针刺预防偏头痛远期疗效评价(续2)
The baseline characteristics and clinical outcomes described are based on the intention-to-treat (ITT) population, which included participants who had at least 1 treatment and 1 primary outcome measure (n = 245). Continuous variables are presented as the mean (SD) with 95% CIs. Categorical variables are described as numbers and percentages. The missing data of participants who dropped out were replaced by the last observation carried forward method. The significance level used for the statistical analysis with 2-tailed testing was 5%. The analysis plan was determined before the study was conducted. If the data were normally distributed, we planned to use the analysis of covariance to detect differences among the 3 groups; if not, we planned to use the Kruskal-Wallis test. Secondary outcome measures were evaluated using the χ2 test for categorical data, and analysis of variance or KruskalWallis tests were used for quantitative variables according to the data distribution. If the global test among 3 arms was significant, the least significant difference (LSD) test was used for pairwise comparisons when the data were normally distributed; otherwise, the LSD was applied after rank-transformation when the variables showed nonnormality.All data in this trial were commissioned to BrightechMagnsoft Data Services for analysis using SAS statistical software (version 9.3; SAS Institute Inc).ResultsParticipants and Baseline Characteristics
After the screening of 662 patients, 249 participants 18 to 65 years old were randomized. One hundred eighty-nine (77.1%) were women. A total of 245 patients (83 in the TA group, 80 in the SA group, and 82 in the WL group) were included in the ITT population (Figure 1). Table 1 shows the patient characteristics at baseline and acupuncture expectation before treatment. They were comparable across the 3 groups. Six patients (2.4%) were unable to undergo follow-up (2 in the TA group, 3 in the SA group, and 1 in the WL group). During the reatment period, the mean number of treatments was 19.31 in the TA group and 19.23 in the SA group.
Primary Outcome
The change in frequency of migraine attacks differed significantly among the 3 groups at 16 weeks after randomization (Table 2). The frequency of attacks decreased in the TA group by 3.2, in the SA group by 2.1, and the WL group by 1.4; a greater reduction was observed in the TA than in the SA group (difference of 1.1 attacks; 95% CI, 0.4-1.9; P = .002) and in the TA vs WL group (difference of 1.8 attacks; 95% CI, 1.1 to 2.5; P < .001). The SA group was not statistically different from the WL group (difference of 0.7 attacks; 95% CI, -0.1 to 1.4; P = .07) (Table 2). The per-protocol analysis showed similar results.
Secondary Outcomes
The effects of acupuncture on the secondary outcomes seemed to be persistent during follow-up. The frequency of migraine attacks (Figure 2), migraine days, and VAS scores
were significantly lower in the TA group than in the other 2 control groups in each interview during weeks 4 to 24 (Table 2). Significant differences in frequency of migraine and migraine days between the 2 control groups were only found at weeks 8, 12, and 20 after inclusion within the follow-up period (Table 2).
At the end of week 4, no differences were observed between the TA group and the SA group in the MSQ, SAS, or SDS scores (P > .05 for all comparisons) except for the emotional functional subscale in MSQ. Compared with the WL group, however, the TA group showed a significant improvement in all subscales of the MSQ and SAS scores (P < .05 for all comparisons). Furthermore, patients in the SA group only had a better score in the restrictive subscale of MSQ than those in the WL group (Table 3). The number of patients using acute pain medication, such as ibuprofen, significantly differed among the 3 groups both at the treatment and at follow-up. Compared with the WL control group, TA and SA group have reduced acute medication(Table 2).
Safety
Seven patients (5 in the TA group and 2 in the SA group) reported AEs during the 24 weeks. Three patients from the TA group complained of a tingling sensation after insertion in the acupoints located on the head. One described swelling of the left ankle after a needle was removed from GB40. The other 3 patients (1 in the TA group and 2 in the SA group) had subcutaneous hemorrhage in the needle insertion area. All AEs were reported as mild or moderate, and none required special medical interventions. The 7 patients fully recovered from the AEs and did not withdraw from the trial.
DiscussionTrue acupuncture exhibited persistent, superior, and clinically relevant benefits for migraine prophylaxis, reducing the migraine frequency, number of days with migraine, and pain intensity to a greater degree than SA or WL. Improvements in the emotional domain of quality of life were also found. Moreover, compared with no treatment, SA may obtain arelatively better effect in controlling the migraine frequency and number of days with migraine within 8 weeks after treatment rather than at the end of the treatment session. Acupuncture should be considered as one option for migraine prophylaxis in light of our findings. To the best of our knowl edge, our study is one of the largest trials that have used rigorous methods to test the efficacy of true acupuncture over 24 weeks of follow-up. We provided daily treatment during workdays for 4 weeks to achieve a long-lasting effect for 20 weeks. We had a lower loss to follow-up rate (1.61%) than other migraine prophylaxis studies.
We found that TA was more effective than the WL control group for migraine prophylaxis. Our findings were congruent with those of a previous clinical trial and individual patient data meta-analysis for chronic pain Furthermore, the findings of the current study demonstrated that TA was significantly better than SA for migraine prophylaxis, which has been supported by several other RCTs.These findings were not completely in accordance with those of our previous study, which showed no significant differences between the TA group and the SA group in weeks 5 to 8; instead, the difference appeared later, in weeks 13 to 16. We speculate that the inconsistency was attributed to the different acupoints prescribed. A standardized prescription was used in our previous study; however, semistandard therapy according to syndrome differentiation of meridians—a more practical approach—was used in the TA group in the present study.
Of note, a large trial from Germany demonstrated no statistical difference between TA and SA.We speculate that the clinical benefits and superiority found in our trial were due to several factors. The first was the type of treatment. We added electrostimulation to manual acupuncture because manual acupuncture requires more time until it reaches a similar analgesic effect as electrical stimulation.Previous studies have reported that electrostimulation is better than manual acupuncture in relieving pain and could induce a longerlasting effect.
Second, only patients with migraines without aura were chosen in the present study; however, all other similar studies have included migraineurs with other types. As an acute
therapy, sumatriptan was less effective for migraine attacks with aura than that for attacks without aura. We hypothesized that the type of migraine attack may have an impact on the therapeutic outcome, and that patients with migraine without aura are more responsive to acupuncture than migraine with aura owing to their distinct pathogeneses.
Finally, the severity of pain that patients reported during the baseline period might have influenced the therapeutic effects. The mean days with migraine in our trial ranged from 5.9 to 6.0 days per 4 weeks, and the mean attack frequency was approximately 4.9 during the baseline. However, Linde et alreported fewer days with migraine and fewer migraine attacks during the baseline, and no significant difference be tween TA and SA was observed either at the end of treatment or at the 12-week follow-up. Reductions in migraine severity and frequency increased benefits in patients with more severe headaches.This finding might explain the significant difference between the TA and SA groups in our study, and the absence of such a finding in the aforementioned RCT with a similar study design.
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