By Dr. Geoffrey Modest
Although there have been many studies confirming a role of hypertension in the development of atrial fibrillation (AF), a secondary analysis of the LIFE trial gives insight into the effects of achieving different levels of blood pressure on the frequency of development of AF (see Hypertension. 2015;66:368). The LIFE trial (Lancet. 2002;359:99) used 2 different hypertensive agents (losartan and atenolol) in patients with EKG-documented LVH to assess differences in clinical outcomes.
Details:
- 8831 hypertensive patients (mean age 66.6, 45% male, 6% Black race, 13% with diabetes, 18% ischemic heart disease, 7% MI, 5% stroke, 15% smokers, BMI 28), with EKG LVH and no history of AF, in sinus rhythm on baseline EKG, were randomly assigned to losartan or atenolol, and followed 4.6 years
- Patients with in-treatment achieved SBP ≤ 130 mmHg (lowest quintile at last measurement in the study) were compared to those with SBP 131-141 vs those with ≥142
Results:
- New onset AF developed in 701 patients (7.9%)
- In multivariate analyses (controlling for age, sex, race, DM, history ischemic heart disease/MI/heart failure, serum glucose/creatinine/microalbumin, prior BP therapy), comparing achieved SBP of ≥142 mmmHg:
- Achieved SBP of ≤130 mmHg was associated with a 40% lower risk of AF (18-55%, p=0.001)
- Achieved SBP of 131-141 mmHg was associated with a 24% lower risk of AF (7-38%, p=0.007)
- For each 10mmHg decrease in SBP: 13% lower risk of AF (9-17%, p<0.001)
- And, no difference in benefit of lower SBPand AF in those > or <60yo
- But, lowering SBP to ≤125 mmHg was no longer associated with reduced risk of AF (all achieved SBPs less than 125 were nonsignificantly related to the development of AF, though the hazards ratio trended to increasing risk with progressively lower SBP)
So, a few points:
- Although the LIFE cohort included only patients with LVH on EKG, it has the advantage of using 2 different BP meds with 2 different mechanisms of actions. This makes it more likely that it is the achieved blood pressure which correlated with the development of AF. (With only one medication, one might wonder if the association was the blood pressure lowering effect or perhaps some other unrelated effect of the med).
- But, one concern here is that those on losartan had somewhat lower likelihood of developing AF (in those who developed AF, 46.2% were on losartan vs 50.6% on atenolol). And we know from the LIFE study that those on losartan had more regression of their LVH than those on atenolol, and this was the purported reason that in the overall LIFE trial there were overall fewer cardiac events in the losartan group. In fact, the incidence of cardiac events in the LIFE study overall was equivalently lower in both the losartan and atenolol groups when there was regression of LVH, but regression was more common in the losartan group. So, it may be that looking at the post-hoc analysis of hypertensive patients with LVH and their likelihood of developing AF might not be so generalizable to hypertensives without LVH (.e., if the development of AF were at least partly related to LVH on EKG).
- Prior articles have had somewhat mixed results: the Cardio-Sis trial (Lancet. 2009;374:525) found statistically fewer cases of new onset AF in those on tighter control (achieved SBP of 131.9 mmHg was better than 135.6), though another study did not (Am J Hypertens. 2008;21:1111)
- So, this trial adds to the argument that more dramatic lowering of the blood pressure may have another positive effect: decreasing the likelihood of developing AF. And, of course, this is a really important clinical endpoint (stroke, other emboli, risks of prolonged anticoagulation and/or cardiac procedures, risk of sudden cardiac death and heart failure, risk of cognitive decline, …). though there were also limitations of the SPRINT trial (see https://stg-blogs.bmj.com/bmjebmspotlight/2015/11/19/primary-care-corner-with-geoffrey-modest-md-tighter-blood-pressure-control-the-sprint-trial/ , which did not include diabetics but did find a pretty much all-endpoint benefit of tighter control at an achieved SBP of 121 mmHg), this current study does add to the literature suggesting more aggressive goals of therapy, with SBP target in the 125-130 mmHg range, at least in those with EKG-LVH. Though, it should be added, that this study had too few diabetics to make a meaningful argument about their blood pressure goal, and another recent blog (see https://stg-blogs.bmj.com/bmjebmspotlight/2016/03/07/primary-care-corner-with-geoffrey-modest-md-hypertension-goal-in-diabetes/ ) assessed a systematic review finding that the goal for diabetics should perhaps be higher than others, with a target of 140/75-80. And I will add my usual caveat to be less aggressive with elderly, since postural hypotension/risk of falls is so common(?autonomic dysfunction, see https://stg-blogs.bmj.com/bmjebmspotlight/2014/12/18/primary-care-corner-with-geoffrey-modest-md-orthostatic-hypotension/) and too low a blood pressure can be associated with cognitive decline (see https://stg-blogs.bmj.com/bmjebmspotlight/2015/04/23/primary-care-corner-with-geoffrey-modest-md-too-low-blood-pressure-and-cognitive-decline-in-elderly/ ).
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