Taking Blood Pressure Medication At Bedtime Lowers Risk Of Death, Stroke And Heart Attack

When should you take your once daily BP meds?

Increasingly, the skeptical cardiologist has been recommending to patients that they take BP meds at bedtime as evidence has mounted  that this does a better job of normalizing asleep blood pressure and minimizing daytime side effects.

Now a study published in European Heart Journal in October has demonstrated that routine ingestion of BP meds at bedtime as opposed to waking results in improved 24 hour BP control with enhanced decrease in asleep BP and increased sleep-time relative BP decline (known as BP dipping.)

More importantly, bedtime BP med ingestion in this randomized trial of over 19 thousand hypertensive Spaniards resulted in highly significant reductions in cardiovascular events including death, heart attack, heart failure and stroke over a 6 year median follow-up

The so-called Hygia Chronotherapy Trial was extremely well done and the results are powerful and should modify clinical practice immediately.

This figure demonstrates the dramatic and highly significant 45% reduction in all types of cardiovascular events measured. Note that stroke rate was halved!

Screen Shot 2019-11-05 at 7.56.12 AM

Here are the Kaplan-Meier curves showing early and progressive separation of the treatment curves.

Screen Shot 2019-11-05 at 7.50.10 AM

There was no difference side effects or compliance between the two groups.

The remarkable aspect of this intervention is that it costs nothing, introduces no new medications and has no increased side effects.

This study is practice-changing for me. We will be advising all hypertensive patients to take their once daily BP meds at bedtime.

Chronotherapically Yours,

-ACP

h/t Reader Lee Sacry for bringing this study to my attention

 

 

30 thoughts on “Taking Blood Pressure Medication At Bedtime Lowers Risk Of Death, Stroke And Heart Attack”

    1. This was exactly my question too. But the study does not look into this specific aspect of the question…
      However: this is a very strong study: large cohort, prospective, long followup, smart, real-life endpoints… Very impressive.
      So I guess if you do have sleep apnea (as I do), treat it… but whatever: take your BP meds in the evening.
      A bunch of pills of mine just switched location today…
      🙂

  1. What about someone who now takes metoprolol tartrate 100 mg twice daily, after rising in the morning and with after the evening meal? Might that achieve some of the benefits mentioned above?

    1. This study doesn’t answer that question. For example, there is a long acting form of metoprolol. Would it be better to take that at bedtime than to take tartrate twice dailly? We also don’t know it taking at bedtime (as was done in this study) is better than say after dinner. I’m inclined to recommend bedtime and adhere to how the drugs were administered in this very positive trial.

  2. I really enjoyed the findings and conclusions in this article. I will be putting all my B P pills in the bedtime slot from now on.
    Thanks
    dad

  3. My wife takes three meds, one at breakfast, one at dinner and one at bedtime (Amlodapine, HCTZ, Losartin) How might this study apply to multiple med patients?

  4. What might this suggest for those who take multiple meds at different times of day – say HCTZ with breakfast, Amlodapine with dinner and Losartan at bedtime?

  5. All right. We will be smart and take the med at bedtime. One must wonder what is the cause for this improvement in results? After about 7 days of taking the med once per day at the same hour, regardless of the time of day taken, the concentration in the bloodstream will be at steady state. So why does the pm administration change things?

    1. I’m not an expert in this, but my assumption is that there actually never is a true steady state. What I suspect you have, rather, is a sinusoidal concentration pattern, with the fluctuations all (hopefully) remaining within a therapeutic range, never going above the maximum safe level or below the minimum effective level–but that range might be pretty wide and I’d suspect that there could be some variation in efficacy between the high and low levels.

      1. Exactly. They all tend to have a peak BP lowering effect some time after ingestion and before 12 hours which corresponds to the peak levels in the blood. The longer lasting ones have a very flat curve with minimal difference between peak and trough levels over a 24 hour period when taken consistently.

  6. I think a likely mechanism is the (mentioned) enhancement of the dipping phenomena. Patients who don’t dip are at significantly higher risk stroke and MI than nondippers. I, however, wouldn’t take a diuretic such as lasix before bed.

    1. The diuretics that I use are thiazine diuretics and spironolactone which over time have very little immediate diuresis after being taken.
      I don’t use loop diuretics (like furosemide for hypertension which maintain their potent diuretic effect over time.

  7. Since learning about this a month so ago, I have taken my once daily dose of beta blocker at bedtime.

    Sleeping very well, and waking BEABT (bright eyed and bushy tailed) meaning bright alert and enthusiastic for the coming day, with none of the beta brain fog that often happened when taking beta blocker in the morning.

    The waking BP measurement will now be augmented by a bedtime check as well.

    Beta brain fog is a common issue, and improvements with bedtime dosing are an added benefit.

    Time will tell whether the daytime BP is as well controlled as the previous routine.

    1. I also had brain fog and symptoms of depression under atenolol. For years! When I switched to nebivolol, the very clear and almost immediate result was that these symptoms just vanished.
      (I switched because I wanted more cardiac adaptability to exercise/running…).
      I was quite surprised because as an older man, one just gets to believe that being grumpy and even sometimes hostile just goes with age… my symptoms went unrecognized for a very long time.
      Surprising but real result! Thanks to my cardiologist.

      1. I have a post in the works on nebivolol (bystolic) and I may have mentioned it in a prior post on beta blockers and feeling logy.
        It’s definitely got the least side effects of the beta blockers. I’m on it myself and I can’t wait until it goes generic and becomes less expensive for my patients.

        1. OH! I’ll go read that post now.
          And you ARE right! Bystolic is not generic! Surprising, because it’s been around since the ’90s… I’m lucky to have good insurance.
          I really really like that medication… As a mostly ß1-blocker (at doses lower than 10 mg/day), it does not slow down the heart as much, and works by enhancing peripheral vasodilation and cardiac output. It is not associated with depression or anxiety, or “brain fog” as much as other ß-blockers.
          I love it for that, and also because my HR can increase more when I exercise: 135/min this afternoon while running my (almost) daily 2.5 km. On atenolol my HR would hardly go over 105-115…
          I just love my cardiologist!
          AND this blog! Thanks for that!
          🙂

  8. The results are SO good that one wonders: why was this study not discontinued at the 5, or 6-year mark?
    By then, had they not reached statistical significance sufficient that a safety-monitoring committee would have stopped that study?

  9. I just took my BP at 6:10 mountain time using the EVOLV Omron cuff after slope running for 48 minutes today starting at 9:05 AM. BP is 97/57 and RHR 55 BPM. I wonder how slope running compares with blood pressure medications over say a 5 year period. I always find that for me personally slope running, that is running at least 5.5 mph at a 18% gradient reduces my BP for 1 or 2 days afterwards. You can slope run using an incline treadmill with up to a 30% gradient. In my case, there is a nearby mountain with just the right slope. This being said, for those who don’t do slope running and rely on medications, this well-done study suggest bedtime is the time to dose up. Be sure to leave out the booze because booze will most like negate the benefit of taking BP medications just before going to bed.

    1. Erwin I have to wonder why you write this about “booze negating the benefit of taking BP medications just before going to bed.”
      This was not looked at in the Hygia study, apparently not considered to be an important variable…
      Do you know of any studies that would support your assertion?
      I just really enjoy a little scotch in the evening, or 1-2 glasses of wine with supper.
      I don’t know that this would cause any harm! 🙂
      I sure do hope not!

      1. In my own situation no alcohol at all, from one glass of wine with evening meal, resulted in lowered BP, and PVCs and PACs incidence reduced significantly. That helped with beta blocker at night.

        Kardia band on Apple Watch for EKGs, and Omron HEM 7280T for BP.

        So overall I feel the benefits of no alcohol are worthwhile. My wife continues with her small glass with dinner, and I feel no temptation seeing her enjoy it.

        Surprisingly easy, but not sure how I will go with the upcoming festive season.

  10. Slightly off topic, but perhaps still in the same general category of simple steps that might reduce BP (and hopefully risk of adverse outcomes), I wonder if TSK would comment on this. I have encountered the suggestion that an important and often unrecognized dietary factor in hypertension is low potassium intake, or perhaps more specifically, a low ratio of dietary potassium to sodium. A quick search on Pubmed now pointed me to several abstracts:

    https://www.ncbi.nlm.nih.gov/pubmed/25016398
    https://www.ncbi.nlm.nih.gov/pubmed/26039623
    https://www.ncbi.nlm.nih.gov/pubmed/30125063
    https://www.ncbi.nlm.nih.gov/pubmed/28678188
    https://www.ncbi.nlm.nih.gov/pubmed/26039623

    I wonder what TSC thinks of replacing essentially all added dietary table salt (sodium chloride) with powdered potassium chloride, such as in this product:

    https://www.swansonvitamins.com/now-foods-potassium-chloride-powder-8-oz-pwdr

    I tried this some time back and though I did not track my BP (it is fairly low to start with, so I don’t worry about it much), I did notice a reduction in my tendency toward palpitations (probably PVCs associated with a baseline slow pulse rate).

    If this is something TSK has experimented with or explored, I would be glad for his comments on the likely utility of such an approach, along with comments about what kind of medications would make this approach dangerous (I presume BP medications that impair potassium excretion).

    Thanks.

    1. Although a 2006 Cochrane review concluded there was insufficient evidence to recommend potassium supplementation in the treatment of hypertension more recent meta-analyses suggest a modest effect (5 mm Hg drop in systolic). A recent JACC review of treatment of hypertension had this to say “Increasing potassium intake lowers BP in hypertensive adults (46–50), especially among those who are black, older, or consuming a high intake of dietary sodium (51). Because of its BP-lowering effects, increased potassium intake would be expected to prevent CVD events, and several studies have demonstrated an inverse relationship of potassium intake to stroke as well as other forms of CVD (52). Increased potassium intake can be achieved either by augmenting dietary potassium intake or by use of potassium supplements. The former approach is preferable, with the DASH diet providing the recommended daily consumption of 4,700 mg for a 2,000-calorie intake (29).”
      My take on the data has been that increased potassium goes along with eating more healthy things-vegetables and fruit so I encourage that as opposed to taking supplements.
      I have also found potassium as a salt substitute is unpalatable.

  11. I’m already taking Ramipril at 5pm so that’s easy to move to bedtime. I’m also taking 5mg Amlodipine in the AM and Metaprolol 25mg twice a day. Should they be moved to bedtime as well.

    They are also for blood pressure. Thanks

  12. For someone taking the following meds, all dosed once a day, is there any reason all could not be taken at bedtime?

    ROSUVASTATIN, EZETIMIBE, METOPROLOL, HYDROCHLOROTHIAZIDE.

    Would the lipid-lowering meds be okay to take at bedtime? Would the diuretic cause the person to wake up and have to urinate in the middle of the night?

    Thank you.

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