Nighttime blood pressure strongly predicts cardiovascular events ( CVEs ) .
Further , a preliminary trial has shown decreased CVEs from evening vs morning dosing of antihypertensive therapy .
Unlike other EDTs , the Heart Outcomes Prevention Evaluation ( HOPE ) study administered its entire antihypertensive dose prior to sleep and gave the greatest risk reduction .
This study provides a third type of evidence suggesting a beneficial effect from evening dosing of antihypertensive therapy .
INFLUENCE OF CIRCADIAN TIME OF HYPERTENSION TREATMENT ON CARDIOVASCULAR RISK: RESULTS OF THE MAPEC STUDY
Clinical studies have documented morning-evening , administration-time differences of several different classes of hypertension medications in blood pressure (BP)-lowering efficacy , duration of action , safety profile , and /or effects on the circadian BP pattern . In spite of these published findings , most hypertensive subjects , including those under combination therapy  , are instructed by their physicians and pharmacists to ingest all of their BP-lowering medications in the morning . The potential differential reduction of cardiovascular ( CVD ) morbidity and mortality risk by a bedtime versus upon-awakening treatment schedule has never been evaluated prospect ively . The prospect i ve MAPEC study was specifically design ed to test the hypothesis that bedtime chronotherapy with ≥1 hypertension medications exerts better BP control and CVD risk reduction than conventional therapy , i.e. , all medications ingested in the morning . A total of 2156 hypertensive subjects , 1044 men/1112 women , 55.6 ± 13.6 ( mean ± SD ) yrs of age , were r and omized to ingest all their prescribed hypertension medications upon awakening or ≥1 of them at bedtime . At baseline , BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h. Physical activity was simultaneously monitored every min by wrist actigraphy to accurately determine the beginning and end of daytime activity and nocturnal sleep . Identical assessment was scheduled annually and more frequently ( quarterly ) if treatment adjustment was required . Despite lack of differences in ambulatory BP between groups at baseline , subjects ingesting medication at bedtime showed at their last available evaluation significantly lower mean sleep-time BP , higher sleep-time relative BP decline , reduced prevalence of non-dipping ( 34 % versus 62 % ; p < .001 ) , and higher prevalence of controlled ambulatory BP ( 62 % versus 53 % ; p < .001 ) . After a median follow-up of 5.6 yrs , subjects ingesting ≥1 BP-lowering medications at bedtime exhibited a significantly lower relative risk of total CVD events than those ingesting all medications upon awakening ( 0.39 [ 0.29–0.51 ] ; number of events 187 versus 68 ; p < .001 ) . The difference between the treatment-time groups in the relative risk of major events ( including CVD death , myocardial infa rct ion , ischemic stroke , and hemorrhagic stroke ) was also highly statistically significant ( 0.33 [ 0.19–0.55 ] ; number of events : 55 versus 18 ; p < .001 ) . The progressive decrease in asleep BP and increase in sleep-time relative BP decline towards a more normal dipping pattern , two novel therapeutic targets requiring proper patient evaluation by ambulatory BP , were best achieved with bedtime therapy , and they were the most significant predictors of event-free survival . Bedtime chronotherapy with ≥1 BP-lowering medications , compared to conventional upon-waking treatment with all medications , more effectively improved BP control , better decreased the prevalence of non-dipping , and , most importantly , significantly reduced CVD morbidity and mortality . ( Author correspondence : rhermida@uvigo.es
Nighttime blood pressure strongly predicts cardiovascular events ( CVEs ) .
Further , a preliminary trial has shown decreased CVEs from evening vs morning dosing of antihypertensive therapy .
Unlike other EDTs , the Heart Outcomes Prevention Evaluation ( HOPE ) study administered its entire antihypertensive dose prior to sleep and gave the greatest risk reduction .
This study provides a third type of evidence suggesting a beneficial effect from evening dosing of antihypertensive therapy .