Non-vitamin K Oral Anticoagulants Versus Warfarin for Patients with Atrial Fibrillation: Absolute Benefit and Harm Assessments Yield Novel Insights.

BACKGROUND AND OBJECTIVES: Benefits and/or harms (including costs) of non-vitamin K oral anticoagulants (NOACs) versus warfarin therapy need appreciation in relative and absolute terms. METHODS: Accordingly, we derived clinically relevant relative and absolute benefit/harm parameters for NOACs (apixaban, dabigatran, rivaroxaban, edoxaban) compared to warfarin from four clinical trials involving atrial fibrillation (AF) patients. For each trial, we tabulated patient numbers enduring four important outcomes and calculated unadjusted relative risk reduction (RRR) and number needed to treat (NNT)/year values (and 95% confidence intervals) for the NAOC compared to warfarin. These outcomes were as follows: stroke/systemic embolism (primary endpoint), hemorrhagic stroke, major bleeds, and death. We also addressed drug acquisition costs. RESULTS: Each NOAC was noninferior to warfarin for primary-outcome prevention; RRRs were 12-33% and NNT/year values were 182-481, and all but one indicated statistically significant superiority. All the NOACs yielded statistically significant reductions in hemorrhagic stroke risk; RRRs were 42-74% and NNT/year values were 364-528. Major bleeding risk was comparable in both groups. Apixaban yielded a lower NNT/year for preventing death than for primary-outcome prevention. Compared to warfarin, NOAC acquisition costs were 70- to 140-fold greater. CONCLUSIONS: For the primary outcome, the absolute benefits of NOACs were modest (NNT/year values being large). Reduced hemorrhagic stroke rates with NOACs could be due to superior embolic infarct prevention and fewer consequential hemorrhagic transformations. Among apixaban recipients, the absolute mortality benefit exceeded that for the primary outcome, indicating prevention of additional unrelated deaths. The substantially greater NOAC acquisition costs need viewing against probable greater safety and the avoidance of monitoring bleeding risks.

Rhythm vs. rate control of atrial fibrillation meta-analysed by number needed to treat.

BACKGROUND: Whenever feasible, rhythm control of atrial fibrillation (AF) was generally preferred over rate control, in the belief that it offered better symptomatic relief and quality of life, and eliminated the need for anticoagulation. However, recent trials appear to challenge these assumptions. AIMS: To explore the desirability of rhythm vs. rate control of AF by systematic review of pertinent, published, randomized controlled trials (RCTs) and a meta-analysis by number needed to treat (NNT) year(-1), with respect to diverse clinically important outcomes. METHODS: RCTs of outcome primarily comparing rate vs. rhythm control in patients with spontaneous AF were identified. For each outcome and assuming rhythm control to be the active treatment, relative risk reduction (RRR) and NNT year(-1) were derived for individual trials together with an NNT year(-1) for all trials combined; corresponding 95% confidence intervals (CI) were also calculated. Adverse drug reaction (ADR) and quality of life reporting were also assessed. RESULTS: In all, data from five suitable RCTs (entailing 5239 patients) were analysed. For hospitalization, available RRRs and NNT year(-1) values were all clinically and statistically significant. Overall, one additional patient was hospitalized for every 35 assigned to rhythm control (95% CI 27, 48). For the endpoints of death, 'ischaemic' stroke and 'non-CNS' bleeding, there was no significant difference. ADRs were significantly more common in rhythm control patients, whereas quality of life assessments revealed no difference. Thromboembolism was associated with cessation of or subtherapeutic anticoagulation, irrespective of treatment assignment. CONCLUSION: Reduced risk of hospitalization and non-inferiority for other endpoints all favour rate control, the less costly strategy. If symptoms of AF are not a problem, treatment should target optimizing rate control and more widespread and effective prophylactic anticoagulation.

Screening for fever by remote-sensing infrared thermographic camera.

BACKGROUND: Following the severe acute respiratory syndrome (SARS) outbreak, remote-sensing infrared thermography (IRT) has been advocated as a possible means of screening for fever in travelers at airports and border crossings, but its applicability has not been established. We therefore set out to evaluate (1) the feasibility of IRT imaging to identify subjects with fever, and (2) the optimal instrumental configuration and validity for such testing. METHODS: Over a 20-day inclusive period, 176 subjects (49 hospital inpatients without SARS or suspected SARS, 99 health clinic attendees and 28 healthy volunteers) were recruited. Remotely sensed IRT readings were obtained from various parts of the front and side of the face (at distances of 1.5 and 0.5 m), and compared to concurrently determined body temperature measurements using conventional means (aural tympanic IRT and oral mercury thermometry). The resulting data were submitted to linear regression/correlation and sensitivity analyses. All recruits gave prior informed consent and our Faculty Institutional Review Board approved the protocol. RESULTS: Optimal correlations were found between conventionally measured body temperatures and IRT readings from (1) the front of the face at 1.5m with the mouth open (r=0.80), (2) the ear at 0.5 m (r=0.79), and (3) the side of the face at 1.5m (r=0.76). Average IRT readings from the forehead and elsewhere were 1 degrees C to 2 degrees C lower and correlated less well. Ear IRT readings at 0.5 m yielded the narrowest confidence intervals and could be used to predict conventional body temperature readings of < or = 38 degrees C with a sensitivity and specificity of 83% and 88% respectively. CONCLUSIONS: IRT readings from the side of the face, especially from the ear at 0.5 m, yielded the most reliable, precise and consistent estimates of conventionally determined body temperatures. Our results have important implications for walk-through IRT scanning/screening systems at airports and border crossings, particularly as the point prevalence of fever in such subjects would be very low.

Meta-analysis of large randomized controlled trials to evaluate the impact of statins on cardiovascular outcomes.

AIMS: Since 2002, there have been five major outcome trials of statins reporting findings from more than 47,000 subjects. As individual trial results differed, we performed a meta-analysis to ascertain the effectiveness and safety of statins overall and in subgroups. The aim of the study was to estimate the effect of statins on major coronary events and strokes, all-cause mortality and noncardiovascular mortality, and in different subgroups. METHODS: PubMed was searched for trials published in English. Randomized placebo-controlled statin trials with an average follow up of at least 3 years and at least 100 major coronary events were included. For each trial, the statin used, number and type of subjects, proportion of women, mean age and follow up, baseline and change in lipid profile, cardiovascular and non-cardiovascular outcomes were recorded. RESULTS: Ten trials involving 79,494 subjects were included in the meta-analysis. Due to heterogeneity, ALLHAT-LLT was excluded from some analyses. Statin therapy reduced major coronary events by 27% (95%CI 23, 30%), stroke by 18% (95%CI 10, 25%) and all-cause mortality by 15% (95%CI 8, 21%). There was a 4% (95%CI -10, 3%) nonsignificant reduction in noncardiovascular mortality. The reduction in major coronary events is independent of gender and presence of hypertension or diabetes. The risk reduction was greater in smokers (P < 0.05). Coronary events were reduced by 23% (95%CI 18, 29%) in pravastatin trials and 29% (95%CI 25, 33%) in five trials using other statins. Pravastatin reduced strokes by 12% (95%CI 1, 21%) whilst other statins reduced strokes by 24% (95%CI 16, 32%) (P = 0.04). CONCLUSIONS: Statins reduce coronary events, strokes and all-cause mortality without increasing noncoronary mortality. The benefits accrue in men and women, hypertensives and normotensives, diabetics and nondiabetics, and particularly in smokers. Pravastatin appears to have less impact on strokes.

A community study of sleep-disordered breathing in middle-aged Chinese women in Hong Kong: prevalence and gender differences.

STUDY OBJECTIVES: To investigate the prevalence of sleep-disordered breathing (SDB) and obstructive sleep apnea syndrome (OSAS) in community-based, middle-aged Chinese women, and to compare the differences between gender with a similar study in men. DESIGN: A cross-sectional study conducted in Hong Kong from 1998 to 2000. SETTING: Sleep questionnaires were distributed to women (30 to 60 years old) in three offices and two community centers. All were invited to undergo full polysomnography in a sleep laboratory. PARTICIPANTS: Questionnaires were distributed to 1,532 women, and 854 questionnaires were returned. Polysomnography was conducted in 106 respondents. MEASUREMENTS AND RESULTS: Conservative estimated prevalence of SDB (apnea-hypopnea index [AHI] > = 5) and OSAS (AHI > or = 5 plus excessive daytime sleepiness [EDS]) were 3.7% and 2.1%, respectively. Age-specific prevalence of OSAS was 0.5%, 2.2%, and 6.1% in the 30- to 39-year-old, 40- to 49-year-old, and 50- to 60-year-old age groups, respectively. Stepwise multiple logistic regression analysis identified body mass index (BMI) and age as predictors of SDB. Compared to Chinese men, the prevalence of SDB and OSAS in women was lower, but the gender difference decreased with age. The AHI of affected women was also significantly lower despite comparable BMI. Compared to men, women with SDB had same degree of self-reported snoring and a similar degree of EDS despite the lower AHI. CONCLUSIONS: This study demonstrated an estimated prevalence of OSAS at 2.1% among middle-aged Chinese women in Hong Kong, with a 12-fold rise from the fourth to the sixth decade of life. BMI and age were significant independent predictors of SDB. Compared to men, women with SDB had lower AHIs, despite similar BMIs.

Diltiazem co-treatment in renal transplant patients receiving microemulsion cyclosporin.

BACKGROUND: Usage of cyclosporin (the Hong Kong Hospital Authority's single largest item of drug expenditure) continues to increase, mainly due to increasing numbers of renal allograft patients taking it as long-term antirejection therapy. Diltiazem, an antihypertensive agent, interferes with the first pass extraction of oral cyclosporin, thus serving to conserve its dosage. AIMS: In renal transplant patients, to assess whether diltiazem co-treatment could achieve worthwhile dosage conservation of Neoral (a relatively new microemulsified cyclosporin formulation), safely. METHODS: A randomized, placebo-controlled, double-blind clinical trial was undertaken at three local hospitals. Renal transplant recipients receiving Neoral as prophylactic immunosuppression were randomized to two treatment arms. Active treatment consisted of diltiazem tablets 30 or 60 mg twice daily for patients weighing < 60 or >or= 60 kg, respectively. One hundred and ten eligible patients gave their informed consent, and were followed up for at least six months. The mean difference in the dollar cost in the sixth month was the primary outcome. Secondary/ancillary outcomes included changes in cyclosporin dosage and blood level, and untoward clinical events including rejection. Outcomes were evaluated by intention to treat analyses. RESULTS: During weeks 23-26 (sixth month) post randomization, diltiazem co-treatment yielded an estimated average cost saving per patient on drugs of 15%[the 95% confidence interval (CI) of the difference being HK dollars 609 +/- 517 or pound 50 +/- 42], with no apparent excess of untoward or adverse events, complications, hospitalization, outpatient visits, or inferior quality of life. CONCLUSIONS: This diltiazem co-treatment regime applied to the nearly 1800 surviving renal allograft patients followed up in Hospital Authority hospitals could have saved approximately HK dollars 14.3 million ( pound 1.17 million) annually, without adverse sequelae.

The effect of health-related quality of life (HRQOL) on health service utilisation of a Chinese population.

This study was designed to find out whether health-related quality of life (HRQOL) was an independent determinant of health service utilisation of a Chinese population and to determine whether the addition of HRQOL data to sociodemographic and morbidity factors could significantly increase the explanatory power of risk-adjustment models. A cross-sectional random telephone survey of the general adult Chinese population in Hong Kong was conducted among 2410 Chinese aged 18-88yr old, 52% were females and 38% had one or more chronic diseases. Health service utilisation was measured by annual consultation, monthly consultation and hospitalisation rates. HRQOL was measured by the SF-36. Multivariate regressions were used to test the dependence of service utilisation rates on sociodemographic factors, chronic morbidity and the SF-36 scores. Structured multiphase regression analyses were used to determine the magnitude of the effect of the SF-36 scores, in addition to those of sociodemographic and chronic morbidity factors, on service utilisation. Five of eight SF-36 scores were independent determinants of consultation rates. They doubled and tripled the percentages of variance explained for annual and monthly consultation rates, respectively. Role limitation by physical problems and bodily pain scores had a significant effect on hospitalisation rates. This was the first study showing a linear relationship between HRQOL and service utilisation on a Chinese population. It confirmed the clinical relevance of the SF-36 to a culture and health care system that is different from that of the United States where the instrument originated.