Current Medical Research & Opinion
Curr Med Res Opin Downloaded from informahealthcare.com by University of Otago on 07/06/15 For personal use only.
0300-7995 doi:10.1185/03007995.2014.960072
Vol. 31, No. 1, 2015, 183–186
Article RT-0289.R1/960072 All rights reserved: reproduction in whole or part not permitted
2015 Supplement S1: Lercanidipine therapy: New experiences from Eastern Countries Efficacy and safety evaluation of perindopril–lercanidipine combined therapy in patients with mild essential hypertension
Zhengyu Yang Department of Cardiology, Wuxi People’s Hospital, Jiangsu Province, China Address for correspondence: Zhengyu Yang MD, Department of Cardiology, Wuxi People’s Hospital, Qingyang Road 299, Wuxi, Jiangsu Province, 214023 China. [email protected] Keywords: Combined therapy – Hypertension – Lercanidipine – Perindopril Accepted: 18 August 2014; published online: 26 November 2014 Citation: Curr Med Res Opin 2015; 31:183–6
Abstract Objective: To investigate the efficacy and safety of perindopril–lercanidipine combination versus perindopril or lercanidipine monotherapies in patients with mild essential hypertension. Methods: A total of 180 patients with mild essential hypertension were randomly assigned to three groups: group A (perindopril 2 mg plus lercanidipine 5 mg; n ¼ 60), group B (lercanidipine 10 mg; n ¼ 60) and group C (perindopril 4 mg; n ¼ 60). The treatment efficacy and the incidence of adverse events were evaluated at the end of 4, 8 and 12 weeks after treatment initiation. Results: The blood pressure in group A was already lower than in group B and group C at week 4 after treatment initiation. Systolic blood pressure was 148 13 mmHg in group A, 151 14 mmHg in group B, and 153 13 in group C (p50.001); diastolic blood pressure was 89 8, 92 7 and 92 6 mmHg, respectively (p50.001). At the end of treatment the normalization rate was significantly higher in group A, compared with group B and group C (71.7%, 68.3%, and 48.3%, respectively; p50.05). Four adverse events were observed in group A, while seven and nineteen adverse events occurred in group B and in group C, respectively. Statistically significant differences in adverse reaction incidence were reported among three groups. Conclusion: Although its results were collected in an overall limited number of patients in a single center, this study shows that the combination of perindopril and lercanidipine, compared with lercanidipine alone or perindopril alone, was effective in improving blood pressure in mild essential hypertensive patients, and also decreased the incidence of adverse events.
Introduction Hypertension, which is characterized by an increase of arterial blood pressure (BP), is one major risk factor for heart and cerebrovascular disease and ranks first among fatal diseases in urban residents in China1. Although a great variety of antihypertensive drugs is available, monotherapy for level one hypertensive patients seems not completely effective in providing BP control. On the other ! 2015 Informa UK Ltd www.cmrojournal.com
Efficacy/safety of perindopril–lercanidipine in hypertension Yang
183
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Current Medical Research & Opinion Volume 31, Number 1
January 2015
hand, combination therapy with two or more antihypertensive drugs gives better results in BP control (rates close to 60%)1. Combined treatment significantly improves the normalization rate and increases compliance, with a possible reduction of the incidence of cardiovascular and cerebrovascular diseases and mortality. Perindopril is a third generation angiotensinconverting enzyme inhibitor (ACEI). Lercanidipine is a new lipophilic calcium channel blocker (CCB)2. The combination of ACEIs and CCBs is one of the most important recommended treatment strategies by Chinese and international hypertension guidelines1,3–5. In clinical practice, much data regarding the safety and efficacy of monotherapy with perindopril or lercanidipine is available; on the other hand, the efficacy and safety for ACEIs combined with CCBs needs further investigation. The aim of this study was to investigate the efficacy and safety of perindopril and lercanidipine combination versus perindopril or lercanidipine alone in patients with mild essential hypertension.
Patients and methods This was a monocentric, randomized, controlled study. From March 2013 to September 2013, 180 patients with mild primary hypertension were enrolled at Wuxi People’s Hospital (Wuxi, China). The inclusion criteria were as follows: (1) diagnosis of mild hypertension according to the diagnostic criteria in the Chinese Guidelines for Hypertension Prevention and Treatment (2010) (90 mmHg (DBP)5110 mmHg, SBP5180 mmHg); (2) age 18–70 years; (3) agreement to study participation by signing a specific informed consent form. The exclusion criteria were: severe hypertension or secondary hypertension; diabetes; cardiovascular and cerebrovascular diseases, associated with liver and kidney damage; other serious diseases (e.g., cancer or severe ongoing infections); allergy to or poor tolerability of CCBs or ACEIs; edema or cough. Concomitant treatments were not permitted. In total, 180 patients were randomly assigned to three groups: group A (perindopril plus lercanidipine; n ¼ 60), group B (lercanidipine alone; n ¼ 60) and group C (perindopril alone; n ¼ 60). Group A received perindopril (Les Laboratoires ServierIndustrie, Gridy, France) 2 mg/day þ lercanidipine (Recordati, Milano, Italy) 5 mg/day. Group B was given lercanidipine 10 mg/day. Group C (perindopril alone) was administered perindopril 4 mg/day. After screening, all patients took the study treatment in the morning within 24 hours since study enrollment. Follow-up visits were performed at week 4, week 8 and week 12. BP and adverse events (AEs) such as ankle edema, flushing, tachycardia, headache and cough were 184
Efficacy/safety of perindopril–lercanidipine in hypertension Yang
recorded. At baseline and after 12 weeks’ treatment, routine hematologic assessments, urinalysis, liver–renal function and ECG tests were performed in all patients. BP was assessed as follows: rest of at least 5 minutes in sitting position, and measurement of BP three times on patients’ right arm by a mercury sphygmomanometer. The mean value of the three assessed values was considered for study analysis. Normalization rate was defined as the proportion of patients with SBP5140 mmHg and DBP590 mmHg. Statistical analysis was performed using SPS11.0 software. Data were analyzed by descriptive statistics; comparisons between groups were performed by paired t test or chi-square test, as appropriate. A two-tailed p-value 50.05 was considered statistically significant.
Results The baseline characteristics of the three groups are shown in Table 1. No differences between the three groups in any parameter were observed at baseline. At week 4, the normalization rate of the three groups was not different. However, at weeks 8 and 12, the normalization rate in groups A and B was greater than in group C (week 12: group A, 71.7%; group B, 68.3%; group C, 48.3%; p50.05) (Table 2). During the treatment period, BP decreased in all groups. However, the reduction in SBP was significantly higher in group A than in the other groups (week 12 vs baseline: group A, 38 mmHg; group B, 36 mmHg; group C, 33 mmHg; p50.05) (Table 3). The same trend was observed for DBP (Table 4). During the study, 4 AEs occurred in group A (2 cases of cough, 1 of headache and 1 of flushing); 7 AEs occurred in group B (1 case of cough, 3 of edema and 3 of flushing), and 19 AEs occurred in group C (12 cases of cough, 4 of headache and 3 of flushing). The incidence of AEs in group A and group B is lower than group C, with the difference being statistically significant (p50.05). All AEs were of mild intensity. No changes in hematologic parameters (e.g. white blood cells), urinalysis, liver (ALT/AST) and renal (estimated glomerular filtration rate and creatinine) function and ECG were reported.
Discussion Hypertension is a major risk factor for cardiovascular disease; hypertension control can effectively prevent the occurrence of these events1. Despite this, in China several patients fail to achieve BP control (only about 10% of the hypertensive population)1. This study was focused on lercanidipine–perindopril combined treatment in mild hypertensive patients, and www.cmrojournal.com ! 2015 Informa UK Ltd
Current Medical Research & Opinion
Volume 31, Number 1
January 2015
Table 1. Baseline characteristics of three groups at baseline. N Male Group A Group B Group C
40 34 38
Age
DBP
SBP
TC
TG
HDL
LDL
60.6 6.6 62.5 5.3 61.7 5.7 F ¼ 0.15 p40.05
100 3 101 2 102 3 F ¼ 0.4 p40.05
169 7 171 8 170 5 F ¼ 0.04 p40.05
4.8 0.5 4.8 0.5 4.7 0.4 F ¼ 0.27 p40.05
1.7 0.2 1.7 0.3 1.6 0.2 F ¼ 0.32 p40.05
1.5 0.2 1.6 0.1 1.5 0.1 F ¼ 0.28 p40.05
2.5 0.3 2.6 0.2 2.5 0.3 F ¼ 0.84 p40.05
Female
20 26 22 2 ¼ 5.699 p40.05
Curr Med Res Opin Downloaded from informahealthcare.com by University of Otago on 07/06/15 For personal use only.
2 ¼ chi-square; F ¼ distribution; TC ¼ total cholesterol mmol/L; TG ¼ triglycerides mmol/L; HDL ¼ high-density lipoprotein mmol/L; LDL ¼ low-density lipoprotein mmol/L; DBP: diastolic blood pressure; SBP: systolic blood pressure.
Table 2. Normalization rate in the three groups. All values are given as % (number of patients).
Group A Group B Group C
Week 4
Week 8
Week 12
38.3 (23) 26.7 (16) 23.3 (14) 2 ¼ 3.58, p40.05
63.3 (38) 51.7 (31) 36.7 (22) 2 ¼ 8.5, p50.05
71.7 (43) 68.3 (41) 48.3 (29) 2 ¼ 8.18, p50.05
2 ¼ chi-square.
Table 3. Changes in systolic blood pressure (SBP) in the three patient groups throughout the study. BP (mmHg)
Group A Group B Group C
Treatment time
SBP SBP SBP
Baseline
Week 4
Week 8
Week 12
169 11 171 10 170 9 F ¼ 0.04, p40.05
148 13 151 14 153 13 F ¼ 16.71, p50.01
135 9 139 8 141 7 F ¼ 102.79, p50.01
131 10 135 9 137 9 F ¼ 0.017, p40.05
Table 4. Changes in diastolic blood pressure (DBP) in the three patient groups throughout the study. DBP (mmHg)
Group A Group B Group C
Treatment Time
DBP DBP DBP
Baseline
Week 4
Week 8
Week 12
100 9 101 11 102 9 F ¼ 0.4, p40.05
89 8 92 7 92 6 F ¼ 14.51, p50.01
85 7 86 6 89 7 F ¼ 13.34, p50.01
82 6 85 5 87 7 F ¼ 0.05, p40.05
the results confirmed the efficacy and safety of the combination of the two drugs, in particular when considering the normalization rate, the BP reduction and the incidence of adverse events during treatment. However, the doses of perindopril and lercanidipine in monotherapies were higher than those in drug combination. We cannot rule out that if these higher doses were used in the combination, patients might have experienced an even better ! 2015 Informa UK Ltd www.cmrojournal.com
control of hypertension but also more side-effects. Importantly, data on obesity and the presence of concomitant metabolic syndrome were not immediately available at the time of data analysis: this finding should be taken into account – together with the overall limited number of patients and the monocentric nature of the study – for a comprehensive evaluation of the results. The effect of combined antihypertensive therapy was remarkable and it can be attributed to different mechanisms of action which lead to a synergistic treatment effect4. According to the American Joint National Committee (JNC) 7, early initiation of a combined treatment for hypertensive patients is essential3. Several studies showed that antihypertensive combination therapy can reduce BP, with a normalization rate of about 45%; moreover, the different mechanisms of action of the single therapies help reduce the incidence of adverse reactions1,3. The National Institute for Health and Care Excellence guidelines suggests the combined ACEI–CCB therapy as an initial antihypertensive treatment for young and elderly patients6. ACEIs and CCBs are indeed two of the most commonly used drugs for treating hypertension, and are associated with efficacy in BP reduction, protection of target organs (heart and kidney), efficacy in reversing cardiovascular remodeling, and neutral effect on glucose and lipid metabolism. In this study, lercanidipine was evaluated as it is a third generation long-acting CCB. Differing from other similar drugs, lercanidipine does not produce significant reflex tachycardia and shows a marked lipophilicity: thereby its slow releasing effect can be maintained for 24 hours2. Lercanidipine acts on vascular smooth muscle cells by blocking L-type calcium channels and calcium influx, with a consequent evident antihypertensive effect. Furthermore, lercanidipine presents a renal protective effect, as it dilates both efferent and afferent arterioles7. Perindopril is an ACEI, which exerts a long-term inhibition of the conversion of angiotensin I to angiotensin II. The incidence of AEs observed in this study in the monotherapy groups is consistent with previous reports8. The combination therapy reduced the incidence of AEs, possibly because of the action of both drugs at a microEfficacy/safety of perindopril–lercanidipine in hypertension Yang
185
Current Medical Research & Opinion Volume 31, Number 1
January 2015
vascular level: during calcium entry blockade, an increase in intracapillary pressure is observed as a consequence of a selective diminution of the precapillary arteriolar tone. ACEIs reduce this process caused by CCBs, most likely because of their ability to dilate both the arterial vascular bed and the venous capacitance vessels5.
Curr Med Res Opin Downloaded from informahealthcare.com by University of Otago on 07/06/15 For personal use only.
Conclusion The results obtained in this randomized study suggest that lercanidipine combined with perindopril might be considered for combination therapy for mild essential hypertension. However, other studies assessing the effects of lercanidipine plus perindopril in improving clinical outcomes in hypertensive patients are warranted.
Transparency Declaration of funding Editorial support for this manuscript was funded by Recordati. Declaration of financial/other relationships Z.Y. has disclosed that she/he has no significant relationships with or financial interests in any commercial companies related to this study or article.
186
Efficacy/safety of perindopril–lercanidipine in hypertension Yang
CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose. Acknowledgments Editorial assistance was provided by Chiara Mossali PhD and Luca Giacomelli PhD of Content Ed Net.
References 1. Guidelines for the prevention and treatment of hypertension China revision committee. Guidelines for the prevention and treatment of hypertension Chinese 2010. Chin J Cardiovasc Dis 2011;39:579-81 2. Bang LM, Chapman TM, Goa KL. Lercanidipine: a review of its efficacy in the management of hypertension. Drugs 2003;63:2449-72 3. Chobanian AV, Bakris GL, Blaek HR, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (The JNC 7 Report). J Am Med Assoc 2003;289:2560-72 4. McInnes GT. Antihypertensive drugs in combination: additive or greater than additive? J Hum Hypertens 2007;21:914-16 5. Egan BM. Combination therapy with an angiotensin-converting enzyme inhibitor and a calcium channel blocker. J Clin Hypertens (Greenwich) 2007;9:783-9 6. National Institute for Health and Clinical Excellence. Hypertension (CG127): clinical management of primary hypertension in adults. http://www.nice. org.uk/guidance/CG127. Last accessed 3rd November 2014 7. Burnier M. Renal protection with calcium antagonists: the role of lercanidipine. Curr Med Res Opin 2013;29:1727-35 8. Sun RX. The 18th American Society of Hypertension: lercanidipine special report. Foreign Med Sci (section of Cardiovasc Dis) 2003;30:260-1
www.cmrojournal.com ! 2015 Informa UK Ltd
Curr Med Res Opin Downloaded from informahealthcare.com by University of Otago on 07/06/15 For personal use only.
0300-7995 doi:10.1185/03007995.2014.960072
Vol. 31, No. 1, 2015, 183–186
Article RT-0289.R1/960072 All rights reserved: reproduction in whole or part not permitted
2015 Supplement S1: Lercanidipine therapy: New experiences from Eastern Countries Efficacy and safety evaluation of perindopril–lercanidipine combined therapy in patients with mild essential hypertension
Zhengyu Yang Department of Cardiology, Wuxi People’s Hospital, Jiangsu Province, China Address for correspondence: Zhengyu Yang MD, Department of Cardiology, Wuxi People’s Hospital, Qingyang Road 299, Wuxi, Jiangsu Province, 214023 China. [email protected] Keywords: Combined therapy – Hypertension – Lercanidipine – Perindopril Accepted: 18 August 2014; published online: 26 November 2014 Citation: Curr Med Res Opin 2015; 31:183–6
Abstract Objective: To investigate the efficacy and safety of perindopril–lercanidipine combination versus perindopril or lercanidipine monotherapies in patients with mild essential hypertension. Methods: A total of 180 patients with mild essential hypertension were randomly assigned to three groups: group A (perindopril 2 mg plus lercanidipine 5 mg; n ¼ 60), group B (lercanidipine 10 mg; n ¼ 60) and group C (perindopril 4 mg; n ¼ 60). The treatment efficacy and the incidence of adverse events were evaluated at the end of 4, 8 and 12 weeks after treatment initiation. Results: The blood pressure in group A was already lower than in group B and group C at week 4 after treatment initiation. Systolic blood pressure was 148 13 mmHg in group A, 151 14 mmHg in group B, and 153 13 in group C (p50.001); diastolic blood pressure was 89 8, 92 7 and 92 6 mmHg, respectively (p50.001). At the end of treatment the normalization rate was significantly higher in group A, compared with group B and group C (71.7%, 68.3%, and 48.3%, respectively; p50.05). Four adverse events were observed in group A, while seven and nineteen adverse events occurred in group B and in group C, respectively. Statistically significant differences in adverse reaction incidence were reported among three groups. Conclusion: Although its results were collected in an overall limited number of patients in a single center, this study shows that the combination of perindopril and lercanidipine, compared with lercanidipine alone or perindopril alone, was effective in improving blood pressure in mild essential hypertensive patients, and also decreased the incidence of adverse events.
Introduction Hypertension, which is characterized by an increase of arterial blood pressure (BP), is one major risk factor for heart and cerebrovascular disease and ranks first among fatal diseases in urban residents in China1. Although a great variety of antihypertensive drugs is available, monotherapy for level one hypertensive patients seems not completely effective in providing BP control. On the other ! 2015 Informa UK Ltd www.cmrojournal.com
Efficacy/safety of perindopril–lercanidipine in hypertension Yang
183
Curr Med Res Opin Downloaded from informahealthcare.com by University of Otago on 07/06/15 For personal use only.
Current Medical Research & Opinion Volume 31, Number 1
January 2015
hand, combination therapy with two or more antihypertensive drugs gives better results in BP control (rates close to 60%)1. Combined treatment significantly improves the normalization rate and increases compliance, with a possible reduction of the incidence of cardiovascular and cerebrovascular diseases and mortality. Perindopril is a third generation angiotensinconverting enzyme inhibitor (ACEI). Lercanidipine is a new lipophilic calcium channel blocker (CCB)2. The combination of ACEIs and CCBs is one of the most important recommended treatment strategies by Chinese and international hypertension guidelines1,3–5. In clinical practice, much data regarding the safety and efficacy of monotherapy with perindopril or lercanidipine is available; on the other hand, the efficacy and safety for ACEIs combined with CCBs needs further investigation. The aim of this study was to investigate the efficacy and safety of perindopril and lercanidipine combination versus perindopril or lercanidipine alone in patients with mild essential hypertension.
Patients and methods This was a monocentric, randomized, controlled study. From March 2013 to September 2013, 180 patients with mild primary hypertension were enrolled at Wuxi People’s Hospital (Wuxi, China). The inclusion criteria were as follows: (1) diagnosis of mild hypertension according to the diagnostic criteria in the Chinese Guidelines for Hypertension Prevention and Treatment (2010) (90 mmHg (DBP)5110 mmHg, SBP5180 mmHg); (2) age 18–70 years; (3) agreement to study participation by signing a specific informed consent form. The exclusion criteria were: severe hypertension or secondary hypertension; diabetes; cardiovascular and cerebrovascular diseases, associated with liver and kidney damage; other serious diseases (e.g., cancer or severe ongoing infections); allergy to or poor tolerability of CCBs or ACEIs; edema or cough. Concomitant treatments were not permitted. In total, 180 patients were randomly assigned to three groups: group A (perindopril plus lercanidipine; n ¼ 60), group B (lercanidipine alone; n ¼ 60) and group C (perindopril alone; n ¼ 60). Group A received perindopril (Les Laboratoires ServierIndustrie, Gridy, France) 2 mg/day þ lercanidipine (Recordati, Milano, Italy) 5 mg/day. Group B was given lercanidipine 10 mg/day. Group C (perindopril alone) was administered perindopril 4 mg/day. After screening, all patients took the study treatment in the morning within 24 hours since study enrollment. Follow-up visits were performed at week 4, week 8 and week 12. BP and adverse events (AEs) such as ankle edema, flushing, tachycardia, headache and cough were 184
Efficacy/safety of perindopril–lercanidipine in hypertension Yang
recorded. At baseline and after 12 weeks’ treatment, routine hematologic assessments, urinalysis, liver–renal function and ECG tests were performed in all patients. BP was assessed as follows: rest of at least 5 minutes in sitting position, and measurement of BP three times on patients’ right arm by a mercury sphygmomanometer. The mean value of the three assessed values was considered for study analysis. Normalization rate was defined as the proportion of patients with SBP5140 mmHg and DBP590 mmHg. Statistical analysis was performed using SPS11.0 software. Data were analyzed by descriptive statistics; comparisons between groups were performed by paired t test or chi-square test, as appropriate. A two-tailed p-value 50.05 was considered statistically significant.
Results The baseline characteristics of the three groups are shown in Table 1. No differences between the three groups in any parameter were observed at baseline. At week 4, the normalization rate of the three groups was not different. However, at weeks 8 and 12, the normalization rate in groups A and B was greater than in group C (week 12: group A, 71.7%; group B, 68.3%; group C, 48.3%; p50.05) (Table 2). During the treatment period, BP decreased in all groups. However, the reduction in SBP was significantly higher in group A than in the other groups (week 12 vs baseline: group A, 38 mmHg; group B, 36 mmHg; group C, 33 mmHg; p50.05) (Table 3). The same trend was observed for DBP (Table 4). During the study, 4 AEs occurred in group A (2 cases of cough, 1 of headache and 1 of flushing); 7 AEs occurred in group B (1 case of cough, 3 of edema and 3 of flushing), and 19 AEs occurred in group C (12 cases of cough, 4 of headache and 3 of flushing). The incidence of AEs in group A and group B is lower than group C, with the difference being statistically significant (p50.05). All AEs were of mild intensity. No changes in hematologic parameters (e.g. white blood cells), urinalysis, liver (ALT/AST) and renal (estimated glomerular filtration rate and creatinine) function and ECG were reported.
Discussion Hypertension is a major risk factor for cardiovascular disease; hypertension control can effectively prevent the occurrence of these events1. Despite this, in China several patients fail to achieve BP control (only about 10% of the hypertensive population)1. This study was focused on lercanidipine–perindopril combined treatment in mild hypertensive patients, and www.cmrojournal.com ! 2015 Informa UK Ltd
Current Medical Research & Opinion
Volume 31, Number 1
January 2015
Table 1. Baseline characteristics of three groups at baseline. N Male Group A Group B Group C
40 34 38
Age
DBP
SBP
TC
TG
HDL
LDL
60.6 6.6 62.5 5.3 61.7 5.7 F ¼ 0.15 p40.05
100 3 101 2 102 3 F ¼ 0.4 p40.05
169 7 171 8 170 5 F ¼ 0.04 p40.05
4.8 0.5 4.8 0.5 4.7 0.4 F ¼ 0.27 p40.05
1.7 0.2 1.7 0.3 1.6 0.2 F ¼ 0.32 p40.05
1.5 0.2 1.6 0.1 1.5 0.1 F ¼ 0.28 p40.05
2.5 0.3 2.6 0.2 2.5 0.3 F ¼ 0.84 p40.05
Female
20 26 22 2 ¼ 5.699 p40.05
Curr Med Res Opin Downloaded from informahealthcare.com by University of Otago on 07/06/15 For personal use only.
2 ¼ chi-square; F ¼ distribution; TC ¼ total cholesterol mmol/L; TG ¼ triglycerides mmol/L; HDL ¼ high-density lipoprotein mmol/L; LDL ¼ low-density lipoprotein mmol/L; DBP: diastolic blood pressure; SBP: systolic blood pressure.
Table 2. Normalization rate in the three groups. All values are given as % (number of patients).
Group A Group B Group C
Week 4
Week 8
Week 12
38.3 (23) 26.7 (16) 23.3 (14) 2 ¼ 3.58, p40.05
63.3 (38) 51.7 (31) 36.7 (22) 2 ¼ 8.5, p50.05
71.7 (43) 68.3 (41) 48.3 (29) 2 ¼ 8.18, p50.05
2 ¼ chi-square.
Table 3. Changes in systolic blood pressure (SBP) in the three patient groups throughout the study. BP (mmHg)
Group A Group B Group C
Treatment time
SBP SBP SBP
Baseline
Week 4
Week 8
Week 12
169 11 171 10 170 9 F ¼ 0.04, p40.05
148 13 151 14 153 13 F ¼ 16.71, p50.01
135 9 139 8 141 7 F ¼ 102.79, p50.01
131 10 135 9 137 9 F ¼ 0.017, p40.05
Table 4. Changes in diastolic blood pressure (DBP) in the three patient groups throughout the study. DBP (mmHg)
Group A Group B Group C
Treatment Time
DBP DBP DBP
Baseline
Week 4
Week 8
Week 12
100 9 101 11 102 9 F ¼ 0.4, p40.05
89 8 92 7 92 6 F ¼ 14.51, p50.01
85 7 86 6 89 7 F ¼ 13.34, p50.01
82 6 85 5 87 7 F ¼ 0.05, p40.05
the results confirmed the efficacy and safety of the combination of the two drugs, in particular when considering the normalization rate, the BP reduction and the incidence of adverse events during treatment. However, the doses of perindopril and lercanidipine in monotherapies were higher than those in drug combination. We cannot rule out that if these higher doses were used in the combination, patients might have experienced an even better ! 2015 Informa UK Ltd www.cmrojournal.com
control of hypertension but also more side-effects. Importantly, data on obesity and the presence of concomitant metabolic syndrome were not immediately available at the time of data analysis: this finding should be taken into account – together with the overall limited number of patients and the monocentric nature of the study – for a comprehensive evaluation of the results. The effect of combined antihypertensive therapy was remarkable and it can be attributed to different mechanisms of action which lead to a synergistic treatment effect4. According to the American Joint National Committee (JNC) 7, early initiation of a combined treatment for hypertensive patients is essential3. Several studies showed that antihypertensive combination therapy can reduce BP, with a normalization rate of about 45%; moreover, the different mechanisms of action of the single therapies help reduce the incidence of adverse reactions1,3. The National Institute for Health and Care Excellence guidelines suggests the combined ACEI–CCB therapy as an initial antihypertensive treatment for young and elderly patients6. ACEIs and CCBs are indeed two of the most commonly used drugs for treating hypertension, and are associated with efficacy in BP reduction, protection of target organs (heart and kidney), efficacy in reversing cardiovascular remodeling, and neutral effect on glucose and lipid metabolism. In this study, lercanidipine was evaluated as it is a third generation long-acting CCB. Differing from other similar drugs, lercanidipine does not produce significant reflex tachycardia and shows a marked lipophilicity: thereby its slow releasing effect can be maintained for 24 hours2. Lercanidipine acts on vascular smooth muscle cells by blocking L-type calcium channels and calcium influx, with a consequent evident antihypertensive effect. Furthermore, lercanidipine presents a renal protective effect, as it dilates both efferent and afferent arterioles7. Perindopril is an ACEI, which exerts a long-term inhibition of the conversion of angiotensin I to angiotensin II. The incidence of AEs observed in this study in the monotherapy groups is consistent with previous reports8. The combination therapy reduced the incidence of AEs, possibly because of the action of both drugs at a microEfficacy/safety of perindopril–lercanidipine in hypertension Yang
185
Current Medical Research & Opinion Volume 31, Number 1
January 2015
vascular level: during calcium entry blockade, an increase in intracapillary pressure is observed as a consequence of a selective diminution of the precapillary arteriolar tone. ACEIs reduce this process caused by CCBs, most likely because of their ability to dilate both the arterial vascular bed and the venous capacitance vessels5.
Curr Med Res Opin Downloaded from informahealthcare.com by University of Otago on 07/06/15 For personal use only.
Conclusion The results obtained in this randomized study suggest that lercanidipine combined with perindopril might be considered for combination therapy for mild essential hypertension. However, other studies assessing the effects of lercanidipine plus perindopril in improving clinical outcomes in hypertensive patients are warranted.
Transparency Declaration of funding Editorial support for this manuscript was funded by Recordati. Declaration of financial/other relationships Z.Y. has disclosed that she/he has no significant relationships with or financial interests in any commercial companies related to this study or article.
186
Efficacy/safety of perindopril–lercanidipine in hypertension Yang
CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose. Acknowledgments Editorial assistance was provided by Chiara Mossali PhD and Luca Giacomelli PhD of Content Ed Net.
References 1. Guidelines for the prevention and treatment of hypertension China revision committee. Guidelines for the prevention and treatment of hypertension Chinese 2010. Chin J Cardiovasc Dis 2011;39:579-81 2. Bang LM, Chapman TM, Goa KL. Lercanidipine: a review of its efficacy in the management of hypertension. Drugs 2003;63:2449-72 3. Chobanian AV, Bakris GL, Blaek HR, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (The JNC 7 Report). J Am Med Assoc 2003;289:2560-72 4. McInnes GT. Antihypertensive drugs in combination: additive or greater than additive? J Hum Hypertens 2007;21:914-16 5. Egan BM. Combination therapy with an angiotensin-converting enzyme inhibitor and a calcium channel blocker. J Clin Hypertens (Greenwich) 2007;9:783-9 6. National Institute for Health and Clinical Excellence. Hypertension (CG127): clinical management of primary hypertension in adults. http://www.nice. org.uk/guidance/CG127. Last accessed 3rd November 2014 7. Burnier M. Renal protection with calcium antagonists: the role of lercanidipine. Curr Med Res Opin 2013;29:1727-35 8. Sun RX. The 18th American Society of Hypertension: lercanidipine special report. Foreign Med Sci (section of Cardiovasc Dis) 2003;30:260-1
www.cmrojournal.com ! 2015 Informa UK Ltd
