Should my patients take their blood pressure medications at night to improve cardiovascular benefit?
No. Although the cardiovascular benefits of controlled blood pressure (BP) are clear, current evidence is insufficient to recommend routine dosing of antihypertensive medications in the evening rather than in the morning for cardiovascular benefits.
However, hypotension carries its own risks regardless of the time of day. Clinicians should employ shared decision making with patients to individualize dosing practices based on risk factors and preferences.
Scenario 1: High blood pressure in the morning A patient with primary arterial hypertension and coronary artery disease takes antihypertensive medications in the morning. Blood pressure is well controlled throughout the day, but the patient reports that it is elevated in the morning. The physician considers switching the patient to a nighttime dosing regimen for cardiovascular benefits. |
BP follows a diurnal rhythm , generally lower at night (nocturnal decline) and rising in the morning. Because morning BP surges have been associated with cardiovascular events, it follows that administration of antihypertensive medications in the evening could confer cardiovascular protection.
Patients with hypertension can be subdivided according to the pattern of nocturnal decline in systolic BP observed on 24-hour ambulatory monitoring:
- Extreme Dippers : a drop of more than 20%
- Dippers : a drop of 10% to 20%
- Non dippers : a drop of less than 10%
- Reverse or inverted dippers : no change or increase in nocturnal systolic BP.
There is evidence that non-dippers have a higher risk of adverse cardiovascular events. Therefore, it makes sense that nocturnal dosing could induce a drop in the non-dipper phenotype.
Hermida et al examined this hypothesis in 2 main studies:
The MAPEC 4 (Ambulatory Monitoring for Prediction of Cardiovascular Events) trial included 2,156 patients with untreated or resistant hypertension. Patients were instructed to take blood pressure medications before going to bed or upon waking up . The primary endpoint, a composite of all-cause mortality and cardiovascular events, was significantly lower in the bedtime group , with a hazard ratio (HR) of 0.39 (confidence interval [CI] 95%: 0.29 to 0.51; p < 0.001).
The Hygia Chronotherapy Trial examined the risk of cardiovascular disease in patients taking blood pressure medications before bed compared to when they woke up . The primary outcome was a composite endpoint consisting of cardiovascular disease-related death, myocardial infarction, coronary revascularization, heart failure, or stroke. As in the MAPEC trial, the group dosed at bedtime had a significantly better outcome, with a reported HR of 0.55 (95% CI, 0.50 to 0.61; P < 0.001). 5
These results appeared to favor bedtime dosing of antihypertensive medications, but the unlikely effect size led others to question the methodology (problematic randomization), the results (no independent assessment of cardiovascular events), and the conclusions.
In response, the HARMONY 7 (Hellenic-Anglo Research Into Morning or Night Antihypertensive Drug Delivery) trial in 2018 randomized patients to morning or evening antihypertensive doses and used a crossover design for 12 weeks. Clinic and 24-hour ambulatory BP were compared and no differences were detected between groups.
In 2022, Mackenzie et al 8 published the results of the TIME ( Treatment in Morning vs Evening ) study , which included more than 21,000 patients randomized to once-daily, daytime or nighttime medication dosing. Patients were followed for a median of 5.2 years . The primary outcome examined was a composite score that included hospitalization for nonfatal myocardial infarction or stroke and vascular death.
The primary endpoint was observed in 3.4% of patients in the evening dosing group and 3.7% of patients in the morning dosing group (HR 0.95, 95% CI 0.83 to 1.10; P = 0.53). The authors concluded that patients should take their antihypertensive medications when convenient and when they experience the fewest side effects.
Scenario 2: Risk of falls and worsening of glaucoma A 67-year-old woman with a history of glaucoma, hypertension, and type 2 diabetes mellitus presents for care. Her blood pressure is not controlled and she reports that she forgets to take her medication in the morning due to her fluctuating schedule. She had been told to avoid taking blood pressure medications at night, when she usually takes the rest of her medications, to minimize the risk of falls and worsening glaucoma. |
The risk of falls is a major concern with dosing of nocturnal antihypertensive medications. After older studies linked low blood pressure (systolic BP < 120 mm Hg) with an increased risk of falls, many doctors avoided prescribing nighttime antihypertensive medications to prevent orthostatic symptoms in the morning and minimize the risk of falls.
More recent data examining intensive BP control (systolic BP <120 mm Hg) showed a possible increased risk of syncope, but not falls .
The TIME 8 (Morning versus Evening Treatment) study examined dizziness, falls, and fractures as secondary endpoints. Patients in the group receiving the evening dose reported fewer falls than those receiving the morning dose . The number of fractures reported was similar in both groups. The group that received the morning dose reported more episodes of dizziness or lightheadedness.
Another concern with nighttime dosing of antihypertensive drugs is glaucoma , a debilitating disease worldwide. It has been postulated that nocturnal decreases in systemic BP lead to a decrease in ocular perfusion pressure, which may decrease blood flow to the optic nerve and perpetuate glaucomatous damage.
Studies have yielded equivocal results, but there is growing evidence that both high and low BP are associated with an increased risk of glaucoma .
A meta-analysis found that a fall in nocturnal BP is a risk factor for worsening glaucomatous damage and visual field loss, suggesting that nocturnal dosing of antihypertensive medications may be inadvisable in glaucoma patients who have a pronounced fall in BP. nocturnal BP. However, the available data are not robust enough to generate practical guidelines. Shared decision-making is key, given the potential risk of glaucoma progression with lower nocturnal blood pressure.
Regarding the 67-year-old patient in scenario 2, her comorbidities, including glaucoma, suggest the need for shared decision-making to weigh the potential risks of worsening her glaucoma with nocturnal dosing of BP medications against the risk. of compromising adherence if morning dosing is recommended.
Conclusions
Cardiovascular outcomes and overall side effects appear to be similar. Patients who take their medications at night do not appear to have an increased risk of falls or fractures, but they also do not appear to have better cardiovascular outcomes. The goal should be to achieve BP control and facilitate compliance, regardless of when antihypertensive medications are taken. It is unclear whether dippers and reverse dippers, or even patients with early morning blood pressure spikes, would have better cardiovascular outcomes with a regimen that includes nocturnal dosing of the medication. Data on these patient subgroups are lacking, and identifying them remains a challenge given the limited use of ambulatory BP monitoring. For most patients with hypertension, the act of taking the medication as directed is more important than the timing. |
