|
| ||
|
|
||
Cardiovascular Risk Profile (cardiovascular + risk_profile)
Selected AbstractsHaem oxygenase-1 genotype and cardiovascular adverse events in patients with peripheral artery diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2005P. Dick Abstract Background, A functional GT dinucleotide length polymorphism in the haem oxygenase-1 (HO-1) gene promoter is thought to be involved in the pathogenesis of cardiovascular disease. Short (< 25) (GT)n repeats are suggested to facilitate enhanced HO-1 up-regulation in response to injury and confer potent anti-inflammatory and antioxidative effects. Materials and methods, We investigated the association between the HO-1 GT-polymorphism and cardiovascular outcome in 472 patients with advanced peripheral artery disease. Cardiovascular risk profile and DNA samples for determination of the HO-1 genotype (carrier vs. noncarrier of a short (GT)n repeat allele) were obtained at baseline, and patients were followed for median 21 months for the occurrence of coronary events (myocardial infarction, percutaneous coronary interventions and coronary artery bypass graft), cerebrovascular events (stroke or carotid revascularization) and all-cause mortality. Results, Coronary events occurred in 48 patients (9%), cerebrovascular events in 40 patients (9%) and 59 patients (13%) died. In total, 173 major adverse cardiovascular events (MACE) occurred in 133 patients (28%). Carriers of the short (GT)n repeat allele had a 0·46-fold reduced adjusted hazard ratio for coronary events (P = 0·016) as compared to noncarriers. No significant difference was found for cerebrovascular events, mortality and overall MACE. Conclusion, Apparently, the HO-1 genotype exerts potentially protective effects against coronary adverse events in patients with peripheral artery disease. Homozygous and heterozygous carriers of < 25 (GT)n repeats had lower rates of myocardial infarction, percutaneous coronary interventions and coronary bypass operations compared to patients with longer (GT)n repeats. [source] Comparing risk profiles of individuals diagnosed with diabetes by OGTT and HbA1cThe Danish Inter99 studyDIABETIC MEDICINE, Issue 8 2010R. Borg Diabet. Med. 27, 906,910 (2010) Abstract Aims, Glycated haemoglobin (HbA1c) has been proposed as an alternative to the oral glucose tolerance test for diagnosing diabetes. We compared the cardiovascular risk profile of individuals identified by these two alternative methods. Methods, We assessed the prevalence of cardiovascular risk factors in individuals with undiagnosed diabetes according to the World Health Organization classification or by the newly proposed HbA1c level , 6.5% among 6258 participants of the Danish Inter99 study. Receiver operating curve analysis assessed the ability of fasting: 2-h plasma glucose and HbA1c to distinguish between individuals at high and low risk of ischemic heart disease, predicted by the PRECARD program. Results, Prevalence of undiagnosed diabetes was 4.1% [95% confidence interval (CI) 3.7,4.7%] by the current oral glucose tolerance test definition, whereas 6.6% (95% CI 6.0,7.2%) had diabetes by HbA1c levels. HbA1c -defined individuals were relatively older with higher proportions of men, smokers, lipid abnormalities and macro-albuminuria, but they were leaner and had lower blood pressure. HbA1c was better than fasting- and 2-h plasma glucose at distinguishing between individuals of high and low predicted risk of ischaemic heart disease; however, the difference between HbA1c and fasting- and 2-h plasma glucose was not statistically significant. Conclusions, Compared with the current oral glucose tolerance test definition, more individuals were classified as having diabetes based on the HbA1c criteria. This group had as unfavourable a risk profile as those identified by the oral glucose tolerance test. [source] Heterogeneity of non-insulin-dependent diabetes expressed as variability in insulin sensitivity, ,-cell function and cardiovascular risk profileDIABETIC MEDICINE, Issue 1 2003K. I. Birkeland Abstract Aims The present study investigated the variability in insulin sensitivity and ,-cell function and their relationship to anti-glutamic acid decarboxylase (GAD) positivity and the metabolic syndrome in a group of patients with non-insulin-dependent diabetes mellitus (NIDDM). Methods Fifty-four subjects aged 59.5 ± 6.1 (mean ± sd) years with NIDDM for 7.9 ± 3.9 years referred to hospital due to poor glycaemic control, were investigated. Insulin sensitivity was determined by the euglycaemic hyperinsulinaemic glucose clamp technique as the glucose disposal rate relative to the insulin level obtained (GDRI), and also estimated with the homeostasis model assessment (HOMA-S). ,-cell function was measured by assaying the fasting and glucagon-stimulated C-peptide levels and with the HOMA-B. Results The insulin sensitivity varied 18-fold between subjects when estimated with the clamp and six-fold when estimated with HOMA-S, and was lower the more criteria for the metabolic syndrome present (P = 0.0001 by anova). The ,-cell function varied four-fold when measured as stimulated C-peptide, and eight-fold when estimated with the HOMA-B. The levels of fasting C-peptide and HOMA-B values tended to be lower in anti-GAD+ (n = 11) than in anti-GAD,subjects (P = 0.06 and P = 0.08, respectively). From previously published coronary risk charts, we estimated the 10-year risk of a coronary heart disease (CHD) event to be > 20% in 17 of 39 patients free from cardiovascular disease at the time of study, 16 of whom qualified for a diagnosis of the metabolic syndrome. Conclusions The wide variations in insulin sensitivity and ,-cell function found among subjects with NIDDM support the notion that the disorder is highly heterogeneous. Reduced insulin sensitivity was clearly related to the metabolic syndrome and an increased risk for CHD. [source] Relevance of post-methionine homocysteine and lipoprotein (a) in evaluating the cardiovascular risk in young CAD patientsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2005R. Marcucci Abstract Background, Aims of our study were to evaluate the prevalence of high lipoprotein (a) [Lp(a)] and homocysteine levels , both in the fasting state (FHcy) and post-methionine (PMHcy) , in young coronary artery disease (CAD) patients, and to investigate the role of genetic and environmental factors for hyperhomocysteinaemia. Materials and methods, We studied 140 patients with angiographically documented CAD (24 women , 55 years and 116 men , 50 years) and 140 healthy subjects as controls. Results, Both FHcy [13·2 (5·4,45·8) vs. 9·0 (5·1,24) µmol L,1); P < 0·0001] and PMHcy [(39·4 (9·0,66·4) vs. 25·2 (16·4,33·9); P < 0·0001] were significantly higher in patients than in controls. Lp(a) levels were significantly higher in patients than in controls (200 (3,1486) mg L,1 vs. 97 (10,412) mg L,1; P < 0·0001). At the multivariate analysis, adjusted for the classical cardiovascular risk factors and creatinine levels, the OR (95% CI) for CAD at young age significantly increased in the fourth quartile of the distribution of FHcy, PMHcy and Lp(a) levels [FHcy: 14·9 (4·1,58), P < 0·0001; PMHcy: 19·2 (4·0,86·3); P < 0·0001; Lp(a): 19·6 (4·7,78·6): < 0·0001]. Vitamin deficiencies were detected in 28/140 (20%) patients. The prevalence of the homozygous C677T (+/+) methylenetetrahydrofolatereductase genotype was higher, but not significantly different, in patients (22·8%) than in controls (18·6%). The allele frequency of the 844ins68 insertion variant in the cystathionine beta-synthase gene was 0·08 in the control group and 0·06 in the patient group. Conclusions, Results of the present study indicate the usefulness of including fasting and post-methionine Hcy, and Lp(a) determination in the diagnostic panels of young CAD patients, in order to obtain a better assessment of their cardiovascular risk profile. [source] Uric Acid as a Marker for Renal Dysfunction in Hypertensive Women on Diuretic and Nondiuretic TherapyJOURNAL OF CLINICAL HYPERTENSION, Issue 5 2009Rodolfo. Hyperuricemia is a common finding in hypertensive patients, especially among those who are on diuretic therapy. However, its clinical relevance regarding cardiovascular and chronic kidney disease (CKD) has not clearly been established. The authors assessed whether, in a population of 385 hypertensive women categorized according to diuretic therapy, the stratification in quartiles by uric acid levels would identify a gradient of changes in renal function and in risk factors for cardiovascular disease. The following were evaluated: serum uric acid, glycemia, total and fractional cholesterol, triglycerides, apolipoprotein (Apo) B, Apo A-I, and C-reactive protein. Renal function was assessed by serum creatinine, albuminuria, and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease equation, whereas cardiovascular risk was estimated through the Framingham score. A total of 246 women were on diuretic therapy; 139 were taking other antihypertensive medications. There was a reduction in eGFR parallel to the increase in uric acid levels, regardless of diuretic use and without a concomitant increase in albuminuria. In both groups, higher uric acid levels translated into an increase in metabolic syndrome components, in markers of insulin resistance, triglyceride/high-density lipoprotein levels, and Apo B/Apo A-I ratios, as well as in Framingham scores. Hyperuricemia was associated with an increase in inflammatory markers only in patients on diuretic therapy. In a binary logistic regression, hyperuricemia (uric acid >6.0 mg/dL) was independently associated with CKD (eGFR <60 mL/min/1.73 m²) (odds ratio, 2.63; 95% confidence interval, 1.61,4.3; P<.001). In hypertensive women, the presence of hyperuricemia indicated a substantial degree of kidney dysfunction as well as a greater cardiovascular risk profile. [source] Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapyJOURNAL OF INTERNAL MEDICINE, Issue 5 2002T. Apeland Abstract. Apeland T, Mansoor MA, Seljeflot I, Brønstad I, Gøransson L, Strandjord RE (Rogaland Central Hospital, Stavanger; and Ullevål University Hospital, Oslo; Norway). Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapy. J Intern Med 2002; 252: 456,464. Objectives. Haemodialysis patients have elevated levels of the atherogenic amino acid homocysteine. We wanted to assess the effects of small doses of intravenous folinic acid (the active form of folic acid) on some biochemical risk factors of cardiovascular disease. Design. Longitudinal and open intervention study. Setting. Two dialysis units in the County of Rogaland. Subjects. All patients on maintenance haemodialysis were invited, and 32 of 35 patients gave their informed consent. Interventions. After each dialysis session, the patients were given 1.0 mg of folinic acid intravenously thrice a week for a period of 3 months. Prior to and during the study, all patients were on maintenance supplementation with small doses of vitamins B1, B2, B3, B5, B6 and B12. Main outcome measures. Changes in the levels of (i) plasma total homocysteine (p-tHcy) and folate, (ii) circulating endothelium related proteins , markers of endothelial activation and (iii) serum malondialdehyde (S-MDA) , a marker of oxidative stress and lipid peroxidation. Results. The p-tHcy levels were reduced by 37% (P < 0.0001), whilst the serum and erythrocyte folate levels increased by 95 and 104%, respectively (P < 0.0001 for both). The circulating levels of endothelium related cellular adhesion molecules and haemostatic factors remained high and unchanged, except the thrombomodulin (TM) levels increased (P = 0.0004). The high levels of S-MDA were reduced by 26% (P = 0.003). Conclusions. Low doses of folinic acid given intravenously to dialysis patients reduced their levels of p-tHcy and S-MDA and thus improved their cardiovascular risk profile. The concurrent increment in TM levels was unexpected and of unknown clinical significance. [source] Renal function and cardiovascular risk profile after conversion from ciclosporin to tacrolimus: prospective study in 80 liver transplant recipientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2009S. BECKEBAUM Aliment Pharmacol Ther,30, 834,842 Summary Background, Increased risk of cardiovascular and cerebrovascular disease in liver transplant recipients results in particular from the side effects of calcineurin inhibitor-based immunosuppressive therapy. Several studies have demonstrated a more favourable outcome for patients receiving tacrolimus (TAC) as compared with ciclosporin (CS). Aim, To investigate the effects of conversion from CS to TAC on cardiovascular risk factors and renal function in liver transplant recipients. Methods, In a prospective study, all except two patients had chronic kidney disease stages 2,4 (n = 80), according to estimated glomerular filtration rate using the abbreviated Modification of Diet in Renal Disease equation. Results, Conversion was accompanied with a mean decrease of total cholesterol from 194.6 ± 54.0 mg/dL to 175.8 ± 44.2 mg/dL (P < 0.001), low density lipoprotein cholesterol from 106.7 ± 39.2 mg/dL to 90.9 ± 28.6 mg/dL (P < 0.001) and mean arterial blood pressure values from 102.2 ± 13.2 mm Hg to 95.9 ± 11.7 mm Hg (P < 0.001). Renal function remained stable. No cases of de novo diabetes mellitus were identified. The Framingham risk score was significantly reduced from 5.2 ± 4.4 at baseline to 4.4 ± 5.3 after 12 months (P = 0.006). Conclusions, Conversion from CS to TAC has been shown to improve the cardiovascular risk profile and may retard further decline of renal function after liver transplantation. [source] The trade-off between cardiovascular and gastrointestinal effects of rofecoxib,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2005Stefan R. Florentinus PharmD Abstract An Erratum has been published for this article in Pharmacoepidemiology and Drug Safety 14(9), 2005, 669. Background The cyclooxygenase-2 (COX-2) inhibitor rofecoxib was registered in 1999. By 2000, the first reports were published indicating that the agent was possibly associated with an increased risk of myocardial infarction. Since then a surge of data supporting this association has become available. To interpret these data it is essential to ascertain the cardiovascular risk profile of users of rofecoxib relative to other non-steroidal anti-inflammatory drug (NSAID) recipients. Objective To assess differences in cardiovascular risk between starters of rofecoxib versus starters of any other NSAID. Setting Data sampled from a representative research network of Dutch general practitioners (GPs) in 2001. Design New users (starters) of rofecoxib were compared to starters of any other NSAID, unmatched and matched on age, gender, and indication nested in the cohort of the second Dutch National Survey of General Practice. Results A total of 40.4% of patients starting on rofecoxib had cardiovascular co-morbidity. Patients starting on rofecoxib were twice more likely to have a history of gastrointestinal (GI) morbidity, compared to patients starting on other NSAIDs (ORadj,=,2.09; 95%CI,=,1.65,2.66). These patients were also more likely to have cardiovascular co-morbidity (OR,=,1.90; 95%CI,=,1.60,2.24) compared to recipients of rofecoxib with no GI co-morbidity. Cardiovascular morbidity was present at the time of rofecoxib exposure in over 61% of carriers of a composite risk profile including age 60 years or older, GI co-morbidity and diagnosis of rheumatoid arthritis and osteoarthritis. Conclusions In general, a typical recipient of an NSAID is aged and carrier of a serious cardiovascular risk profile. Selective prescribing of rofecoxib to provide claimed gastroprotection, indirectly and unintentionally resulted in prescribing rofecoxib in a population with high frequencies of cardiovascular morbidities. Copyright © 2005 John Wiley & Sons, Ltd. [source] Latest news and product developmentsPRESCRIBER, Issue 12 2007Article first published online: 4 OCT 200 NAO: GPs still not prescribing efficiently The National Audit Office (NAO) says NHS funds are being wasted through inefficient GP prescribing and patients not taking their medicines. The NAO's long-awaited report, Prescribing Costs in Primary Care (www.nao.org.uk), found large variations between PCTs in generic prescribing of statins, ACE inhibitors and angiotensin-II antagonists, and protonpump inhibitors; PCTs were also paying widely differing prices for these products. There was a five-fold variation in prescribing volume for clopidogrel between PCTs. These four drugs accounted for only 19 per cent of total spending but, if all practices matched the performance of the best 25 per cent, the NHS would save £200 million annually. PCTs should do more to rationalise prescribing and support their GPs, the NAO concludes. The NAO says that the cost of medicines dispensed for but not taken by patients lies somewhere in the range £100-£800 million annually. Strategies to reduce waste include public awareness campaigns and restricting supplies to four weeks (or two weeks for new medicines). Rosiglitazone may increase CV death risk A meta-analysis of 42 clinical trials has suggested that rosiglitazone is associated with increased risks of myocardial infarction (MI) and cardiovascular death (N Engl J Med 2007; published online 21 May: doi 10.1056/ NEJMoa072761). Like the COX-2 inhibitors, rosiglitazone was licensed without determining its possible effects on long-term cardiovascular outcomes, and interpretation of the latest findings is complicated by the multiple comparisons involved. For risk of MI, there was no significant difference between rosiglitazone and placebo (though this was of borderline statistical signifi-cance , p=0.07), metformin, sulphonylureas or insulin. Rosiglitazone was associated with a statistically significant 43 per cent increased risk compared with all comparators combined but the absolute increase in risk was very small (0.02 per cent). The trends were similar for risk of cardiovascular death, though rosiglitazone was associated with a 64 per cent increased risk compared with all comparators combined that was of borderline statistical significance (p=0.06). The authors acknowledge that their analysis pooled short-term studies that excluded patients at risk of heart disease and was not designed to determine cardiovascular outcomes, and they had no access to patientlevel data; as a result, there is uncertainty about their findings. Nevertheless, they say there is now an urgent need to clarify the risk associated with rosiglitazone. GlaxoSmithKline has rebutted the findings, stating that the cardiovascular risk profile of rosiglitazone is comparable with that of other oral antidiabetic drugs. The MHRA says warnings in the current SPCs for Avandia and Avandamet already reflect most of the data in the latest US review. The possible effects of rosiglitazone on cardiovascular events is currently being evaluated in the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycaemia in Diabetes (RECORD) study. Good management tool The Department of Health has published a disease management tool to enable PCTs to model local interventions that could reduce emergency admissions. The web-based ,voluntary good practice tool' will demonstrate how interventions in primary care and social care settings can improve the management of long-term conditions including cardiovascular disease, asthma and COPD, and dementia and depression. Counterfeit medicines The MHRA has issued an unprecedented three alerts about fake medicines in the legitimate supply chain, recalling all affected lot numbers. Three batches of Zyprexa 10mg tablets (olanzapine) were withdrawn after a company printing labels became suspicious and alerted Eli Lilly. Two of the batches, which contained 60 per cent of the stated active ingredient, had reached patients but no adverse events were reported. Two lots of parallel-imported Plavix 75mg tablets (clopidogrel) have been withdrawn after counterfeit packs were identified. The lots were in French original packaging but will have been overlabelled for the UK market. The counterfeits were mixed with genuine packs from Sanofi-Aventis. Fake Casodex 50mg tablets (bicalutamide) have been identified in a parallel import from France. The Royal Pharmaceutical Society reports that the fake contains 75 per cent of the stated dose of bicalutamide. Alcohol-free mometasone Schering-plough has introduced an alcohol-free formulation of mometasone furoate nasal spray (Nasonex) for hay fever. The company says that an alcohol vehicle causes nasal irritation and leaves an unpleasant aftertaste, adding that over 40 per cent of patients cite this as the main reason for stopping treatment, and over 50 per cent state a preference for an alcohol-free product. Aid to improve statin adherence Adherence to statin therapy can be improved if patients use a decision aid when they are offered treatment,US investigators say (Arch Intern Med 2007;167:1076-82). The decision aid estimated the individual's 10-year cardiovascular risk and the risk reduction from treatment, and summarised the disadvantages of statins.Patients with diabetes who used the aid knew more about their risk and were less indecisive about treatment than those who did not. The odds of having missed a dose over three months were three times higher for patients who had not used the aid. Online tool calculates switch savings A new online tool can help GPs estimate the savings achievable from switching patients to cheaper medicines. The Switch Saving Calculator, developed by the Prescribing Analysis & Support Team at the NHS Regional Drug and Therapeutics Centre in Newcastle, calculates potential savings based on past, current or projected use of the target drug. It can be applied to individual prescribers or scaled up to practice, commissioning group, PCT, health authority or even national level. Separate calculators are available for primary and secondary care. The current version calculates potential savings by switching from atorvastatin to simvastatin. The Newcastle team says other drugs will be added and they will update prices regularly. The calculator is at www.nyrdtc.nhs.uk:80/Services/presc_supp/ switch_saving_calculator/switch_saving_calculator.html. No improvement in drug information for patients leaving hospital The information given to patients discharged from hospital is not improving, according to the Healthcare Commission's annual patient survey (www.healthcare commission.org.uk). The 2006 survey found that the commonest reason patients were kept waiting for at least four hours to leave hospital was the delay in providing discharge medicines. Provision of written information increased from 62 per cent of patients in 2005 to 65 per cent in 2006. However, only 76 per cent said they had been told about their medicines in a way they could ,completely' understand (79 per cent in 2002). The proportion of patients reporting complete information about sideeffects also fell (from 40 per cent in 2005 to 37 per cent). Aspirin in preeclampsia A new meta-analysis has found that primary prevention with low-dose aspirin modestly but consistently reduces the risk of preeclampsia (Lancet 2007; published online 18 May). The study of 31 trials involving 32 217 women at low to moderate risk found that antiplatelet agents (mostly aspirin) reduced the risk of pre-eclampsia and preterm birth by 10 per cent without an increased risk of bleeding. The benefit was similar across subgroups. There were also nonsignificant reductions in the risk of small for age, stillborn and death before discharge. New from NICE NICE approves varenicline for NHS NICE has endorsed the use of varenicline (Champix) as an aid to smoking cessation within the NHS for England and Wales; it has already been approved for use in Scotland by the Scottish Medicines Consortium. Varenicline is a partial agonist at the ,4,2 nicotinic receptor. It alleviates craving and withdrawal symptoms, and reduces the rewarding and reinforcing effects of smoking. The commonest adverse effect is mild to moderate nausea, which improves with time.1 Varenicline is licensed for smoking cessation in adults; NICE says it should be offered as an option for smokers who say they want to quit as part of a programme of behavioural support. However, treatment should not be withheld if counselling and support are not available. NICE was critical of manufacturer Pfizer's economic arguments in favour of varenicline, which inappropriately included US data, assumed a single quit attempt and may have overestimated its efficacy. It nonetheless concluded that varenicline is more effective than nicotine replacement therapy (NRT) or bupropion (Zyban) in achieving continuous abstinence. NICE estimated that, compared with NRT, the odds of abstinence at one year with varenicline were 54 per cent greater. A Cochrane review1 concluded that abstinence was 66 per cent more likely with varenicline than with bupropion, and three times more likely than with placebo. There was also a benefit from offering smokers a wider choice of treatments. A 12-week course of varenicline costs £163.80; it is also licensed for an additional 12-week course and dose tapering may be considered for those at high risk of relapse. The final appraisal determination does not state which is the treatment of first choice for smoking cessation. NICE is currently preparing guidance on smoking cessation in pri-mary care, pharmacies and workplaces. Copyright © 2007 Wiley Interface Ltd [source] Analysis of the cardiovascular risk profile in stable kidney transplant recipients after 50% cyclosporine reduction,CLINICAL TRANSPLANTATION, Issue 4 2004Waichi Wong Abstract:, Background:, Long-term use of cyclosporine (CsA) contributes to post-transplant cardiovascular disease (CVD). Hence, a reduction in CsA dosage in kidney transplant recipients (KTR) may improve long-term outcomes. We analyzed the effects of 50% CsA dose reduction on the CVD risk profile in stable KTR. Method:, Thirty-one KTR on a regimen of CsA, prednisone and mycophenolate mofetil (MMF) were studied. Patients were randomized to either a) continue their previously determined CsA dose (control group, n = 15) or b) lower their CsA dose by 50% (CsA reduction group, n = 16). Renal function, blood pressure, lipid profile, plasma homocysteine (HCY), C-reactive protein (CRP), fibrinogen, and uric acid were compared at baseline and at 6 months. Results:, At 6 months, there was a significant improvement in allograft function, systolic blood pressure, number of anti-hypertensive medications and serum uric acid levels in the CsA reduction group. No significant decrease in plasma HCY, CRP, fibrinogen or improvement in lipid profile was found. In contrast, in the Control group, there was a significant increase in HCY, uric acid, and triglycerides. No acute rejection occurred in either group. Conclusions:, A greater reduction in CsA dose could further improve CVD risk profiles, although this may increase the risk of acute or subclinical rejection. [source] Thiazolidinediones: effects on the development and progression of type 2 diabetes and associated vascular complicationsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2009Andrew Krentz Abstract In addition to reducing hyperglycaemia, the metabolic actions of TZDs (pioglitazone and rosiglitazone) in theory might improve the prognosis of patients with type 2 diabetes. However, it appears from recent data that pioglitazone and rosiglitazone have different cardiovascular risk profiles. The scope of this paper is to examine the benefits and risks of pioglitazone and rosiglitazone. Three large clinical studies (DREAM, and ADOPT with rosiglitazone; PROactive with pioglitazone) have recently been reported. A lower annual rate of decline of ß-cell function observed with rosiglitazone in the ADOPT study, compared with metformin and glyburide (glibenclamide), along with a reduced progression to insulin use seen with pioglitazone in the PROactive study, provides evidence that TZDs are effective in treating progressive hyperglycaemia. In PROactive, although the primary endpoint was not met, pioglitazone was associated with a reduction in a secondary composite endpoint of clinical cardiovascular events in high-risk patients with existing macrovascular disease who were already receiving other glycaemic and cardiovascular medications. Further evidence supporting an anti-atherogenic effect of pioglitazone was gained from the PERISCOPE study of carotid intima-media thickness. Recent controversy concerning a possible increased risk of myocardial infarction associated with rosiglitazone has fuelled uncertainty about the risk,benefit profile of this agent. In 2008, an update of an American Diabetes Association,European Association for the Study of Diabetes consensus statement on initiation and adjustment of therapy in patients with type 2 diabetes advised clinicians against using rosiglitazone. Skeletal fractures have recently emerged as a side effect of both TZDs. Available data suggest that cardiovascular benefits observed with pioglitazone might not be a class effect of TZDs. Copyright © 2009 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||