Long-Term Renal and Cardiovascular Outcomes in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Participants by Baseline Estimated GFR

Abstract

SummaryBackground and objectives CKD is common among older patients. This article assesses long-term renal and cardiovascular outcomes in older high-risk hypertensive patients, stratified by baseline estimated GFR (eGFR), and long-term outcome efficacy of 5-year first-step treatment with amlodipine or lisinopril, each compared with chlorthalidone.Design, setting, participants, & measurements This was a long-term post-trial follow-up of hypertensive participants (n=31,350), aged $55 years, randomized to receive chlorthalidone, amlodipine, or lisinopril for 4-8 years at 593 centers. Participants were stratified by baseline eGFR (ml/min per 1.73 m 2 ) as follows: normal/ increased ($90; n=8027), mild reduction (60-89; n=17,778), and moderate/severe reduction (,60; n=5545). Outcomes were cardiovascular mortality (primary outcome), total mortality, coronary heart disease, cardiovascular disease, stroke, heart failure, and ESRD.Results After an average 8.8-year follow-up, total mortality was significantly higher in participants with moderate/severe eGFR reduction compared with those with normal and mildly reduced eGFR (P,0.001). In participants with an eGFR ,60, there was no significant difference in cardiovascular mortality between chlorthalidone and amlodipine (P=0.64), or chlorthalidone and lisinopril (P=0.56). Likewise, no significant differences were observed for total mortality, coronary heart disease, cardiovascular disease, stroke, or ESRD.Conclusions CKD is associated with significantly higher long-term risk of cardiovascular events and mortality in older hypertensive patients. By eGFR stratum, 5-year treatment with amlodipine or lisinopril was not superior to chlorthalidone in preventing cardiovascular events, mortality, or ESRD during 9-year follow-up. Because data on proteinuria were not available, these findings may not be extrapolated to proteinuric CKD.

Are Thiazide Diuretics Safe and Effective Antihypertensive Therapy in Kidney Transplant Recipients?

“…To our knowledge, this is the first study published to specifically analyze the antihypertensive effectiveness of thiazide therapy in KTX recipients [7]. These data are congruent with recent analyses demonstrating the efficacy of thiazides as antihypertensives in the general population with moderate to severe CKD [12,13,14]. As HTN is poorly controlled [8,9] and the most significant CVD risk factor encountered within KTX [4,5,17,18], these results provide important preliminary evidence to increase the armamentarium of antihypertensive agents that may effectively manage posttransplant HTN.…”

“…non-diuretic actions within the kidney [19,20]. The data presented within this study, as well as other recently published studies, add clinical credence to this mechanistic argument [12]. The presence or severity of CKD had little to no bearing on the antihypertensive efficacy of thiazides within this study.…”

“…Thiazides are considered first-line antihypertensive therapy based on JNC-VII [10], yet have historically been thought to be ineffective in controlling HTN in patients with moderate to severe CKD. However, recent analyses, including a long-term subanalysis of ALLHAT, have demonstrated that thiazides are effective antihypertensives in CKD patients [12,13,14]. Despite this, there is paucity in the literature examining the safety and efficacy of thiazide diuretics as antihypertensive medications in KTX recipients [7].…”

Preclinical Cardiorenal Interrelationships in Essential Hypertension

“…In particular, a baseline GFR of <53 ml/min/1.73 m 2 was independently associated with a 32% higher risk of coronary heart disease [18]. Furthermore, after an average 8.8-year post-trial follow-up, total mortality was significantly higher in participants with a moderate-to-severe GFR reduction compared to those with a normal and mildly reduced GFR [19]. Based on the VALUE trial, the risk in individuals with CKD stage 3 at baseline was again greater than in those with better renal function; however, GFR calculated with the MDRD formula turned out to be more informative than the estimated creatinine clearance (Cockcroft-Gault) in the prediction of cardiovascular outcomes [20].…”

Initial Choice of Antihypertensive on Long-Term Cardiovascular Outcomes in CKD

“…Since completion, the collaborative group has explored the cohort post hoc for various outcomes and has reported kidney and CVD outcomes at 5 (5) and 6 years (6). In this issue of CJASN, Rahman et al (7) report data on ;9 years of follow-up from the original cohort.…”