Long-term effects of losartan and enalapril, alone or with a diuretic, on ambulatory blood pressure and cardiac performance in hypertension: a case-control study.
BACKGROUND
The long-term effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on ambulatory blood pressure and cardiac performance have never been examined comparatively.


OBJECTIVE
We compared losartan and enalapril in their long-term effects on office and ambulatory blood pressure, cardiac structure and function, and routine biochemical tests.


METHODS
In the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study, 22 hypertensive subjects were studied with ambulatory blood pressure monitoring and echocardiography before and after an average of 3.3 years of treatment with losartan 50mg daily. These subjects were matched in a 1:3 ratio with a group of 66 subjects treated with enalapril 20mg daily. Case-control sampling was based on age (+/-5years), sex, pre-treatment office blood pressure (+/-5mmHg) and ambulatory blood pressure (+/-5mmHg), and duration of treatment (+/-6months). An additional group of subjects who interrupted their treatment with enalapril (n=18) or losartan (n =2) because of unwanted effects before execution of the follow-up study was not included in the analysis.


RESULTS
Hydrochlorothiazide was added during follow-up in order to optimize blood pressure control (office blood pressure <140mmHg systolic and 90mmHg diastolic) in 10 subjects (45%) in the losartan group and 34 subjects (52%) in the enalapril group. Office and ambulatory blood pressures were lowered to a similar extent by losartan and enalapril. Left ventricular mass decreased from 98 to 87g/m(2) with losartan (P <0.01) and from 98 to 89 g/m(2) with enalapril (P <0.01). The change in left ventricular mass over time was more closely associated with the change in ambulatory blood pressure than with office blood pressure in both groups. Left ventricular internal diameter did not change with either drug. The endocardial shortening fraction, mid-wall shortening fraction and Doppler indexes of active diastolic relaxation did not change with either drug. None of the biochemical parameters showed a significant change. Serum uric acid showed a slight and non-significant reduction only in the losartan group.


CONCLUSIONS
In this case-control study in uncomplicated subjects with essential hypertension, losartan and enalapril, alone or combined with a diuretic, effectively and equally lowered office and ambulatory blood pressure and induced a significant reduction in left ventricular mass during long-term treatment. Left ventricular systolic and diastolic function remained unchanged with either regimen.
Verdecchia
P
P
Ospedale Raffaello Silvestrini, Unità Operativa di Malattie Cardiovascolari, Perugia, Italy. verdec@tin.it
Schillaci
G
G
Reboldi
G P
GP
Sacchi
N
N
Bruni
B
B
Benemio
G
G
Porcellati
C
C
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D002352:Carrier Proteins / Q000187:drug effects; D016022:Case-Control Studies; D004232:Diuretics; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004452:Echocardiography; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014527:Uric Acid / Q000097:blood; D016277:Ventricular Function, Left / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002352:Carrier Proteins; D004232:Diuretics; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; D049993:Sodium Chloride Symporter Inhibitors; C103862:urate transporter; D006852:Hydrochlorothiazide; D014527:Uric Acid; D004656:Enalapril; D019808:Losartan