Comparison of single-pill strategies first line in hypertension: perindopril/amlodipine versus valsartan/amlodipine.
OBJECTIVE
An international double-blind, parallel-group, randomized controlled trial was performed to determine the efficacy and safety of a new first-line strategy in mild to moderate hypertension based on a single-pill combination of perindopril/amlodipine versus a validated stepped-care strategy (initiation with valsartan monotherapy, up-titrating to valsartan/amlodipine after 2 months).


METHODS
At inclusion, patients received perindopril/amlodipine 3.5/2.5 mg or valsartan 80 mg. At 1, 2, and 3 months, patients were up-titrated if they had uncontrolled hypertension (≥140/90 mmHg). The up-titration steps were: perindopril/amlodipine 7/5 mg, 14/10 mg, and 14/10 mg + indapamide sustained release 1.5 mg; or valsartan 160 mg, valsartan/amlodipine 160/5 mg, and 160/10 mg. The two groups were similar at baseline (55.5 years, 53% men, blood pressure 163.5/100.2 mmHg); 881 perindopril/amlodipine and 876 valsartan/amlodipine patients were analyzed for efficacy.


RESULTS
After 1 month, the rate of controlled hypertension was 33% with perindopril/amlodipine versus 27% with valsartan/amlodipine (estimate of difference, +6.1%; P = 0.005); this between-strategy difference remained significant at every visit (P < 0.05). After 3 months, blood pressure was 137.8 ± 12.4/83.3 ± 8.7 and 139.7 ± 13.3/84.8 ± 9.0 mmHg, respectively, with greater reductions from baseline with perindopril/amlodipine (primary endpoint -2.0/-1.5 mmHg; both P < 0.001). Similar results were observed at all other visits (all P ≤ 0.001). The safety of the two strategies was equivalent.


CONCLUSIONS
The three-step strategy of initiation with single-pill perindopril/amlodipine produces greater reductions in blood pressure, and better and quicker rates of control of hypertension. This can be expected to be associated with benefits beyond blood pressure control, notably improved compliance and better cardioprotection.
aUniversity of Milano-Bicocca, Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Istituto Auxologico Italiano IRCCS, Milan, Italy bFoundation Medical Research Institutes, Paris, France cInstituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil dCHU Avicenne, Unité Médecine Interne-Hypertension Artérielle, Bobigny, France eUniversity of Pisa/School of Medicine, Pisa, Italy fInstituto de Corazón de Querétaro, Querétaro, Mexico gMinistry of Health of the Russian Federation, Cardiology Research Complex, Moscow, Russia hServicio de Medicina Interna, Unidad Metabólico-Vascular, Hospital Universitario La Paz, IdiPaz, Madrid, Spain.
Giuseppe
G
Mancia
Roland
R
Asmar
Celso
C
Amodeo
Jean-Jacques
JJ
Mourad
Stefano
S
Taddei
Marco Antonio Alcocer
MA
Gamba
Irina E
IE
Chazova
Juan G
JG
Puig
D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use*; D000068838:Amlodipine, Valsartan Drug Combination / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007190:Indapamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000627:therapeutic use*; D000068756:Valsartan / Q000008:administration & dosage
D000068838:Amlodipine, Valsartan Drug Combination; D000959:Antihypertensive Agents; D004338:Drug Combinations; C542336:amlodipine, perindopril drug combination; D017311:Amlodipine; D000068756:Valsartan; D007190:Indapamide; D020913:Perindopril