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Primary Care Corner with Geoffrey Modest MD: Fludrocortisone for Vasovagal Syncope

22 Sep, 16 | by EBM

By Dr. Geoffrey Modest

Vasovagal syncope is pretty common, but there are no documented effective treatments. Fludrocortisone has potential by improving venous return: its efficacy was evaluated in the Prevention of Syncope Trial 2 — POST 2 trial (see Sheldon R. JACC 2016; 68: 1).


  • 210 patients (71% female, median age 30, BMI 24, HR 70 bpm, BP 112/70) with a mean of 15 syncopal episodes over 9 years
  • Randomized to fludrocortisone at the highest tolerated doses (from 0.05-0.2 mg/d, titrated over 2 weeks, with most achieving the 0.2  mg dose) vs placebo and followed for 1 year
  • Inclusion criteria: >13 yo, >2 lifetime syncopal episodes; exclusions: diabetes, hepatic disease BP>135/85, “significant comorbidities”, or if when standing 5 minutes they had postural tachycardia of >30 bpm, or orthostatic hypotension of >20/10 mmHg.


  • 96 patients had at least 1 syncopal episode
  • Overall there was a 31% marginally non-significant reduction in syncope in those on fludrocortisone [HR 0.69 (0.46-1.03), p=0.069]: 44.0% vs 60.5%. the most benefit was in those with systolic BP<110, BMI>20, and syncope frequency >7/yr
  • But, in multivariable model, fludrocortisone conferred a significant 37% decrease [HR 0.63 (0.42-0.94), p=0.024]
  • And, when analysis was restricted to being on the fludrocorisone after dose stabilization, there was an even more significant 49% decrease [HR 0.51 (0.28-0.89), p=0.019]: approx 60% vs 30% in those achieving the 0.2 mg dose


  • There are a myriad of etiologies for syncope to consider, especially cardiac or neurologic (all excluded in the above study). And the preferred treatment for the syncope is to treat the underlying condition.
  • The above applies to those with classic “fainting” episodes: vasovagal syncope, which can happen even in patients with underlying cardiac or neuro morbidities, often triggered by stress, noxious stimuli, anxiety (including venipuncture, blood donation), prolonged standing or sitting, heat exposure, exertion, orthostasis,  (and in older people can be associated with micturition, defecation, cough), and clinically associated with the typical prodrome of light-headedness, along with vagal symptoms of nausea, pallor, diaphoresis. Symptoms typically gets better with lying down, though there can be some residual fatigue. And there can be brief episodes of myoclonic/involuntary esp. limb movements. But there should be no post-ictal state
  • Fludrocortisone seemed pretty effective when at the 0.2 mg dose, and likely more effective than midodrine (a few small studies finding effectiveness but less impressively)
  • Fludrocortisone has been used effectively in those with autonomic failure and orthostatic hypotension, presumably from its increased renal sodium absorption and plasma volume expansion.
  • In my experience, fludrocortisone is very well-tolerated in fragile patients with multiple comorbidities: I have prescribed fludrocortisone (sometimes with midodrine) very effectively in my reasonably large group of older patients with orthostatic hypotension, presumably from autonomic dysfunction (workup otherwise negative, or perhaps some diabetes, but often just from aging…). In this young group in the study above, without comorbidities and with just vasovagal syncope, there were no serious adverse events. And for those with orthostatic hypotension, of course, caffeine helps (1-3 cups of coffee/d, or 2-5 cups of tea). And, though I have not used them, NSAIDs can also help when used with fludrocortisone.
  • So, bottom line: vasovagal syncope is common (overall about 20-35% of syncope causes), a pretty high % (up to 34% in one study) have no warning symptoms prior to syncope, and can be associated with bad accidents (e.g., car crashes), so the above study may really prove to be clinically useful. One wonders if using the max dose of 0.3 mg might be even more useful, and I do have several elderly patients tolerating this dose well)

Primary Care Corner with Geoffrey Modest MD: Orthostatic hypotension

18 Dec, 14 | by EBM

By: Dr. Geoffrey Modest

Circulation had an article on the prevalence of orthostatic hypotension in Ireland (see doi:10.1161/CIRCULATIONAHA.114.009831​). This study involved 4475 community-based people over age 50 from a nationally representative cohort study (TILDA — The Irish Longitudinal Study on Ageing — that’s how they spell “aging”…), recording blood pressure and pulse response to standing. They looked at initial orthostatic hypotension, defined as a BP decrease of >40 mmHg systolic or >20 mmHg diastolic within 15 seconds of standing and associated with symptoms of cerebral hypoperfusion, and typical orthostatic hypotension, defines as a BP decrease of >20 mmHg in systolic or >10 mmHg in systolic after 3 minutes of standing.


–Cohort baseline characteristics: average age 62.8, 51.8% female, 19% smokers, 7.5% diabetes, 34.5% hypertensive, total of <11% with any cardiovascular history — so pretty healthy

–Initial orthostatic hypotension in 32.9% of those >50yo, no difference by age or gender

–Typical orthostatic hypotension in 6.9% overall, increasing from 4.2% in 50 yo to 18.5% in those >80yo

–Prevalence of failure to return to baseline blood pressure after standing 40 seconds increased with age: from 9.1% in 50 yo to 41.2% in those >80yo

So, a few points.

  1. The pathophysiology and epidemiology of initial orthostatic hypotension is somewhat different from the typical orthostatic hypotension. With initial orthostatic hypotension, there is a rapid temporal mismatch between cardiac output and vascular resistance. This typically happens in thin young people (who need to dangle their legs prior to getting out of bed, for example) and those on a-blockers (including reports with tamsulosin for BPH). The typical orthostatic hypotension results from standing, pooling of blood in the legs, decreased venous return, which usually triggers a baroreceptor reflex inducing vasoconstriction (so the the usual change is a decrease of about 5 mmHg systolic and a slight increase in diastolic, which rapidly reverses with rapid vasoconstriction). but without this vasoconstriction, there is subsequent decrease in cardiac output and hypotension. This tends to happen in older people who have diminished baroreceptor responsiveness, and in those with hypovolemia, on aggressive diuretics, tricyclic antidepressants, etc.
  2. I don’t want to overinterpret this study. The population studied was racially and ethnically pretty uniform. There was no information on whether there was a difference if they had underlying hypertension or what medications they were taking​. and there are no data on whether the typical orthostatic hypotension was symptomatic. And the limited data available do not all point to asymptomatic hypotension as a cause of falls, for example. BUT, to me, these numbers are very impressive. I do typically check orthostatics on my elderly patients and very often do find marked hypotension on standing, sometimes symptomatic and sometimes not. when the patient is symptomatic (either by history at home, eg when standing, or in the office), I do not hesitate to back off on BP meds (or if they are not on them, I sometimes need to use fludrocortisone and high salt diets to raise the blood pressure). in asymptomatic patients, the decision is harder. In general, I am pretty concerned that they may have an even more exaggerated hypotensive orthostatic response if they are a little dehydrated (hot summer day), or don’t drink their usual amounts of fluids, or even postprandially, when blood pressure tends to be lower. It is also impressive that symptomatic initial orthostatic hypotension happens in about 1/3 of the patients over 50 yo. So, seems reasonable to ask specifically about that, as well as falls…

So, my approach is that if the blood pressure really drops on standing (eg a systolic less than 120), I do back off on blood pressure meds even if the patient is asymptomatic. Given the lack of data in the elderly that a lower systolic is beneficial (perhaps because the studies did look at lower blood pressures, leading JNC8 to suggest a target of 150/90), seems like the better part of valor to back off on blood pressure meds.

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