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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.


The change of systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline (week 2) to end of study (week 14) for each treatment regimen. Four treatment regimens, DXM0, DXM2.5, DXM7.5, and DXM30, were consisted of 31, 16, 6, and 25 patients respectively. P value was examined by paired t test for the comparison of BP value (mmHg) or percentage of change (%) between week 2 and week 14.
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Figure 2: The change of systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline (week 2) to end of study (week 14) for each treatment regimen. Four treatment regimens, DXM0, DXM2.5, DXM7.5, and DXM30, were consisted of 31, 16, 6, and 25 patients respectively. P value was examined by paired t test for the comparison of BP value (mmHg) or percentage of change (%) between week 2 and week 14.

Mentions: In the DXM0 group (n = 31), the mean SBP was 127.2 ± 6.9 mmHg at week 2, which remained stable with AM 5 mg daily through the end of the study. In the DXM2.5 group (n = 16), SBP reduced significantly and constantly from baseline. The reductions were 14.0 ± 8.1 mmHg (P < 0.001), 9.4 ± 12.1 mmHg (P = 0.007), and 11.9 ± 10.8 mmHg (P = 0.003) at week 6, 10, and 14, respectively. In the DXM7.5 group (n = 6), SBP was constantly reduced from baseline by 10.8 ± 10.2 mmHg (P = 0.049) and 7.7 ± 3.4 mmHg (P = 0.003) at week 10 and week 14, respectively. In DXM30 group (n = 25), there was no change in mean SBP from baseline to the end of the study. Among them, only 4 patients achieved the BP goal by a significant reduction of 15.3 ± 5.5 mmHg in SBP (P = 0.011). The numeric SBP changes (mmHg) and the percentage of change at the end of study (week 14) from baseline (week 2) with different treatment regimens were shown in Figure 2. There were significant reductions in percentage of SBP changes at the end of the study from baseline in DXM2.5 (−7.9% ± 7.0%, P < 0.001) and in DXM7.5 group (−5.4% ± 2.4%, P = 0.003) respectively. The similar trend of DBP reduction was also found in DXM2.5 group and DXM7.5 group (Figure 2).


Combination With Low-dose Dextromethorphan Improves the Effect of Amlodipine Monotherapy in Clinical Hypertension
The change of systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline (week 2) to end of study (week 14) for each treatment regimen. Four treatment regimens, DXM0, DXM2.5, DXM7.5, and DXM30, were consisted of 31, 16, 6, and 25 patients respectively. P value was examined by paired t test for the comparison of BP value (mmHg) or percentage of change (%) between week 2 and week 14.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 2: The change of systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline (week 2) to end of study (week 14) for each treatment regimen. Four treatment regimens, DXM0, DXM2.5, DXM7.5, and DXM30, were consisted of 31, 16, 6, and 25 patients respectively. P value was examined by paired t test for the comparison of BP value (mmHg) or percentage of change (%) between week 2 and week 14.
Mentions: In the DXM0 group (n = 31), the mean SBP was 127.2 ± 6.9 mmHg at week 2, which remained stable with AM 5 mg daily through the end of the study. In the DXM2.5 group (n = 16), SBP reduced significantly and constantly from baseline. The reductions were 14.0 ± 8.1 mmHg (P < 0.001), 9.4 ± 12.1 mmHg (P = 0.007), and 11.9 ± 10.8 mmHg (P = 0.003) at week 6, 10, and 14, respectively. In the DXM7.5 group (n = 6), SBP was constantly reduced from baseline by 10.8 ± 10.2 mmHg (P = 0.049) and 7.7 ± 3.4 mmHg (P = 0.003) at week 10 and week 14, respectively. In DXM30 group (n = 25), there was no change in mean SBP from baseline to the end of the study. Among them, only 4 patients achieved the BP goal by a significant reduction of 15.3 ± 5.5 mmHg in SBP (P = 0.011). The numeric SBP changes (mmHg) and the percentage of change at the end of study (week 14) from baseline (week 2) with different treatment regimens were shown in Figure 2. There were significant reductions in percentage of SBP changes at the end of the study from baseline in DXM2.5 (−7.9% ± 7.0%, P < 0.001) and in DXM7.5 group (−5.4% ± 2.4%, P = 0.003) respectively. The similar trend of DBP reduction was also found in DXM2.5 group and DXM7.5 group (Figure 2).

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.