27 Feb, 17 | by EBM
By Dr. Geoffrey Modest
The American College of Physicians and the American Academy of Family Physicians just published guidelines on the pharmacologic treatment of hypertension in adults over 60 yo, with both a systematic review and meta-analysis (see doi:10.7326/M16-1785), and a clinical practice guideline (see http://annals.org/aim/article/2598413/pharmacologic-treatment-hypertension-adults-aged-60-years-older-higher-versus )
- They analyzed 46 publications representing 21 randomized controlled trials and 3 cohort studies
- 9 trials show that intensive blood pressure treatment substantially improved outcomes in patients with moderate to severe hypertension, with SBP >160 mmHg. The data on lower systolic blood pressures also showed benefit but the results were less consistent.
- Overall studies of patients achieving SBP <140 mmHg were similar to those that achieved 140, although the reduction in stroke risk was more consistent in the studies where patients achieved the higher SBP
- In 6 trials comparing different treatment targets with 41,491 patients, treatment targets of SBP <140 mmHg or diastolic blood pressure of <85 mmHg were associated with only marginal benefit, with wide confidence intervals:
- 14% nonsignificant reduction all-cause mortality, RR 0.86 (0.69-1.06)
- 21% reduction in stroke, RR 0.79 (0.59-0.99)
- 18% marginally significant reduction in cardiac events, RR 0.82 (0.64-1.00)
- Because of their size and the event rates found, these analyses were dominated by the SPRINT and ACCORD trials. SPRINT (which excluded diabetics as well as those with SBP >180, prior stroke, urinary protein excretion >1 g per day or symptomatic heart failure/EF <35%) found marked reductions in mortality in cardiac events, though the ACCORD trial (which included only diabetics, though did achieve an SBP of 119 mmHg, similar to SPRINT) did not find any reduction in mortality or major cardiovascular events with intensive treatment [though other trials found benefit of hypertension treatment to be at least as strong in diabetics]. Also, the SPRINT trial stopped earlier than projected because of benefit, which, as mentioned in my blog on it noted below, will tend to exaggerate benefits and perhaps decrease finding risks.
- Overall, tighter control “may prevent on average, roughly 10 to 20 events for every 1000 high-risk patients treated over 5 years across a population”
- Harms of more intensive therapy: in general the evidence was relatively low to moderate strength, but did not find clear evidence of more renal, cognitive impairment, deterioration of quality-of-life/functional status, or increase in fractures or falls, though there was low-quality evidence for increase in syncope.
- Initiate treatments in adults over 60 years old who have systolic blood pressure persistently at or above 150 mmHg, to reduce the risk for mortality, stroke, and cardiac events (strong recommendation, high quality evidence).
- Consider initiating or intensifying pharmacologic therapy in patients over 60 years old with a history of stroke or TIA to achieve a targeted systolic pressure of less than 140 mmHg to reduce the risk of recurrent stroke. (Weak recommendation, moderate quality evidence)
- Consider initiating or intensifying pharmacologic treatment in some adults greater than 60 years old at high cardiovascular risk to achieve a target systolic pressure of less than 140 mmHg to reduce the risk of stroke and cardiac events. (Weak recommendation, low quality evidence)
- And for all of these recommendations, the risks and benefits should be periodically discussed with the patient.
- There are really no studies that include the real elderly. The SPRINT elderly subgroup (those patients over 75 at enrollment), still had a mean age of 80, with SD of only 4 years, so really does not inform my practice with lots of people in the 85-100 age range. one might glean from the above trials that the lower blood pressure may well be better, since there was no evidence that age mattered in the groups analyzed (again, not including the very old), subgroup analyses from SPRINT as well as the HYVET trials found that frailty did not matter, and there was more absolute benefit in those with higher cardiovascular risk (and age plays into that). But, at least my practice in the elderly and especially in the very old is to check orthostatics regularly (looking for both initial and standard orthostatic hypotension: See http://blogs.bmj.com/ebm/2016/05/20/primary-care-corner-with-geoffrey-modest-md-orthostatic-hypotension-revisited/for details), try to get home-based BP measurements (and preferentially use these to guide therapy, as long as I have confirmed that the patient measures blood pressure accurately and the cuff is accurate), and assess cognitive function more aggressively (see http://blogs.bmj.com/ebm/2015/04/23/primary-care-corner-with-geoffrey-modest-md-too-low-blood-pressure-and-cognitive-decline-in-elderly/ which is an Italian prospective study in patients mean age of 79 with some baseline cognitive impairment, finding that those in the lowest BP group (SBP<128 mmHg) had more cognitive decline than those with higher pressures). So, my guess (without data) is that the benefits will persist in the very old, though I suspect the harms will be greater (patients more frail, more comorbidities, and more sensitive to meds)
- My major concern with these articles on tighter blood pressure control in general is that there is a tendency in clinical practice to attempt to achieve the goal blood pressure they achieved in the study. However, this brings up a few issues:
- In general the studies have very specific ways that they measured the blood pressure. The general real-world approach, at least in my experience, is to have a medical assistant bring the patient into the room and measure the blood pressure/record it in the electronic medical record. I have consistently been measuring manual blood pressures myself for the past many years, typically with the patient sitting on the exam table and resting a few minutes while I write my notes in the other room, and often find striking differences from the recorded blood pressure, not uncommonly 30 to 40 mmHg difference. Although most often my recording is much less than that of the medical assistance, at times it is much more (the 118/68, which really is 190/110!!!). So in general I am concerned about relying on automated blood pressure recordings (which in general is less reliable in people with atrial fibrillation and arrhythmias, as well), though my main concern is that the patients, perhaps somewhat deconditioned, walk into the room and sit down without resting and have largely unreliable readings.
- For example, in the SPRINT study, which did achieve lower blood pressure in the tight control group than often found in other trials (123/62, in the elderly subgroup), they measured the blood pressure as follows: the staff person would tell a patient that they needed to rest for 5 minutes before taking the blood pressure, would leave the room completely, would return but not speak a word with the patient and immediately take the blood pressure. Argument has been raised in the literature that the blood pressure measured in randomized controlled trials is typically 5 to 10 mmHg lower than the clinic-based blood pressure (i.e. a randomized trial with an achieved systolic blood pressure of 123, as above, may be equivalent to a clinic-based blood pressure of 130 or so). For details of the SPRINT trial, see http://blogs.bmj.com/ebm/2015/11/19/primary-care-corner-with-geoffrey-modest-md-tighter-blood-pressure-control-the-sprint-trial/, which reviews the results of the overall trial, as well as http://blogs.bmj.com/ebm/2016/06/02/primary-care-corner-with-geoffrey-modest-md-sprint-trial-elderly-subgroup-study-of-lower-blood-pressure-goal/ which looked at the predesignated subgroup of those greater than 75 years old).
- There are also significant questions as to the general reliability of office-based blood pressure, both because of whitecoat hypertension as well as masked hypertension (see http://blogs.bmj.com/ebm/2016/12/12/primary-care-corner-with-geoffrey-modest-md-masked-hypertension/ , as well as the frequent observation that ambulatory blood pressure monitoring is much more predictive of clinical events, leading to the USPSTF and other international groups suggesting this is the preferred mechanism to diagnose hypertension (see http://blogs.bmj.com/ebm/2015/01/15/primary-care-corner-with-geoffrey-modest-md-uspstf-recs-on-ambulatory-blood-pressure-monitoring/
- So, my real concern is that we may be basing important clinical decisions based on inaccurate data, and that we may be significantly over-treating (predominately) or under-treating hypertension, with their attendant potential adverse outcomes
By the way, there was a review of intensive lowering of blood pressure in the elderly (defined as >65 yo), essentially simultaneous with the above, in the Journal of the American College of Cardiology, which identified only 4 studies (all included above) with 10,857 patients that met their criteria, finding that intensive blood pressure control with SBP <140 lead to a significant decrease in major cardiovascular events, including cardiovascular mortality and heart failure, but no difference in stroke or MI (see DOI: 10.1016/j.jacc.2016.10.077). This exemplifies one of the points I made in my blog http://blogs.bmj.com/ebm/2016/11/21/primary-care-with-geoffrey-modest-md-lessons-ive-learned-from-looking-at-the-medical-literature/ , that systematic reviews and meta-analyses may well come to different conclusions based on their own inclusion and exclusion criteria, and that we in the trenches (who are responsible for reading and considering implementing important changes in clinical practice) really need to assess how those authors configured their analyses and the relevance of their conclusions to our clinical practice. Not a simple feat.