Purpose: To compare the effectiveness on blood pressure (BP) of initial two‐drug therapy versus monotherapy in hypertensive patients.Methods: Using the Clinical Practice Research Datalink, linked with Hospital Episode Statistics and Office for National Statistics, we identified a cohort of adults with uncontrolled hypertension, initiating one or two antihypertensive drug classes between 2006 and 2014. New users of two drugs and monotherapy were matched 1:2 by propensity score. Main exposure was “as‐treated,” ie, until first regimen change. Primary and secondary endpoints were systolic and diastolic BP control and major adverse cardiovascular event (MACE), respectively. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard models.Results: Of 54 523 eligible patients, 3256 (6.0%) were initiated to a two‐drug combination. Of these, 2807 were matched to 5614 monotherapy users. Mean exposure duration was 12.7 months, with 76.5% patients changing their initial regimen. Two‐drug therapy was associated with a clinically significant BP control increase in all hypertensive patients (HR = 1.17 [95%CI: 1.09‐1.26]), more so in patients with grade 2‐3 hypertension (HR = 1.28 [1.17‐1.41]). An increase of 27% in BP control (HR = 1.27 [1.08‐1.49]) was observed in patients initiating an ACEi+CCB combination compared with initiators of either single class. No significant association was found between two‐drug therapy and MACE. Several sensitivity analyses confirmed the main findings.Conclusions: Few patients initiated therapy with two drugs, reflecting UK guidelines' recommendation to start with monotherapy. This study supports the greater effectiveness of two‐drug therapy as the initial regimen for BP control.

Purpose: Validating cases of acute liver injury (ALI) in health care data sources is challenging. Previous validation studies reported low positive predictive values (PPVs).Methods: Case validation was undertaken in a study conducted from 2009 to 2014 assessing the risk of ALI in antidepressants users in databases in Spain (EpiChron and SIDIAP) and the Danish National Health Registers. Three ALI definitions were evaluated: primary (specific hospital discharge codes), secondary (specific and nonspecific hospital discharge codes), and tertiary (specific and nonspecific hospital and outpatient codes). The validation included review of patient profiles (EpiChron and SIDIAP) and of clinical data from medical records (EpiChron and Denmark). ALI cases were confirmed when liver enzyme values met a definition by an international working group.Results: Overall PPVs (95% CIs) for the study ALI definitions were, for the primary ALI definition, 84% (60%‐97%) (EpiChron), 60% (26%‐88%) (SIDIAP), and 74% (60%‐85%) (Denmark); for the secondary ALI definition, 65% (45%‐81%) (EpiChron), 40% (19%‐64%) (SIDIAP), and 70% (64%‐77%) (Denmark); and for the tertiary ALI definition, 25% (18%‐34%) (EpiChron), 8% (7%‐9%) (SIDIAP), and 47% (42%‐52%) (Denmark). The overall PPVs were higher for specific than for nonspecific codes and for hospital discharge than for outpatient codes. The nonspecific code “unspecified jaundice” had high PPVs in Denmark.Conclusions: PPVs obtained apply to patients using antidepressants without preexisting liver disease or ALI risk factors. To maximize validity, studies on ALI should prioritize hospital specific discharge codes and should include hospital codes for unspecified jaundice. Case validation is required when ALI outpatient cases are considered.

The mpox 2022 outbreak was declared a public health emergency in July 2022. In August 2022, the MVA–BN vaccine received emergency use authorization in the United States (US) to target at-risk groups. This study (EUPAS104386) used HealthVerity’s administrative US healthcare data to generate real-world evidence for MVA–BN vaccine effectiveness and safety to prevent mpox disease in men who have sex with men (MSM) and transgender women, the most affected population during the 2022 mpox outbreak. Fully vaccinated subjects (two doses ≥ 28 days apart) were initially matched with five unvaccinated subjects on calendar date, age, US region, and insurance type. Subjects were followed from index date (14 days after the second dose) until death or data end to ascertain mpox occurrence. After propensity score adjustment, the MVA–BN vaccine effectiveness against mpox disease was 89% (95% CI: 12%, 99%) among those fully vaccinated; attenuated to 64% (95% CI: 40%, 78%) among those with any dose and 70% (95% CI: 44%, 84%) for those with only a single dose. One pericarditis adverse event of special interest was observed when the risk window was extended to 28 days. These results contribute to the totality of evidence supporting the favorable benefit/risk profile of the MVA–BN vaccine.