Single Incision versus Conventional Laparoscopic Cholecystectomy Outcomes: A Meta-Analysis of Randomized Controlled Trials

Background

Previous meta-analyses that compared the outcome of SILC and CLC have not presented consistent conclusions. This meta-analysis was performed after adding many recent RCTs, to clarify this issue.

Methods

Relevant articles published in English were identified by searching PubMed, Embase, Web of Knowledge, and the Cochrane Controlled Trial Register from January 1997 to February 2013. Reference lists of the retrieved articles were reviewed to identify additional articles. Primary outcomes (postoperative pain scores, cosmetic score, and length of incision) and secondary outcomes (operating time, blood loss, conversion rates, postoperative complications, postoperative hospital stay, time to initial oral intake, and time to resume work) were pooled. Quantitative variables were calculated using the weighted mean difference (WMD), and qualitative variables were pooled using odds ratios (OR).

Results

25 appropriate RCTs were identified from 2128 published articles. 1841 patients were treated, 944 with SILC and 897 with CLC. SILC was superior to CLC in cosmetic score (WMD = 1.155, P<0.001), shorter length of incision (WMD = -3.285, P = 0.029), and postoperative pain within 12 h (VAS in 3-4 h, WMD = -0.704, P = 0.026; VAS in 6-8 h, WMD = -0.613, P = 0.010). CLC was superior to SILC in operating time (OT) (WMD = 13.613, P<0.001) and need of additional instruments (OR = 7.448, P<0.001). Other secondary outcomes were similar.

Conclusions

SILC offered a better cosmetic result and less postoperative pain for patients with uncomplicated cholelithiasis or polypoid lesions of the gallbladder. However, SILC was associated with a longer OT and required additional instruments.     

Effect of Antioxidant Vitamin Supplementation on Cardiovascular Outcomes: A Meta-Analysis of Randomized Controlled Trials

Background

Antioxidant vitamin (vitamin E, beta-carotene, and vitamin C) are widely used for preventing major cardiovascular outcomes. However, the effect of antioxidant vitamin on cardiovascular events remains unclear.

Methodology and Principal Findings

We searched PubMed, EmBase, the Cochrane Central Register of Controlled Trials, and the proceedings of major conferences for relevant literature. Eligible studies were randomized controlled trials that reported on the effects of antioxidant vitamin on cardiovascular outcomes as compared to placebo. Outcomes analyzed were major cardiovascular events, myocardial infarction, stroke, cardiac death, total death, and any possible adverse events. We used the I² statistic to measure heterogeneity between trials and calculated risk estimates for cardiovascular outcomes with random-effect meta-analysis. Independent extraction was performed by two reviewers and consensus was reached. Of 293 identified studies, we included 15 trials reporting data on 188209 participants. These studies reported 12749 major cardiovascular events, 6699 myocardial infarction, 3749 strokes, 14122 total death, and 5980 cardiac deaths. Overall, antioxidant vitamin supplementation as compared to placebo had no effect on major cardiovascular events (RR, 1.00; 95%CI, 0.96–1.03), myocardial infarction (RR, 0.98; 95%CI, 0.92–1.04), stroke (RR, 0.99; 95%CI, 0.93–1.05), total death (RR, 1.03; 95%CI, 0.98–1.07), cardiac death (RR, 1.02; 95%CI, 0.97–1.07), revascularization (RR, 1.00; 95%CI, 0.95–1.05), total CHD (RR, 0.96; 95%CI, 0.87–1.05), angina (RR, 0.98; 95%CI, 0.90–1.07), and congestive heart failure (RR, 1.07; 95%CI, 0.96 to 1.19).

Conclusion/Significance

Antioxidant vitamin supplementation has no effect on the incidence of major cardiovascular events, myocardial infarction, stroke, total death, and cardiac death.     

Treatment Success in Cancer: Industry Compared to Publicly Sponsored Randomized Controlled Trials

Objective

To assess if commercially sponsored trials are associated with higher success rates than publicly-sponsored trials.

Study Design and Settings

We undertook a systematic review of all consecutive, published and unpublished phase III cancer randomized controlled trials (RCTs) conducted by GlaxoSmithKline (GSK) and the NCIC Clinical Trials Group (CTG). We included all phase III cancer RCTs assessing treatment superiority from 1980 to 2010. Three metrics were assessed to determine treatment successes: (1) the proportion of statistically significant trials favouring the experimental treatment, (2) the proportion of the trials in which new treatments were considered superior according to the investigators, and (3) quantitative synthesis of data for primary outcomes as defined in each trial.

Results

GSK conducted 40 cancer RCTs accruing 19,889 patients and CTG conducted 77 trials enrolling 33,260 patients. 42% (99%CI 24 to 60) of the results were statistically significant favouring experimental treatments in GSK compared to 25% (99%CI 13 to 37) in the CTG cohort (RR = 1.68; p = 0.04). Investigators concluded that new treatments were superior to standard treatments in 80% of GSK compared to 44% of CTG trials (RR = 1.81; p<0.001). Meta-analysis of the primary outcome indicated larger effects in GSK trials (odds ratio = 0.61 [99%CI 0.47–0.78] compared to 0.86 [0.74–1.00]; p = 0.003). However, testing for the effect of treatment over time indicated that treatment success has become comparable in the last decade.

Conclusions

While overall industry sponsorship is associated with higher success rates than publicly-sponsored trials, the difference seems to have disappeared over time.     

Association between B Vitamins Supplementation and Risk of Cardiovascular Outcomes: A Cumulative Meta-Analysis of Randomized Controlled Trials

Background

Observational studies suggest that B vitamin supplementation reduces cardiovascular risk in adults, but this association remains controversial. This study aimed to summarize the evidence from randomized controlled trials (RCTs) investigating B vitamin supplementation for the primary or secondary prevention of major adverse cardiovascular outcomes and to perform a cumulative meta-analysis to determine the evidence base.

Methodology and Principal Findings

In April 2013, we searched PubMed, Embase, and the Cochrane Library to identify relevant RCTs. We included RCTs investigating the effect of B vitamin supplementation on cardiovascular outcome. Relative risk (RR) was used to measure the effect using a random-effect model. Statistical heterogeneity scores were assessed using the Q statistic. We included data on 57,952 individuals from 24 RCTs: 12 primary prevention trials and 12 secondary prevention trials. In 23 of these trials, 10,917 major adverse cardiovascular events (MACE) occurred; in 20 trials, 7,203 deaths occurred; in 15 trials, 3,422 cardiac deaths occurred; in 19 trials, 3,623 myocardial infarctions (MI) occurred; and in 18 trials, 2,465 strokes occurred. B vitamin supplementation had little or no effect on the incidence of MACE (RR, 0.98; 95% confidence interval [CI]: 0.93–1.03; P = 0.37), total mortality (RR, 1.01; 95% CI: 0.97–1.05; P = 0.77), cardiac death (RR, 0.96; 95% CI: 0.90–1.02; P = 0.21), MI (RR, 0.99; 95% CI: 0.93–1.06; P = 0.82), or stroke (RR, 0.94; 95% CI: 0.85–1.03; P = 0.18).

Conclusion/Significance

B vitamin supplementation, when used for primary or secondary prevention, is not associated with a reduction in MACE, total mortality, cardiac death, MI, or stroke.     

Generalized Estimating Equations in Controlled Clinical Trials: Hypotheses Testing

Generalized estimating equations (GEE) for the analysis of clustered data have gained increasing popularity. Recently, the first monograph on this method has been published. GEE have been repeatedly applied in controlled clinical trials. They have, however, been generally used as secondary or supplementary analysis. Instead, the primary analysis was mostly based on a classical method that usually ignored the clustered – mostly longitudinal – nature of the data. In this paper, we discuss the applicability of GEE as primary analysis in controlled clinical trials. From theoretical results in the literature, we derive recommendations how GEE should be used in therapeutic studies for testing statistical hypotheses. We hope that our paper is the starting point for a thorough discussion on the most appropriate analysis of controlled clinical trials with clustered dependent variables. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

The Influence of the Patient-Clinician Relationship on Healthcare Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective

To determine whether the patient-clinician relationship has a beneficial effect on either objective or validated subjective healthcare outcomes.

Design

Systematic review and meta-analysis.

Data Sources

Electronic databases EMBASE and MEDLINE and the reference sections of previous reviews.

Eligibility Criteria for Selecting Studies

Included studies were randomized controlled trials (RCTs) in adult patients in which the patient-clinician relationship was systematically manipulated and healthcare outcomes were either objective (e.g., blood pressure) or validated subjective measures (e.g., pain scores). Studies were excluded if the encounter was a routine physical, or a mental health or substance abuse visit; if the outcome was an intermediate outcome such as patient satisfaction or adherence to treatment; if the patient-clinician relationship was manipulated solely by intervening with patients; or if the duration of the clinical encounter was unequal across conditions.

Results

Thirteen RCTs met eligibility criteria. Observed effect sizes for the individual studies ranged from d = −.23 to .66. Using a random-effects model, the estimate of the overall effect size was small (d = .11), but statistically significant (p = .02).

Conclusions

This systematic review and meta-analysis of RCTs suggests that the patient-clinician relationship has a small, but statistically significant effect on healthcare outcomes. Given that relatively few RCTs met our eligibility criteria, and that the majority of these trials were not specifically designed to test the effect of the patient-clinician relationship on healthcare outcomes, we conclude with a call for more research on this important topic.     

Impact of Including Korean Randomized Controlled Trials in Cochrane Reviews of Acupuncture

Objective

Acupuncture is commonly practiced in Korea and is regularly evaluated in clinical trials. Although many Cochrane reviews of acupuncture include searches of both English and Chinese databases, there is no information on the value of searching Korean databases. This study aimed to investigate the impact of searching Korean databasesand journals for trials eligible for inclusion in existing Cochrane acupuncture reviews.

Methods

We searched 12 Korean databases and seven Korean journals to identify randomised trials meeting the inclusion criteria for acupuncture reviews in the Cochrane Database of Systematic Reviews. We compared risk of bias assessments of the Korean trials with the trials included in the Cochrane acupuncture reviews. Where possible, we added data from the Korean trials to the existing meta-analyses in the relevant Cochrane review and conducted sensitivity analyses to test the robustness of the results.

Results

Sixteen Korean trials (742 participants) met the inclusion criteria for eight Cochrane acupuncture reviews (125 trials; 13,041 participants). Inclusion of the Korean trials provided data for 20% of existing meta-analyses (24 out of 120). Inclusion of the Korean trials did not change the direction of effect in any of the existing meta-analyses. The effect size and heterogeneity remained mostly unchanged. In only one meta-analysis did the significance change. Compared to the studies included in the Cochrane acupuncture reviews, the risk of bias in the Korean trials was higher in terms of outcome assessor blinding and allocation concealment.

Conclusions

Many Korean studies contributed additional data to the existing meta-analyses in Cochrane acupuncture reviews. Although inclusion of these studies did not alter the results of the meta-analyses, comprehensive searches of the literature are important to avoid potential language bias. The identification and inclusion of eligible Korean trials should be considered for reviews of acupuncture.     

Using Regression Models to Analyze Randomized Trials: Asymptotically Valid Hypothesis Tests Despite Incorrectly Specified Models

Summary .  Regression models are often used to test for cause-effect relationships from data collected in randomized trials or experiments. This practice has deservedly come under heavy scrutiny, because commonly used models such as linear and logistic regression will often not capture the actual relationships between variables, and incorrectly specified models potentially lead to incorrect conclusions. In this article, we focus on hypothesis tests of whether the treatment given in a randomized trial has any effect on the mean of the primary outcome, within strata of baseline variables such as age, sex, and health status. Our primary concern is ensuring that such hypothesis tests have correct type I error for large samples. Our main result is that for a surprisingly large class of commonly used regression models, standard regression-based hypothesis tests (but using robust variance estimators) are guaranteed to have correct type I error for large samples, even when the models are incorrectly specified. To the best of our knowledge, this robustness of such model-based hypothesis tests to incorrectly specified models was previously unknown for Poisson regression models and for other commonly used models we consider. Our results have practical implications for understanding the reliability of commonly used, model-based tests for analyzing randomized trials.     

Mini-Incision versus Standard Incision Total Hip Arthroplasty Regarding Surgical Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Purpose

It remains controversial whether mini-incision (MI) benefits patients in total hip arthroplasty (THA). We performed a meta-analysis of randomized controlled trials (RCTs) to assess the effects of MI on surgical and functional outcomes in THA patients.

Methods

A systematic electronic literature search (up to May 2013) was conducted to identify RCTs comparing MI with standard incision (SI) THA. The primary outcome measures were surgical and functional outcomes. According to the surgical approach taken, MI THA patients were divided into four subgroups for sub-group meta-analysis. Standardized mean differences (SMDs) or risk differences (RDs) with accompanying 95% confidence intervals (CIs) were calculated and pooled using a fixed-effect or random-effect model according to the heterogeneity.

Results

A total of 14 RCTs involving THA 1,174 patients met the inclusion criteria. The trials were medium risk of bias. The overall meta-analysis showed MI THA reduced total blood loss (95% CI, -201.83 to -21.18; p=.02) and length of hospital stay ( 95% CI, -0.67 to -0.08; p=.01) with significant heterogeneity. However, subgroup meta-analysis revealed posterior MI THA had perioperative advantages of reduced surgical duration ( 95% CI, -8.45 to -2.67; P<.001), less blood loss ( 95% CI, -107.20 to -1.73; P=.04) and shorter hospital stay ( 95% CI, -0.74 to -0.06; p=.002) with low heterogeneity. There were no significant differences between MI and SI THA groups in term of pain medication dose, functional outcome (HHS), radiological outcome or complications (P>.05, respectively).

Conclusions

Although no definite overall conclusion can be arrived at on whether MI THA is superior to SI THA, posterior MI THA clearly result in a significant decrease in surgical duration, blood loss and hospital stay. It seems to be a safe minimally invasive surgical procedure without increasing the risk of component malposition or complications.     

Reporting of Positive Results in Randomized Controlled Trials of Mindfulness-Based Mental Health Interventions

BackgroundA large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of “positive” results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based therapy trial registrations for indications of possible reporting bias and reviewed recent systematic reviews and meta-analyses to determine whether reporting biases were identified.MethodsCINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS databases were searched for randomized controlled trials of mindfulness-based therapy. The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression. Trial registries were searched for mindfulness-based therapy registrations. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS were also searched for mindfulness-based therapy systematic reviews and meta-analyses.Results108 (87%) of 124 published trials reported ≥1 positive outcome in the abstract, and 109 (88%) concluded that mindfulness-based therapy was effective, 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 (expected number positive trials = 65.7). Of 21 trial registrations, 13 (62%) remained unpublished 30 months post-trial completion. No trial registrations adequately specified a single primary outcome measure with time of assessment. None of 36 systematic reviews and meta-analyses concluded that effect estimates were overestimated due to reporting biases.ConclusionsThe proportion of mindfulness-based therapy trials with statistically significant results may overstate what would occur in practice.     

Randomized Controlled Trials of Maternal‐Fetal Surgery: A Challenge to Clinical Equipoise

This article focuses on maternal‐fetal surgery (MFS) and on the concept of clinical equipoise that is a widely accepted requirement for conducting randomized controlled trials (RCT). There are at least three reasons why equipoise is unsuitable for MFS. First, the concept is based on a misconception about the nature of clinical research and the status of research subjects. Second, given that it is not clear who the research subject/s in MFS is/are, if clinical equipoise is to be used as a criterion to test the ethical appropriateness of RCT, its meaning should be unambiguous. Third, because of the multidisciplinary character of MFS, it is not clear who should be in equipoise. As a result, we lack an adequate criterion for the ethical review of MFS protocols. In our account, which is based on Chervenak and McCullough's seminal work in the field of obstetric ethics, equipoise is abandoned. and RCT involving MFS can be ethically initiated when a multidisciplinary ethics review board (ERB), having an evidence‐based assessment of the risks involved, is convinced that the value of answering the research hypothesis, for the sake of the health interests of future pregnant women carrying fetuses with certain congenital birth defects, justifies the actual risks research participants might suffer within a set limit of low/manageable.     

Endoscopic Vascular Harvest in Coronary Artery Bypass Grafting Surgery: A Meta-Analysis of Randomized Trials and Controlled Trials

OBJECTIVE:: This meta-analysis sought to determine whether endoscopic vascular graft harvesting (EVH) improves clinical and resource outcomes compared with conventional open graft harvesting (OVH) in adults undergoing coronary artery bypass surgery. METHODS:: A comprehensive search was undertaken to identify all randomized and nonrandomized trials of EVH versus OVH up to April 2005. The primary outcome was wound complications. Secondary outcomes included any other clinical morbidity and resource utilization. Odds ratios (OR), weighted mean differences (WMD), or standardized mean differences (SMD) and their 95% confidence intervals (95% CI) were analyzed. RESULTS:: Thirty-six trials of 9,632 patients undergoing saphenous vein harvest met the inclusion criteria (13 randomized; 23 nonrandomized). Risk of wound complications was significantly reduced by EVH compared with OVH (OR 0.31, 95% CI 0.23-0.41). Similarly, the risk of wound infections was significantly reduced (OR 0.23, 95% CI 0.20-0.53; P < 0.0001). Need for surgical wound intervention was also significantly reduced (OR 0.16, 95% CI 0.08-0.29). The incidence of pain, neuralgia, and patient satisfaction was improved with EVH compared with OVH. Postoperative myocardial infarction, stroke, reintervention for ischemia or angina recurrence, and mortality were not significantly different. Operative time was significantly increased (WMD 15.26 minutes; 95% CI 0.01, 30.51), hospital length of stay was reduced (WMD -0.85 days; 95% CI -1.55, -0.15), and readmissions were reduced (OR 0.53, 95% CI 0.29-0.98). Costs were insufficiently reported to allow for aggregate analysis. CONCLUSIONS:: Endoscopic vascular graft harvesting of the saphenous vein reduces wound complications and improves patient satisfaction and resource utilization. Further research is required to determine the incremental cost-effectiveness of EVH versus OVH.     

Dezocine for Preventing Postoperative Pain: A Meta-Analysis of Randomized Controlled Trials

Background

Dezocine is considered to be an alternative medication for managing postoperative pain. The aim of this study was to assess the efficacy and safety of this drug in this regard.

Methods

Medline, EMBASE and the Cochrane Central Register of Control Trials (CENTRAL) were searched to identify all randomized controlled trials (RCTs) that compare dezocine with placebo or dezocine with morphine on postoperative pain. The data were extracted and pooled using Mantel-Haenszel random effects model. Heterogeneity was tested using the I ² statistic with values >50% and Chi² test with P ≤ 0.05 indicating obvious heterogeneity between the studies.

Results

Seven trials evaluating 665 patients were included. The number of patients with at least 50% pain relief was increased (N = 234; RR 3.04, 95% CI 2.27 to 4.08) and physician (N = 465; RR 2.84, 95% CI 1.66 to 4.84) and patient satisfaction (N = 390; RR 2.81, 95% CI 1.85 to 4.26) were improved following the administration of dezocine compared with the placebo. The effects of dezocine were similar to those of morphine in terms of the number of patients reporting at least 50% pain relief within 2–6 h after surgery (N = 235; RR 1.29, 95% CI 1.15 to 1.46) and physician (N = 234; RR 1.18, 95% CI 0.93 to 1.49) and patient (N = 158; RR 1.33, 95% CI 0.93 to 1.92) satisfaction. While, the number of patients with at least 50% pain relief within 0–1 h after surgery increased following dezocine compared with morphine treatment (N = 79; RR 1.45, 95% CI 1.18 to 1.77). There was no difference in the incidence of postoperative nausea and vomiting (PONV) following dezocine treatment compared with the placebo (N = 391; RR 1.06, 95% CI 0.42 to 2.68) or morphine treatment (N = 235; RR 0.65, 95% CI 0.14 to 2.93).

Conclusion

Dezocine is a promising analgesic for preventing postoperative pain, but further studies are required to evaluate its safety.     

Characteristics of Randomized Controlled Trials Designed for Elderly: A Systematic Review

ObjectivesTo quantify the proportion of randomized controlled trials (RCTs) specifically designed for elderly, and to assess their characteristics, as compared to RCTs not specifically designed for elderly.DesignReview and synthesis of published literature.MeasurementsWe searched PubMed for articles published in the year 2012. We included RCTs. Articles were excluded if not conducted with human subjects or if findings of secondary analyses were reported. A random sample of 10% was drawn and of this selection the following trial characteristics were extracted: sample size, disease category, age of sample, and age-related inclusion criteria. Clinical trials were defined to be specifically designed for elderly if a lower age cut-off of ≥ 55 years was used, or when participants had an average age of ≥ 70 years.ResultsThe search strategy yielded 26,740 articles, from which a random sample was drawn, resulting in 2375 articles. After exclusion, data was extracted from 1369 publications. Of these 1369 RCTs, 96 (7%) were specifically designed for elderly. In comparison with trials not designed for older adults, trials designed for elderly contained a significantly larger median number of participants (125 vs. 80, p = 0.008) significantly more trials designed for elderly fell into the disease categories eye (6% vs. 2%, p = 0.005), musculoskeletal (13% vs. 7%, p = 0.023) and circulatory system (16% vs. 9%, p = 0.039). No significant difference was observed with regard to the other disease categories.ConclusionThere is a low proportion of RCTs specifically designed for elderly. As older patients will increasingly form the majority in medical practice, there is an urgent need for stronger evidence for the formulation of treatment guidelines specifically for older adults.     

Primary Prevention of Cannabis Use: A Systematic Review of Randomized Controlled Trials

A systematic review of primary prevention was conducted for cannabis use outcomes in youth and young adults. The aim of the review was to develop a comprehensive understanding of prevention programming by assessing universal, targeted, uni-modal, and multi-modal approaches as well as individual program characteristics. Twenty-eight articles, representing 25 unique studies, identified from eight electronic databases (EMBASE, MEDLINE, CINAHL, ERIC, PsycINFO, DRUG, EBM Reviews, and Project CORK), were eligible for inclusion. Results indicated that primary prevention programs can be effective in reducing cannabis use in youth populations, with statistically significant effect sizes ranging from trivial (0.07) to extremely large (5.26), with the majority of significant effect sizes being trivial to small. Given that the preponderance of significant effect sizes were trivial to small and that percentages of statistically significant and non-statistically significant findings were often equivalent across program type and individual components, the effectiveness of primary prevention for cannabis use should be interpreted with caution. Universal multi-modal programs appeared to outperform other program types (i.e, universal uni-modal, targeted multi-modal, targeted unimodal). Specifically, universal multi-modal programs that targeted early adolescents (10–13 year olds), utilised non-teacher or multiple facilitators, were short in duration (10 sessions or less), and implemented boosters sessions were associated with large median effect sizes. While there were studies in these areas that contradicted these results, the results highlight the importance of assessing the interdependent relationship of program components and program types. Finally, results indicated that the overall quality of included studies was poor, with an average quality rating of 4.64 out of 9. Thus, further quality research and reporting and the development of new innovative programs are required.     

Pharmacogenetics-Based versus Conventional Dosing of Warfarin: A Meta-Analysis of Randomized Controlled Trials

Background

Recently, using the patient’s genotype to guide warfarin dosing has gained interest; however, whether pharmacogenetics-based dosing (PD) improves clinical outcomes compared to conventional dosing (CD) remains unclear. Thus, we performed a meta-analysis to evaluate these two strategies.

Methods

The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese VIP and Chinese Wan-fang databases were searched. The Cochrane Collaboration’s tool was used to assess the risk of bias in randomized controlled trials (RCTs). The primary outcome was time within the therapeutic range (TTR); the secondary end points were the time to maintenance dose and time to first therapeutic international normalized ratio (INR), an INR greater than 4, adverse events, major bleeding, thromboembolism and death from any cause.

Results

A total of 11 trials involving 2,678 patients were included in our meta-analysis. The results showed that PD did not improve the TTR compared to CD, although PD significantly shortened the time to maintenance dose (MD = -8.80; 95% CI: -11.99 to -5.60; P<0.00001) and the time to first therapeutic INR (MD = -2.80; 95% CI: -3.45 to -2.15; P<0.00001). Additionally, PD significantly reduced the risk of adverse events (RR = 0.86; 95% CI: 0.75 to 0.99; P = 0.03) and major bleeding (RR = 0.36; 95% CI: 0.15 to 0.89, P = 0.03), although it did not reduce the percentage of INR greater than 4, the risk of thromboembolic events and death from any cause. Subgroup analysis showed that PD resulted in a better improvement in the endpoints of TTR and over-anticoagulation at a fixed initial dosage rather than a non-fixed initial dosage.

Conclusions

The use of genotype testing in the management of warfarin anticoagulation was associated with significant improvements in INR-related and clinical outcomes. Thus, genotype-based regimens can be considered a reliable and accurate method to determine warfarin dosing and may be preferred over fixed-dose regimens.

Trial Registration PROSPERO

Database registration: CRD42015024127.