The effect of blood pressure lowering medications on the prevention of episodic migraine: A systematic review and meta-analysis.

BACKGROUND: Currently, only a few specific blood pressure-lowering medications are recommended for migraine prevention. Whether benefits extend to other classes or drugs is uncertain. METHODS: Embase, MEDLINE, and the Cochrane Central Registry of Controlled Trials were searched for randomized control trials on the effect of blood pressure-lowering medications compared with placebo in participants with episodic migraine. Data were collected on four outcomes - monthly headache or migraine days, and monthly headache or migraine attacks, with a standardised mean difference calculated for overall. Random effect meta-analysis was performed. RESULTS: In total, 50 trials (70% of which were crossover) were included, comprising 60 comparisons. Overall mean age was 39 years, and 79% were female. Monthly headache days were fewer in all classes compared to placebo, and this was statistically significant for all but one class: alpha-blockers -0.7 (95% CI: -1.2, -0.1), angiotensin-converting enzyme inhibitors -1.3 (95% CI: -2.9, 0.2), angiotensin II receptor blockers -0.9 (-1.6, -0.1), beta-blocker -0.4 (-0.8, -0.0) and calcium channel blockers -1.8 (-3.4, -0.2). Standardised mean difference was significantly reduced for all drug classes and was separately significant for numerous specific drugs: clonidine, candesartan, atenolol, bisoprolol, metoprolol, propranolol, timolol, nicardipine and verapamil. CONCLUSION: Among people with episodic migraine, a broader number of blood pressure-lowering medication classes and drugs reduce headache frequency than those currently included in treatment guidelines.Trial Registration: The study was registered at PROSPERO (CRD42017079176).

Representation of Women in Stroke Clinical Trials: A Review of 281 Trials Involving More Than 500,000 Participants.

BACKGROUND AND OBJECTIVES: Women have been underrepresented in cardiovascular disease clinical trials but there is less certainty over the level of disparity specifically in stroke. We examined the participation of women in trials according to stroke prevalence in the population. METHODS: Published randomized controlled trials with ≥100 participants enrolled between 1990 and 2020 were identified from ClinicalTrials.gov. To quantify sex disparities in enrollment, we calculated the participation to prevalence ratio (PPR), defined as the percentage of women participating in a trial vs the prevalence of women in the disease population. RESULTS: There were 281 stroke trials eligible for analyses with a total of 588,887 participants, of whom 37.4% were women. Overall, women were represented at a lower proportion relative to their prevalence in the underlying population (mean PPR 0.84; 95% confidence interval [CI] 0.81-0.87). The greatest differences were observed in trials of intracerebral hemorrhage (PPR 0.73; 95% CI 0.71-0.74), trials with a mean age of participants <70 years (PPR 0.81; 95% CI 0.78-0.84), nonacute interventions (PPR 0.80; 95% CI 0.76-0.84), and rehabilitation trials (PPR 0.77; 95% CI 0.71-0.83). These findings did not significantly change over the period from 1990 to 2020 (p for trend = 0.201). DISCUSSION: Women are disproportionately underrepresented in stroke trials relative to the burden of disease in the population. Clear guidance and effective implementation strategies are required to improve the inclusion of women and thus broader knowledge of the impact of interventions in clinical trials.

Preventing adverse cardiac events (PACE) in chronic obstructive pulmonary disease (COPD): study protocol for a double-blind, placebo controlled, randomised controlled trial of bisoprolol in COPD.

INTRODUCTION: Heart disease in chronic obstructive pulmonary disease (COPD) is a common but neglected comorbidity. Patients with COPD are frequently excluded from clinical trials of treatments aimed at reducing cardiac morbidity and mortality, which has led to undertreatment of cardiovascular disease in patients with COPD. A particular concern in COPD is the underuse of beta (ß)-blockers. There is observational evidence that cardioselective ß-blockers are safe and may even reduce mortality risk in COPD, although some evidence is conflicting. There is an urgent need to answer the research question: Are cardioselective ß-blockers safe and of benefit in people with moderately severe COPD? The proposed study will investigate whether cardioselective ß-blocker treatment in patients with COPD reduces mortality and cardiac and respiratory morbidity. METHODS AND ANALYSES: This is a double-blind, randomised controlled trial to be conducted in approximately 26 sites in Australia, New Zealand, India, Sri Lanka and other countries as required. Participants with COPD will be randomised to either bisoprolol once daily (range 1.25-5 mg, dependent on tolerated dose) or matched placebo, in addition to receiving usual care for their COPD over the study duration of 24 months.The study will enrol 1164 participants with moderate to severe COPD, aged 40-85 years. Participants will be symptomatic from their COPD and have a postbronchodilator forced expiratory volume in 1 s (FEV1) ≥30% and ≤70% predicted and a history of at least one exacerbation requiring systemic corticosteroids, antibiotics or both in the prior 24 months. ETHICS AND DISSEMINATION: The study protocol has been approved by the Sydney Local Health District Human Research Ethics Committee at The Concord Repatriation General Hospital. TRIAL REGISTRATION NUMBERS: NCT03917914; CTRI/2020/08/027322.

Trends in recruitment of women and reporting of sex differences in large-scale published randomized controlled trials in stroke.

BACKGROUND: Understanding of sex differences, especially in terms of the influence of sex on therapeutic interventions, can lead to improved treatment and management for all. AIM: We examined temporal and regional trends in female participation and the reporting of sex differences in stroke randomized controlled trials. METHODS: Randomized controlled trials from 1990 to 2018 were identified from ClinicalTrials.gov, using keywords "stroke" and "cerebrovascular accidents." Studies were selected if they enrolled ≥100 participants, included both sexes and were published trials (identified using PubMed, Google Scholar, and Scopus). RESULTS: Of 1700 stroke randomized controlled trials identified, 277 were published and eligible for analysis. Overall, these randomized controlled trials enrolled only 40% females, and in the past 10 years, this percentage barely changed, peaking at 41% in 2008-2009 and 2012-2013. North American randomized controlled trials recruited the most women, at 43%, and Asia the lowest, at 40%. Among the 277 randomized controlled trials, 101 (36%) reported results according to sex, of which 91 (33%) were pre-specified analyses. The increasing trend in the number of studies reporting sex-differentiated results from 2008 to 2018 merely paralleled the increase in the number of papers published during the same time period. North American randomized controlled trials most often reported sex-specific results (42%), and Australia and Europe least often (31%). CONCLUSION: Little progress has been made in the inclusion of females and the reporting of sex in stroke randomized controlled trials. This highlights the need for key stakeholders, such as funders and journal editors, to provide clear guidance and effective implementation strategies to researchers in the scientific reporting of sex.