Abstract
Background
Implementation of evidence-based medicine requires minimising delays between data generation and guideline creation. We examined the temporal relationship between accumulating evidence from randomized controlled trials (RCTs) of blood pressure (BP) lowering drug therapy among individuals with SBP<140 mmHg, DBP<90 mmHg, or both, and hypertension guideline recommendations over time.
Methods
A systematic review was conducted by searching MEDLINE for RCTs between January 1966 and February 2018. Included trials randomized patients to BP lowering drug(s) vs placebo/no treatment or to more vs less BP lowering with at least 1000 patient-years of follow-up per treatment group, and provided data relevant to BP lowering in patients with SBP<140 mmHg, DBP<90 mmHg, or both (hereafter <140/90 mmHg). Included trials were classified according to major patient groups and whether all patients had baseline BP <140/90 mmHg, or most control group patients had BP <140/90 mmHg during follow-up, which was selected because this is the BP against which interventions were compared. Two reviewers independently extracted relevant data from included RCTs and hypertension guidelines. Cumulative meta-analyses of cardiovascular events were conducted and were compared to hypertension guideline recommendations. The primary outcome was major cardiovascular events.
Results
A total of 73 trials (n=300,805) were included, including 16 trials/subgroups with all participants baseline BP <140/90mmHg. Benefits of BP lowering in individuals with usual BP <140/90 mmHg began to emerge in the 1970s (Figure). Most evidence was from trials that included some or all patients with hypertension at baseline, but most patients had BP <140/90 mmHg during follow-up due to regression to the mean and background treatment. Starting from 1992, 22 trials reported results by baseline hypertension status with no difference in cardiovascular event relative risk reduction among those with and without hypertension (relative risk 0.87 [95% CI 0.84–0.90] vs 0.86 [0.83–0.90], respectively. Until 2017, no major guidelines recommended treatment initiation or intensification for patients with baseline BP <140/90 mmHg, apart from the periods during which some guidelines recommended treatment at lower thresholds for patients with diabetes and chronic kidney disease (Joint National Committee 1997 to 2014; European Society of Hypertension 2007 to 2009).
Cumulative meta-analyses of trials
Conclusions
Evidence of benefits of BP lowering among individuals with usual BP <140/90 mmHg have been demonstrated for decades. However, there has been a substantial delay between data generation and guideline recommendations. This delay was may be due to the inappropriate emphasis on baseline rather than usual BP levels, and relatively narrow evidence synthesis, which does not fully account for evidence generated across various major patient groups.
2018 Korean Society of Hypertension Guideline for the Management of Hypertension: A Comparison of American, European, and Korean Blood Pressure Guidelines
