Observed and expected serious adverse event rates in randomised clinical trials for hypertension: An observational study comparing trials which do and do not focus on older people

Peter Hanlon, Neave Corcoran, Guy Rughani, Anoop S V Shah, Frances S Mair, Bruce Guthrie, Joanne P Renton, David A McAllister

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction
Representativeness of ‘standard’ antihypertensive drug trials is uncertain, with limited recruitment of older-people. Some trials specifically recruit older participants to address this. If such older-people’s trials are representative, we would expect rates of hospitalisation and death in each trial to be similar to community rates, and higher than rates in standard trials.

Methods
We identified trials of Renin-Angiotensin-Aldosterone system (RAAS) drugs for hypertension. Serious Adverse Events (SAEs) are routinely included in trial reports and are predominantly accounted for by all-cause hospitalisations and death. We compared SAE rates in older-people’s and standard trials, adjusting for trial characteristics (phase/drug/comparison/outcome). We identified a community cohort of adults with hypertension commencing similar drugs to obtain an expected rate of hospitalisations/deaths, and compared this to observed SAE rates in each trial.

Results
Included 110 trials: 11 older-people’s trials exclusively recruited people over 60 years; 99 standard trials included general adult populations (over and under 60-years). Older-people’s trials had higher SAEs rate than standard trials (0.18 versus 0.11 events/person/year, adjusted IRR 1.74, 95% CI 1.03-2.92). The hospitalisation and death rate in the community for those taking RAAS antihypertensives was much greater than the rate of SAEs reported in standard (ratio 3.70 (3.12-4.55)) and older-people’s trials (4.35 (2.56-7.69)), adjusting for age and sex.

Discussion
Trials report substantially fewer SAEs than expected from rates of hospitalisations and deaths among similar-aged people receiving equivalent treatments in the community. SAE rates may be a useful metric to assess trial representativeness. Clinicians should be cautious when applying trial recommendations to older people, even when trials focus on older participants.
Original languageEnglish
JournalThe Lancet
DOIs
Publication statusPublished - 10 Jun 2021

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