Cox proportional hazards regression models are frequently used to determine the association between exposure and time-to-event outcomes in both randomized controlled trials and in observational cohort studies. The resultant hazard ratio is a relative measure of effect that provides limited clinical information.
A method is described for deriving absolute reductions in the risk of an event occurring within a given duration of follow-up time from a Cox regression model. The associated number needed to treat can be derived from this quantity. The method involves determining the probability of the outcome occurring within the specified duration of follow-up if each subject in the cohort was treated and if each subject was untreated, based on the covariates in the regression model. These probabilities are then averaged across the study population to determine the average probability of the occurrence of an event within a specific duration of follow-up in the population if all subjects were treated and if all subjects were untreated.
Risk differences and numbers needed to treat.
Absolute measures of treatment effect can be derived in prospective studies when Cox regression is used to adjust for possible imbalance in prognostically important baseline covariates.
British Columbia's central prescription database, PharmaNet, is often used for both clinical and research applications. However, PharmaNet details prescription transactions, not actual medication consumption, resulting in many potential sources of inaccuracy when the information is assumed to reflect population or individual drug utilization.
To assess the accuracy of PharmaNet for adherence assessment in patients with heart failure who are taking beta-blockers.
A 6-month prospective, longitudinal assessment of adherence to the prescribed beta-blocker regimen was carried out using both PharmaNet data and the Medication Event Monitoring System (MEMS) for each patient enrolled. The limit of agreement between the 2 adherence assessment methods was assessed using the Bland-Altman approach.
Fifteen of 58 patients initially enrolled in the study were excluded, most due to misuse of MEMS or failure to return the MEMS vial despite thorough follow-up. For the 43 patients included in the final analysis, mean +/- SD adherence was 97.8 +/- 11.8% when assessed by PharmaNet and 97.1 +/- 7.3% when MEMS was used. However, the limit of agreement, reported as the mean of the differences +/- 2SD, was 6.8 +/- 18.5%, indicating a moderate-to-high level of agreement between the 2 methods when the confidence interval is taken into consideration.
These results suggest that PharmaNet data accurately reflect medication adherence for most patients. The MEMS system proved unreliable in several cases, illustrating the difficulty of identifying a gold standard for adherence assessment.
Division of Cardiology, Department of Medicine and Cardiovascular Research Group, Faculty of Medicine, 2C2 Walter MacKenzie Health Sciences Centre, University of Alberta, Edmonton, AB T6G 2R7, Canada. email@example.com
The elderly population (age > or =65) is increasing and with it morbidity, hospitalizations, costs and mortality due to heart failure (HF). HF is a progressive disorder that is superimposed on an on-going aging process. The two broad categories of HF, HF with left ventricular (LV) systolic dysfunction or low ejection fraction (HF/low-EF) and HF with preserved ejection fraction (HF/PEF) are equally prevalent in the elderly. Trials of therapy for HF/low-EF in primarily non-elderly patients showed mortality benefit in elderly patients. In contrast, trials for HF/PEF have not shown mortality benefit in elderly or non-elderly patients. HF pharmacotherapy in the elderly is challenging and needs to be individualized and consider several aging-related changes. More research into the biology of aging and more clinical trials in elderly patients are needed to improve morbidity and mortality in elderly HF patients.
Several randomized controlled trials demonstrate that angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure (CHF). However, whether ACE inhibitors benefit both sexes is not adequately addressed.
Our objective was to determine the effectiveness of ACE inhibitors in women with CHF.
The Quebec hospital discharge database was linked with the physician and drug claims database to identify a cohort with a discharge diagnosis of CHF between January 1998 and March 2003. In this retrospective cohort study, subjects who filled a prescription for ACE inhibitors (19,220 exposed) were compared to those who never filled such prescription (8617 non-exposed). The primary outcome was survival by exposure to ACE inhibitors.
There were 14,693 women (67% exposed) and 13,144 men (72% exposed). The 1 year mortality was 19.5% and 30% in those exposed and non-exposed, respectively. A significant survival benefit was demonstrated in both sexes exposed to ACE inhibitors [adjusted hazard ratio (95% confidence interval): women 0.80 (0.76-0.85); men 0.71 (0.67-0.75)].
ACE inhibitors improve survival in both sexes with CHF, but the protective effect appears to be greater in men. Our results support the current recommendations for the management of women with CHF.
To examine the class effect of angiotensin II receptor blockers (ARBs) on mortality in patients with heart failure who were aged 65 years or older.
Retrospective population-based study.
Administrative database that stores information on hospital discharge summaries for the Canadian provinces of Quebec, Ontario, and British Columbia.
A total of 6876 patients aged 65 years or older who were discharged with a primary diagnosis of heart failure between January 1, 1998, and March 31, 2003, and who filled at least one prescription for an ARB within 90 days of discharge.
Times to all-cause death in patients receiving individual ARBs were compared. Models were adjusted for demographic, clinical, physician, and hospital characteristics; models were also adjusted for dosage categories, which were represented by time-dependent variables. The cohort of 6876 patients had a mean +/- SD age of 78 +/- 7 years, and most (62%) were women. Losartan was the most frequently prescribed ARB (61%), followed by irbesartan (14%), valsartan (13%), candesartan (10%), and telmisartan (2%). Irbesartan, valsartan, and candesartan were associated with better survival rates than losartan (adjusted hazard ratios [HRs] and 95% confidence intervals [CIs] 0.65 [0.53-0.79], 0.63 [0.51-0.79], and 0.71 [0.57-0.90], respectively). No difference was noted in mortality in patients prescribed telmisartan compared with those receiving losartan (HR 0.92 [95% CI 0.55-1.54]).
Elderly patients with heart failure who were prescribed losartan had worse survival rates compared with those prescribed other commonly used ARBs. The absence of a class effect for ARBs is consistent with data showing pharmacologic differences among the drugs.
This study describes the long-term outcome of 163 patients with stable mild to moderate heart failure (NYHA II-III), who already were enrolled in a heart failure clinic and now were randomized to continued follow-up in the heart failure (HF) clinic or else to usual care (UC). The primary outcome was unplanned hospitalisations and death, the secondary endpoints were pharmacological therapy, NYHA class, six-minute-walking distances and NT-pro BNP level.
At the end of follow-up we found no significant differences in total number of hospitalisation (p = 0.2) or mortality (16% vs. 16%) between the two groups. Patients in the HF clinic cohort achieved a significantly better NYHA score (p
Bridging the primary and secondary sector, health-care centres aim to reduce morbidity and prevent further hospitalization in patients with chronic heart diseases. The aim of this study was to describe the quality of drug treatment in patients with chronic heart diseases in two Copenhagen health-care centres.
Over a period of three months, 28 patients with heart failure (HF) or ischaemic heart disease (IHD) were included. The participants were interviewed and clinically examined.
The patients received an average of nine drugs, and only about one third were clinically well-treated. Among IHD patients, 74% received beta blockers and 64% angiotensin converting enzyme-inhibitors (ACE-I) as indicated. All received statins and 92% acetylsalicylic acid. Among HF patients, 67% received ACE-I, 87% beta blockers and 77% diuretics as indicated. Overall, 10%, 31% and 40% of the HF patients received smaller than recommended doses of ACE-I, beta blockers, and diuretics, respectively. In 68% of the patients, 35 potential drug interactions were identified, none of which were deemed potentially harmful.
This small descriptive study indicates that patients in health-care centres might be undertreated and receive drug therapy only partly in accordance with the guidelines. However, since we had no access to medical charts, any reasons for not treating patients with a certain drug or selecting a lower than recommended dose could not be evaluated. Nevertheless, patients may benefit from closer involvement of clinicians or GPs in the multidisciplinary teams of the health-care centres.
Heart failure (CHF) guidelines recommend mineralocorticoid receptor antagonists for all symptomatic patients treated with a combination of ACE inhibitors/angiotensin receptor blockers (ARBs) and beta-blockers. As opposed to both eplerenone trials, patients in RALES (spironolactone) received almost no beta-blockers. Since pharmacological properties differ between eplerenone and spironolactone, the prognostic benefit of spironolactone added to this baseline combination therapy needs clarification.
We included 4,832 CHF patients with chronic systolic dysfunction from the Norwegian Heart Failure Registry and the heart failure outpatients' clinic of the University of Heidelberg. Propensity scores for spironolactone receipt were calculated for each patient and used for matching to patients without spironolactone.
During a total follow-up of 17,869 patient-years, 881 patients (27.0 %) died in the non-spironolactone group and 445 (28.4 %) in the spironolactone group. Spironolactone was not associated with improved survival, neither in the complete sample (HR 0.82; 95 % CI 0.64-1.07; HR 1.03; 95 % CI 0.88-1.20; multivariate and propensity score adjusted respectively), nor in the propensity-matched cohort (HR 0.98; 95 % CI 0.82-1.18).
In CHF outpatients we were unable to observe an association between the use of spironolactone and improved survival when administered in addition to a combination of ACE/ARB and beta-blockers.
Heart failure with preserved ejection fraction (HFPEF) may be as common and may have similar mortality as heart failure with reduced ejection fraction (HFREF). ß-Blockers reduce mortality in HFREF but are inadequately studied in HFPEF.
To test the hypothesis that ß-blockers are associated with reduced all-cause mortality in HFPEF.
Propensity score-matched cohort study using the Swedish Heart Failure Registry. Propensity scores for ß-blocker use were derived from 52 baseline clinical and socioeconomic variables.
Nationwide registry of 67 hospitals with inpatient and outpatient units and 95 outpatient primary care clinics in Sweden with patients entered into the registry between July 1, 2005, and December 30, 2012, and followed up until December 31, 2012.
From a consecutive sample of 41,976 patients, 19,083 patients with HFPEF (mean [SD] age, 76  years; 46% women). Of these, 8244 were matched 2:1 based on age and propensity score for ß-blocker use, yielding 5496 treated and 2748 untreated patients with HFPEF. Also we conducted a positive-control consistency analysis involving 22,893 patients with HFREF, of whom 6081 were matched yielding 4054 treated and 2027 untreated patients.
ß-Blockers prescribed at discharge from the hospital or during an outpatient visit, analyzed 2 ways: without consideration of crossover and per-protocol analysis with censoring at crossover, if applicable.
The prespecified primary outcome was all-cause mortality and the secondary outcome was combined all-cause mortality or heart failure hospitalization.
Median follow-up in HFPEF was 755 days, overall; 709 days in the matched cohort; no patients were lost to follow-up. In the matched HFPEF cohort, 1-year survival was 80% vs 79% for treated vs untreated patients, and 5-year survival was 45% vs 42%, with 2279 (41%) vs 1244 (45%) total deaths and 177 vs 191 deaths per 1000 patient-years (hazard ratio [HR], 0.93; 95% CI, 0.86-0.996; P?=?.04). ß-Blockers were not associated with reduced combined mortality or heart failure hospitalizations: 3368 (61%) vs 1753 (64%) total for first events, with 371 vs 378 first events per 1000 patient-years (HR, 0.98; 95% CI, 0.92-1.04; P?=?.46). In the matched HFREF cohort, ß-blockers were associated with reduced mortality (HR, 0.89; 95% CI, 0.82-0.97, P=.005) and also with reduced combined mortality or heart failure hospitalization (HR, 0.89; 95% CI, 0.84-0.95; P?=?.001).
In patients with HFPEF, use of ß-blockers was associated with lower all-cause mortality but not with combined all-cause mortality or heart failure hospitalization. ß-Blockers in HFPEF should be examined in a large randomized clinical trial.
Comment In: JAMA. 2014 Nov 19;312(19):1977-825399271
Heart failure with preserved ejection fraction (HFPEF) may be as common and as lethal as heart failure with reduced ejection fraction (HFREF). Three randomized trials of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ie, renin-angiotensin system [RAS] antagonists) did not reach primary end points but may have had selection bias or been underpowered.
To test the hypothesis that use of RAS antagonists is associated with reduced all-cause mortality in an unselected population with HFPEF.
Prospective study using the Swedish Heart Failure Registry of 41,791 unique patients registered from 64 hospitals and 84 outpatient clinics between 2000 and 2011. Of these, 16,216 patients with HFPEF (ejection fraction =40%; mean [SD] age, 75  years; 46% women) were either treated (n = 12,543) or not treated (n = 3673) with RAS antagonists. Propensity scores for RAS antagonist use were derived from 43 variables. The association between use of RAS antagonists and all-cause mortality was assessed in a cohort matched 1:1 based on age and propensity score and in the overall cohort with adjustment for propensity score as a continuous covariate. To assess consistency, separate age and propensity score-matched analyses were performed according to RAS antagonist dose in patients with HFPEF and in 20,111 patients with HFREF (ejection fraction
Comment In: JAMA. 2013 Mar 20;309(11):1107-823512046
Comment In: JAMA. 2013 Mar 20;309(11):110723512045
Comment In: Evid Based Med. 2013 Dec;18(6):226-723585078
Comment In: JAMA. 2012 Nov 28;308(20):2144-623188032