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Combination With Low-dose Dextromethorphan Improves the Effect of Amlodipine Monotherapy in Clinical Hypertension

View Article: PubMed Central - PubMed

ABSTRACT

The combination of low rather than high dose of dextromethorphan (DXM) with amlodipine (AM) could improve blood pressure (BP) reduction in hypertensive animals. The study aimed to evaluate the feasibility of different doses of DXM combined with standard AM treatment in clinical hypertension.

This was a prospective, 14-week, dose-escalation, multicenter study. After 2-week run-in period with AM 5 mg/day, hypertensive patients who got the BP goal of 140/90 mmHg kept receiving AM monotherapy for another 12 weeks. The nonresponders, while kept on AM 5 mg/day, received additional DXM treatment for 3 sequential dose-titrated periods with initially 2.5 mg/day, followed by 7.5 mg/day, and finally 30 mg/day. Each period was for 4 weeks. The patients at BP goal after each treatment period were defined as the responders and kept on the same combination till the end of the study. The responder rate of each treatment period was recorded. The changes of BP and serum antioxidant/endothelial markers between week 14 and week 2 were evaluated.

Of the 103 patients initially enrolled, 89 entered the treatment period. In the 78 patients completing the study, 31 (40%) at BP goal after 2-week AM run-in kept on AM monotherapy (DXM0). The addition of 2.5 (DXM2.5) and 7.5 mg/day (DXM7.5) of DXM enabled BP goal achievement in 22 (47%) nonresponders to AM monotherapy including 16 (29%) with DXM2.5 and 6 (18%) with DXM7.5. Only 4 patients (16%) reached BP goal with the combination of DXM 30 mg/day (DXM30). Overall, 73% of the 78 patients reached BP goal at the end of the 14-week study. Mean systolic BP was reduced by 7.9% ± 7.0% with DXM2.5 (P < 0.001) and by 5.4% ± 2.4% with DXM7.5 (P = 0.003) respectively at week 14 from that at week 2, which was unchanged in either DXM0 or DXM30 group. Besides, the effects of combination treatment were particularly significant in the patients with impaired endothelial function suggested by reduced serum NOx level at baseline.

Accordingly, the combination with low dose of DXM was feasible to improve BP control in patients who failed to achieve the BP goal by standard AM monotherapy. The benefit effects might be significant especially in patients with impaired endothelial function.

No MeSH data available.


Enrollment and disposition of subjects.
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Figure 1: Enrollment and disposition of subjects.

Mentions: Patients who fulfilled the enrollment criteria were asked to stop all the cardiovascular medications that might alter BP if there were. In each patient, the sitting BP was re-checked as the standard method to confirm the presence of hypertension just before the enrollment in the morning hours. Initially, they were administered with AM 5 mg (in a capsule) daily for 2 weeks as the run-in period of the study. Two weeks later, the hypertensive patients who met the treatment BP goal (sitting BP <140/90 mmHg in the morning hours) were kept with AM monotherapy (in a same capsule) for another 12 weeks till the end of the study (DXM0). The others were then given AM 5 mg (in a same capsule) combined with DXM 2.5 mg (in another capsule) daily for 4 weeks as the first combination treatment period. After the 4-week treatment, the patients who met the BP goal were kept with the combination of AM 5 mg and DXM 2.5 mg daily for another 8 weeks till the end of the study (DXM2.5). The others who did not meet the BP goal were then given AM 5 mg (in a same capsule) combined with DXM 7.5 mg (in another capsule similar to that of DXM 2.5 mg) daily for another 4 weeks as the second combination treatment period. After the 4-week treatment, the patients who met the BP goal were kept with the combination of AM 5 mg and DXM 7.5 mg daily for another 4 weeks till the end of the study (DXM7.5). The patients who did not meet the BP goal were given AM 5 mg (in a capsule) with the highest combination dose of DXM 30 mg (in another capsule similar to that of DXM 2.5 mg) daily for the final 4 weeks as the third combination treatment period. Therefore, the patients enrolled in this study were allocated to 4 different regimens (DXM0 group, DXM2.5 group, DXM7.5 group, and DXM30 group) according to their response of BP to different doses of DXM. The subject enrollment and diagram of study design were shown in Figure 1.


Combination With Low-dose Dextromethorphan Improves the Effect of Amlodipine Monotherapy in Clinical Hypertension
Enrollment and disposition of subjects.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998419&req=5

Figure 1: Enrollment and disposition of subjects.
Mentions: Patients who fulfilled the enrollment criteria were asked to stop all the cardiovascular medications that might alter BP if there were. In each patient, the sitting BP was re-checked as the standard method to confirm the presence of hypertension just before the enrollment in the morning hours. Initially, they were administered with AM 5 mg (in a capsule) daily for 2 weeks as the run-in period of the study. Two weeks later, the hypertensive patients who met the treatment BP goal (sitting BP <140/90 mmHg in the morning hours) were kept with AM monotherapy (in a same capsule) for another 12 weeks till the end of the study (DXM0). The others were then given AM 5 mg (in a same capsule) combined with DXM 2.5 mg (in another capsule) daily for 4 weeks as the first combination treatment period. After the 4-week treatment, the patients who met the BP goal were kept with the combination of AM 5 mg and DXM 2.5 mg daily for another 8 weeks till the end of the study (DXM2.5). The others who did not meet the BP goal were then given AM 5 mg (in a same capsule) combined with DXM 7.5 mg (in another capsule similar to that of DXM 2.5 mg) daily for another 4 weeks as the second combination treatment period. After the 4-week treatment, the patients who met the BP goal were kept with the combination of AM 5 mg and DXM 7.5 mg daily for another 4 weeks till the end of the study (DXM7.5). The patients who did not meet the BP goal were given AM 5 mg (in a capsule) with the highest combination dose of DXM 30 mg (in another capsule similar to that of DXM 2.5 mg) daily for the final 4 weeks as the third combination treatment period. Therefore, the patients enrolled in this study were allocated to 4 different regimens (DXM0 group, DXM2.5 group, DXM7.5 group, and DXM30 group) according to their response of BP to different doses of DXM. The subject enrollment and diagram of study design were shown in Figure 1.

View Article: PubMed Central - PubMed

ABSTRACT

The combination of low rather than high dose of dextromethorphan (DXM) with amlodipine (AM) could improve blood pressure (BP) reduction in hypertensive animals. The study aimed to evaluate the feasibility of different doses of DXM combined with standard AM treatment in clinical hypertension.

This was a prospective, 14-week, dose-escalation, multicenter study. After 2-week run-in period with AM 5&#8202;mg/day, hypertensive patients who got the BP goal of 140/90&#8202;mmHg kept receiving AM monotherapy for another 12 weeks. The nonresponders, while kept on AM 5&#8202;mg/day, received additional DXM treatment for 3 sequential dose-titrated periods with initially 2.5&#8202;mg/day, followed by 7.5&#8202;mg/day, and finally 30&#8202;mg/day. Each period was for 4 weeks. The patients at BP goal after each treatment period were defined as the responders and kept on the same combination till the end of the study. The responder rate of each treatment period was recorded. The changes of BP and serum antioxidant/endothelial markers between week 14 and week 2 were evaluated.

Of the 103 patients initially enrolled, 89 entered the treatment period. In the 78 patients completing the study, 31 (40%) at BP goal after 2-week AM run-in kept on AM monotherapy (DXM0). The addition of 2.5 (DXM2.5) and 7.5&#8202;mg/day (DXM7.5) of DXM enabled BP goal achievement in 22 (47%) nonresponders to AM monotherapy including 16 (29%) with DXM2.5 and 6 (18%) with DXM7.5. Only 4 patients (16%) reached BP goal with the combination of DXM 30&#8202;mg/day (DXM30). Overall, 73% of the 78 patients reached BP goal at the end of the 14-week study. Mean systolic BP was reduced by 7.9%&#8202;&plusmn;&#8202;7.0% with DXM2.5 (P&#8202;&lt;&#8202;0.001) and by 5.4%&#8202;&plusmn;&#8202;2.4% with DXM7.5 (P&#8202;=&#8202;0.003) respectively at week 14 from that at week 2, which was unchanged in either DXM0 or DXM30 group. Besides, the effects of combination treatment were particularly significant in the patients with impaired endothelial function suggested by reduced serum NOx level at baseline.

Accordingly, the combination with low dose of DXM was feasible to improve BP control in patients who failed to achieve the BP goal by standard AM monotherapy. The benefit effects might be significant especially in patients with impaired endothelial function.

No MeSH data available.