Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy (MAPEC)

Prognostic Value of Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy in Relation to Risk (the MAPEC Study).

The MAPEC study was designed to investigate whether normalizing the circadian blood pressure profile towards a more dipper pattern (increasing the diurnal/nocturnal ratio of blood pressure) by the use of Chronotherapy (that is, taking into account the time of day of administration of antihypertensive medications) reduces cardiovascular risk.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Device: Ambulatory blood pressure monitoring; Procedure: Chronotherapy, timing of antihypertensive medication; Drug: ACEI (including spirapril, enalapril, quinapril, lisinopril); Drug: ARB (including valsartan, telmisartan, olmesartan); Drug: beta blockers (including nebivolol, atenolol, carvedilol); Drug: diuretics (torasemide, indapamide, HTCZ) and doxazosin; Procedure: Combination therapy in essential hypertension

Detailed Description

Target organ damage is more closely associated with ambulatory (ABPM) than with clinic blood pressure (BP). In particular, the reduction of the normal 10 to 20% sleep-time BP decline (non-dipper pattern) is associated with elevated risk of end-organ injury, particularly to the heart, brain and kidney. These results suggest that cardiovascular risk could be influenced not by BP elevation alone, but also by the magnitude of the circadian BP variability. Moreover, at least two independent prospective studies have suggested that nighttime BP is a better predictor of risk than daytime BP. Common to all previous trials is that prognostic significance of ABPM has relied on a single baseline profile from each participant, without accounting for possible changes in the BP pattern, mainly associated to antihypertensive therapy and aging during follow-up. The MAPEC study investigates, first, the comparative prognostic value of several BP parameters (including, among many others, BP variability, the diurnal/nocturnal ratio, diurnal and nocturnal means, slope of morning rise, etc) in the prediction of cardiovascular morbidity and mortality; and, second, whether potential changes in the circadian BP pattern after Chronotherapy with antihypertensive drugs are associated to changes in cardiovascular risk.

• Study Type: Interventional
• Enrollment (Actual): 3344
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Santiago de Compostela, Spain, 15706
    • Hospital Clinico Universitario

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Essential hypertension

Exclusion Criteria:

• AIDS
• shift workers
• secondary hypertension
• intolerant to ABPM

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1; Treatment on awakening	Device: Ambulatory blood pressure monitoring; Sampling at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours; Procedure: Chronotherapy, timing of antihypertensive medication; Comparison of effects of awakening versus bedtime dosing; Drug: ACEI (including spirapril, enalapril, quinapril, lisinopril); Treatment at awakening versus bedtime; Drug: ARB (including valsartan, telmisartan, olmesartan); Treatment at awakening versus bedtime; Drug: beta blockers (including nebivolol, atenolol, carvedilol); Treatment at awakening versus bedtime; Drug: diuretics (torasemide, indapamide, HTCZ) and doxazosin; Treatment at awakening versus bedtime; Procedure: Combination therapy in essential hypertension; Treatment at awakening versus bedtime
ACTIVE_COMPARATOR: 2; Treatment at bedtime	Device: Ambulatory blood pressure monitoring; Sampling at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours; Procedure: Chronotherapy, timing of antihypertensive medication; Comparison of effects of awakening versus bedtime dosing; Drug: ACEI (including spirapril, enalapril, quinapril, lisinopril); Treatment at awakening versus bedtime; Drug: ARB (including valsartan, telmisartan, olmesartan); Treatment at awakening versus bedtime; Drug: beta blockers (including nebivolol, atenolol, carvedilol); Treatment at awakening versus bedtime; Drug: diuretics (torasemide, indapamide, HTCZ) and doxazosin; Treatment at awakening versus bedtime; Procedure: Combination therapy in essential hypertension; Treatment at awakening versus bedtime

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Prognostic value of ABPM, impact of changes in ambulatory BP and impact of circadian time of antihypertensive treatment in cardiovascular, cerebrovascular and renal risk assessment.	Five years

Secondary Outcome Measures

Outcome Measure	Time Frame
Influence of circadian time of antihypertensive treatment in BP control and the remodeling of the circadian BP pattern of hypertensive patients.	Five years
Prevalence of an altered BP profile as a function of the circadian time of treatment.	Five years

Collaborators and Investigators

• Sponsor: University of Vigo
• Collaborators: Hospital Clinico Universitario de Santiago; Xunta de Galicia; Ministerio de Educacion y Ciencia, Spain

Publications and helpful links

General Publications

• Hermida RC, Ayala DE, Mojon A, Fernandez JR. Bedtime ingestion of hypertension medications reduces the risk of new-onset type 2 diabetes: a randomised controlled trial. Diabetologia. 2016 Feb;59(2):255-65. doi: 10.1007/s00125-015-3749-7. Epub 2015 Sep 23. Erratum In: Diabetologia. 2016 Feb;59(2):395.
• Hermida RC, Ayala DE, Mojon A, Fernandez JR. Decreasing sleep-time blood pressure determined by ambulatory monitoring reduces cardiovascular risk. J Am Coll Cardiol. 2011 Sep 6;58(11):1165-73. doi: 10.1016/j.jacc.2011.04.043.
• Hermida RC, Ayala DE, Mojon A, Fernandez JR. Influence of time of day of blood pressure-lowering treatment on cardiovascular risk in hypertensive patients with type 2 diabetes. Diabetes Care. 2011 Jun;34(6):1270-6. doi: 10.2337/dc11-0297.
• Hermida RC, Ayala DE, Mojon A, Fernandez JR. Ambulatory blood pressure control with bedtime aspirin administration in subjects with prehypertension. Am J Hypertens. 2009 Aug;22(8):896-903. doi: 10.1038/ajh.2009.83. Epub 2009 Apr 30.

Study record dates

Study Major Dates

• Study Start: March 1, 2000
• Primary Completion (ACTUAL): April 1, 2009
• Study Completion (ACTUAL): April 1, 2009

Study Registration Dates

• First Submitted: February 21, 2006
• First Submitted That Met QC Criteria: February 22, 2006
• First Posted (ESTIMATE): February 23, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): April 28, 2009
• Last Update Submitted That Met QC Criteria: April 27, 2009
• Last Verified: April 1, 2009

More Information

Terms related to this study

• Keywords: ambulatory blood pressure monitoring; cardiovascular risk; chronotherapy; circadian pattern
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Protease Inhibitors; Protective Agents; Adrenergic Agonists; Natriuretic Agents; Cardiotonic Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Antioxidants; Angiotensin-Converting Enzyme Inhibitors; Adrenergic beta-Agonists; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Adrenergic beta-1 Receptor Agonists; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Sodium Potassium Chloride Symporter Inhibitors; Valsartan; Antihypertensive Agents; Enalapril; Olmesartan; Nebivolol; Carvedilol; Telmisartan; Diuretics; Lisinopril; Doxazosin; Indapamide; Atenolol; Adrenergic beta-Antagonists; Torsemide; Quinapril; Spirapril
• Other Study ID Numbers: PGIDIT03-PXIB-32201PR; SAF2006-6254; INCITE07-PXI-322003ES