Impact of antihypertensive combination and monotreatments on blood pressure variability: assessment by old and new indices. Data from a large ambulatory blood pressure monitoring database.
OBJECTIVE
High 24-h ambulatory blood pressure (ABP) variability is associated with poor cardiovascular outcomes. We analysed a large ABP monitoring database containing data from hypertensive patients treated with telmisartan/amlodipine combination or various monotherapies with the aim of quantifying the 24-h distribution of blood pressure (BP) reduction by treatment through the smoothness index and of developing and testing a new treatment-on-variability index (TOVI) to quantify the effects of treatment on both mean BP and BP variability.


METHODS
ABP data were pooled from 10 studies (N = 4294) with a median follow-up of 60 days. Smoothness index was calculated by dividing the mean of treatment-induced hourly BP reductions by its SD. TOVI was calculated as the ratio of the mean of hourly BP reductions to weighted 24-h BP SD (weighted mean of daytime and night-time SDs) under treatment.


RESULTS
The SBP/DBP smoothness index and TOVI values of telmisartan/amlodipine combination were significantly (P < 0.0001) higher (smoothness index: 1.81/1.51; TOVI: 2.71/2.13) compared with telmisartan 80  mg (smoothness index: 1.12/0.90; TOVI: 1.55/1.23), amlodipine 10  mg (smoothness index: 1.33/1.09; TOVI: 2.09/1.58), valsartan 160  mg (smoothness index: 1.01/0.81; TOVI: 1.35/1.07), ramipril 10  mg (smoothness index: 0.83/0.63; TOVI: 1.11/0.87) and placebo (smoothness index: 0.23/0.18; TOVI: 0.34/0.30), indicating a smoother 24-h BP reduction profile (higher smoothness index) as well as the achievement of significantly lower and smoother BP levels over 24  h (higher TOVI) with the combination.


CONCLUSIONS
As compared with various monotherapies, the telmisartan/amlodipine combination was associated with a smoother BP reduction over 24  h and with a more favourable balance between mean 24-h BP reduction and the degree of BP variability on treatment, reflecting both its effectiveness in lowering BP levels and its longer duration of action. The agreement between smoothness index and TOVI demonstrates that they are similarly effective in the differentiation of antihypertensive treatments, although providing conceptually different information, the clinical relevance of which needs to be tested by ad-hoc outcome studies.
aDepartment of Cardiology, San Luca Hospital, IRCCS Istituto Auxologico Italiano bDepartment of Health Sciences, University of Milano-Bicocca, Milan, Italy cStroke and Hypertension Unit, Connolly Hospital Blanchardstown, Dublin, Ireland dBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany.
Gianfranco
G
Parati
Eamon
E
Dolan
Ludwin
L
Ley
Helmut
H
Schumacher
D000328:Adult; D000368:Aged; D000465:Algorithms; D017311:Amlodipine / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage; D001565:Benzoates / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory / Q000379:methods*; D002986:Clinical Trials as Topic; D016208:Databases, Factual; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D000077333:Telmisartan; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D004338:Drug Combinations; D017311:Amlodipine; D000077333:Telmisartan