Serious statin-associated myotoxicity and rhabdomyolysis in Aboriginal and Torres Strait Islanders: a case series.

BACKGROUND: Statins are associated with skeletal muscle adverse effects. These are generally considered mild and reversible, with more severe toxicity occurring rarely. There is little known regarding statin myotoxicity in Aboriginal and Torres Strait Islander Australians who are at high cardiovascular risk and likely to receive statins. AIMS: To describe features of serious statin-associated myotoxicity (SSAM) occurring in Indigenous Australians and increase awareness of this condition. METHODS: Observational case series of SSAM in Aboriginal or Torres Strait Islanders. Cases were identified from personal clinical experience, referrals, reports to the Therapeutic Goods Administration, medical literature, an Internet search and reports from a histopathology laboratory. Information was collected onto a standardised data collection form. RESULTS: Fifteen cases of serious myotoxicity in Aboriginal or Torres Strait Islanders exposed to statins were identified from 2006 to 2012. The mean age was 55 (range 35-69). Painless weakness was the most common presentation. Interacting drugs were involved in seven cases. Biopsies were done in eight cases, three showed inflammatory polymyositis and five necrotising myositis. Three patients died and two had permanent severe disability. Resolution of symptoms after statin cessation was variable. CONCLUSIONS: SSAM has occurred in the Indigenous Australian population with some fatalities. Awareness of the potential for SSAM is essential for early recognition and effective management to reduce probability of avoidable catastrophic harm. Safe, as well as effective use of medication, is essential for optimum health outcomes. Effective pharmacovigilance and therapeutic risk management are important for Aboriginal and Torres Strait Islander Australians.

Low-dose diuretic and/or dietary sodium restriction when blood pressure is resistant to ACE inhibitor.

AIM: To compare the efficacy of indapamide (1.25 mg daily) and low-salt diet (<100 mmol/day) separately and in combination in essential hypertensive patients with inadequate BP response to perindopril. DESIGN AND METHODS: Randomized double-blind, double-dummy, crossover design. The randomized treatments were indapamide 1.25 mg daily, sodium chloride 80 mmol daily, the combination of indapamide and sodium chloride and placebo. All patients received perindopril 4 mg daily and maintained a low-sodium diet. RESULTS: 19 patients entered and 17 completed the study. Prior to randomization, average clinic sitting blood pressure was 162/101 mm Hg and average 24-h urine sodium excretion was 157 mmol/day. Compared to the phase in which patients received perindopril with sodium repletion, clinic and ambulatory BPs were significantly reduced (p<0.01) in all the other phases. Indapamide had a greater effect on BP than dietary sodium restriction, and in combination their effects were additive. The effect of indapamide on ambulatory BP persisted throughout 24 h, but the effect of the low-salt diet was predominantly observed during waking hours. CONCLUSIONS: In hypertensives with BP resistant to the angiotensin converting enzyme (ACE) inhibitor perindopril, the diuretic indapamide had greater additional efficacy and longer duration of action than dietary sodium restriction. In combination they had additive effects on BP.

Epidemiological study of angioedema and ACE inhibitors.

BACKGROUND: Angioedema is an uncommon and poorly recognised adverse reaction to angiotensin converting enzyme inhibitors (ACE-Is). The epidemiology of this association has not been described. AIMS: To examine the epidemiology of angioedema and its relation to ACE inhibitor prescribing. To examine the characteristics of angioedema occurring in patients taking ACE inhibitors. METHODS: A retrospective case control study and a case note audit were conducted of 40 patients who presented to a teaching hospital Accident and Emergency Department with angioedema on 48 occasions. One hundred and sixty control subjects presenting to the same Accident and Emergency Department but without angioedema were matched to cases by age, sex and presentation date. An ecological study comparing the numbers of angioedema admissions by age cohorts to South Australian (SA) public hospitals with the prescription volumes of ACE-Is in Australia was also undertaken. RESULTS: Case control study: In patients presenting with angioedema compared with controls, the exposure odds ratio for ACE-Is was 5.1 (95% CI 2.03-12.89) and for non-steroidal anti-inflammatory drugs (NSAIDs) was 4.13 (95% CI 1.28-13.39). CASE NOTE AUDIT: 15/40 (38%) patients presenting with angioedema on 19/48 (40%) occasions were taking an ACE-I. These patients were older and less likely to have an atopic history than those not taking an ACE-I. The onset of angioedema after starting an ACE-I was delayed for greater than six months in nine patients. ACE-I therapy was continued after 53% of presentations. ECOLOGICAL STUDY: The number of admissions with angioedema to SA public hospitals increased between 1985-86 and 1994-95, predominantly in older patients, and paralleled the increasing prescription volumes of ACE-Is. CONCLUSIONS: A considerable proportion of patients presenting with angioedema will be taking an ACE-I or a NSAID. The association of ACE-Is and angioedema is not well recognised, partly because the onset of angioedema may be delayed for months or years after commencement of an ACE-I. A persisting risk of angioedema is present in patients who have initially commenced an ACE-I uneventfully. The epidemiology of angioedema is now changing in parallel with the increasing use of ACE-Is.

Bronchial responsiveness to exercise after human cardiopulmonary transplantation.

Heart-lung transplant (HLT) recipients characteristically display marked bronchial hyperresponsiveness (BHR) to inhaled methacholine, but their bronchial responsiveness (BR) to exercise has not been reported. We measured BR to exercise in 13 stable HLT recipients, 13 normal control (NC) subjects and 13 asthmatic patients (AS). All subjects exercised for eight minutes on a bicycle ergometer at a work level designed to obtain and maintain 80 percent maximum heart rate, or to tolerance. The postexercise fall in FEV1 was equivalent in the HLT group and the NC group (0 +/- 0.2 L vs 0 +/- 0.2 L:p = NS) in contrast to the AS group (-0.6 +/- 0.5 L:p less than 0.01). Stable HLT recipients do not exhibit BHR to exercise at tolerable work loads. This observation supports the hypothesis that BHR to methacholine after HLT is due to denervation hypersensitivity of muscarinic receptors rather than other causes.