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Review: In diabetes, benefits of lowering BP depend on baseline BP being 140 mm Hg or more

Question In patients with diabetes mellitus, what is the effect of antihypertensive treatment at different blood pressure (BP) levels? Review scope Included studies compared any antihypertensive drug with placebo, any 2 drugs with 1 drug, or any BP target with another in 100 patients with diabetes for 12 months. Exclusion criteria were trials comparing 2 individual drugs or combined interventions. Outcomes included all-cause mortality, cardiovascular (CV) mortality, myocardial infarction (MI), stroke, heart failure, and end-stage renal disease (ESRD). Review methods MEDLINE, EMBASE/Excerpta Medica, Cochrane CENTRAL, BIOSIS (all to Feb 2013), and reference lists were searched for randomized controlled trials (RCTs). Authors, pharmaceutical companies, and authorities were contacted. 49 RCTs (n =73738, mean follow-up 3.7 y) met selection criteria. 24 RCTs included only patients with diabetes, and 25 included subgroups with diabetes; most patients had type 2 diabetes. 38 RCTs compared antihypertensive treatment with placebo. Risk for bias was low for randomization (45 RCTs), concealed allocation (39 RCTs), blinding of patients and personnel (26 RCTs), and blinding of outcome assessors (36 RCTs). Meta-analysis presented in this abstract was stratified by mean baseline systolic BP (SBP) within trials. Main results For trials with mean baseline SBP >150 mm Hg, antihypertensive treatment reduced all-cause mortality, CV mortality, MI, stroke, and ESRD (Table). For mean baseline SBP 140 to 150 mm Hg, antihypertensive treatment reduced all-cause mortality, MI, and heart failure (Table). For baseline SBP <140 mm Hg, antihypertensive treatment showed a borderline increase in CV mortality and did not differ for other outcomes (Table). Metaregression showed that, for each 10-mm Hg lower baseline SBP, hypertensive treatment increased risk for CV mortality (relative risk [RR] 1.15, 95% CI 1.03 to 1.29) and MI (RR 1.12, CI 1.03 to 1.22). Conclusions In patients with diabetes mellitus and systolic blood pressure 140 mm Hg, antihypertensive treatment reduces mortality and myocardial infarction. In patients with systolic blood pressure <140 mm Hg, antihypertensive treatment does not reduce mortality and is associated with increased cardiovascular mortality. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus* Outcomes Relative risk (95% CI) SBP >150 mm Hg SBP 140 to 150 mm Hg SBP <140 mm Hg All-cause mortality 0.89 (0.80 to 0.99) 0.87 (0.78 to 0.98) 1.05 (0.95 to 1.16) Cardiovascular mortality 0.75 (0.57 to 0.99) 0.87 (0.71 to 1.05) 1.15 (1.00 to 1.32) Myocardial infarction 0.74 (0.63 to 0.87) 0.84 (0.76 to 0.93) 1.00 (0.87 to 1.15) Stroke 0.77 (0.65 to 0.91) 0.92 (0.83 to 1.01) 0.81 (0.53 to 1.22) Heart failure 0.73 (0.53 to 1.01) 0.80 (0.66 to 0.97) 0.90 (0.79 to 1.02) End-stage renal disease 0.82 (0.71 to 0.94) 0.91 (0.74 to 1.12) 0.97 (0.80 to 1.17) *SBP = systolic blood pressure; other abbreviations defined in Glossary. Meta-analysis was stratified by mean baseline SBP within trials. Commentary Establishing optimal BP targets in patients with and without diabetes remains controversial. The systematic review by Brunstrm and Carlberg supports the view that lowering BP is most beneficial for patients with higher BP levels who are at increased risk for adverse CV outcomes. Further, it provides context for studies showing that intensive BP control is not necessarily beneficial to all patients, such as those with mildly elevated BP, low CV risk, frailty, or multiple morbidities (1, 2). The controversy continues, in part because the evidence is primarily from industry trials designed to compare the efficacy of antihypertensive agents, often with placebo, rather than to evaluate specific BP targets or reductions. The reliability of the review is affected by use of summary rather than individual patient data (which increases the risk for so-called ecological bias in the analyses stratified by baseline mean SBP) and analyses stratified by attained SBP (an outcome of the trials). Current guidelines seem to strike the right balance: After reduction of SBP levels to about 140 to 150 mm Hg, lower BP targets should take into account potential harms, inconvenience of additional treatment, personal and social contexts of patients, and CV risk and comorbidities (3). For many patients, perfect BP may turn out to be the enemy of good enough.