Understanding medicines with a propensity to increase the risk of heart failure: Combining existing knowledge with targeted population assessment.

PURPOSE: Existing knowledge of medicines that increase the risk of an adverse event may be corroborated and augmented by population studies specifically assessing the risk associated with the concurrent use of these medicines and use by patients with existing comorbidity. An American Heart Association review recently identified a variety of medicines that may cause or exacerbate heart failure (HF), many with evidence from limited evaluation of population data. We assessed the risk of first-time HF associated with the use of 50 of these medicines by New Zealand's primary care population. METHODS: Case-control study utilising national pharmaceutical use and hospital admissions data 2007-2015; 22,989 patients with first-time HF 2008-2015 were matched with 114 498 control patients. The primary outcome was first-time HF and its association with medicine exposure in the prior 90 days, estimated using conditional logistic regression. We also assessed the risk associated with new use of medicines in the prior month, concurrent use, and in patients with existing comorbidity. RESULTS: Eleven medicines were significantly associated with HF with several other infrequently used medicines providing signals of increased risk. A high risk was associated with the use of salbutamol (adjusted odds ratio 2.63; 95% CI, 2.48-2.78), clozapine (2.70; 2.46-4.98), diltiazem (1.52; 1.44-1.60), indomethacin (2.51; 1.54-4.10), pioglitazone (1.50; 1.16-1.95), and antifungal medicines. New use of medicines and use of medicine combinations increased this risk in many cases. CONCLUSIONS: Our study provides further evidence to inform cautious use of these medicines in patients with HF or at risk of developing HF.

Trends in prescription medicine use by older people in New Zealand 2010- 2015: a national population-based study.

BACKGROUND: Research investigating trends in the general prescription medicine use of older people in New Zealand is limited. AIM: To examine trends in the use of outpatient medicines by older adults and assess changing patterns in use from 2010 to 2015. METHODS: A retrospective cohort study including all New Zealand primary care patients over 65 years of age utilising data from the national pharmaceutical claims database. We calculated the prevalence of use within three age groups and by sex in each year by anatomical therapeutic class, therapeutic group and individual medicine. Rate ratios were calculated to compare the prevalence of use in 2010 and 2015. RESULTS: The study included 829,026 patients with a mean of 4.4 years of potential drug exposure. Overall prevalence of medicine use was 92% in 2010 and 93% in 2015. The mean number of prescriptions per patient-year for patients >=85 years of age (39.2) was almost double that of patients 65-74 years (21.8). Prevalence of use was similar between females (94%) and males (92%). Antibacterials, analgesics, cardiovascular drugs and proton pump inhibitors were the most widely used medicines. The use of systemic antibiotics increased by 2% between 2010 and 2015, but there were significant decreases in use of antithrombotics (6%), beta blockers (6%), diuretics (19%), nitrates (19%) and antiarrhythmics (24%). CONCLUSION: Our findings indicate both positive changes in response to guidance on safe and appropriate medicine use and several areas of concern. Continued monitoring of changing patterns in the medicine use of older people will be important, particularly with regard to the use of combinations of medicines that increase their risk of adverse events.

Trends in Outpatient Prescription Medicine Use in New Zealand Children 2010-2015: A National Population-Based Study.

BACKGROUND: Research examining trends in the outpatient prescription medicine use of New Zealand children is limited. OBJECTIVES: Our objective was to provide an overview of prescription medicine use in New Zealand children and assess changing patterns in use from 2010 to 2015. METHODS: We conducted a retrospective cohort study including all New Zealand primary care-registered children aged < 18 years using data from the national pharmaceutical claims database. We calculated the prevalence of use within four age groups in each year by anatomical therapeutic class, therapeutic group and drug. Rate ratios were calculated to compare the prevalence of use in 2010 and 2015. RESULTS: In total, 1,496,026 children with a mean of 2.7 years of potential drug exposure were included. The overall prevalence of drug use was 70% in 2010 and 73% in 2015. In 2015, medicine use was highest in children aged < 2 years (90%) and lowest in children aged 12-17 years (65%). Antibacterials, analgesics, topical corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and antihistamines were the most widely used medicines. The prevalence of use of systemic and topical antibiotics decreased by 2 and 10%, respectively, between 2010 and 2015, but there was increased use of analgesics (10%), NSAIDs (39%), antihistamines (15%) and antinausea and vertigo agents (306%). CONCLUSIONS: Our findings indicate areas for further research focusing on inappropriate prescribing to children and safety issues in children's medicine use. Monitoring changing patterns of use over time is important for the evaluation of effective therapies in children and any potential harmful consequences of prescribing.

A Pharmacoepidemiology Database System for Monitoring Risk Due to the Use of Medicines by New Zealand Primary Care Patients.

INTRODUCTION: The use of large record-linked healthcare databases for drug safety research and surveillance is now accepted practice. New Zealand's standardized national healthcare datasets provide the potential to automate the conduct of pharmacoepidemiological studies to provide rapid validation of medicine safety signals. OBJECTIVES: Our objectives were to describe the methodology undertaken by a semi-automated computer system developed to rapidly assess risk due to drug exposure in New Zealand's population of primary care patients and to compare results from three studies with previously published findings. METHODS: Data from three national databases were linked at the patient level in the automated studies. A retrospective nested case-control design was used to evaluate risk for upper gastrointestinal bleeding (UGIB), acute kidney failure (AKF), and serious arrhythmia associated with individual medicines, therapeutic classes of medicines, and concurrent use of medicines from multiple therapeutic classes. RESULTS: The patient cohort available for each study included 5,194,256 patients registered between 2007 and 2014, with a total of 34,630,673 patient-years at risk. An increased risk for UGIB was associated with non-steroidal anti-inflammatory drugs (NSAIDs) (adjusted odds ratio [AOR] 4.16, 95% confidence interval [CI] 3.90-4.43, p < 0.001) and selective serotonin reuptake inhibitors (AOR 1.39, 95% CI 1.20-1.62, p < 0.001); an increased risk for AKF was associated with NSAIDs (AOR 1.78, 95% CI 1.73-1.83, p < 0.001) and proton pump inhibitors (AOR 1.78, 95% CI 1.72-1.83, p < 0.001); and an increased risk for serious arrhythmia was associated with fluoroquinolones (AOR 1.38, 95% CI 1.26-151, p < 0.001) and penicillins (AOR 1.69, 95% CI 1.61-1.77, p < 0.001). CONCLUSIONS: Automated case-control studies using New Zealand's healthcare datasets can replicate associations of risk with drug exposure consistent with previous findings. Their speed of conduct enables systematic monitoring of risk for adverse events associated with a wide range of medicines.

Guarana: Paullinia cupana, P. sorbilis; also known as Brazilian cocoa and 'zoom'.

The main constituent of guarana is caffeine, with smaller quantities of theophylline and theobromine. There is no evidence that the berries or extracts contain anything else that is therapeutically useful.Guarana is associated with many therapeutic properties, but there is no evidence to support these other than effects that can be attributed to caffeine. Guarana is widely available in herbal products and energy drinks. Excessive intake can cause the same effects as too much caffeine. It is not widely recognised that guarana has a high caffeine content and the labelling on some products is misleading.Although not specifically studied, guarana would be expected to exhibit the same range of adverse effects and drug interactions as those associated with caffeine.