Sustained antihypertensive activity of telmisartan compared with valsartan.
BACKGROUND
Early morning blood pressure (BP) surge and 24 h mean BP are linked to target-organ damage and cardiovascular events. Antihypertensive agents should sustain BP control, particularly in the last 6 h of the dosing interval or if dosing is missed. The efficacies of the long half-life telmisartan compared with shorter half-life valsartan in the last 6 h of the dosing interval following active treatment and during 24 h after a missed dose were compared.


METHODS
In two identically designed multinational, randomized, double-blind, forced-titration studies, hypertensive patients (seated diastolic blood pressure (DBP), 95-109 mm Hg, 24 h mean ambulatory DBP, > or = 85 mm Hg) received once-daily telmisartan (40- 80 mg) or valsartan (80-160 mg) for a total of 8 weeks; uptitration occurred after 2 weeks low-dose treatment. After 4 weeks high-dose treatment, patients were given either 1 days double-blind active therapy or placebo (that is, missed dose). Following a further 2 weeks active treatment, a cross-over was performed: patients who had previously received 1 days placebo received active therapy and vice versa. At baseline and after the two active or missed doses, 24 h ambulatory BP monitoring was performed. Data from the studies were pooled, as prospectively planned and analyzed using the intent-to-treat population.


RESULTS
After active therapy, last 6 h mean DBP was reduced by 7.6+/-7.9 mm Hg with telmisartan (n=447) compared with 5.8+/-7.8 mm Hg with valsartan (n=430) (P=0.0044). Last 6 h mean systolic blood pressure (SBP) was reduced by 11.1 mm Hg with telmisartan compared with 9.1 mm Hg with valsartan (P=0.0066). After a missed dose, 24 h mean DBP was reduced by 7.2+/-6.5 mm Hg with telmisartan (n=437) compared with 5.5+/-6.2 mm Hg with valsartan (n=431) (P=0.0004). The reduction in 24 h mean SBP after a missed dose was 10.7 mm Hg with telmisartan and 8.7 mm Hg with valsartan (P=0.0024). Absence of treatment-by-study interaction indicated that pooling of studies was appropriate. All 24 hourly mean reductions in DBP and SBP were greater for telmisartan than valsartan. Both treatments were well tolerated.


CONCLUSIONS
Due to its longer half-life, telmisartan offers more sustained BP control, especially at the end of the dosing period and provides sustained efficacy in poorly compliant patients in the event of a missed dose with a statistical superiority compared with valsartan.
Hypertension Research Unit, Centre Hospitalier l'Université de Quebec, Ste Foy, Quebec, Canada. yves.lacourciere@crchul.ulaval.ca
Yves
Y
Lacourcière
Jean-Marie
JM
Krzesinski
William B
WB
White
Giora
G
Davidai
Helmut
H
Schumacher
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001565:Benzoates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory / Q000379:methods; D003971:Diastole / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016037:Single-Blind Method; D013599:Systole / Q000187:drug effects; D000077333:Telmisartan; D013777:Tetrazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068756:Valsartan
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D010919:Placebos; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; D000077333:Telmisartan