Extended-release niacin/laropiprant for lipid management: observational study in clinical practice.

AIMS: Patients with dyslipidaemia or hypercholesterolemia carry a substantially increased cardiovascular risk and need optimal treatment of this key risk factor. We aimed to investigate the utilisation, efficacy and tolerability of the single pill combination extended-release niacin/laropiprant 1000 mg/20 mg or 2000 mg /40 mg under conditions of primary care practice. METHODS: The present study was a prospective, non-interventional, observational study involving 885 primary care physicians throughout Germany. Data on adult patients treated with niacin/laropiprant one or two tablets daily within the labelled indication were documented for an average of 23 ± 7 weeks. The study was registered in the Association of research-based pharmaceutical companies (VFA) database under no. 354. RESULTS: A total of 2359 patients were analysed in the intent-to-treat population (mean age 61.1 years, 67% males) of whom 1917 could be followed up. Background statin therapy was often discontinued and only about 50% of patients received two tables niacin/laropiprant at the end of the study. Individual goal attainment rates as subjectively determined by the investigator were for LDL-C 59.4%, total cholesterol 59.5%, HDL-C 72.8% and TG 51.5%, respectively. Objective (laboratory) goal attainment rates according to NCEP ATP III criteria were lower: LDL-C <100 mg/dl goal was achieved in 17.8%, HDL-C >40 in males or >50 mg/dl in females in 37.9% and TG <150 mg/dl in 18.7%. Totally, 422 adverse events were noted in 231 patients (9.7%), of which 317 were considered drug-related. Flushing occurred in 15%. CONCLUSION: Niacin/laropiprant resulted in beneficial effects on serum lipids and was generally well tolerated. The full potential of the drug combination was not explored by most physicians due to discontinuation of statins and lack of titration of the combination. Overall, treatment effects were consistent with those seen in controlled trials.

Aliskiren for the treatment of essential hypertension under real-life practice conditions: design and baseline data of the prospective 3A registry.

BACKGROUND: The renin-angiotensin system (RAS) is a key target for blood pressure control and for cardiovascular and renal protection. Aliskiren is the first-in-class direct oral inhibitor of renin that controls the rate-limiting step in the RAS cascade. So far little is known about the use and efficacy of aliskiren in the treatment of essential hypertension under clinical practice conditions. METHODS: The 3A registry was an open, prospective cohort study (observational registry) of 14,988 patients in 899 offices throughout Germany. Consecutive patients were eligible for inclusion if their physician had decided to modify their antihypertensive therapy. This included treatment with aliskiren or an angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB) or agents not blocking the RAS, alone or on top of an existing drug regimen. RESULTS: Mean age of patients was 65 years, their mean body mass index was 28.2 kg/m(2) 53.5% were men, 36% working, 90% in statutory health insurance and 26% in any disease management programme. Patients in the aliskiren and the RAS groups compared with the non-RAS group were older, more often men, had a longer history of hypertension, and had a higher prevalence of comorbidities (diabetes, chronic heart failure, ischaemic heart disease, renal disease). Mean systolic, but not diastolic blood pressure was substantially higher in the aliskiren group (158/91 mmHg vs. 154/89 mmHg in ACE-I/ARB vs. 152/89 mmHg in non-RAS). Mean number of antihypertensive drugs was higher in the aliskiren group compared with the other groups (3.0 drugs vs. 2.5 in ACE-I/ARB vs. 1.6 in non-RAS; p < 0.0001). CONCLUSIONS: In this large cohort of outpatients with hypertension, aliskiren was used mainly in patients with more severe stages of hypertension and those with concomitant diseases such as diabetes mellitus and impaired renal function. The 3A registry will provide important information about the use and efficacy of aliskiren in a real-life setting.

[Longitudinal associations between depressive symptoms and type 2 diabetes and their impact on mortality in primary care patients]. / Longitudinale Assoziationen zwischen depressiven Symptomen und Typ-2-Diabetes sowie deren Auswirkung auf die Mortalität von Hausarztpatienten.

It is unclear whether depressive symptoms are a risk factor for incident diabetes or diabetes is a risk factor for depressive conditions. Therefore, we examined the longitudinal bidirectional associations between depressive symptoms and type 2 diabetes (T2D) as well as the impact of both diseases on (all cause) mortality in a sample of primary care patients over a 3.5-years follow-up period on average. Depressive symptomatology, defined by the Depression Screening Questionnaire (DSQ), was examined both categorically and dimensionally. Patients were categorized as normal fasting glucose (NFG), impaired fasting glucose (IFG), and T2D (untreated, oral antidiabetics, insulin/combined treatment) according to physician ratings and baseline lab values. Incidence rates of T2D were 25.6 and 20.9 per 1000 person-years for those with and without depressive symptoms, respectively. The unadjusted risk of incident type 2 diabetes was 1.03 times higher (CI(95%): 1.01-1.06) for each 1-point increment in DSQ score. The incidence rates of elevated depressive symptoms per 1000 person-years were 30.5 for NFG, 34.2 for IFG, 36.4 for untreated T2D, 32.3 for oral treated T2D, and 47.8 for insulin/combined-treated T2D patients. Compared to NFG patients, insulin-treated patients had a higher risk of incident depressive symptoms (HR: 1.71; CI(95%): 1.03-2.83) and oral-treated patients had a lower risk (HR: 0.58; CI(95%): 0.36-0.96). Higher mortality rates were associated with both diseases compared to patients without T2D or depressive symptoms at baseline (HR: 2.49; CI(95%):1.45-4.28). Results indicate that especially insulin treatment in T2D patients is associated with incident depressive symptoms.

[Individual risk screening and visualization as a central element of health days through the interactive electronic GloRiA program]. / Individuelles Risikoscreening und Visualisierung als zentrales Element von Gesundheitstagen. Einsatz des interaktiven elektronischen GloRiA-programms.

BACKGROUND: Health days are an established forum for prevention and health promotion for different groups in the general population. Through the use of modular questionnaires "Global Risk Assessment" (GloRiA) on computers (handheld and desktop), the recording of patient data and presentation of the results can be optimized. Possible applications include identification of risk factors, early detection of patients at risk, epidemiology and health services research, promotion of patient adherence by visualizations (e.g. risk scores). Up to 12 different question modules are available (e.g. risk for the occurrence of cardiovascularevents by Framingham score, forfuture riskof diabetes mellitus using FindRisk score, smoking, COPD, pain, comorbidities). METHODS AND RESULTS: During 57 health days in 2010 and 2011, data were collected from 3451 persons (53% women, mean age 59.6 +/- 15.4 years) using GloRiA. The percentage of former smokers was 32.7%, while that of current smokers was 14.7%. The average 10-year risk based on the Framingham score (calculated with 1739 persons) in 53.7% of respondents was at <10%, in 37.0% at 10-20%, and in 9.3% at > 20%. In men risk was higher than in women. Smoking cessation would theoretically reduce the mean 10-year risk from 10.9 +/- 9.2% to 7.4 +/- 6.6%. In 50.5% of participants blood pressure measurement revealed elevated values, and in 10% or 2%, respectively, a moderately high or high 10-year riskof incident diabetes mellitus according to FindRisk. CONCLUSION: The use of GloRiA for the consolidation of health data under the framework of health days provides new and sustained possibilities in early detection of cardiovascular disease. The calculation and visualization of risks and the impact of treatment decisions, e.g. reduction of cardiovascular risk by smoking cessation, were communicated directly to the participants. The individual health report facilitates the diagnostic procedures bya physician.

Management of patients with peripheral arterial disease in primary care: a cross-sectional study in Germany.

BACKGROUND: Studies in the primary care setting are of high interest for assessing the management situation of patients with manifestations of atherothrombosis. AIMS: Therefore, we documented diagnostic procedures, characteristics, and management of patients with symptomatic and asymptomatic peripheral arterial disease (PAD). MATERIALS & METHODS: Prospective cross-sectional study in primary care practices throughout Germany. RESULTS: A total of 671 patients with newly diagnosed PAD were included (mean age 69.1 years; 62.1% men). Cardiovascular risk factors were highly prevalent in the total PAD group: arterial hypertension in 84.2%, hyperlipidaemia in 75.5%, present smoking in 45.0% and diabetes mellitus in 47.3%. Atherothrombotic comorbidities were also frequent: coronary artery disease in 44.9% and cerebrovascular disease in 28.1%. For confirmation of diagnosis, patients were referred to specialists in 66.9% of cases. Overall, ankle brachial index was measured in 89.0%, and a clinical PAD score assessed in 66.6% (agreement of both measures with Cohen's kappa only, kappa = 0.039; p = 0.209). Drug treatment of risk factors (as secondary prophylaxis) in line with current guidelines was reported in a high percentage of patients: 88.6% with any antiplatelet drug, 69.3% with statins, 62.4% with angiotensin converting enzyme inhibitors, 23.5% with AT(1) receptor blockers and 43.9% with beta-blockers. Between asymptomatic and symptomatic PAD, differences in the risk factor/comorbidity profiles were small; however, the latter group received intensified treatment. CONCLUSION: Our findings confirm that patients with PAD pose a substantial challenge to physicians because of their high number of comorbidities. Compared with previous studies, management of such patients appears to have improved.

Endothelin receptor selectivity in chronic kidney disease: rationale and review of recent evidence.

Endothelin (ET) is a potent vasoconstrictory peptide with proinflammatory and profibrotic properties that exerts its biological effects through two pharmacologically distinct receptor subtypes, namely ET(A) and ET(B). In addition to its substantial contribution to normal renal function, a large body of evidence suggests that derangement of the renal ET system is involved in the initiation and progression of chronic kidney disease (CKD) in diabetes, hypertension and glomerulonephritis. Thus, the use of ET receptor antagonists (ERAs) may offer potential novel treatment strategies in CKD. Recent literature on the role of the renal ET system in the healthy kidney was reviewed. In addition, an unbiased PubMed search was performed for studies published during the last 5 years that addressed the effects of ERAs in CKD. A particular objective was to extract information regarding whether selective or nonselective ERAs may have therapeutic potential in humans. ET-1 acts primarily as an autocrine or paracrine factor in the kidney. In normal physiology, ET-1 promotes diuresis and natriuresis by local production and action through ET(B) receptors in the renal medulla. In pathology, ET-1 mediates vasoconstriction, mesangial-cell proliferation, extracellular matrix production and inflammation, effects that are primarily conveyed by ET(A) receptors. Results obtained in animal models and in humans with the use of ERAs in CKD are encouraging; nevertheless, it is still under debate which receptor subtype should be targeted. According to most studies, selective inhibition of ET(A) receptors appears superior compared with nonselective ERAs because this approach does not interfere with the natriuretic, antihypertensive and ET clearance effects of ET(B) receptors. Although preliminary data in humans are promising, the potential role of ERAs in patients with CKD and the question of which receptor subtype should be targeted can only be clarified in randomized clinical trials.

Bleeding events in pulmonary arterial hypertension.

Despite limited evidence from clinical studies, anticoagulant drugs such as vitamin K antagonists (VKA) (e.g., warfarin or phenprocoumon) are widely used in the background treatment of patients with pulmonary arterial hypertension (PAH). According to current guidelines, they are generally accepted as efficacious drugs, although their efficacy is neither supported by randomised controlled trials, nor formally approved by regulatory agencies for use in the specific PAH indication. The use of these drugs is not without problems, as a paradoxical situation has to be managed in the treatment of this condition. On one hand, thrombosis is one of the key pathophysiologic features of PAH (besides vasoconstriction, proliferation and inflammation). On the other hand, the incidence of bleeding events is increased in PAH patients. This applies particularly to PAH that is related to connective tissue diseases, congenital heart disease and chronic thromboembolic pulmonary hypertension. In patients receiving VKA, caution must be observed in particular when concomitantly using prostanoids or sildenafil. Similarly, VKA doses have to be adjusted according to the labelling when using sitaxentan concomitantly. Regular International Normalized Ratio monitoring contributes to the safety of PAH patients on VKA.

The role of gender and anxiety in the association between somatic diseases and depression: findings from three combined epidemiological studies in primary care.

AIMS: Although associations between various somatic diseases and depression are well established, findings concerning the role of gender and anxiety disorders for these associations remain fragmented and partly inconsistent. Combining data from three large-scaled epidemiological studies in primary care, we aim to investigate interactions of somatic diseases with gender and anxiety disorders in the association with depression. METHODS: Self-reported depression according to the International Classification of Diseases, Tenth Edition (ICD-10) was assessed in n = 83 737 patients from three independent studies [DETECT (Diabetes Cardiovascular Risk Evaluation: Targets and Essential Data for Commitment of Treatment), Depression-2000 and Generalized Anxiety and Depression in Primary Care (GAD-P)] using the Depression Screening Questionnaire (DSQ). Diagnoses of depression, anxiety disorders and somatic diseases were obtained from treating physicians via standardised clinical appraisal forms. RESULTS: In logistic regressions, adjusted for gender, age group and study, each somatic disease except for arterial hypertension and endocrine diseases was associated with self-reported depression (odds ratio, OR 1.3-2.6) and each somatic disease was associated with physician-diagnosed depression (OR 1.1-2.4). Most of these associations remained significant after additional adjustment for anxiety disorders and other somatic diseases. The associations with depression increased with a higher number of somatic diseases. Cardiovascular diseases (OR 0.8), diabetes mellitus (OR 0.8) and neurological diseases (OR 0.8) interacted with gender in the association with self-reported depression, while endocrine diseases (OR 0.8) interacted with gender in the association with physician-diagnosed depression. That is, the associations between respective somatic diseases and depression were less pronounced in females v. males. Moreover, cardiovascular diseases (OR 0.7), arterial hypertension (OR 0.8), gastrointestinal diseases (OR 0.7) and neurological diseases (OR 0.6) interacted with anxiety disorders in the association with self-reported depression, and each somatic disease interacted with anxiety disorders in the association with physician-diagnosed depression (OR 0.6-0.8). That is, the associations between respective somatic diseases and depression were less pronounced in patients with v. without anxiety disorders; arterial hypertension was negatively associated with self-reported depression only in patients with anxiety disorders, but not in patients without anxiety disorders. CONCLUSIONS: A range of somatic diseases as well as anxiety disorders are linked to depression - and especially patients with co-/multi-morbidity are affected. However, interactions with gender and anxiety disorders are noteworthy and of relevance to potentially improve recognition and treatment of depression by physicians. Somatic diseases are associated more strongly with depression in males v. females as well as in patients without v. with anxiety disorders, primarily because women and patients with anxiety disorders per se are characterised by considerably increased depression prevalence that only marginally changes in the presence of somatic comorbidity.

Screening for PAH in patients with systemic sclerosis: focus on Doppler echocardiography.

It is well established that patients with CTDs such as SSc carry a considerable risk of developing pulmonary arterial hypertension (PAH). Such SSc-PAH patients have an even worse prognosis than patients with only one of these two conditions. In view of the high incidence and prevalence of PAH in SSc, and the available treatment options that improve quality of life, exercise capacity and possibly survival, systematic screening has been recommended. The present article reviews current recommendations from PAH guidelines, focusing on studies that used Doppler echocardiography for screening, and describes limitations associated with the procedure. Furthermore, characteristics and parameters used to identify patients at high risk of developing PAH are summarized.

Unmet needs in the diagnosis and treatment of dyslipidemia in the primary care setting in Germany.

OBJECTIVES AND METHODS: DETECT is a cross-sectional study of 55,518 unselected consecutive patients in 3188 representative primary care offices in Germany. In a random subset of 7519 patients, an extensive standardized laboratory program was undertaken. The study investigated the prevalence of cardiovascular disease, known risk factors (such as diabetes, hypertension and dyslipidemia and their co-morbid manifestation), as well as treatment patterns. The present analysis of the DETECT laboratory dataset focused on the prevalence and treatment of dyslipidemia in primary medical care in Germany. Coronary artery disease (CAD), risk categories and LDL-C target achievement rates were determined in the subset of 6815 patients according to the National Cholesterol Education Program (NCEP) ATP III Guidelines. RESULTS: Of all patients, 54.3% had dyslipidemia. Only 54.4% of the NCEP-classified dyslipidemic patients were diagnosed as 'dyslipidemic' by their physicians. Only 27% of all dyslipidemic patients (and 40.7% of the recognized dyslipidemic patients) were treated with lipid-lowering medications, and 11.1% of all dyslipidemic patients (41.4% of the patients treated with lipid-lowering drugs) achieved their LDL-C treatment goals. In conclusion, 80.3% of patients in the sample with dyslipidemia went undiagnosed, un-treated or under-treated.

Cardiovascular risk factors in primary care: methods and baseline prevalence rates--the DETECT program.

OBJECTIVES: DETECT is an epidemiological study in primary care to examine (a) the prevalence rates and comorbidity of diabetes mellitus, hypertension, hyperlipidaemia and coronary heart disease (CHD), and associated conditions; (b) the frequency of behavioural and clinical risk factors for onset and progression; (c) the 12-month course and outcome; and (d) the met and unmet needs for these patients. METHODS: Three-stage, cross-sectional clinical-epidemiological study with a prospective-longitudinal component in a nationally representative sample of N = 3795 primary care settings [response rate (RR): 60.2%] and N = 55518 patients (RR: 95.5%). Patients completed a standardized assessment, including questionnaires for patients and the physician and diagnostic screening measures (i.e. blood pressure, heart rate, body mass index and waist circumference assessments). A subsample of patients (N = 7519) also completed a standardized laboratory screening program and was followed-up after 12 months. Data were weighted to adjust for non-response, regional distribution and attrition. RESULTS: (1) Doctors and patients sample can be regarded as representative for primary care settings in Germany. (2) The clinician-rated point prevalence of hypertension is highest (35.5%), followed by hyperlipidaemia (29.1%), diabetes (14.1%) and CHD (12.1%); prevalence rates of each disorder as well as their co-incidence rates increase markedly with age. (3) The vast majority (78%) of all patients revealed multiple (3+) behavioural and clinical risk factors. CONCLUSION: The findings of DETECT underline the considerable burden for primary care doctors in managing a highly morbid patient population, with predominantly complex risk factor constellations, in routine care. Our data provide, in unprecedented detail, a basis for calculating age-, gender- and risk-group-adjusted risk-factor profiles in routine care.

One-year safety and quality of life outcomes in patients with atrial fibrillation on dronedarone: prospective, non-interventional study in German ambulatory care.

BACKGROUND AND AIMS: The multichannel blocker dronedarone is currently indicated for the maintenance of sinus rhythm after successful cardioversion in adult clinically stable patients with paroxysmal or persistent atrial fibrillation (AF), with careful monitoring of cardiac, hepatic and renal function. We aimed to investigate patients' quality of life (QoL) and tolerability and effectiveness of dronedarone under real life conditions. METHODS: In the 1-year prospective, non-interventional IMPULS study, 161 office-based cardiologists, general practitioners and internists throughout Germany documented 549 patients with AF who were currently or newly prescribed dronedarone (safety set, SS). Of those, 342 patients (full analysis set, FAS) provided data on QoL at baseline, 6 months and 12 months). RESULTS: Mean age of patients was 67.6/66.3 years; 53.0 %/57.3 % were men (SS/FAS). AF type at inclusion in the SS/FAS was paroxysmal in 71.9 %/71.3 % and persistent in 26.0 %/26.6 % (missing in 2.0 %/2.0 %). The proportion of patients in sinus rhythm increased from 44.6 % at baseline to 70.2 % (SS). The mean value on the 100-point visual analogue scale (EuroQol EQ-5D) increased from 62.3 ± 17.1 at baseline by 11.4 ± 18.7 points (FAS, p<0.0001). The AF-QoL Psychological Domain improved from 44.6 ± 22.6 at baseline by 16.0 ± 23.5 points at 1 year (p<0.0001), the AF-QoL physical domain from 49.5 ± 22.1 by 10.9 ± 22.5 points (p<0.0001), and the AF-QoL sexual domain from 61.8 ± 27.1 by 6.6 ± 28.2 points (p<0.0001). In all, 136 patients (24.8 % of all patients in the safety set) had at least one adverse drug reaction (ADR) causally related to dronedarone. CONCLUSIONS: Various dimensions of quality of life of patients with AF were improved on dronedarone under clinical practice conditions. No previously unknown safety issues were noted.

The impact of age on the benefits and risks of aliskiren treatment: analyses of the 3A registry.

We aimed to analyze benefits and risks of aliskiren treatment in older adults (⩾ 65 years) in clinical practice. Patients (n = 14,986) were assigned to either aliskiren (ALIS), an angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker (ACEi/ARB), or an agent not blocking the renin-angiotensin system (non-RAS). Older adults (n = 7396) had a longer history of hypertension (8.7 vs 4.7 years; P < 0.0001), lower mean diastolic blood pressure (DBP; 87.7 ± 11.0 vs 92.1 ± 11.0 mm Hg) and more renal (12.0 vs 5.6%; P < 0.0001) or cardiovascular disease (44.0 vs 18.9%; P < 0.0001); 4548 received aliskiren (68.8%), 1215 ACEi/ARBs (18.4%) and 850 non-RAS treatments (12.9%). Office BP at 1 year was reduced by 18.4 ± 21.5/7.2 ± 12.0 mm Hg. BP reductions were greater (19.5 ± 21.7/7.6 ± 12.1 mm Hg) in the aliskiren group than in the ACEi/ARB (15.6 ± 20.9/6.4 ± 11.9) and non-RAS groups (16.1 ± 20.7/6.5 ± 11.7 mm Hg), respectively (P<0.0001 for systolic BP (SBP) and <0.01 for DBP). After multivariable adjustment, differences in SBP reductions were clinically irrelevant and no differences were noted for DBP. Adverse effects were higher in older adults with no differences between treatment groups. In conclusion, the present analysis of a large, unselected cohort of patients in clinical practice from the 3A study, offers real-life evidence of the effectiveness and safety of aliskiren for the treatment of hypertension in older adults.

Different concepts in first-line treatment of essential hypertension. Comparison of a low-dose reserpine-thiazide combination with nitrendipine monotherapy. German Reserpine in Hypertension Study Group.

Low-dose combination therapy has been proposed as a rational first-line approach to hypertension treatment. We compared the efficacy and tolerability of the fixed combination of reserpine (0.1 mg) plus the thiazide clopamid (5 mg) with its single components and the calcium-antagonist nitrendipine (20 mg) in a randomized, double-blind, parallel study of 273 hypertensive patients with diastolic blood pressure (BP) between 100 and 114 mm Hg. The four groups did not differ regarding baseline characteristics (mean age, 58 years; 51% men; mean BP after a 2-week placebo period, 158 to 160/103 to 104 mm Hg). After 6 weeks of treatment with one capsule daily, mean reductions in sitting BP from baseline at 24 hours after dosing in the reserpine-clopamid combination, reserpine, clopamid, and nitrendipine groups were -23.0/-17.1, -14.0/-11.7, -13.6/-11.9, and -11.6/-12.3 mm Hg, respectively (2P < .01). The corresponding normalization rates (diastolic BP < 90 mm Hg) were 55%, 40%, 36%, and 33% (2P = .11). All patients whose BP had not been normalized at this point received two capsules of the respective medication once daily from weeks 7 to 12. At week 12, mean BP reductions were -25.7/-18.1, -14.6/-12.2, -17.7/-13.4, and -14.9/-15.3 mm Hg in the four groups, respectively (2P < .01). The respective normalization rates were 69%, 35%, 39%, and 45% (2P < .0001). Linear regression modeling indicated that reserpine and clopamid combined acted more than additively. As regards tolerability, adverse experiences were observed in 27%, 28%, 29%, and 48% of patients, respectively (2P < .05). The respective rates of premature discontinuation because of adverse effects were 3%, 3%, 7%, and 13% (2P = .06). In conclusion, a low-dose combination of reserpine and clopamid lowered BP significantly more than both the components alone and nitrendipine. Moreover, the combination was tolerated as well as its components and significantly better than nitrendipine. Thus, the use of this low-dose reserpine-thiazide combination appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension.

Artesunate and mefloquine given simultaneously for three days via a prepacked blister is equally effective and tolerated as a standard sequential treatment of uncomplicated acute Plasmodium falciparum malaria: randomized, double-blind study in Thailand.

The combination of artesunate and mefloquine is currently one of the most effective treatments against multidrug-resistant Plasmodium falciparum malaria. To improve patient compliance to such a combination, the two agents have been combined in a prepacked single blister. Patients were instructed to simultaneously co-administer the drugs once a day for three days. In the present randomized, double-blind, parallel group, comparative, single center study in Thailand, this concept was investigated in 204 adults and children with acute, uncomplicated P. falciparum malaria. Patients were randomized into two treatment groups and received once a day over a three-day period the following: Group A received artesunate, 4-5 mg/kg/day, and mefloquine, total dose = 25 mg/kg, approximately 8.5 mg/kg/day, simultaneously. Group B received artesunate, 4-5 mg/kg/day, and mefloquine, total dose = 25 mg/kg, sequentially (i.e., no mefloquine dose on the first day, 15 mg/kg on the second day, and 10 mg/kg on the third day). Both treatment groups showed no relevant differences in baseline demographic and clinical characteristics. Intent-to-treat analysis revealed a cure rate at day 28 (primary endpoint) of 100% in group A and 99% in group B (difference not significant). The secondary endpoints of mean time to fever clearance (group A = 34 hours, group B = 31 hours) and mean time to parasite clearance (group A = 44 hours group B = 48 hours) were similar between groups (both differences not significant). Tolerability was good in both treatment groups, with no difference in the overall incidence of adverse events. There was a low incidence of nausea/vomiting (4.9% in both groups) and central nervous system side effects (4.9% in group A versus 8.8% in group B). These were comparable between groups and generally of a mild nature. The three-day combination of artesunate and mefloquine (Artequin, Mepha, Ltd., Aesch, Switzerland) with the introduction of mefloquine on day 1 offers a practical dosing regimen that is highly effective and well tolerated in patients of different ages with uncomplicated P. falciparum malaria. It is likely that the prepacked blister approach translates clinically into a better patient compliance, thereby contributing to limit the development of drug resistance.

The effect of irbesartan in reducing cardiovascular risk in hypertensive type 2 diabetic patients: an observational study in 16,600 patients in primary care.

OBJECTIVES: As arterial hypertension substantially increases the risk of premature death, cardiovascular disease and renal insufficiency in patients with type 2 diabetes, effective and safe antihypertensive therapy is of importance. Therefore, the effect of irbesartan as monotherapy, or in fixed combination with hydrochlorothiazide, on blood pressure, metabolic parameters and microalbuminuria and the safety and tolerability of the drug were assessed. RESEARCH DESIGN AND METHODS: Multicentric, prospective, open phase IV study over 3 months in 16,600 patients with the clinical diagnoses of hypertension and type 2 diabetes. Blood pressure was measured sphygmometrically and albuminuria was assessed with semi-quantitative urine dipsticks. MAIN OUTCOME MEASURES: Systolic (SBP) and diastolic (DBP) blood pressure reduction, proportion of patients with microalbuminuria and cardiovascular risk calculated based on the SCORE score, each after a follow-up of 3 months compared to baseline. Number and nature of adverse events (AEs). RESULTS: The sample consisted of 51.3% men, mean age was 62.2+/-10.7 years, 53.9% of patients were overweight and 26.4% were obese. Mean SBP/DBP decrease after 3 months was 22.3/11.2 mmHg. The BP lowering effect was similar in the analyses of various subgroups (according to age group, sex, presence of micro- or macrovascular complications). Irbesartan treatment reduced the percentage of patients with microalbuminuria from 45.6% to 30.6% at 3 months (32.9% relative reduction). Metabolic parameters (lipids, blood glucose, HbA1c) and weight were improved significantly or showed trends for improvement, respectively. The mean 10-year cardiovascular risk as calculated with the SCORE score was decreased from a baseline value of 9.8% to 5.7% (-58% relative reduction). Tolerability was excellent: only 0.3% experienced an AE. CONCLUSIONS: Treatment with irbesartan in patients with concomitant hypertension and type 2 diabetes led to large blood pressure reductions. In view of the renoprotective effect documented by the reduced rate of patients with albuminuria, and the improvement of further metabolic parameters, these changes translate into a reduction of cardiovascular risk.