Low-Dose Perindopril and Indapamide Combination Compared with Losartan in the Treatment of Systemic Hypertension: a Randomized, Double-Blind Study

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Original ArticlePerindopril and Indapamide versus Losartan in the Treatment of Acta Hypertension Cardiol Sin 2005;21:199-206

Hypertension Low-Dose Perindopril and Indapamide Combination Compared with Losartan in the Treatment of Systemic Hypertension: A Randomized, Double-Blind Study

Chien-Hsun Hsia1 and Yu-Deh Su2

Background and Purpose: We compared the efficacy and safety of a low-dose combination of perindopril and indapamide (P/I, 2/0.625 mg) with losartan (50 mg) in Taiwanese patients with mild to moderate essential hypertension. Methods: Fifty patients with mild to moderate essential hypertension were randomized to receive either P/I or losartan once daily for a period of 12 weeks after a 2-week run-in phase. After 8 weeks treatment, if the office blood pressure (BP) was 140/90 mmHg or greater, the dose was doubled. Response and normalization rates (systolic blood pressure [SBP] less than 140 mmHg and diastolic blood pressure [DBP] less than 90 mmHg), extent of BP reduction, and proportion of patients necessitating increase of dose were compared both in full set and per protocol set analyses. Results: The baseline characteristics were comparable between the two patient groups. Normalization rate was significantly higher in the P/I group than in the losartan group (69.2% vs 41.7%) (p < 0.05); so was the response rate (80.8% vs 54.2%) (p < 0.05). Mean sitting SBP and sitting DBP fell by 15.2 ± 10.0 and 9.5 ± 4.7 mmHg, respectively, in the P/I group (p < 0.001) and by 11.6 ± 12.3 and 6.7 ± 7.4 mmHg, respectively, in the losartan group (p < 0.001). The falls were greater with P/I than those with losartan; however, these differences did not reach statistical significance. Both treatments were well tolerated, and laboratory examinations did not show any significant difference between two groups. Conclusions: A low-dose combination of P/I is more effective than losartan in the treatment of mild to moderate essential hypertension, with similar safety profiles. The results suggest that low-dose combination of P/I can be considered as an alternative for the first-line antihypertensive treatment.

Key Words: Hypertension · Low-dose combination therapy · Perindopril · Indapamide · Losartan

INTRODUCTION end-organ damage.1,2 A case control study in northwest England3 suggested that the quality of hypertension con- Treating hypertension is of benefit for preventing trol correlated strongly with risk of stroke. Compared with non-hypertensive subjects, hypertensive patients receiving treatment whose average pre-event systolic blood pressure (SBP) was controlled to 140 mmHg or Received: October 4, 2005 Accepted: October 26, 2005 1Department of Cardiology, 2Department of Family Medicine, less had an adjusted odds ratio for stroke of 1.3 (95% Changhua Christian Hospital, Changhua, Taiwan. confidence interval [95% CI], 0.6-2.7). Those with fairly Address correspondence and reprint requests to: Dr. Chien-Hsun well controlled (SBP, 140-149 mmHg), moderately con- Hsia, Department of Cardiology, Changhua Christian Hospital, No. 135 Nanhsiao Street, Changhua 500, Taiwan. Tel: 886-2-2568-1380 trolled (SBP, 150-159 mmHg), or poorly controlled ext. 323; Fax: 886-2-2568-1390; E-mail: [email protected] (SBP, ³ 160 mmHg) hypertension, or those untreated

199 Acta Cardiol Sin 2005;21:199-206 Chien-Hsun Hsia et al. had progressively increasing risks of stroke: 1.6, 2.2, 3.2 consent. and 3.5, respectively. Moreover, 21% of the cases of The active treatment phase consisted of a fixed-dose stroke were attributable to inadequate control with an- period for 8 weeks (W0 to W8) and titration period for 4 tihypertensive treatment.3 Despite the evidence of the weeks (W8 to W12). Patients in the P/I group received 1 need to treat hypertension, blood pressure (BP) is still capsule of P/I plus a placebo daily, while those in the poorly controlled in 27% and 6% of patients in USA4 losartan group received 1 capsule of losartan 50 mg plus and England,5 respectively. The reasons for failure to a placebo daily in the morning at breakfast with a glass achieve satisfactory BP control are multifactorial, and of water. The dose was doubled during the first 8 weeks poor compliance with the antihypertensive therapy and of treatment if the patient’s sitting SBP (sSBP) was 140 adverse effects resulting from the treatment may be con- mmHg or greater or sitting diastolic BP (sDBP) was 90 tributory. mmHg or greater. The study was approved by the Insti- Fixed low-dose combination of two antihypertensive tutional Review Board (IRB) of Changhua Christian drugs is a new approach to the treatment of hyperten- Hospital (CHCH). sion. The combination of two antihypertensive drugs used each at infra-therapeutic levels but acting synergis- tically offers many advantages. If different patients METHODS respond differently to different groups of antihypertensive agents, then a combination of antihypertensive To be enrolled, patients had to be 18 to 75 years of agents acting together would have a greater chance of age and non-obese (body mass index (BMI) < 30 kg/m2), success in achieving satisfactory BP control.6 Because and were required to have essential uncomplicated, mild many, and probably most, side effects are dose-related, to moderate hypertension, defined as the mean sSBP of and because side effects differ between drug groups, it three consecutive measurements at W0 of 140-180 follows that when an equivalent antihypertensive effect mmHg and sDBP of 90-105 mmHg. Exclusion criteria is obtained by combination of two drugs at a low dose included: pregnancy; breast feeding; participation in a from two different drug groups, the side effect profiles previous drug trial over the past one month; currently can be expected to be lower.6 taking more than two antihypertensive agents; secondary In this randomized, double-blind, active-control hypertension; complicated hypertension with target or- study, we aimed to compare the efficacy and safety of a gan damage, which included retinopathy, macroalbu- low-dose combination, perindopril and indapamide, (P/I, minuria, or renal failure (serum creatinine > 2.0 mg/dL); 2/0.625 mg) with losartan (50 mg) as the first-line treat- history of myocardial infarction; Class III and IV ment for mild to moderate hypertension in Taiwanese chronic heart failure; abdominal aneurysm or peripheral patients. artery disease; history of strokes; history of allergy to perindopril, indapamide, losartan, or sulfonamides; re- cent history of unstable angina or undergoing percu- PATIENTS AND METHODS taneous coronary angioplasty, coronary bypass surgery or arterial surgery within the previous 3 months; deep Study Design vein thrombosis or pulmonary embolism within the pre- This was a prospective, randomized, double-blind, vious 6 months; acute infection which would preclude parallel-group study to compare the efficacy and safety end-point evaluation or the progress in the study; anemia between perindopril/indapamine (P/I, 2/0.625 mg) com- (hemoglobin < 10 gm/dL); cancer; AIDS; requirement of bination therapy and losartan (50 mg) once daily for 12 transfusion or hemodialysis; current bleeding; history of weeks (W0 to W12) in Taiwanese patients with mild or Quincke edema in relationship with angiotensin- moderate hypertension. Following a 2-week single-blind converting enzyme inhibitor (ACEI); hepatic disease placebo run-in period (W-2 to W0), enrolled patients with or without complications, defined as abnormal liver were randomized to receive either P/I (2/0.625 mg) or function tests > 3-fold of upper limit of normal or biliru- losartan (50 mg) treatment after giving their informed bin total > 2-fold of upper limit of normal; alcoholism;

Acta Cardiol Sin 2005;21:199-206 200 Perindopril and Indapamide versus Losartan in the Treatment of Hypertension drug abuse; hypokalemia (< 3.5 mmol/L) or hyper- mmHg or greater, or reduction of sSBP by 20 mmHg or kalemia (> 5.5 mmol/L); electrocardiogram (ECG) at the greater; the variation in sSBP and sDBP between W0 selection visit showing a bradycardia (< 50 beat per and W12; the between-group comparisons in terms of re- minute), torsades de pointe, ventricular tachycardia, ven- sponse rate and reduction of sDBP; and proportion of tricular extrasystoles (except isolated), or significant patients requiring dose adjustment at visit W8. increase in the QT interval. The heart rate was measured at each visit in sitting Oral potassium supplements were given immedi- position. A 12-lead ECG was carried out before and after ately to any patient whose potassium level measured at treatment. Hematological and biochemical analysis, W8 was 3.5 mmol/L or less. All concomitant medi- which included sodium, potassium, chloride, uric acid, cations specified as contraindicated, and all other anti- urea nitrogen, creatinine, hemoglobin and white blood hypertensive treatments or any treatment having an cell count with differentials, platelets, fasting blood glu- effect (direct or not) on the BP were not allowed during cose, total protein, lipids profiles (total cholesterol, the study. Other concomitant treatments required during triglycerides, high-density lipoprotein (HDL) chole- the study because of the patient’s condition and modifi- sterol, low-density lipoprotein (LDL) cholesterol), ami- cation of these concomitant treatments were recorded. notransaminases, and alkaline phosphatase, were mea- Concomitant treatment contraindicated in patients sured before and after 12 weeks of therapy. receiving perindopril included: lithium, while those con- Any symptoms or signs presented or reported by the traindicated in patients receiving indapamide included lit- participant and any abnormal values of biological sam- hium, baclofen; iodine-containing preparation (risk of renal ples considered to be clinically relevant were recorded as failure); treatments at risk of causing torsades de pointe “adverse event” at each visit. (amiodarone, astemizole, disopyramide, sotalol, sultopride, vincamine); and class 1 antiarrhythmic agents. Concomi- Statistical Analysis tant treatments contraindicated in patients receiving The study data management and statistical analysis losartan were spironolactone, triamterene, lithium, and were performed by iStat. All tests were two-sided and baclofen. Treatment could be prematurely and definitively were performed at a type I error of 5%. Descriptive statis- discontinued for a participant for one of the following tics were supplied as effective, mean, standard deviation reasons: non-medical cause; major deviation from the pro- (and median if variables were not known to be normally tocol; pregnancy; loss to follow-up; personal wish; adverse distributed) for continuous variables, and effective and events; and onset of a severe hypertension with sDBP of percentage for categorical variables. The analysis was 110 mmHg or greater or sSBP of 190 mmHg or greater. performed in terms of variation between baseline and the Three measurements of sSBP and sDBP were taken last visit (W12) with paired t-test and Wilcoxon signed- at office on the same arm chosen at the selection visit, rank sum test, respectively. Response rates and proportion and prior to ingestion of drugs after the patient was of patients requiring dose adjustment were compared us- seated for 5 minutes, and the means of the three readings ing Chi-square or Fisher’s exact test. Ninety-five percent were calculated at the selection visit and visits W0, W4, confidence intervals (95% CI) associated with the be- W8, W12. There should be a period of two minutes tween-group difference were given. between each sitting BP measurement; thus, it was man- Two analysis sets were defined: the full analysis set datory that the visits were scheduled in the morning, consisted of those randomized patients having received before 12.00 am. Patients were instructed to refrain from at least one treatment dose and a baseline of DBP and smoking or ingesting caffeine during the 30 minutes pre- SBP value; the per protocol set was defined as those ran- ceding the measurement. domized patients having an efficacy evaluation after at The primary efficacy endpoint was the between- least one month of treatment and without any major de- group comparison in terms of reduction of sSBP. The viation that could influence the evaluation. secondary endpoint was the percentage of response de- For dropout patients, the last measurement was taken fined by either of the following two criteria: sSBP £ 140 into account. Variation between baseline value (W0) and mmHg and sDBP £ 90 mmHg; reduction of sDBP by 10 the last recorded value (even if it was the baseline) of

201 Acta Cardiol Sin 2005;21:199-206 Chien-Hsun Hsia et al. sitting BP measured was adjusted for baseline demo- 26 patients who received P/I (2/0.625 mg) and 24 pa- graphic data. The safety was evaluated in a descriptive tients who received losartan treatment (Figure 1). Base- way by the frequency in each group of the following line characteristics were comparable in both treatment events: adverse events, ECG abnormalities, mean va- groups and are summarized in Table 1. The mean riation of heart rate, clinically significant laboratory ab- systolic BP (SBP) was 150.4 ± 9.2 mmHg in the P/I normalities. Mean variation of heart rate and biological (2/0.625 mg) group and 151.8 ± 9.0. mmHg in the los- safety data were described. artan group. The mean DBP was 96.9 ± 4.7 mmHg in the P/I (2/0.625 mg) group and 97.5 ± 5.3 mmHg in the losartan group. RESULTS The mean sSBP and sDBP at each visit and changes of blood pressure from baseline (visit week 0) to each A total of 50 patients completed the study, including visit in both treatment groups for full analysis set are

N=70 Patients screened

N=50 Patients randomized

N=20 Screening failures

N=50 Patients receiving double-blind Medication

N=26 N=24 Perindopril/Indapamide Losartan

N=23 N = 3 Withdrawn: adverse N=21 N=3 Completed effect (1); non-medical Completed Withdrawn:Protocol reason(2) violation (1); non-medical reason (2)

Figure 1. Disposition of patients.

Acta Cardiol Sin 2005;21:199-206 202 Perindopril and Indapamide versus Losartan in the Treatment of Hypertension

Table 1. Baseline characteristics of the patients with mild to ther group (p < 0.001) (Table 2). The mean reductions of moderate hypertension who were randomized to sSBP between visit week 12/last visit and the baseline receive perindopril/indapamide (2/0.625 mg) or were 15.2 ± 10.0 mmHg in the P/I group and 11.6 ± 12.2 losartan (50 mg) therapy mmHg in the losartan group. The mean reductions of Perindopril/indapamide Losartan p-value sDBP between visit week 12/last visit and the baseline (N = 26) (N = 24) were 9.5 ± 4.7 mmHg in the P/I group and 6.7 ± 7.4 Age (years) mmHg in the losartan group. The differences in mean re- a Mean 53.4 49.9 0.285 duction of sSBP/sDBP between the two groups were of (SD) (10.43) (10.90) no statistical significance. Sex One patient in each group was excluded from analy- b Male 9 (34.6%) 12 (50.0%) 0.271 sis: one patient in the P/I group with no data from visit Female 17 (65.4%) 12 (50.0%) W4 to W12 and one in the losartan group considered a BMI (kg/m2) deviation from protocol. Mean 25.94 25.85 0.816a (SD) (2.89) (2.39) The response rates were 80.8% in the PI group (95% CI, 60.0%, 92.7%) and 54.2% (95% CI, 33.2%, 73.8%) SBP (mmHg) mean 150.4 151.8 0.546a in the losartan group in the full analysis set (Table 3). (SD) (9.23) (8.95) The difference in response rate between the two groups was of borderline statistical significance (p = 0.044), DBP (mmHg) mean 96.9 97.5 0.861a with a difference in response rate of 26.6% (95% CI, (SD) (4.69) (5.28) -2.4%, 55.7%). In per protocol set analysis, the response rates were 84.0% in the PI group (95% CI, 63.1%, a: Wilcoxon rank sum test. b: Chi-Square test. 94.8%) and 52.2% (95% CI, 31.1, 72.6%) in the losartan group (p = 0.018) (Table 4). The normalization rate was shown in Table 2. Within-group analysis demonstrated higher in the P/I group (69.2%) than in the losartan that both SBP and DBP were significantly reduced in ei- group (41.7%) (p = 0.0498).

Table 2. Change of blood pressure from baseline (visit W0) to final visit for full analysis set Perindopril/indapamide Losartan Full analysis seta p-valueb n Mean (SD) n Mean (SD) SBP/DBP (mmHg) Baseline 26 150.4(9.2)/96.9(4.7) 24 151.8(9.0)/97.5(5.3) 0.546/0.861 Final visit (W12) 26 135.1(12.7)/87.4(6.1) 24 140.2(12.6)/90.8(9.0) 0.130/0.210 Change 26 -15.2(10.0)/-9.5(4.7) 24 -11.6(12.2)/-6.7(7.4) 0.240/0.060 Signed-rank test <0.001 <0.001 a: LOCF was applied; b: Wilcoxon rank sum test.

Table 3. Response rate of blood pressure at visit W12-last visit for full analysis set Full analysis seta Perindopril/indapamide (N = 26) Losartan (N = 24) p-valueb Responderc (%) 21 (80.8%) 13 (54.2%) 0.044 95% confidence interval (60.0%; 92.7%) (33.2%; 73.8%) Difference in response rate (95% confidence interval) 26.6% (-2.4%; 55.7%) a: LOCF was applied. b: Chi-square test. c: Defined as either of the following two criteria: (1) sSBP 140mmHgandsDBP 90 mmHg. (2) Change of sDBP by 10 mmHg or greater, or change of sSBP by 20 mmHg or greater.

203 Acta Cardiol Sin 2005;21:199-206 Chien-Hsun Hsia et al.

Table 4. Response rate of blood pressure at visit W12 for per protocol set Per protocol set Perindopril/indapamide+ (N = 25) Losartan++ (N = 23) p-valuea Responderb (percent) 21 (84.0%) 12 (52.2%) 0.018 95% confidence interval (63.1%, 94.8%) (31.1%, 72.6%) Difference in response rate (95% confidence interval) 31.8% (2.7%, 60.9%) a: Chi-square test. b: Defined as either of the following two criteria: (1) sSBP 140 mmHg and sDBP 90 mmHg (2) Change of sDBP by 10 mmHg or greater, or change of sSBP by 20 mmHg or greater. +: One patient had no data from visit W4 to visit W12 and was not taken into account. ++: One patient was considered deviation and was not taken into account.

Four patients among 23 patients (17.4%) in the P/I (Table 5). There were no changes in ECG parameters group and seven patients among 21 patients (33.3%) in between both groups, including rate change and QT inter- the losartan group required dose adjustment at visit W8. vals, after 12 weeks’ therapy. The difference in proportion of patients requiring dose Compliance was measured by the tablet count; in P/I adjustment between the two groups was of no statistical therapy, compliances were 95.46%, 93.21%, and 95.65% significance (p = 0.223). at visits W4, W8, and W12, respectively, while those Regardless of treatment, most of the adverse events with losartan were 90.25%, 97.33%, and 89.90%, re- reported were mild and considered not related to the spectively (p > 0.05 in each comparison). study treatment. Three adverse events reported in the P/I group (cough, bronchitis, and hypokalemia) and two adverse events (hyperlipidemia and hypokalemia) reported DISCUSSION from the losartan group were considered related to treatment. In the study, only one patient experienced one A fixed low-dose combination of two antihyper- serious adverse event, suspected cerebrovascular acci- tensive drugs is a new approach in the treatment of dent, which was considered not related to the treatment. hypertension. The combination of two antihypertensive Slight changes in uric acid levels were noted without any drugs used each at subtherapeutic level but acting syn- clinical consequences. Though there were statistically ergistically offers many advantages. Different drug significant changes in potassium, total cholesterol, LDL- groups have complimentary properties in addition to cholesterol between the two groups, there were no differ- improved efficacy, thereby neutralizing the adverse ef- ences in the treatment of P/I compared with baseline fects of the individual components. Metabolic side

Table 5. Mean (± SD) changes of blood biochemistry test before and after W12 treatment Perindopril/Indapamide Losartan Before After Before After Sodium (meq/L) (135~153) 140 140 141 140 Potassium (meq/L) (3.5~5.3) 4.1 4.0 4.0 4.1 Creatinine (mg/L) (0.8~1.4) 1.0 1.0 1.1 1.0 SGOT (U/L) (14~38) 28 26 27 24 SGPT (U/L) (14~38) 30 32 30 32 Uric acid (mg/dL) (< 8.0) 6.2 7.1 6.9 6.9 Cholesterol (mg/dL) (< 200) 197.7 204.8 193.9 189.0 Triglyceride (mg/dL) (< 200) 146.6 132.8 168.5 205.2 HDL-cholesterol (mg/dL) (> 40) 054.9 055.7 046.4 046.6 LDL-cholesterol (mg/dL) (< 130) 110.4 114.3 108.6 103.4

Acta Cardiol Sin 2005;21:199-206 204 Perindopril and Indapamide versus Losartan in the Treatment of Hypertension effects of diuretics can be diminished by combination the patients in both groups. of low-dose diuretics with an ACEI. Different groups In conclusion, perindopril combined with indapa- of drugs have varying hemodynamic features, which mide at a low dose was more effective than losartan in could be additive.6 Diuretics decrease circulating blood the treatment of patients with mild to moderate hyperten- volume, and ACEIs decrease peripheral resistance. The sion, and the safety profiles were comparable to those importance of such a fixed low-dose combination has with losartan. been emphasized by the JNC-VI recommending this strategy as a first-line treatment of hypertension.4 The major argument against combination therapy is that any REFERENCES increase in the number of capsules that must be taken each day leads to a loss of compliance. This objection 1. Mensah G, Pappas T, Koren M, et al. Comparison of classification can be overcome by the use of fixed combination cap- to hypertension severity by blood pressure level and World Health Organisation criteria for prediction of concurrent cardiac sules suggested by WHO-ISH.7 These advantages have abnormalities and subsequent complications in essential 8 been emphasized by 2003 ESH/ESC guidelines. hypertension. J Hypertens 1993;11:1429-40. In this randomized, double-blind, active-control 2. Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke, and study of a 12-week study period in Taiwanese patients coronary heart disease. Lancet 1990;335:827-38. who had mild to moderate hypertension, we found that 3. Du X, Cruickshank K, McNamee R, et al. Case-control study of P/I was superior to losartan in the response rate in both stroke and the quality of hypertension control in northwest England. Br Med J 1997;314:272-6. full set analysis (80.8% vs 54.2%) and per protocol 4. Joint National Committee on Detection, Evaluation, and Treatment analysis (84.0% vs 52.2%) and in normalization rate of High Blood Pressure. The Sixth Report of the Joint National (69.2% vs 41.7%), although both regimens resulted in Committee on Detection, Evaluation and Treatment of High significant reduction of sSBP and sDBP (p < 0.001) Blood Pressure (JNC-VI). Arch Intern Med. 1997;157:2413-46. between visit week 12/last visit and the baseline. In ad- 5. Colhoun HM, Dong W, Poulter NR. Blood pressure screening, dition, more patients in the losartan group than in the management and control in England: results from the Health P/I group required dose doubling after an eight-week Survey for England 1994. J Hypertens. 1998;16:747-52. 6. Opie LH. Principles of combination therapy for hypertension: duration of treatment to ensure the therapeutic goal. what we learn from the HOT and other studies a personal point of These results were comparable to the previously con- view. Cardiovasc Drug Ther 1998;12:425-9. ducted studies, which demonstrated that such a fixed 7. 1999 WHO-ISH guidelines for the management of mild combination of low-dose perindopril (2 mg) with in- hypertension. J Hypertens 1999;17:151-83. dapamide (0.625 mg) offered a normalization rate of 8. 2003 European Society of Hypertension-European Society of 80% or greater after 12 weeks of treatment and 84% Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003;21:1011-53. after one year of treatment and was superior to los- 9. Chalmers J, Castaigne A, Morgan T, Chastang C. Long term 9,10 11 artan or irbesartan. efficacy of a new fixed very-low-dose angiotensin-converting In this study, we found that treatment with P/I was enzyme-inhibitor/diuretic combination as first line therapy in well tolerated, with a similar incidence of adverse events elderly hypertensive patients. J Hypertens 2000;18:327-37. to that of previous studies, which showed a low inci- 10. Chanudet X, De Champvallins. Antihypertensive efficacy and dence of withdrawal due to adverse drug reactions.9-11 tolerability of low-dose perindopril/indapamide combination Most of the adverse effects were mild in severity and compared with losartan in the treatment of essential hypertension. Int J Clin Pract 2001;55:233-9. were considered not related to the study treatment. No 11. Morgan T, Anderson A. Low-dose combination therapy with clinically significant changes of hematologic or bio- perindopril and indapamide compared with irbesartan. Clin Drug chemical investigations or ECG were detected in all of Invest 2002;22:553-60.

205 Acta Cardiol Sin 2005;21:199-206 Original Article Acta Cardiol Sin 2005;21:199−206

比較低劑量複方藥物 Perindopril/Indapamide 與 Losartan 在高血壓病人治療之隨機雙盲研究

夏建勳 1 蘇育德2 財團法人彰化基督教醫院心臟內科 1 家庭醫學科 ²

背景比較滴劑量複方藥物 Perindopril/Indapamine (P/I, 2/0.625 mg) 與 Losartan (50 mg)，在治療台灣地區輕至中度高血壓病人的效果及安全性。

方法 50 位輕至中度高血壓病人，經過 2 週的評估及非藥物控制後，隨機分配接受 P/I 及 Losartan 治療。經過 8 週治療後，如果在門診測量之血壓仍高於 140/90 毫米汞柱，則加倍劑量治療。經由分析比較兩組經治療後的反應性，正常血壓的比例，及需要加量治療的比率，以判定其效果。

結果兩組基本資料無差異，達到正常血壓的比例在 P/I 組顯著的較 Losartan 為高 (69.2% vs 41.1%) (p 值 < 0.05)。有反應的比例也是 P/I 組為高 (80.8% vs 54.2%) (p 值 < 0.05)。平均坐姿收縮期及舒張期血壓下降的程度在 P/I 組為 15.2 ± 10.0 及 9.5 ± 4.9 mmHg，而 Losartan 組則為 11.6 ± 12.3 及 6.7 ± 7.4 mmHg。但無顯著意義的差別。兩組藥物使用的耐受性及生化檢查方面，皆無顯著差異。

結論使用低劑量複方藥物 P/I 較 Losartan 在治療輕至中度高血壓病人，較為有效且一樣安全，這個結果提示低劑量複方藥物 P/I 適用於第一線治療輕至中度高血壓病患。

關鍵詞：高血壓、低劑量複方藥物、 Perindopril、Indapamine、Losartan。

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