Lisa Demos

Clozapine-associated myocarditis: a review of 116 cases of suspected myocarditis associated with the use of clozapine in Australia during 1993-2003.

AbstractBackground: Clozapine is an antipsychotic medication associated with a lower suicide rate compared with other antipsychotic agents. Clozapine is used specifically in patients for whom previous therapy was inadequate or not tolerated, and is the only antipsychotic agent associated with the development of myocarditis. Objective: To retrospectively review all adverse drug reaction reports voluntarily submitted to the Australian Adverse Drug Reactions Unit mentioning suspected myocarditis in clozapine-treated patients. Patients and methods: We accessed all electronic database entries and case reports citing suspected myocarditis associated with clozapine therapy from January 1993 through to December 2003, inclusive. Results: 116 case reports of suspected myocarditis amongst clozapine-treated patients were identified during the specified time frame (incidence between 0.7% and 1.2% of treated patients). Median patient age for these cases was 30 years (SD 11.1 years) compared with 37 years from the Clopine® registry. The condition developed within a median 16 days (mean 19.8 days; SD 17.3 days) of commencing clozapine for the bulk of patients developing myocarditis within 6 months (n = 93, 80.2%). For all cases with known treatment commencement and cessation dates (n = 106), the condition developed within a median 17 days (mean 171.7 days, SD 530.9 days). Over nine-tenths of cases were prescribed clozapine within the dose range of 100 mg/day to 450 mg/day. Sixty patients (51.8%) recovered from their episode when reported or during follow-up reports, whereas 17 patients (14.7%) had not yet recovered: 27 patients (23.3%) had unknown outcome when reported and the remaining 12 patients (10.3%) died. Conclusion: Clozapine is uncommonly but importantly related to myocarditis, often fatal or near fatal and sometimes in relatively young patients with early onset after treatment initiation. The most striking feature about this condition is the wide diversity of nonspecific symptoms that occur in afflicted patients. Additional pharmacovigilance, improved reporting systems and further investigation of mechanisms of drug-induced myocarditis and related cardiovascular conditions (such as heart failure) are clearly warranted. A case-control study would be suitable for investigation of baseline predictors.

The Melbourne Atherosclerosis Vitamin E Trial (MAVET): A study of high dose vitamin E in smokers

Objective Our aim was to evaluate whether vitamin E (500IU) slowed the progression of carotid atherosclerosis in a population of chronic smokers over 4 years as measured by ultrasound determination of carotid intima-media thickness (IMT) and systemic arterial compliance (SAC). Methods The Melbourne Atherosclerosis Vitamin E Trial (MAVET) was a randomized, double-blind, placebo-controlled trial in which 409 male and female smokers aged 55 years and over were randomized to receive 500IU per day of natural vitamin E or placebo. The primary endpoint was progression of carotid atherosclerosis determined by intima-media thickness of the right common carotid artery. Secondary outcomes were change in systemic arterial compliance and low-density lipoprotein (LDL) oxidative susceptibility over time. Results The mean increase in intima-media thickness over time in the vitamin E group was 0.0041 mm/year faster than placebo (95% confidence interval −0.0021 to 0.0102 mm/year, P=0.20). Similarly, a non-significant difference between vitamin E and placebo was found for rate of change in systemic arterial compliance (P=0.11). Vitamin E supplementation did, however, significantly reduce LDL oxidative susceptibility (P>0.001). Conclusion Vitamin E supplementation is ineffective in reducing the progression of carotid atherosclerosis as measured by intima-media thickness in chronic smokers. This finding extends our knowledge of lack of effectiveness of vitamin E supplementation in populations with high oxidant stress. Eur J Cardiovasc Prev Rehabil 13:341-347

Atherosclerosis and folic acid supplementation trial in chronic renal failure: Baseline results

Background:  Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) is a randomized placebo controlled trial assessing whether high‐dose folic acid can reduce cardiovascular events and atherosclerosis progression in patients with chronic renal failure (CRF). Here we report the baseline results and compare indices of arterial structure (carotid intima‐medial thickness (IMT)) and function (systemic arterial compliance (SAC)), pressure augmentation index (AIx) and pulse wave velocity (PWV a‐f and PWV f‐d)) to age‐ and sex‐matched controls.

Suboptimal management of cardiovascular risk factors in coronary heart disease patients in primary care occurs particularly in women.

Background:  Patients with established coronary heart disease (CHD) are at the highest risk of further events. Despite proven therapies, secondary prevention is often suboptimal. General practitioners (GPs) are in an ideal position to improve secondary prevention.