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Research findings

Statin treatment and risk of developing diabetes

27 Jun, 13 | by kuppell

A study looking into whether there is an association between statin use and new onset diabetes found that patients treated with atorvastatin, rosuvastatin, or simvastatin were at an increased risk of new onset diabetes compared with those treated with pravastatin.

Researchers conducted a population-based retrospective cohort study in patients aged 66 years and older in Ontario, Canada who started treatment with a statin from 1 August 1997 to 31 March 2010. They examined the healthcare records of more than 1.5 million older people. The analysis was restricted to new users who had not been prescribed a statin in at least the preceding year and patients with established diabetes before the start of treatment were excluded. The primary outcome was incident diabetes. Over the 14 year study period, the researchers identified 471,250 patients with no history of diabetes who were newly treated with a statin. Of these patients, 227,994 (48.3%) received a statin for primary prevention, while 243,256 (51.7%) received a statin for secondary prevention.

Reporting their findings in the British Medical Journal the researchers say that, compared with pravastatin, there was an increased risk of incident diabetes with atorvastatin (adjusted HR 1.22, 95% CI 1.15 to 1.29), rosuvastatin (1.18, 1.10 to 1.26) and simvastatin (1.10, 1.04 to 1.17). There was no significantly increased risk among patients who received fluvastatin or lovastatin and the risk of incident diabetes was similar whether statins were used for primary or secondary prevention. BMJ 2013;346:f2610.

Short-term course of glucocorticoids for COPD

18 Jun, 13 | by kuppell

A short-term 5-day, rather than 14-day, course of glucocorticoid treatment should be used for acute exacerbations of chronic obstructive pulmonary disease (COPD) according to a study published in JAMA. The Reduction in the Use of Corticosteroids in Exacerbated COPD (REDUCE) study was a randomised, non-inferiority Swiss trial which enrolled 314 patients (from March 2006 to February 2011) presenting to the emergency departments of five hospitals with acute COPD exacerbations. Patients were past or present smokers (≥20 pack-years) without a history of asthma.

Patients received 40mg of prednisone daily for either 5 or 14 days in a placebo-controlled double-blind manner. The main outcome was time to next COPD exacerbation during a follow-up of 6 months.

Of the 314 patients, 311 were included in the intention-to-treat analysis and 296 in the per-protocol analysis. Hazard ratios (HRs) for the short-term versus 14-day treatment group were 0.95 (90% CI, 0.70 to 1.29; p=0.006 for non-inferiority) in the intention-to-treat analysis and 0.93 (90% CI, 0.68 to 1.26; p=0.005 for non-inferiority) in the per-protocol analysis, meeting the researchers non-inferiority criterion. In the 5-day treatment group, 56 patients (35.9%) reached the primary end point and 57 (36.8%) in the 14-day group. Estimates of reexacerbation rates within 6 months were 37.2% (95% CI, 29.5% to 44.9%) in the short-term group with median time to event being 43.5 days and were 38.4% (95% CI, 30.6% to 46.3%) in the 14-day treatment group with median time to event of 29 days.

The authors conclude that: ‘In patients presenting to the emergency department with acute exacerbations of COPD, 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment with regard to reexacerbation within 6 months of follow-up but significantly reduced glucocorticoid exposure. These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD.’ JAMA 2013;309:2223-31.

Continuous infliximab treatment rather than intermittent for plaque psoriasis

11 Jun, 13 | by kuppell

Continuous therapy with infliximab is more effective than intermittent therapy and is associated with fewer side effects in patients with moderate to severe plaque-type psoriasis according to a study published in the British Journal of Dermatology.

Eligible patients for inclusion in the extension study, RESTORE2, had received infliximab for 26 weeks and achieved Psoriasis Area and Severity Index (PASI) score of 75 in the initial RESTORE1 study. Of these, 222 patients were randomised to receive continuous infliximab treatment (5mg/kg every 8 weeks) and 219 received intermittent treatment (no infliximab until >50% loss of PASI improvement). The researchers say that more serious infusion-related reactions occurred with intermittent treatment (8/219 patients, 4%) than with continuous treatment (1/222 patients, <1%) which lead to termination of the study.  Although no formal efficacy analyses were conducted, continuous therapy led to greater PASI 75 at week 52 in the continuous group (81/101, 80%) than in the intermittent group (39/83, 47%).

‘For patients with moderate-to-severe plaque-type psoriasis, continuous therapy with infliximab may be more effective than intermittent therapy. The incidence of serious infusion-related reactions in the intermittent group suggests that clinicians should avoid intermittent therapy in this population,’ advise the researchers. Br J of Dermatol 2013;168:1325-34.

Triple therapy with antihypertensives and NSAIDs linked to acute kidney injury

19 Apr, 13 | by kuppell

Triple therapy combination consisting of diuretics with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and NSAIDs is associated with an increased risk of acute kidney injury according to a UK study.

In a retrospective cohort study researchers assessed whether double therapy consisting of a diuretic or an ACE inhibitor or an ARB with the addition of a NSAID, and triple therapy consisting of a diuretic plus an ACE inhibitor or an ARB in addition to a NSAID increased the risk of acute kidney injury. A total of 487 372 people using antihypertensive drugs between 1 January 1997 and 31 December 2008 were identified from the UK Clinical Practice Research Datalink (CPRD). Reporting their finding in the British Medical Journal the researchers say that during a mean follow-up of 5.9 years, 2215 cases of acute kidney injury were identified (incidence rate 7/10 000 person years). ‘Current use of a triple therapy combination was associated with an increased rate of acute kidney injury (rate ratio 1.31, 95% confidence interval 1.12 to 1.53). In secondary analyses, the highest risk was observed in the first 30 days of use (rate ratio 1.82, 1.35 to 2.46),’ say the researchers. However, double therapy combination was not associated with an increased rate of acute kidney injury.

The researchers say that, to their knowledge, it is the first large population based study of patients using antihypertensive drugs to have investigated the association between the use of different combinations of antihypertensive drugs with NSAIDs on the risk of acute kidney injury. ‘Increased vigilance may be warranted when diuretics and ACE inhibitors or ARBs are used concurrently with NSAIDs. In particular, major attention should be paid early in the course of treatment, and a more appropriate use and choice among the available anti-inflammatory or analgesic drugs could therefore be applied in clinical practice,’ they suggest. BMJ 2013;346:e8525.


Impact of benzodiazepines on pneumonia

13 Mar, 13 | by kuppell

Benzodiazepines are associated with an increased risk of, and mortality from, community-acquired pneumonia (CAP) suggesting further research is required into the immune safety profile of benzodiazepines, according to a study published in Thorax. Using data from The Health Improvement Network (THIN) database, British researchers identified 29,697 controls and 4964 cases of CAP. They used conditional logistic regression to investigate the association between benzodiazepines and pneumonia occurrence, and Cox regression to determine the impact of benzodiazepines on mortality in the 4964 cases of CAP.

The researchers report that: ‘Exposure to benzodiazepines was associated with an increased risk of pneumonia (OR 1.54, 95% CI 1.42 to 1.67). Individually diazepam, lorazepam and temazepam, but not chlordiazepoxide, were associated with an increased incidence of CAP’. They also found that, as a class, benzodiazepines were associated with increased 30-day (HR 1.22 [95% CI 1.06 to 1.39]) and long-term mortality (HR 1.32 [95% CI 1.19 to 1.47]) in patients with a prior diagnosis of CAP. Individually diazepam, chlordiazepoxide, lorazepam and temazepam affected long-term mortality in these patients. ‘Given the widespread use of benzodiazepine drugs, further studies are required to evaluate their safety in the context of infection’, add the researchers. Thorax 2013;68:163-170.

Statin therapy and reduction in recurrent pulmonary embolism

13 Mar, 13 | by kuppell

A study carried out in the Netherlands suggests that statin treatment could decrease the risk of recurrent pulmonary embolism (PE) and might be an alternative to anticoagulant treatment in the long-term treatment of PE. Researchers identified patients hospitalized with an acute episode of PE between 1998 and 2008 by using data from a Dutch population-based registry of pharmacy records linked with hospital discharge records. Prescription-based use of statins and vitamin K antagonist (VKA) were identified starting at hospital discharge and during follow-up.  The researchers used Cox regression analysis to assess the incidence of recurrences, cardiovascular events and death.

The median duration of VKA treatment after acute PE was 199 (45–3793) days. Twenty-four per cent of the patients (n = 737) had at least one prescription of statins during the follow-up period and the median duration of statin therapy was 1557 (5–4055) days.

Reporting their findings in the European Heart Journal the researchers say that during a median follow-up of 1529 (1–4155) days, 285 (9.2%) patients experienced a recurrence. Treatment with statins was associated with a reduced risk of recurrent PE (adjusted hazard ratio [HR] 0.50, 95% CI: 0.36–0.70), both during and after stopping VKA treatment. A dose–response relationship was shown for potency, with the largest reduction in those with the most potent statins. ’Statin treatment also reduced the risk for cardiovascular events and all-cause mortality’, add the researchers. Eur Heart J (2013)doi: 10.1093/eurheartj/eht046.

Long-term aspirin use linked to age-related macular degeneration

12 Mar, 13 | by kuppell

Regular aspirin use is associated with an increased risk for developing neovascular age-related macular degeneration (AMD), according to a study published in JAMA Internal Medicine.  Researchers analysed data from an Australian population-based cohort. Four examinations were carried out over a 15-year period with participants completing a detailed questionnaire at baseline assessing aspirin use, cardiovascular disease status, and AMD risk factors. Retinal photographs were taken at each study visit to assess the incidence of neovascular (wet) AMD and geographic atrophy (dry AMD) according to the international AMD classification.

Of 2389 participants at baseline, 257 (10.8%) were regular aspirin users and 63 of the 2389 developed neovascular AMD. ‘Persons who were regular aspirin users were more likely to have incident neovascular AMD: the 15-year cumulative incidence was 9.3% in users and 3.7% in nonusers’, report the researchers. They add that the association was independent of potential confounders such as cardiovascular disease, age, sex, smoking, systolic blood pressure, and body mass index. A link was not, however, found between aspirin use and geographic atrophy. The researchers conclude that: ‘Regular aspirin use is associated with increased risk of incident neovascular AMD, independent of a history of cardiovascular disease and smoking’. JAMA Intern Med. 2013;173(4):258-264.

Latest from European Journal of Hospital Pharmacy

Latest from European Journal of Hospital Pharmacy