Optimal Systolic Blood Pressure Target After SPRINT: Insights from a Network Meta- Analysis of Randomized Trials Sripal Bangalore, MD, MHA, Bora Toklu,

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Optimal Systolic Blood Pressure Target After SPRINT: Insights from a Network Meta- Analysis of Randomized Trials Sripal Bangalore, MD, MHA, Bora Toklu, MD, Eugenia Gianos, MD, Arthur Schwartzbard, MD, Howard Weintraub, MD, Gbenga Ogedegbe, MD, Franz H. Messerli, MD The American Journal of Medicine Volume 130, Issue 6, Pages 707-719.e8 (June 2017) DOI: 10.1016/j.amjmed.2017.01.004 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 Network of systolic blood pressure target comparisons. The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 2 (A) Network meta-analysis of various systolic blood pressure targets for the outcome of stroke. (B) Sensitivity analysis based on achieved systolic pressure: Outcome of stroke. (C) Hierarchy of the systolic pressure targets (rankogram) using the rank probabilities for the outcome of stroke. (D) Comparison adjusted funnel plot for the outcome of stroke. (A <160 mm Hg; B <150 mm Hg; C <140 mm Hg; D <130 mm Hg; E <120 mm Hg). CI = confidence interval; RR = rate ratio. The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 3 (A) Hierarchy of the systolic pressure targets (rankogram) using the rank probabilities for the outcome of myocardial infarction. (B) Hierarchy of the systolic pressure targets (rankogram) using the rank probabilities for the outcome of death. (C) Hierarchy of the systolic pressure targets (rankogram) using the rank probabilities for the outcome of cardiovascular death. (D) Hierarchy of the systolic pressure targets (rankogram) using the rank probabilities for the outcome of heart failure. (E) Hierarchy of the systolic pressure targets (rankogram) using the rank probabilities for the outcome of serious adverse effects. The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 4 (A) Cluster plot for stroke vs serious adverse effects. (B) Cluster plot for myocardial infarction vs serious adverse effects (SAE). (C) Cluster plot for death vs serious adverse effects. The higher the surface under the cumulative ranking curve values of a systolic pressure target, the greater is the efficacy or safety. “Star” indicates the ideal systolic pressure target that maximizes outcomes efficacy and safety endpoints. MI = myocardial infarction; SUCRA = surface under the cumulative ranking curve. The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions

Supplementary Figure 1 Study selection. Records identified through database search using terms “hypertension,” “antihypertensive agents,” and individual antihypertensive classes; limited to randomized controlled trial, Humans (n = 22,476). DBP = diastolic blood pressure; MAP = mean arterial pressure. The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions

Supplementary Figure 2 Network meta-analysis of various systolic blood pressure targets for the outcome of myocardial infarction. CI = confidence interval; RR = rate ratio. The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions

Supplementary Figure 3 Comparison adjusted funnel plot for the outcome of myocardial infarction. (A <160 mm Hg; B <150 mm Hg; C <140 mm Hg; D <130 mm Hg; E <120 mm Hg). The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions

Supplementary Figure 4 Network meta-analysis of various systolic blood pressure targets for the outcome of death. CI = confidence interval; RR = rate ratio. The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions

Supplementary Figure 5 Comparison adjusted funnel plot for the outcome of death. (A <160 mm Hg; B <150 mm Hg; C <140 mm Hg; D <130 mm Hg; E <120 mm Hg). The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions

Supplementary Figure 6 Network meta-analysis of various systolic blood pressure targets for the outcome of cardiovascular death. CI = confidence interval; RR = rate ratio. The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions

Supplementary Figure 7 Comparison adjusted funnel plot for the outcome of cardiovascular death. (A <160 mm Hg; B <150 mm Hg; C <140 mm Hg; D <130 mm Hg; E <120 mm Hg). The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions

Supplementary Figure 8 Network meta-analysis of various systolic blood pressure targets for the outcome of heart failure. CI = confidence interval; RR = rate ratio. The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions

Supplementary Figure 9 Comparison adjusted funnel plot for the outcome of heart failure. (A <160 mm Hg; B <150 mm Hg; C <140 mm Hg; D <130 mm Hg; E <120 mm Hg). The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions

Supplementary Figure 10 Network meta-analysis of various systolic blood pressure targets for the outcome of serious adverse events. CI = confidence interval; RR = rate ratio. The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions

Supplementary Figure 11 Comparison adjusted funnel plot for the outcome of serious adverse effects. (A <160 mm Hg; B <150 mm Hg; C <140 mm Hg; D <130 mm Hg; E <120 mm Hg). The American Journal of Medicine 2017 130, 707-719.e8DOI: (10.1016/j.amjmed.2017.01.004) Copyright © 2017 Elsevier Inc. Terms and Conditions