg;). The pharmacies have been randomised to either \u27Pharmacist Care Group\u27 (PCG) or \u27Usual Care Group\u27 (UCG). To check for \u27Hawthorne effect\u27 in the UCG, a third group of patients \u27Hidden Control Group\u27 (HCG) will be identified in the UCG pharmacies, which will be made known to the pharmacists at the end of six months. Each study group requires 182 patients. Data will be collected at baseline, three and six months in the PCG and at baseline and six months in the UCG. Changes in patient adherence and persistence at the end of six months will be measured using the self-reported Morisky score, the Tool for Adherence Behaviour Screening and medication refill data.DiscussionTo our knowledge, this is the first research testing a comprehensive package of evidence-based interventions that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications. The unique features of the HAPPY trial include the use of MedeMine CVD to identify patients who could potentially benefit from the service, control for the \u27Hawthorne effect\u27 in the UCG and the offer of the intervention package at the end of six months to patients in the UCG, a strategy that is expected to improve retention.Trial RegistrationAustralian New Zealand Clinical Trial Registry ACTRN12609000705280<br /

Determining which automatic digital blood pressure device performs adequately: a systematic review

The aim of this study is to systematically examine the proportion of accurate readings attained by automatic digital blood pressure (BP) devices in published validation studies. We included studies of automatic digital BP devices using recognized protocols. We summarized the data as mean and s.d. of differences between measured and observed BP, and proportion of measurements within 5 mm Hg. We included 79 articles (10 783 participants) reporting 113 studies from 22 different countries. Overall, 25/31 (81%), 37/41 (90%) and 34/35 (97%) devices passed the relevant protocols [BHS, AAMI and ESH international protocol (ESH-IP), respectively]. For devices that passed the BHS protocol, the proportion of measured values within 5 mm Hg of the observed value ranged from 60 to 86% (AAMI protocol 47–94% and ESH-IP 54–89%). The results for the same device varied significantly when a different protocol was used (Omron HEM-907 80% of readings were within 5 mm Hg using the AAMI protocol compared with 62% with the ESH-IP). Even devices with a mean difference of zero show high variation: a device with 74% of BP measurements within 5 mm Hg would require six further BP measurements to reduce variation to 95% of readings within 5 mm Hg. Current protocols for validating BP monitors give no guarantee of accuracy in clinical practice. Devices may pass even the most rigorous protocol with as few as 60% of readings within 5 mm Hg of the observed value. Multiple readings are essential to provide clinicians and patients with accurate information on which to base diagnostic and treatment decisions

Targeting effective blood pressure control with angiotensin receptor blockers

Angiotensin receptor blockers (ARBs) have become established as a major class of antihypertensive on the basis of their powerful effects on blood pressure (BP), excellent tolerability and pleiotropic end-organ-protective effects. However, individual ARBs vary in antihypertensive efficacy, which may be important to clinical outcome. Several strategies are available to ensure that BP reductions with ARBs are at least as great as that which can be achieved with other antihypertensive classes. Firstly, several newer ARBs, including irbesartan, candesartan, telmisartan and olmesartan, have been reported to provide equivalent antihypertensive efficacy to amlodipine and greater efficacy than either losartan, valsartan or both. Secondly, increases in dose may improve the antihypertensive efficacy of agents such as valsartan, although clinical studies are necessary to provide characterisation of new, higher-dose monotherapies. Thirdly, fixed dose combinations with hydrochlorothiazide (HCTZ) increase the antihypertensive effect of all ARBs. It is likely that differences in efficacy between newer and older ARBs will in some cases be sustained in combination therapy, such that the most potent ARBs and HCTZ will provide another tier of control. The future use of ARBs is likely to involve a growing emphasis on compound-specific data, with regard to the antihypertensive efficacy and pleiotropic protective actions of agents

Insufficient Control of Blood Pressure and Incident Diabetes

Incidence of type 2 diabetes might be associated with preexisting hypertension. There is no information on whether incident diabetes is predicted by blood pressure control. We evaluated the hazard of diabetes in relation to blood pressure control in treated hypertensive patients.Nondiabetic, otherwise healthy, hypertensive patients (N = 1,754, mean +/- SD age 52 +/- 11 years, 43\% women) participated in a network over 3.4 +/- 1 years of follow-up. Blood pressure was considered uncontrolled if systolic was >or=140 mmHg and/or diastolic was >or=90 mmHg at the last outpatient visit. Diabetes was defined according to American Diabetes Association guidelines.Uncontrolled blood pressure despite antihypertensive treatment was found in 712 patients (41\%). At baseline, patients with uncontrolled blood pressure were slightly younger than patients with controlled blood pressure (51 +/- 11 vs. 53 +/- 12 years, P < 0.001), with no differences in sex distribution, BMI, duration of hypertension, baseline blood pressure, fasting glucose, serum creatinine and potassium, lipid profile, or prevalence of metabolic syndrome. During follow-up, 109 subjects developed diabetes. Incidence of diabetes was significantly higher in patients with uncontrolled (8\%) than in those with controlled blood pressure (4\%, odds ratio 2.08, P < 0.0001). In Cox regression analysis controlling for baseline systolic blood pressure and BMI, family history of diabetes, and physical activity, uncontrolled blood pressure doubled the risk of incident diabetes (hazard ratio [HR] 2.10, P < 0.001), independently of significant effects of age (HR 1.02 per year, P = 0.03) and baseline fasting glucose (HR 1.10 per mg/dl, P < 0.001).In a large sample of treated nondiabetic hypertensive subjects, uncontrolled blood pressure is associated with twofold increased risk of incident diabetes independently of age, BMI, baseline blood pressure, or fasting glucose