Clinical characteristics and lipid lowering treatment of patients initiated on proprotein convertase subtilisin-kexin type 9 inhibitors: a nationwide cohort study.

OBJECTIVES: Given the novelty of proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i), little is known regarding overall implementation or clinical characteristics among patients who initiate treatment. We aimed to assess the total number of patients initiated on PCSK9i along with a description of the clinical characteristics and lipid lowering treatment (LLT) of such patients. SETTING: A register-based descriptive cohort study of patients receiving a PCSK9i in the time period from 01 January 2016 to 31 March 2017 using a cross linkage between three nationwide Danish registers. Information regarding PCSK9i prescriptions, patient demographics, concurrent pharmacotherapy, comorbidities and previous coronary procedures was identified. RESULTS: Overall, 137 patients initiated treatment with PCSK9i in the study period from 11 in the first quarter of 2016 to 40 in the first quarter of 2017. The majority had a history of ischaemic heart disease (IHD) (67.9%) with ischaemic stroke and diabetes mellitus being present in 7.3% and 16.8% of patients, respectively. All patients initiated on PCSK9i had been previously prescribed statin treatment with atorvastatin and simvastatin being most frequently prescribed in 53% and 36% of patients, respectively. The majority of patients had received both statins and ezetimibe (94.9%) and approximately half of these patients had also received bile acid sequestrant (45.3%). Clinical characteristics mainly differed in patients receiving triple LLT compared with patients not receiving triple LLT in the regards of heart failure. CONCLUSION: Patients treated with PCSK9i were rare, characterised by having IHD and had received various and intensive conventional LLT prior to PCSK9i initiation in agreement with current international guidelines.

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview.

OBJECTIVES: Active placebos are control interventions that mimic the side effects of the experimental interventions in randomized trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomized clinical drug trials use active placebo control groups; to provide a catalog, and a characterization, of such trials; and to analyze methodological arguments for and against the use of active placebo. STUDY DESIGN AND SETTING: An overview consisting of three thematically linked substudies. In an observational substudy, we assessed the prevalence of active placebo groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). RESULTS: The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0-2), 0.5% (0-1%). We identified and characterized 89 randomized trials (published 1961-2014) using active placebos, for example, antihistamines, anticholinergic drugs, and sedatives. Such trials typically involved a crossover design, the experimental intervention had noticeable side effects, and the outcomes were patient-reported. The use of active placebos was clustered in specific research settings and did not appear to reflect consistently the side effect profile of the experimental intervention, for example, selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials. We identified and analyzed 25 methods publications with substantial comments. The main argument for active placebo was to reduce risk of unblinding; the main argument against was the risk of unintended therapeutic effect. CONCLUSION: Pharmacological active placebo control interventions are rarely used in randomized clinical trials, but they constitute a methodological tool which merits serious consideration. We suggest that active placebos are used more often in trials of drugs with noticeable side effects, especially in situations where the expected therapeutic effects are modest and the risk of bias due to unblinding is high.