Microalbuminuria in subjects with hypertension attending specialist blood pressure clinics.

Albuminuria is associated with increased risk of cardiovascular disease and target organ damage in patients with diabetes mellitus. In nondiabetic hypertensive patients, the threshold at which microalbuminuria (MAU) increases risk is unclear and there is evidence that cardiovascular risk may be increased in individuals with MAU levels lower than the usual recommended screening thresholds. We compared two definitions of MAU (on the basis of three early morning urine samples) in a cohort of hypertensive patients attending two specialist clinics in Scotland: conventional (MAU(C)) albumin-to-creatinine ratio (ACR) >2.5-25 mg mmol(-1) in males or >3.5-25 mg mmol(-1) in females; and low-grade (MAU(L)) ACR 1.2-2.5 in males or 1.7-3.5 mg mmol(-1) in females. Of the 1059 subjects screened, 786 (74%) were nondiabetic, with estimated glomerular filtration rate ⩾30 ml min(-1) per 1.73 m(2) and without gross proteinuria (low-risk subset). The average age was 58±15 years, body mass index 30±6 kg m(-2) and 46% were males. The prevalence of MAU(C) was 11% and 9.5% in the overall and low-risk subset, respectively, whereas MAU(L) prevalence was 11.1% and 10% respectively. The prevalence of cardiovascular disease was higher (24%) with albuminuria (both MAU(C) and MAU(L)) compared with 14% among those without albuminuria. The use of MAU(L) doubled the number of hypertensive subjects with increased cardiovascular risk who can be targeted for more rigorous risk reduction strategies. Consideration should be given to reducing the current threshold for MAU.

Cardiovascular and heart failure safety profile of vildagliptin: a meta-analysis of 17 000 patients.

AIMS: To report the cardiovascular (CV) safety profile and heart failure (HF) risk of vildagliptin from a large pool of studies, including trials in high-risk patients with type 2 diabetes mellitus (T2DM), such as those with congestive HF and/or moderate/severe renal impairment. METHODS: We conducted a retrospective meta-analysis of prospectively adjudicated CV events. Patient-level data were pooled from 40 double-blind, randomized controlled phase III and IV vildagliptin studies. The primary endpoint was occurrence of major adverse CV events (MACEs; myocardial infarction, stroke and CV death). Assessments of the individual MACE components and HF events (requiring hospitalization or new onset) were secondary endpoints. The risk ratio (RR) of vildagliptin (50 mg once- and twice-daily combined) versus comparators (placebo and all non-vildagliptin treatments) was calculated using the Mantel-Haenszel (M-H) method. RESULTS: Of the 17 446 patients, 9599 received vildagliptin (9251.4 subject-years of exposure) and 7847 received comparators (7317.0 subject-years of exposure). The mean age of the patients was 57 years, body mass index 30.5 kg/m(2) (nearly 50% obese), glycated haemoglobin concentration 8.1% and T2DM duration 5.5 years. A MACE occurred in 83 (0.86%) vildagliptin-treated patients and 85 (1.20%) comparator-treated patients, with an M-H RR of 0.82 [95% confidence interval (CI) 0.61-1.11]. Similar RRs were observed for the individual events. Confirmed HF events were reported in 41 (0.43%) vildagliptin-treated patients and 32 (0.45%) comparator-treated patients, with an M-H RR 1.08 (95% CI 0.68-1.70). CONCLUSIONS: This large meta-analysis indicates that vildagliptin is not associated with an increased risk of adjudicated MACEs relative to comparators. Moreover, this analysis did not find a significant increased risk of HF in vildagliptin-treated patients.

Do we need more long-term outcome trials for the treatment of hypertension?

The epidemiology of arterial hypertension and its treatment has been underlined by a huge research literature. Consistently raised arterial blood pressure in a clinic or home setting is a simple clinical observation that marks a predilection to a variety of fatal and non-fatal vascular disease events. Over the past 50 years tolerable, safe and effective primary and secondary medicines to offset a substantial amount of the associated morbidity and mortality risk of elevated blood pressure have emerged. Due to the nature of the population-relative risk and low absolute risk of this phenomenon it has often taken very large numbers of patients recruited from multiple centres in several countries and huge financial investment to define these profiles. Few national clinical research funds have invested in this process and it has often been left to a relatively small group of investigators to work closely with the commercial producers of new medicines to complete the essential outcome trials on which much of contemporary cardiovascular medical practice is based. Currently there are few, if any, significant new drug entities relevant to raised blood pressure under development. Most of the underlying clinical management principles and associations are clear. Achieved blood pressure, through patient adherence and variable prescriber practice, defines outcomes for individuals. The theoretical likelihood of a major step forward in the understanding of raised arterial blood pressure or a preferred means for population management is low. Moreover, with few new drug entities, investment in major outcome trials is unlikely to be proposed and the target for new trials is perhaps less apparent. While there can be no doubt that few areas in recent medical practice have benefited more from such huge achievements in underlining treatment, is it time to move on from the cardiovascular mega trial in hypertension?

Comparison of the efficacy of candesartan and losartan: a meta-analysis of trials in the treatment of hypertension.

Informed by the findings from prospective observational studies and randomized outcome trials, guidelines for the management of hypertension acknowledge that the benefit of treatment can be attributed largely to blood pressure (BP) reduction. Therefore, quantification of differential BP lowering of different agents within classes of anti-hypertensives is of practical importance. The objective of this analysis was to compare the efficacy of candesartan and losartan with respect to reduction in systolic and diastolic BP (SBP and DBP). A systematic literature search of databases from 1980 to 1 October 2008 identified 13 studies in which candesartan and losartan were compared in randomized trials in hypertensive patients. Data from 4066 patients were included in the analysis using a random effect model. Mean changes in SBP and DBP were compared for each drug alone and after stratification for dose and for combination with hydrochlorothiazide (HCTZ). On the basis of all the data, the weighted mean difference favoured candesartan-3.22 mm Hg (95% confidence interval (CI) 2.16, 4.29) for SBP and 2.21 mm Hg (95% CI 1.34, 3.07) for DBP. These findings were consistent when analyses according to dose and combination with HCTZ were carried out. Thus, it can be concluded that at currently recommended doses, candesartan is more effective than losartan in lowering BP.

Cost-effectiveness of losartan-based therapy in patients with hypertension and left ventricular hypertrophy: a UK-based economic evaluation of the Losartan Intervention for Endpoint reduction in hypertension (LIFE) study.

The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study demonstrated the clinical benefit of losartan-based therapy in hypertensive patients with left ventricular hypertrophy (LVH), mainly due to a highly significant 25% reduction in the relative risk of stroke compared with an atenolol-based regimen, for a similar reduction in blood pressure. The aim of this economic evaluation was to estimate the cost-effectiveness of losartan compared with atenolol from a UK national health system perspective. Quality-adjusted survival and direct medical costs were modelled beyond the trial using the within-trial incidence of stroke. Survival with stroke, study medication use and quality of life by stroke status were taken directly from the LIFE trial. The LIFE data were supplemented with UK data on lifetime direct medical costs of stroke and life expectancy in individuals without stroke. No additional stroke events or use of study treatment were assumed beyond the trial. Costs and benefits were discounted using current UK Treasury rates. In the base-case analysis, the reduction in stroke-related costs (by 968 sterling pound) offset 86% of the increase in study medication costs (1128 sterling pound) among losartan-treated patients. The incremental cost-effectiveness ratio (ICER) for losartan versus atenolol in hypertensive patients with LVH was 2130 sterling pound per quality-adjusted life year (QALY) gained (3195 Euro/QALY), and this increased to 11,352 sterling pound per QALY gained (16,450 Euro/QALY) when the costs of stroke beyond the first 5 years were excluded. Thus, the clinical benefit of losartan was achieved at a cost well within reported thresholds for cost-effectiveness.

Statin administration prior to ischaemic stroke onset and survival: exploratory evidence from matched treatment-control study.

In addition to their lipid-lowering effects, it has been speculated that statins may also have beneficial effects on cerebral circulation and brain parenchyma during ischaemic stroke and reperfusion. We hypothesized that patients who had taken statins prior to stroke onset may have a better survival rate at 1 month and during the follow-up period. We retrospectively studied consecutive ischaemic stroke patients admitted to an acute stroke unit and at least a month's follow-up. From these, we included those patients who, at admission, had reported the use of a statin prior to the stroke onset in the statin group (n = 205). Each patient in the statin group was matched with two patients who reported no statin use (n = 410). Using logistic regression and Cox proportional hazards models, we adjusted for variables that significantly differed between treatment groups or that independently predicted mortality. After adjusting for those variables, statin use was associated with reduced mortality at 1 month [odds ratio 0.24; 95% confidence interval (CI) 0.09-0.67] and during the follow-up period (hazard ratio 0.57; 95% CI 0.35-0.93). The use of statins prior to stroke onset is associated with improved stroke survival within this cohort study with matched controls.