Usage, Risk, and Benefit of Weight-Loss Drugs in Primary Care

Purpose. To investigate the use of the weight-loss drugs rimonabant, sibutramine, and orlistat in primary care and to characterize the patients receiving the drugs. Methods. In this retrospective, descriptive study, 300 randomly selected patients having started weight-loss drug treatment at 15 primary care centres were investigated using the patient's medical records and their complete drug purchase data. Results. Even though 48% of the patients specifically demanded drug treatment, 77% continued treatment less than one year. 28% of rimonabant patients and 32% of sibutramine patients had a history of depression or antidepressant treatment. 41% of sibutramine patients had a history of hypertension and/or cardiovascular disease. 36% had no documented weight after treatment initiation. Conclusions. These results suggest that weight-loss drug treatment was often initiated upon patient request but was of limited clinical benefit as it was managed in a large portion of Swedish primary carecenters

Increased platelet reactivity and platelet–leukocyte aggregation after elective coronary bypass surgery

Inflammatory mechanisms are activated, and thrombotic complications occur during the initial months after coronary artery bypass grafting (CABG). Therefore, changes over time of platelet activation and platelet–leukocyte interactions after CABG are of interest. Whole-blood flow cytometry was performed before, and 4–6 days, one month, and three months after elective CABG in 54 men with stable coronary artery disease treated with acetylsalicylic acid (ASA). Single platelets and platelet–leukocyte aggregates (PLAs) among monocytes (P-Mon), neutrophils (P-Neu), and lymphocytes (P-Lym) were studied without and with stimulation by submaximal concentrations of ADP, thrombin, and the thromboxane analog U46619. White blood cell counts were increased during the initial postoperative course, and platelet counts were increased after one month. Platelet P-selectin expression was significantly enhanced at one month when stimulated by thrombin and U46619 and at three months with ADP and thrombin. All PLAs subtypes were increased at one month without stimulation in vitro. P-Mon and P-Neu stimulated by ADP, thrombin, or U46619 were significantly increased one month after the operation but decreased compared to baseline at three months. Agonist stimulated P-Lyms were increased at one month and remained increased at three months after ADP stimulation. There was significant platelet activation and formation of PLAs unstimulated and after agonist stimulation by ADP, thrombin, and a thromboxane analog after CABG in patients with stable coronary artery disease irrespective of ASA treatment. Changes observed up to three months after CABG support further studies of the clinical implications of protracted increases in platelet activation and platelet–leukocyte interactions

990-53 Effects on Cardiovascular End Points and Psychological Variables of Metoprolol and Verapamil in Patients with Stable Angina Pectoris — The Angina Prognosis Study in Stockholm (APSIS)

The effect of treatment with metoprolol or verapamil was investigated in 809 patients with stable angina pectoris. End points for the study were: death, nonfatal cardiovascular events and three psychological variables reflecting aspects of quality of life. Nonfatal cardiovascular events included acute myocardial infarction, incapacitating or unstable angina, cerebrovascular and peripheral vascular events. The psychological variables were aggregate measures of psychosomatic symptoms and sleep disturbances and an evaluation of life satisfaction on a visual analogue scale. The mean age of the patients was 59±7 years and 30% were women. The patients were followed for a total of 2887 patient years, with a median follow-up time of 3.6 years. Total cardiovascular mortality in the metoprolol versus verapamit group were 5.4% versus 6.2% and 4.7% versus 4.7% respectively. Nonfatal cardiovascular events occurred in 26.4 and 24.1%, respectively. Psychosomatic symptoms and sleep disturbances were significantly improved in both treatment groups. The magnitude of change was small and not significantly different. Life satisfaction did not change on either drug. Withdrawals due to side effects occurred in 11.1 and 14.6%, respectively.ConclusionThis large scale long term study shows that both drugs were well tolerated and had the same effect on mortality, cardiovascular end points and measures of quality of life

Oral anticoagulants in patients with atrial fibrillation at low stroke risk: a multicentre observational study

AIMS: There is currently no consensus on whether atrial fibrillation (AF) patients at low risk for stroke (one non-sex-related CHA2DS2-VASc point) should be treated with an oral anticoagulant. METHODS AND RESULTS: We conducted a multi-country cohort study in Sweden, Denmark, Norway, and Scotland. In total, 59 076 patients diagnosed with AF at low stroke risk were included. We assessed the rates of stroke or major bleeding during treatment with a non-vitamin K antagonist oral anticoagulant (NOAC), a vitamin K antagonist (VKA), or no treatment, using inverse probability of treatment weighted (IPTW) Cox regression. In untreated patients, the rate for ischaemic stroke was 0.70 per 100 person-years and the rate for a bleed was also 0.70 per 100 person-years. Comparing NOAC with no treatment, the stroke rate was lower [hazard ratio (HR) 0.72; 95% confidence interval (CI) 0.56-0.94], and the rate for intracranial haemorrhage (ICH) was not increased (HR 0.84; 95% CI 0.54-1.30). Comparing VKA with no treatment, the rate for stroke tended to be lower (HR 0.81; 95% CI 0.59-1.09), and the rate for ICH tended to be higher during VKA treatment (HR 1.37; 95% CI 0.88-2.14). Comparing NOAC with VKA treatment, the rate for stroke was similar (HR 0.92; 95% CI 0.70-1.22), but the rate for ICH was lower during NOAC treatment (HR 0.63; 95% CI 0.42-0.94). CONCLUSION: These observational data suggest that NOAC treatment may be associated with a positive net clinical benefit compared with no treatment or VKA treatment in patients at low stroke risk, a question that can be tested through a randomized controlled trial

Forecasting drug utilization and expenditure in a metropolitan health region

<p>Abstract</p> <p>Background</p> <p>New pharmacological therapies are challenging the healthcare systems, and there is an increasing need to assess their therapeutic value in relation to existing alternatives as well as their potential budget impact. Consequently, new models to introduce drugs in healthcare are urgently needed. In the metropolitan health region of Stockholm, Sweden, a model has been developed including early warning (horizon scanning), forecasting of drug utilization and expenditure, critical drug evaluation as well as structured programs for the introduction and follow-up of new drugs. The aim of this paper is to present the forecasting model and the predicted growth in all therapeutic areas in 2010 and 2011.</p> <p>Methods</p> <p>Linear regression analysis was applied to aggregate sales data on hospital sales and dispensed drugs in ambulatory care, including both reimbursed expenditure and patient co-payment. The linear regression was applied on each pharmacological group based on four observations 2006-2009, and the crude predictions estimated for the coming two years 2010-2011. The crude predictions were then adjusted for factors likely to increase or decrease future utilization and expenditure, such as patent expiries, new drugs to be launched or new guidelines from national bodies or the regional Drug and Therapeutics Committee. The assessment included a close collaboration with clinical, clinical pharmacological and pharmaceutical experts from the regional Drug and Therapeutics Committee.</p> <p>Results</p> <p>The annual increase in total expenditure for prescription and hospital drugs was predicted to be 2.0% in 2010 and 4.0% in 2011. Expenditures will increase in most therapeutic areas, but most predominantly for antineoplastic and immune modulating agents as well as drugs for the nervous system, infectious diseases, and blood and blood-forming organs.</p> <p>Conclusions</p> <p>The utilisation and expenditure of drugs is difficult to forecast due to uncertainties about the rate of adoption of new medicines and various ongoing healthcare reforms and activities to improve the quality and efficiency of prescribing. Nevertheless, we believe our model will be valuable as an early warning system to start developing guidance for new drugs including systems to monitor their effectiveness, safety and cost-effectiveness in clinical practice.</p

Dose-andtime-dependent antiplateleteffects of aspirin Platelets andBlood Cells

Summary Aspirin is widely used,but dosagesindifferentclinical situations and the possible importance of &quot;aspirin resistance&quot; aredebated. We performeda no penc ross-over study comparing no treatment (baseline)with three aspirindosage regimens -37.5 mg/ dayfor 10 days, 320mg/dayfor 7days, and, finally, asingle 640 mg dose (cumulativedose 960mg) -in15healthymale volunteers. Platelet aggregability was assessedinwholeblood(WB)and plateletrich plasma (PRP).The urinaryexcretions of stable thromboxane (TxM)and prostacyclin (PGI-M)metabolites, and bleeding timewerealsomeasured.Platelet COXinhibitionwas nearly complete already at 37.5 mg aspirin daily, as evidencedby&gt;98 % suppression of serumthromboxane B 2 and almost abolishedarachidonicacid (AA) induced aggregation in PRP2-6 hafter dosing. Bleeding timew as similarlyp rolonged by all dosageso fa s- Keywords Platelet function, thromboxane,prostacyclin,acetylsalicylicacid, dosage pirin. Once daily dosing wasa ssociated with considerabler ecovery of AA inducedplateletaggregation inWB after 24 hours, even after 960 mg aspirin.Collageninduced aggregation in WB with normal extracellular calciumlevels(hirudin anticoagulated) wasi nhibited &lt;40%a ta ll dosages. TxMe xcretion was incompletely suppressed, andi ncreased&lt; 24 hoursa fter the cumulative960 mg dose.Aspirin treatment reducedPGI-M already at thelowestdosage (by ≈ 25%), but PGI-M excretion and platelet aggregability were not correlated. Antiplateleteffects of aspirin arelimited in WB with normalcalcium levels.Since recovery of COX-dependent plateletaggregation occurred within 24 hours, oncedailydosing of aspirinmight be insufficientinpatientswith increasedplateletturnover