The Hygia Chronotherapy Trial sought to determine whether bedtime hypertension therapy better reduced the risk of cardiovascular disease than taking blood pressure medication on awakening, as previous studies have suggested.
And that's exactly what researchers found in their study, published online Oct. 22(academic.oup.com) in the European Heart Journal.
Conducted in a clinical primary care setting in Spain, the multicenter, prospective endpoint trial involved 19,084 patients with hypertension (10,614 men and 8,470 women) and a median age of 60.5. These patients were assigned to take their entire daily dose of one or more hypertension medications either at bedtime or on awakening in the morning.
Initially and during every scheduled clinical visit (at least annually) throughout follow-up, ambulatory blood pressure monitoring was performed for 48 hours.
During a median patient follow-up of 6.3 years, 1,752 participants experienced a primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure or stroke), with patients in the bedtime medication group showing a significantly lower hazard ratio for the primary CVD outcome and each of its single components than their morning medication counterparts.
- The Hygia Chronotherapy Trial found bedtime hypertension therapy better reduced the risk of cardiovascular disease than taking blood pressure medication in the morning.
- Conducted in a clinical primary care setting in Spain, the multicenter, controlled, prospective endpoint trial involved 19,084 patients with hypertension.
- Compared with patients who took their hypertension medication on awakening, those in the bedtime medication group showed a significantly lower hazard ratio for the primary CVD outcome, as well as improved ambulatory blood pressure control.
In addition, patients who routinely took their prescribed BP-lowering medications at bedtime, rather than on awakening, had improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline).
Family Physician's Perspective
AAFP Commission on Health of the Public and Science member James Stevermer, M.D., of Fulton, Mo., told AAFP News he thought this was an intriguing study with a significant effect size, given the simplicity of the intervention.
"It's a study of more than 19,000 patients, and they were followed a median of 6.3 years, with a fairly typical pattern of comorbid diseases," he said. "The hazard ratio for overall mortality was 0.55 (95% CI 0.48-0.63) -- indicating that taking BP medications at bedtime dropped the death rate by 45%. In addition, myocardial infarction (HR = 0.66), strokes (HR = 0.54) and heart failure (HR = 0.58) were all reduced. These are all important patient-oriented outcomes."
Stevermer said based on these findings, he now recommends his patients take their BP medications at bedtime.
"I tell them that I think the result is probably too good to be true," he said. "But given the simplicity (and low risk) of the intervention, it's probably a good idea to do so."
"I'm not sure all people taking a thiazide diuretic will tolerate taking it a bedtime," he continued. "However, it's worth noting that this same (research) group published a smaller study(www.ncbi.nlm.nih.gov) (with 2,156 patients) finding a clinical benefit by moving just one of a patient's BP medications to bedtime."
As for limitations of the study, Stevermer said that although this was a large study, it was completed in a fairly homogenous Spanish population.
Additionally, all patients had their medications adjusted using ABP monitors for 48 hours -- something that's rather uncommon in the United States. And the adherence to treatment and follow-up were excellent, he added.
"All of these factors may limit the generalizability of this study to U.S. patients, but on the other hand, even if the net benefit is only a portion of that reported here, it's still a gain," Stevermer said.
Given the data presented, Stevermer said it's hard to estimate the absolute benefit to calculate a number needed to treat.
"From what I can determine, the overall mortality benefit was not limited to prevention of cardiovascular death alone, so I'll look forward to more information on the effect on other causes of death," he said.
Stevermer said he'd like to see this study's findings replicated in more diverse populations and tested to see how important the ambulatory monitoring is to the overall benefit seen in the Spanish trial.
"This is the largest study looking at hypertension chronotherapy, and it's clear we have more to learn about the timing of BP medication use," he said. "I wonder if there are other diseases we treat with once-daily medications where a similar effect can be found?"
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American Family Physician: AFP by Topic: Hypertension