Results From a Systematic Review and Network Meta-Analysis Suggest that Lower Systolic Blood Pressure Targets Are More Effective for Reducing Risks for Cardiovascular Disease Events and Mortality
Clinical trials have documented that lowering blood pressure reduces cardiovascular disease (CVD) and early death.1 However, the optimal target(s) for reduction of systolic blood pressure (SBP) are uncertain.1-4 Scientists from Tulane University School of Public Health and Tropical Medicine and the School of Medicine, along with scientists from the Medical College of Soochow University, China, conducted a systematic review and meta-analysis to assess the association of mean achieved SBP levels with the risk of CVD and all-cause mortality in adults with hypertension treated with antihypertensive therapy.5 From a MEDLINE and EMBASE search of articles through December 2015, Dr. Joshua Bundy and his colleagues identified 42 clinical trials of 144,200 patients that met their pre-defined criteria of random allocation to an antihypertensive medication, control, or treatment target that reported a difference in mean achieved SBP of 5 mm Hg or more between the groups compared. The results showed that there was a linear association between mean achieved SBP and risks of CVD and mortality. An achieved SBP of 120-124 mm Hg had the lowest risk. Subjects in this lowest category had a hazard ratio (HR) of 0.82 (95% confidence interval [CI] 0.67-0.97) compared to subjects with even slightly higher SBP of 125-129 mm Hg, and this continued linearly through all of the 5 mm SBP cutpoints up to the comparison with the highest level of SBP ≥160 mm Hg, for which the HR for SBP of 120-124 mm Hg was 0.36 (95% CI 0.26-0.51). Similarly, subjects with an achieved SBP of 120-124 mm Hg had a HR for all-cause mortality of 0.74 (95% CI 0.57-0.97) compared with subjects in the 125-129 mm Hg category, and the benefit to all-cause mortality continued to as much as 0.47 (95% CI 0.32-0.67) when compared to subjects with SBP ≥160 mm Hg.
The 2003 7th Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of Blood Pressure recommended SBP goals of <130 mm Hg for patients with type 2 diabetes or chronic kidney disease and <140 mm Hg for individuals at least 60 years of age.1 The 8th Report of the Joint Committee released in 2014, raised these treatment targets to <140 and <150 mm Hg, respectively.2 The investigators of the Systolic Blood Pressure Intervention Trial (SPRINT) examined the association with CVD and all-cause mortality risks of the more intensive treatment goal (SBP <120 mm Hg) compared to <140 mm Hg among men and women with hypertension and at high CVD risk (but without diabetes or stroke).3 The mean achieved SBP was 121.5 mm Hg in the intensive-treatment group and 134.6 mmHg in the standard-treatment group. During a median follow-up of 3.3 years, a 25% reduction in the primary composite outcome of CVD events (HR, 0.75; 95% CI, 0.64-0.89; P < .001) and a 27% reduction in all-cause mortality (HR, 0.73; 95% CI, 0.60-0.90; P = .003) were observed. However, some were concerned that those results were not necessarily generalizable for a variety of reasons.
Current guidelines provide inconsistent recommendations regarding the optimal SBP target, particularly in older adults. Earlier this year, the American College of Physicians and the American Academy of Family Physicians released their joint guideline with evidence-based recommendations on the benefits and harms of higher (<150 mm Hg) versus lower (≤140 mm Hg) SBP targets for hypertension in adults at least 60 years of age.4 They reported that mortality, incidence of stroke, and cardiac events were all reduced with the lower SBP target, but that treating to a lower target did not further reduce mortality, quality of life, or functional status in the target patient population. They also reported increased withdrawals due to adverse events, as well as increased cough, hypotension, and risk of syncope with treating to the lower vs. higher SBP targets. A report from the panel appointed to the Eighth Joint National Committee, recommended a SBP treatment target of 150 mm Hg for adults aged 60 years or older.2
On the other hand, in an analysis6 of data from 2636 SPRINT participants who were ≥75 years of age (mean age, 79.9 years; 37.9% women), at a median follow-up of 3.1 years, there were significantly lower rates of the primary composite outcome, HR = 0.66 (95%CI, 0.51-0.85) and all-cause mortality HR = 0.67 (95%CI, 0.49-0.91). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard ≥treatment group.
The multiple sets of hypertension guidelines and recommendations create confusion about the most appropriate blood pressure targets for patients with hypertension. The results from the meta-analysis by Bundy et al.5 support the interpretation of the SPRINT investigators that a lower target is associated with reduced CVD and mortality risk. Results from the subgroup analysis from SPRINT of elderly participants with a mean age of nearly 80 years suggest that a lower SBP target may produce benefits without unacceptable adverse effects even at advanced ages. These findings suggest that reassessment of the body of evidence for the currently recommended SBP targets may be warranted.
- Chobanian AV, Bakris GL, Black HR, et al. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206-1252.
- James PA, Oparil S, Carter BL, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-520.
- Wright JT, Jr., Williamson JD, Whelton PK, et al.; SPRINT Research Group. A randomized trial of intensive versus standardized blood-pressure control. N Engl J Med. 2015;373:2103-2116.
- Qaseem A, Wilt Tj, Rich R, et al.; Clinical Guidelines Committee of the American College of Physicians and the Commission on Health of the Public and Science of the American Academy of Family Physicians. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: A clinical practice guidelines from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017;166:430-437.
- Bundy JD, Li C, Stuchlik P, Bu X, et al. Systolic blood pressure reduction and risk of cardiovascular disease and mortality: a systematic review and network meta-analysis. JAMA Cardiol. 2017; May 31, 2017 [Epub ahead of print].
- Williamson JD; Supiano MA, Applegate WB et al. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years. A Randomized Clinical Trial. JAMA. 2016;315:2673-2682.