Cardiovascular events with blood pressure lowering in patients with diabetes and systolic blood pressure below 140 mm Hg

Wang et al1 concluded that initiating blood pressure (BP) lowering in patients with diabetes and baseline systolic BP (SBP) 130-140 mm Hg is not beneficial and can increase the risk of serious adverse effects. We suggest these conclusions are incorrect because of inappropriate inclusion of some trials and missing relevant data from other trials. The inclusion and therefore large statistical weight given to dual renin-angiotensin-aldosterone (RAAS) therapy trials ALTITUDE2 and VA-NEPHRON3 is hard to justify, especially as a primary analysis: dual RAAS therapies do not lower BP to any appreciable degree, increase risk of adverse effects, and hence are recommended against by guidelines.4, 5 A recent systematic review6 of BP lowering trials, excluding dual RAAS therapy trials and including individual participant data from many larger trials, provided data from 12 trials for 21 044 patients with diabetes whose baseline SBP was below 140 mm Hg. For these patients, the treatment and control group mean SBP during follow-up was 125 vs 132 mm Hg and the relative risk (RR) for the composite outcome of coronary heart disease or stroke was 0.90 (95% confidence intervals 0.81-1.01), which was not appreciably different from the RR for all patients with baseline SBP <140 mm Hg of 0.84 (0.81-0.88).6 The results among diabetics are compatible with both a similar-sized and a smaller proportional effect compared to non-diabetics, but are not consistent with harm from BP lowering. The totality of evidence from relevant trial data among diabetics indicates benefits of BP lowering, which is likely to be clinically important in size given the high absolute risk faced by diabetic patients. George Health Enterprises, the social enterprise arm of The George Institute for Global Health, has received investment to develop fixed-dose combination products containing aspirin, statin and blood pressure-lowering drugs. George Health Enterprises has submitted patents for low-dose blood pressure combinations, on which AR is listed as one of the inventors. None of the authors have a financial interest in these planned products.