Uncontrolled blood pressure and treatment of hypertension in older chronic kidney disease patients

An influential meta-analysis of 61 studies and over 1 million adults showed an age-specific correlation between elevated systolic blood pressure (SBP) and cardiovascular mortality.1 Subsequently, the SPRINT Senior Trial demonstrated that intensive antihypertensive treatment (SBP target <120 mmHg) for patients over 75 years old resulted in fewer cardiovascular events compared to standard treatment (SBP target <140 mmHg) while having no difference in falls, orthostatic hypotension, or overall severe adverse events.2 In contrast, AHA/ACC, ACP/AAFP, and ESC/ESH guidelines set this cohort's SBP target to be under 130 mmHg, 150 mmHg, and between 130 and 139 mmHg, respectively.3-5 Chronic kidney disease (CKD) also confers risk of cardiovascular disease with the AASK trial finding 3.3% cardiovascular outcomes per patient-year in this population.6 This study also found a low BP goal to be associated with reduced risk of end-stage renal disease and death among patients with CKD. AHA/ACC guidelines suggest a target SBP of under 130 for patients with CKD. When combining age and CKD, however, there is no specific target SBP.4 While the SPRINT Senior trial did not focus on hypertensive older patients with CKD, a group that deserves special attention due to the additional risk of acute kidney injury, in addition to falls, with intensive BP control. We sought to examine local practice patterns for this group. This is a cross-sectional study that examined local practice patterns of hypertension (HTN) treatment for older patients in early stages of CKD. We evaluated the SBP and number of antihypertensive medications among adults with stage 3–4 CKD that visited one of 15 BWH primary care clinics from January 4, 2018 to January 4, 2019. CKD and its stages were defined based on KDIGO guidelines as two prior eGFR 16–59 ml/min/1.73 m2 separated by 90 days within the preceding 2 years.7 eGFR values were calculated by the CKD-EPI creatinine equation.8 Qualified patients were divided into three age groups for analysis: 40–64, 65–79, and ≥80 years old. The mean number of antihypertensive medications and mean SBP were analyzed for each age group to evaluate the intensity and effectiveness of treatment. Antihypertensive medications included ACE-inhibitors, ARBs, beta blockers, calcium channel blockers, diuretics, renin inhibitors, ganglionic blockers, sympatholytic drugs, vasodilators, and combination medications. Significance for the mean SBP and mean number of antihypertensive medications was calculated through a t-test. The significance of the likelihood of being prescribed three or more antihypertensives between age groups was determined through a chi-square test. All data were obtained through Electronic Data Warehouse (EDW) queries and were then stratified by age. This protocol was approved by the Partners Human Research Committee (2018P000692). This trial is registered on clinicaltrials.gov as NCT03679247. During the study, 105,849 patients visited the primary care clinics, of which, 8013 were qualified. They were 59.5% female, 11.7% African American, and 6.4% Hispanic or Latino. The mean SBP was higher for patients aged ≥80 compared to the 65–79 group (132.1 mmHg vs. 129.9 mmHg, p < 0.001) and the 40–64 group (132.1 mmHg vs. 129.1 mmHg, p < 0.001). In a subgroup analysis of patients with SBP ≥140 mmHg, this trend remained for patients aged ≥80 compared to the 65–79 group (152.1 mmHg vs. 150.5 mmHg, p < 0.01) and the 40–64 group (152.1 mmHg vs. 150.2 mmHg, p < 0.02). The mean number of antihypertensive medications in this subgroup for patients aged ≥80 was not significantly different compared to the 65–79 group (2.2 vs. 2.3, p = 0.25) or the 40–64 group (2.2 vs. 2.2, p = 0.78). Additionally, the subgroup had no significant difference in the likelihood of being prescribed three or more antihypertensives for patients aged ≥80 compared to the 65–79 group (p = 0.16) or the 40–64 group (p = 0.61) (Table 1). When compared to the 40–64 or 65–79 groups, those 80 years and over had a greater mean SBP, but there was no significant difference in the intensity of antihypertensive treatment. The current local practice pattern achieves a mean SBP that is in concordance with the SBP goals for older patients set out by the ACP/AAFP and ESC/ESH guidelines, but not the AHA/ACC guidelines.3-5 When taking the SPRINT Senior findings into account, it is possible that the intensive goal of SBP ≤120 mmHg could improve these patients' outcomes, though the trial excluded patients with type 2 diabetes, history of stroke, symptomatic heart failure or reduced left ventricular ejection fraction, dementia, unintentional weight loss, pre-existing orthostatic hypotension, expected survival less than 3 years, or nursing home residence.2 In the context of current HTN treatment guidelines and the SPRINT trial results, this study's findings support future research on the risks and benefits of intensive antihypertensive treatment for older patients with CKD, many of whom would have been excluded from SPRINT, but also stand to benefit the most from intensive control in terms of cardiovascular outcomes and renal failure. Shimon Shaykevich, MS (Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, MA, USA) assisted in data analysis. This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant number R01DK116898. GM reports grants from Allena, other from GSK, outside the submitted work. DB reports grants and personal fees from EarlySense, personal fees from CDI Negev, other from ValeraHealth, other from Clew, other from MDClone, personal fees and other from AESOP, grants from IBM Watson Health, outside the submitted work. SW reports personal fees from Public Health Advocacy Institute, personal fees from CVS, personal fees from Roth Capital Partners, personal fees from Kantum Pharma, personal fees from Mallinckrodt, personal fees from Wolters Kluewer, personal fees from GE Health Care, personal fees from GSK, grants and personal fees from Allena Pharmaceuticals, personal fees from Mass Medical International, personal fees from Barron and Budd (vs. Fresenius), personal fees from JNJ, personal fees from Venbio, personal fees from Strataca, personal fees from Takeda, personal fees from Cerus, personal fees from Pfizer, personal fees from Bunch and James, personal fees from Harvard Clinical Research Institute (aka Baim), personal fees from Oxidien, personal fees from Sironax, personal fees from Metro Biotechnology, personal fees from Biomarin, personal fees from Bain, personal fees from Regeneron, outside the submitted work. Edward Wu and Skye Aaron were involved in data collection. Lipika Samal, David W. Bates, Sushrut Waikar, and Gearoid M. McMahon designed the study. Michael P. Gannon wrote the manuscript. Edward Wu, Gearoid M. McMahon, Skye Aaron, David W. Bates, Sushrut Waikar, and Lipika Samal contributed with critical revisions. Sponsor did not have a role in the design, methods, subject recruitment, data collections, analysis and preparation of this article.