Intensive versus standard blood pressure control in type 2 diabetes: a restricted mean survival time analysis of a randomised controlled trial
Sandra Shi, Natalia Gouskova, Mehdi Najafzadeh, Lee-Jen Wei, Dae Hyun Kim, Sandra Shi, Natalia Gouskova, Mehdi Najafzadeh, Lee-Jen Wei, Dae Hyun Kim
Abstract
Background: Restricted mean survival time analysis offers an intuitive and robust summary of treatment effect compared with HRs.
Objective: To examine the effect of intensive versus standard blood pressure (BP) control on death or cardiovascular events in type 2 diabetes.
Design: Secondary analysis of the Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial.
Setting: 77 sites in the USA and Canada.
Participants: 4733 adults with type 2 diabetes at high risk for cardiovascular events.
Interventions: Systolic BP target <120 mm Hg (n=2371) versus <140 mm Hg (n=2362).
Measurements: Composite endpoint of death, non-fatal myocardial infarction or non-fatal stroke.
Results: The mean event-free survival time over 5 years (1825 days) was similar between intensive and standard BP control (1716 vs 1714 days; mean difference, 1.3 (95% CI -18.1 to 20.7) days). However, intensive BP treatment was more beneficial for those assigned to standard glycaemic control (1725 vs 1697 days; mean difference, 28.1 (95% CI 0.4 to 55.9) days), but not for those assigned to intensive glycaemic control (1706 vs 1731 days; mean difference, -25.2 (95% CI -52.3 to 1.9) days) (p=0.008 for interaction). In subgroup analysis, the mean event-free survival time difference between intensive and standard BP treatment was -76.0 (95% CI -131.8 to -20.3) days for those with cognitive impairment and 21.8 (95% CI -24.0 to 67.5) days for those with normal cognitive function (p=0.008 for interaction). The effect was not different by age, sex and baseline cardiovascular disease status.
Conclusions: Intensive BP treatment may reduce death and cardiovascular events among patients with type 2 diabetes receiving standard glycaemic treatment and without cognitive impairment.
Trial registration number: NCT00000620; Post-results.
Keywords: diabetes & endocrinology; geriatric medicine; hypertension.
Conflict of interest statement
Competing interests: None declared.
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Figures
References
- SPRINT Research Group, Wright JT, Williamson JD, et al. . A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015;373:2103–16. 10.1056/NEJMoa1511939
- Beckett NS, Peters R, Fletcher AE, et al. . Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358:1887–98. 10.1056/NEJMoa0801369
- James PA, Oparil S, Carter BL, et al. . 2014 evidence-based guideline for the management of high blood pressure in adults. JAMA 2014;311:507. 10.1001/jama.2013.284427
- ACCORD Study Group, Cushman WC, Evans GW, et al. . Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575–85. 10.1056/NEJMoa1001286
- Margolis KL, O'Connor PJ, Morgan TM, et al. . Outcomes of combined cardiovascular risk factor management strategies in type 2 diabetes: the Accord randomized trial. Diabetes Care 2014;37:1721–8. 10.2337/dc13-2334
- Pajewski NM, Berlowitz DR, Bress AP, et al. . Intensive vs Standard Blood Pressure Control in Adults 80 Years or Older: A Secondary Analysis of the Systolic Blood Pressure Intervention Trial. J Am Geriatr Soc 2020;68:496–504. 10.1111/jgs.16272
- Kloecker DE, Davies MJ, Khunti K, et al. . Uses and limitations of the restricted mean survival time: illustrative examples from cardiovascular outcomes and mortality trials in type 2 diabetes. Ann Intern Med 2020;172:541–52. 10.7326/M19-3286
- Tian L, Zhao L, Wei LJ. Predicting the restricted mean event time with the subject's baseline covariates in survival analysis. Biostatistics 2014;15:222–33. 10.1093/biostatistics/kxt050
- Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. . Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545–59. 10.1056/NEJMoa0802743
- Cushman WC, Grimm RH, Cutler JA, et al. . Rationale and design for the blood pressure intervention of the action to control cardiovascular risk in diabetes (accord) trial. Am J Cardiol 2007;99:S44–55. 10.1016/j.amjcard.2007.03.005
- Gerstein HC, Riddle MC, Kendall DM, et al. . Glycemia treatment strategies in the action to control cardiovascular risk in diabetes (accord) trial. Am J Cardiol 2007;99:S34–43. 10.1016/j.amjcard.2007.03.004
- Kingry C, Bastien A, Booth G, et al. . Recruitment strategies in the action to control cardiovascular risk in diabetes (accord) trial. Am J Cardiol 2007;99:S68–79. 10.1016/j.amjcard.2007.03.025
- Dluhy RG, McMahon GT. Intensive glycemic control in the ACCORD and advance trials. N Engl J Med 2008;358:2630–3. 10.1056/NEJMe0804182
- Launer LJ, Miller ME, Williamson JD, et al. . Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (accord mind): a randomised open-label substudy. Lancet Neurol 2011;10:969–77. 10.1016/S1474-4422(11)70188-0
- Murray AM, Hsu F-C, Williamson JD, et al. . ACCORDION mind: results of the observational extension of the Accord mind randomised trial. Diabetologia 2017;60:69–80. 10.1007/s00125-016-4118-x
- Zhao L, Tian L, Claggett B, et al. . Estimating treatment effect with clinical interpretation from a comparative clinical trial with an end point subject to competing risks. JAMA Cardiol 2018;3:357–8. 10.1001/jamacardio.2018.0127
- Anderson PK, Hansen MG, Klein J. Regression analysis of restricted mean survival time based on pseudo-observations for competing risks data. Commun Stat - Theory Methods 2018;47:5614–25.
- ACCORD Study Group, Gerstein HC, Miller ME, et al. . Long-Term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 2011;364:818–28. 10.1056/NEJMoa1006524
- Krishnaswami A, Peterson ED, Kim DH, et al. . Efficacy and safety of intensive blood pressure therapy using restricted mean survival Time-Insights from the sprint trial. Am J Med 2020;133:e369–70. 10.1016/j.amjmed.2019.12.050
- Tsujimoto T, Kajio H. Benefits of intensive blood pressure treatment in patients with type 2 diabetes mellitus receiving standard but not intensive glycemic control. Hypertension 2018;72:323–30. 10.1161/HYPERTENSIONAHA.118.11408
- Beddhu S, Chertow GM, Greene T, et al. . Effects of intensive systolic blood pressure lowering on cardiovascular events and mortality in patients with type 2 diabetes mellitus on standard glycemic control and in those without diabetes mellitus: reconciling results from accord bp and sprint. J Am Heart Assoc 2018;7:e009326. 10.1161/JAHA.118.009326
- Aggarwal R, Petrie B, Bala W, et al. . Mortality outcomes with intensive blood pressure targets in chronic kidney disease patients. Hypertension 2019;73:1275–82. 10.1161/HYPERTENSIONAHA.119.12697
- Kim DH, Uno H, Wei L-J. Restricted mean survival time as a measure to interpret clinical trial results. JAMA Cardiol 2017;2:1179–80. 10.1001/jamacardio.2017.2922
- Williamson JD, Launer LJ, Bryan RN, et al. . Cognitive function and brain structure in persons with type 2 diabetes mellitus after intensive lowering of blood pressure and lipid levels: a randomized clinical trial. JAMA Intern Med 2014;174:324–33. 10.1001/jamainternmed.2013.13656
- Lee PY, Alexander KP, Hammill BG, et al. . Representation of elderly persons and women in published randomized trials of acute coronary syndromes. JAMA 2001;286:708–13. 10.1001/jama.286.6.708
- Sardar MR, Badri M, Prince CT, et al. . Underrepresentation of women, elderly patients, and racial minorities in the randomized trials used for cardiovascular guidelines. JAMA Intern Med 2014;174:1868–70. 10.1001/jamainternmed.2014.4758
- Taylor JS, DeMers SM, Vig EK, et al. . The disappearing subject: exclusion of people with cognitive impairment and dementia from geriatrics research. J Am Geriatr Soc 2012;60:413–9. 10.1111/j.1532-5415.2011.03847.x
- Ickowicz E. Guiding principles for the care of older adults with multimorbidity: an approach for clinicians: American geriatrics Society expert panel on the care of older adults with multimorbidity. J Am Geriatr Soc 2012;60:E1–25. 10.1111/j.1532-5415.2012.04188.x
Source: PubMed