Optimal blood pressure in patients with atrial fibrillation

it is unclear from the literature what the goal blood pressure should be in patients with atrial fibrillation, and this is not addressed by any of the guidelines. A post hoc analysis of the AFFIRM trial (Atrial Fibrillation Follow-up Investigation of Rhythm Management, a prospective trial assessing the strategy of rate versus rhythm control) looked retroactively at the relationship of achieved blood pressure and outcomes (see afib optimal bp amjcardiol2014 in dropbox, or Badheka AO. Am J Cardiol 2014; 114: 727)). Details:

-- 3947 patients in the trial were followed 6 years, noting their systolic and diastolic blood pressures (recorded after sitting quietly for at least five minutes) at baseline and at follow-up, divided into 10-mm Hg increments. The follow-up blood pressure was defined as the average of all available blood pressure measurements during each post-baseline visit
-- mean age 69, and the following were significantly (and much) more frequent in patients who had lower blood pressure, with average percentages overall as follows:  60% in men, 70% hypertension, 40% coronary artery disease, 25% in patients with heart failure, 14% smoking
-- the endpoints assessed were all-cause mortality; the combination of all-cause mortality, ventricular tachycardia or fibrillation, pulseless electrical activity, significant bradycardia, stroke, major bleeding, MI, and PE as a composite secondary outcome.

Results:
-- all-cause mortality was observed in 614 people (15.6% of the group)                                                                  
-- the incidence of all-cause mortality was lowest in those with BP 140/78 mm Hg, with a U-shaped curve. All-cause mortality was:
    -- 3.9 fold higher in the group with systolic blood pressure <110; 1.9 fold higher in those with systolic greater >160
    ​-- 3.9 fold higher in the group with diastolic <60; 1.8 fold higher in the group with diastolic >90
--there was a similar U-shaped relationship to the composite secondary outcome.
-- Subgroup analyses also found a similar U-shaped curve with an increased all-cause mortality with blood pressure <110/60, including the following subgroups: whether or not they had CAD, hypertension, heart failure, or reduced ejection fraction.

commentary:
-- one of the complicating factors in assessing the optimal blood pressure in patients with atrial fibrillation is that several of the drugs we use to control rate (e.g. beta-blockers and non-dihydropyiridine calcium channel blockers) also decrease blood pressure. So, one of the complicating factors in interpreting the association between lower blood pressure and increased mortality is inherent in this retrospective observational study: are those who require more medications to control their heart rate at a higher risk of death, just because their harder-to-manage atrial fibrillation is associated with higher mortality? And their higher incidence of hypotension merely reflects their need for more meds (which also lower their blood pressure) to control that rate???
-- Another large issue is the dramatic baseline comorbidities in those with lower blood pressure, reinforcing the fact that these were much sicker patients and raising questions as to whether the study could mathematically adjust for these covariates in their final analysis. The authors did control for age, history of hypertension, history of heart failure, history of MI or revascularization, history of stroke, diabetes, smoking status, use of warfarin, lipid-lowering therapy, diuretics, and which group they were randomized to in the AFFIRM  trial. However, given how apparently sick these patients with low blood pressure were, one wonders if there were other important variables not included (e.g. other medical conditions such as renal failure, or COPD –esp since those with lower BP also had lower BMI, or psychosocial conditions associated with higher mortality such as depression)???
-- And what really is the actual blood pressure in patients with atrial fibrillation? The automated blood pressure cuffs typically use an oscillometric methodology. Studies have shown that many of these cuffs are inaccurate in patients with atrial fibrillation (see afib bp electronic cuff jclinhtn2015 in dropbox, or DOI: 10.1111/jch.12545 ). And, a larger issue to me is that there is a large blood pressure variability between measurements in patients with atrial fibrillation, with one measurement picking up a particularly strong, forceful beat, leading to a systolic blood pressure that may be 30 to 40 mm Hg higher than other readings. Some people suggest averaging several recordings (??how many), but I have no idea whether this correlates with clinical events are not, what the best methodology for determining that clinically-relevant BP really should be, or what would be the optimal goal BP (which also requires a good clinical prospective study using a validated methodology. perhaps 24-hour ambulatory blood pressure monitoring with an approved and accurate automated cuff???). As mentioned, i have seen no guidelines address the blood pressure issue: either its measurement or management goals.
-- one issue that is found frequently in observational studies on hypertension is a J-shaped or U-shaped curve. Of note this tends not to be found in controlled trials (e.g. the SPRINT trial), suggesting that there may be a bias in the uncontrolled trials: those with lower blood pressure have higher mortality related to the fact that they have underlying diseases leading to both a lower blood pressure and higher mortality
-- Of note, there are some data suggesting that we do not need to be overly aggressive in controlling rate (see Van Gelder IC. N Engl J Med 2010; 362: 1363), which also raises the interesting question of whether those with aggressive rate control may have had increased mortality because their blood pressure was lower, balancing perhaps a clinical benefit of the lower rate (ie there might be some benefit for tighter rate control, but only in those who could achieve this without lowering their blood pressure too much). unfortunately in this Van Gelder article they did not mention the achieved blood pressures in the 2 groups.
-- This AFFIRM article suggests that the target blood pressure in those with atrial fibrillation may be higher than in the general population. However, the methodologic issues above, to me, simply amplify the issue that there really are no good clinical data guiding us on either how to measure blood pressure or what the goal should be in those with atrial fibrillation....