Panagiotis Stafylas

The controversial effects of thiazolidinediones on cardiovascular morbidity and mortality

Cardiovascular morbidity and mortality in patients with type 2 diabetes are a major problem in clinical practice. Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator-activated receptor gamma which improve glycaemic control by reducing insulin resistance. TZDs also seem to have beneficial effects on various cardiovascular risk factors and consequently may have the potential to reduce the risk of cardiovascular disease (CVD). Although the first large-scale clinical trial evaluating the effect of a TZD on secondary prevention of major adverse cardiovascular outcomes supported this hypothesis, a recently published meta-analysis raised substantial uncertainty about the cardiovascular safety of rosiglitazone. This article summarises the evidence from completed and ongoing outcome trials with TZDs, as well as the recent meta-analytic data on their cardiovascular safety, aiming to provide an up-to-date and balanced view of a very important field. Data from clinical trials consistently indicate that treatment with glitazones significantly increase the risk of heart failure. Despite the fact that rosiglitazone and pioglitazone have much more similarities than differences with regards to their effects on cardiovascular risk factors, pioglitazone seems to have more favourable effects on major cardiovascular outcomes. This issue also highlights the potential hazards involved in using surrogate end-points for drug approval.

Effects of Renin–Angiotensin System Blockers on Renal Outcomes and All-cause Mortality in Patients With Diabetic Nephropathy: An Updated Meta-analysis

BACKGROUND In contrast to previous studies, recent data questioned the ability of renin-angiotensin-aldosterone system (RAAS) blockers to delay progression of diabetic nephropathy. This study evaluated the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in patients with diabetic nephropathy. METHODS A systematic literature search of MEDLINE/PubMed and EMBASE databases was performed to identify randomized trials published up to June 2007 comparing the effects of ACEIs or ARBs with placebo and/or a regimen not including a RAAS blocker on the incidence of end-stage renal disease (ESRD), doubling of serum creatinine (DSC), or death from any cause in patients with diabetic nephropathy. Treatment effects were summarized as relative risks (RRs) using the Mantel-Haenszel fixed-effects model. RESULTS Of the 1,028 originally identified studies, 24 fulfilled the inclusion criteria (20 using ACEIs and 4 using ARBs). Use of ACEIs was associated with a trend toward reduction of ESRD incidence (RR 0.70; 95% confidence interval (CI) 0.46-1.05) and use of ARBs with significant reduction of ESRD risk (RR 0.78; 95% CI 0.67-0.91). Both drug classes were associated with reduction in the risk of DSC (RR 0.71; 95% CI 0.56-0.91 for ACEIs and RR 0.79; 95% CI 0.68-0.91 for ARBs) but none affected all-cause mortality (RR 0.96; 95% CI 0.85-1.09 for ACEIs and RR 0.99; 95% CI 0.85-1.16 for ARBs). CONCLUSION Treatment of patients with diabetic nephropathy with a RAAS blocker reduces the risks of ESRD and DSC, but does not affect all-cause mortality. These findings are added to the evidence of a renoprotective role of RAAS blockers in such patients.

The medical and socioeconomic burden of heart failure: A comparative delineation with cancer

Cardiovascular disease and cancer represent the two leading causes of death in the Western World. Still, cardiovascular disease causes more deaths and more hospitalizations than cancer. Although mortality rates of both conditions are generally declining, this is not true for heart failure (HF). The prevalence of HF is increasing, although its incidence has been stabilized, mainly because of the population aging. The survival of patients with HF is overall worse than those with cancer. In addition, HF failure is the most common reason for hospitalization in the elderly, while hospitalization for HF is followed by adverse prognosis and represents the main contributor to the huge financial expenditure caused by the syndrome. The outcome of HF patients and thus its medical and socioeconomic burden may be improved by the more efficient in-hospital management of patients, the enhancement of adherence to guideline-recommended therapies, the identification and treatment of comorbid conditions and the introduction of more effective medical therapies.

Generic and therapeutic substitution: a viewpoint on achieving best practice in Europe

Given the current financial climate there is an ever increasing need to substitute drug treatments to optimize expenditure. A closer examination of the beliefs surrounding when substitution is appropriate led a group of European healthcare experts to argue that in some cases these beliefs may be unfounded and that guidelines are needed for clinical practice.

Association between copayment, medication adherence and outcomes in the management of patients with diabetes and heart failure

OBJECTIVE To determine the association between copayment, medication adherence and outcomes in patients with Heart failure (HF) and Diabetes Mellitus (DM). METHODS PubMed, Scopus and Cochrane databases were searched using combinations of four sets of key words for: drug cost sharing; resource use, health and economic outcomes; medication adherence; and chronic disease. RESULTS Thirty eight studies were included in the review. Concerning the direct effect of copayment changes on outcomes, the scarcity and diversity of data, does not allow us to reach a clear conclusion, although there is some evidence indicating that higher copayments may result in poorer health and economic outcomes. Seven and one studies evaluating the relationship between copayment and medication adherence in DM and HF population, respectively, demonstrated an inverse statistically significant association. All studies (29) examining the relationship between medication adherence and outcomes, revealed that increased adherence is associated with health benefits in both DM and HF patients. Finally, the majority of studies in both populations, showed that medication adherence was related to lower resource utilization which in turn may lead to lower total healthcare cost. CONCLUSION The results of our systematic review imply that lower copayments may result in higher medication adherence, which in turn may lead to better health outcomes and lower total healthcare expenses. Future studies are recommended to reinforce these findings.

PCV58 COST-EFFECTIVENESS OF INDAPAMIDE IN PATIENTS WITH MILD-TO-MODERATE HYPERTENSION

PCV57 COST-EFFECTIVENESS OF NEBIVOLOL VERSUS ATENOLOL AND ACE INHIBITOR MONOTHERAPY IN PATIENTS WITH MODERATE HYPERTENSION Lippert B, Brüggenjürgen B,Willich SN MERG, Medical Economics Research Group, Munich, Germany; Charité—Universitätsmedizin Berlin, Institut für Sozialmedizin, Epidemiologie und Gesundheitsökonomie, Berlin, Germany OBJECTIVE: To assess the cost-effectiveness of antihypertensive treatment with nebivolol, atenolol or ACE inhibitor monotherapy in 60-year and 70-year-old patients with moderate hypertension in Germany. METHODS: Using a decision-analytic Markov model, we determined incremental cost-effectiveness ratios (ICER) of treatment with nebivolol, atenolol and ACE inhibitor monotherapy from third party payers’ perspective over a 5-year time horizon. Effects on diastolic blood pressure were obtained from a pooled analysis of published randomized clinical trials using response and compliance data. The 5-year absolute risk for an initial coronary, cerebrovascular event or cardiovascular death was computed using the gender specific algorithm based on Framingham Heart Study data. Costs were derived from published tariff lists. Direct medical costs per patient included cost of drug treatment over the 5-year period and cost of acute care for coronary and cerebrovascular events. RESULTS: The comparison of nebivolol vs. ACE inhibitors showed that 3.5 (60-year-old men) and 3.4 (70-year-old men) life years more per 100 patients could be gained with nebivolol. With higher incremental costs, ICER for nebivolol versus ACE inhibitors was €2025 (60-year-old men) and €1824 (70-year-old men). In comparison to atenolol, 6.3 (60-year-old men) and 5.7 (70-year-old men) life years more per 100 patients could be gained. ICER for nebivolol versus atenolol was €4672 (60-yearold men) and €4704 (70-year-old men) per life-year gained. For women, the number of incremental life years gained was lower. ICER for nebivolol versus ACE inhibitors were €2347 (60-yearold women) and €1,904 (70-year-old women) and for nebivolol versus atenolol €11,648 (60-year-old women) and €9060 (70year-old women) per life-year gained. CONCLUSION: Based on our decision analysis, the use of nebivolol was more effective than antihypertensive therapy with ACE inhibitors and atenolol. Antihypertensive treatment with nebivolol is a cost-effective treatment option from third party payer’s perspective in Germany in the selected patient groups.