Divergent oestrogen receptor-specific breast cancer trends in Ireland (2004-2013): Amassing data from independent Western populations provide etiologic clues.

The aetiology and clinical behaviour of breast cancers vary by oestrogen receptor (ER) expression, HER2 expression and over time. Data from the United States and Denmark show rising incidence rates for ER+ and falling incidence rates for ER- breast cancers. Given that Ireland is a somewhat similar Western population but with distinctive risk exposures (especially for lactation), we analysed breast cancer trends by ER status; and for the first time, by the joint expression of ER±/HER2±. We assessed invasive breast cancers (n = 24,845; 2004-2013) within the population-based National Cancer Registry of Ireland. The population at risk was obtained from the Irish Central Statistics Office (n = 10,401,986). After accounting for missing ER and HER2 data, we assessed receptor-specific secular trends in age-standardised incidence rates (ASRs) with the estimated annual percentage change (EAPC) and corresponding 95% confidence intervals (95% CI). Age-period-cohort models were also fitted to further characterise trends accounting for age, calendar-period and birth-cohort interactions. ASRs increased for ER+ (EAPC: 2.2% per year [95% CI: 0.97, 3.45%/year]) and decreased for ER- cancers (EAPC: -3.43% per year [95% CI: -5.05, -1.78%/year]), as well as for specific age groups at diagnosis (<30-49, 50-64 and ≥65 years). ER+/HER2- cancers rose, ER+/HER2+ cancers were statistically flat and ER-/HER± cancers declined. Secular trends for ER± cancers in Ireland were like those previously observed. Stratification by HER2± expression did not substantively alter ER± trends. The divergence of ER± incidence rates among independent Western populations likely reflects calendar-period and/or risk factor changes with differential effects for ER+ and ER- breast cancers.

Pre-diagnostic statin use, lymph node status and mortality in women with stages I-III breast cancer.

BACKGROUND: Recent meta-analyses suggest that pre-diagnostic statin use is associated with reduced breast cancer-specific mortality. Studies have shown that high breast tumour expression of the statin target (3-hydroxy-3-methylglutaryl coenzyme-A reductase) is associated with lymph-node negative cancer. Therefore, we examined the association between pre-diagnostic statin use and; lymph node status, breast cancer-specific and all-cause mortality. METHODS: Women with stages I-III breast cancer were identified from the National Cancer Registry of Ireland (N=6314). Pre-diagnostic statin users were identified from linked prescription claims data (N=2082). Relative risks were estimated for associations between pre-diagnostic statin use and lymph node status. Hazard ratios (HR) were estimated for associations between pre-diagnostic statin use and breast cancer-specific and all-cause mortality. RESULTS: Pre-diagnostic statin use was not associated with lymph node negative status at diagnosis. In multivariate analyses, pre-diagnostic statin use was associated with reduced all-cause (HR 0.78 95% confidence interval (CI) 0.69, 0.89) and breast cancer-specific mortality (HR 0.81 95% CI 0.68, 0.96). This reduction in cancer-specific mortality was greatest in statin-users with oestrogen (ER) receptor-positive tumours (HR 0.69 95% CI 0.55, 0.85). CONCLUSION: Patients with pre-diagnostic statin exposure had a significant reduction in breast cancer-specific mortality, which was even more pronounced in women with ER+ tumours.

Can demographic, clinical and treatment-related factors available at hormonal therapy initiation predict non-persistence in women with stage I-III breast cancer?

PURPOSE: To investigate whether demographic, clinical and treatment-related risk factors known at treatment initiation can be used to reliably predict future hormonal therapy non-persistence in women with breast cancer, and to inform intervention development. METHODS: Women with stage I-III breast cancer diagnosed 2000-2012 and prescribed hormonal therapy were identified from the National Cancer Registry Ireland (NCRI) and linked to pharmacy claims data from Ireland's Primary Care Reimbursement Services (PCRS). Non-persistence was defined as a treatment gap of ≥180 days within 5 years of initiation. Seventeen demographic, clinical and treatment-related risk factors, identified from a systematic review, were abstracted from the NCRI-PCRS dataset. Multivariate binomial models were used to estimate relative risks (RR) and risk differences (RD) for associations between risk factors and non-persistence. Calibration and discriminative performance of the models were assessed. The analysis was repeated for early non-persistence (<1 year of initiation). RESULTS: Within 5 years of treatment initiation 680 women (19.9%) were non-persistent. Women aged <50 years (adjusted RR 1.41, 95% CI 1.16-1.70) and those prescribed antidepressants (RR 1.22, 95% CI 1.04-1.45) had increased risk of non-persistence. Married women (RR 0.82 95% CI 0.71-0.94) and those with prior medication use (RR 0.62 95% CI 0.51-0.75) had reduced risk of non-persistence. The area under the receiver-operating characteristic (ROC) curve for non-persistence was 0.61. Findings were similar for early non-persistence. CONCLUSION: The risk prediction model did not discriminate well between women at higher and lower risk of non-persistence at treatment initiation. Future studies should consider other factors, such as psychological characteristics and experience of side-effects.

Patterns of statin initiation and continuation in patients with breast or colorectal cancer, towards end-of-life.

PURPOSE: Cross-sectional studies show that statins, used in cardiovascular disease prevention, are often discontinued approaching death. Studies investigating associations between statin exposure and cancer outcomes, not accounting for these exposure changes, are prone to reverse causation bias. The aim of this study was to describe longitudinally the changes in statin initiation and continuation prior to death in patients with breast or colorectal cancer, thus establishing an appropriate exposure lag time. METHODS: This study was carried out using linked cancer registry and prescribing data. We identified patients who died of their cancer (cases) and cancer survivors were used as controls. The probability of initiating or continuing statin use was estimated up to 5 years prior to death (or index date). Conditional binomial models were used to estimate relative risks and risk differences for associations between approaching cancer death and statin use. RESULTS: Compared to controls, the probability of continued statin use in breast cancer cases was significantly lower 3 months prior to death (RR 0.86 95% CI 0.79, 0.94). Similarly, in colorectal cancer cases, the probability of continued statin use was significantly lower 3 months prior to colorectal cancer death (RR 0.77 95% CI 0.68, 0.88). CONCLUSION: A significant proportion of patients will cease statin treatment in the months prior to a colorectal or breast cancer death.

De novo post-diagnosis statin use, breast cancer-specific and overall mortality in women with stage I-III breast cancer.

BACKGROUND: Prior evidence suggests a role for statins in the management of cancer. However, the benefit of statin use in the adjuvant setting remains uncertain. This study investigates associations between statin use initiated after a breast cancer diagnosis and mortality. METHODS: Women with stage I-III breast cancer were identified from the National Cancer Registry of Ireland (N=4243). Post-diagnostic statin initiators were identified from pharmacy claims data (N=837). Multivariate models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between de novo statin use and mortality. RESULTS: The median duration of statin use was 6.7 years. No association was found between post-diagnostic statin use and breast cancer-specific (HR 0.88, 95% CI 0.66, 1.17) or all-cause mortality (HR 1.00, 95% CI 0.82, 1.21). CONCLUSIONS: The results from our study suggest that initiating statin use after a diagnosis of stage I-III breast cancer is not associated with a reduction in breast cancer-specific mortality.

Prediagnostic aspirin use and mortality in women with stage I to III breast cancer: A cohort study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

BACKGROUND: There is a body of evidence indicating that aspirin may reduce the risk of cancer mortality. However, to the authors' knowledge, the optimal exposure timing and mechanism of action remain unclear. In the current study, the authors investigated associations between prediagnostic aspirin use and breast cancer-specific mortality in a US population. METHODS: Postmenopausal women diagnosed with stage I to III breast cancer (1993-2009) were identified (2925 women with a total of 18,073 person-years) from the National Cancer Institute's Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Prediagnostic aspirin use (1274 women) was identified from study questionnaires. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) for associations between aspirin use and breast cancer-specific mortality. Effect modification by lymph node status was evaluated. RESULTS: Prediagnostic aspirin use was not found to be associated with lower breast cancer-specific mortality (HR, 0.95; 95% CI, 0.68-1.31 [P = .74]). In analyses stratified by lymph node status, aspirin use was found to be associated with lower breast cancer-specific mortality among women with lymph node-negative tumors (HR, 0.54; 95% CI, 0.32-0.93 [P = 0.02]), but not those with lymph node-positive tumors (HR, 1.41; 95% CI, 0.92-2.16 [P = 0.11]). Tests for interaction were found to be statistically significant (P for interaction =.006). No association was noted between aspirin use and lymph node status. CONCLUSIONS: Prediagnostic aspirin use was not found to be associated with a reduction in breast cancer-specific mortality overall. However, effect modification by lymph node status was observed and mortality was found to be reduced by approximately one-half among aspirin users with lymph node-negative disease. This represents a clinically significant reduction in breast cancer mortality. These findings contribute to the understanding of aspirin's mechanism of action in breast cancer. However, further etiologic research to understand this association is warranted. Cancer 2016;122:2067-75. © 2016 American Cancer Society.

De Novo Post-Diagnosis Aspirin Use and Mortality in Women with Stage I-III Breast Cancer.

BACKGROUND: Aspirin use has been associated with significant reductions in breast cancer-related mortality in some observational studies. However, these studies included women who initiated aspirin use before breast cancer diagnosis. It is unclear whether initiating aspirin use after diagnosis is associated with similar reductions in mortality. This study investigates associations between de novo post-diagnostic aspirin use and all cause, breast cancer-specific mortality. METHODS: Women, ages 50 to 80, with a diagnosis of stage I-III breast cancer were identified from Ireland's National Cancer Registry (N = 4,540). Initiation of de novo post-diagnostic aspirin use was identified from linked national prescription refill data (N = 764). Adjusted HRs were estimated for associations between de novo aspirin use and all-cause, breast cancer-specific mortality. RESULTS: The median time from diagnosis to aspirin initiation was 1.8 years. The mean number of days' supply of aspirin received was 631, and 95% of users were taking less than 150 mg/d. We found no association between de novo aspirin use and breast cancer-specific mortality [HR, 0.98; 95% confidence interval (CI), 0.74-1.30]. Similar null associations were found in women taking aspirin at high-intensity (HR, 1.03; 95% CI, 0.72-1.47) and women initiating use in the 1.5 years after diagnosis (HR, 1.04; 95% CI, 0.77-1.40). There was no effect modification by estrogen (Pinteraction = 0.81) or progesterone (Pinteraction = 0.41) receptor status. CONCLUSION: Initiating aspirin use after a breast cancer diagnosis was not associated with a reduction in breast cancer-specific mortality. IMPACT: On the basis of our findings, we suggest that a clearer understanding of aspirin's mechanism of action is needed to help inform the design of future studies in breast cancer.

Recent prediagnostic aspirin use, lymph node involvement, and 5-year mortality in women with stage I-III breast cancer: a nationwide population-based cohort study.

Lymph node-positive breast tumors are more likely to express COX2 than node-negative tumors. In preclinical studies, COX2 inhibition prevents breast tumor spread to lymph nodes. Therefore, we examined the association between recent (1 year) prediagnostic use of aspirin (COX1/COX2 inhibitor), lymph node involvement at breast cancer diagnosis, and breast cancer-specific mortality. Women with stage I-III breast cancer diagnosed from 2001 to 2006 (N = 2,796) were identified from Ireland's National Cancer Registry. These data were linked to prescription refill and mammographic screening databases. Relative risks (RR) were estimated for associations between prediagnostic aspirin use and lymph node-positive status at diagnosis. HRs were estimated for associations between pre- and postdiagnostic aspirin use and 5-year mortality, stratified by lymph node status. Women with prediagnostic aspirin use were statistically significantly less likely to present with a lymph node-positive tumor than nonusers [RR = 0.89; 95% confidence interval (CI), 0.81-0.97], particularly those with larger (Pinteraction = 0.036), progesterone receptor (PR)-negative (Pinteraction < 0.001) or estrogen receptor (ER)-negative (Pinteraction = 0.056) tumors. The magnitude of this association increased with dose (Ptrend < 0.01) and dosing intensity (Ptrend < 0.001) and was similar in women with or without screen-detected tumors (Pinteraction = 0.70). Prediagnostic aspirin use was associated with lower 5-year breast cancer-specific mortality among women with lymph node-negative tumors (HR, 0.55; 95% CI, 0.33-0.92) but not node-positive tumors (HR, 0.91; 95% CI, 0.37-1.22). Tests for effect-modification were, however, not statistically significant (Pinteraction = 0.087). Postdiagnostic aspirin use was not associated with breast cancer-specific mortality (HR, 0.99; 95% CI, 0.68-1.45). Our findings indicate that recent prediagnostic aspirin use is protective against lymph node-positive breast cancer. This is a plausible explanation for reductions in breast cancer mortality reported in observational studies of aspirin use.

Prostate specific antigen testing is associated with men's psychological and physical health and their healthcare utilisation in a nationally representative sample: a cross-sectional study.

BACKGROUND: Prostate cancer incidence has risen considerably in recent years, primarily due to Prostate Specific Antigen (PSA) testing in primary care. The objective of this study was to investigate associations between PSA testing and the psychological and physical health, and healthcare utilisation of men in a population where PSA testing is widespread. METHODS: A cross-sectional study was carried out in a population-representative sample of men ≥ 50 years enrolled in The Irish Longitudinal Study on Ageing (TILDA). TILDA participants underwent structured interviews, health assessments and completed standardised questionnaires. Men were classified as ever/never having received a PSA test. Multivariate logistic regression (Odds Ratios (OR) and 95% Confidence Intervals (CI) was used to determine associations between PSA testing, and men's psychological and physical health and healthcare utilisation. RESULTS: This analysis included 3,628 men, 68.2% of whom ever had a PSA test. In adjusted analysis, men with sub-threshold depression were significantly less likely to have had a PSA test, (OR=0.79, 95% CI 0.64-0.97). Likelihood of having a PSA test was inversely associated with anxiety, but this was not significant (OR=0.79, 95% CI 0.57-1.09). Frailty (OR=0.61, 95% CI 0.31-1.05) and eligibility for free primary care (OR=0.63, 95% CI 0.52-0.77) were also inversely associated with PSA testing. Positive associations were observed between PSA testing and more chronic illnesses (OR=1.11, 95% CI 1.05-1.19), more primary care visits (OR=1.03, 95% CI 1.01-1.05) and preventative health practices, including cholesterol testing and influenza vaccination (OR=1.35, 95% CI 1.13-1.60). CONCLUSIONS: Men's psychological and physical health and their healthcare utilisation are associated with PSA testing in primary care. The association between poorer psychological health, in particular sub-threshold depression, and reduced likelihood of PSA testing in primary care requires further investigation. These findings may have wider implications for other cancer screening.

Metformin exposure and disseminated disease in patients with colorectal cancer.

BACKGROUND: Preclinical evidence suggests a role for metformin in inhibiting tumour dissemination and metastasis. Previous studies have identified associations between metformin exposure and improved colorectal cancer survival. This study aimed to examine associations between metformin exposure and the odds of presenting with disseminated disease among colorectal cancer patients. METHODS: Colorectal cancer patients diagnosed 2001-2006 were identified from the National Cancer Registry Ireland. A linked national pharmacy claims database was used to determine exposure to anti-diabetic medications prior to diagnosis. Multivariate logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for associations between metformin use (versus non-metformin anti-diabetic drugs) and odds of presenting with disseminated disease (lymph node positive/metastatic). Analyses were stratified by anti-diabetic drug co-prescription and intensity of metformin exposure. RESULTS: The study population included 241 metformin-exposed diabetics, 129 non-metformin-exposed diabetics, and 4277 non-diabetic patients. In multivariate analysis, odds of disseminated disease were lower in metformin-exposed diabetics, compared with non-metformin-exposed diabetics, though not statistically significant (OR=0.66, 95% CI 0.39-1.12). In analyses stratified by metformin dosing intensity and anti-diabetic drug co-prescription, the odds were further from unity and approached significance in diabetics with high intensity, exclusive metformin use (OR=0.52, 95% CI 0.25-1.10). CONCLUSIONS: While overall there was no statistically significant association between metformin exposure and disseminated colorectal cancer at diagnosis, there was a suggestion that high intensity, exclusive metformin use may be associated with reduced odds of disseminated disease. The number of patients in these subgroup analyses was small, and further investigation in larger studies is warranted.

A cohort study of digoxin exposure and mortality in men with prostate cancer.

OBJECTIVE: To examine the association between digoxin exposure and mortality in men with prostate cancer using linked Irish National Cancer Registry and pharmacy claims data. PATIENTS AND METHODS: Prostate cancer cases were identified from the database and digoxin exposure at prostate cancer diagnosis was identified from prescription claims. Digoxin users were matched to non-users using a propensity score to identify men with similar cardiovascular comorbidity. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between digoxin exposure and all-cause and prostate cancer-specific mortality (PCSM). Analyses were repeated in the propensity score-matched cohort. Effect modification of treatment with radiation or androgen-deprivation therapy by digoxin exposure was also assessed. RESULTS: In all, 5732 men with a prostate cancer diagnosis (2001-2006) were identified (digoxin exposed, 391). The median follow-up was 4.3 years. Digoxin exposure was associated with a small non-significant increase in PCSM in the full cohort (HR 1.13, 95% CI 0.91, 1.42) and the propensity. score-matched cohort (HR 1.17, 95% CI 0.88, 1.57). Adjusted HRs for all-cause mortality were increased for digoxin exposed men (HR 1.24, 95% CI 1.07, 1.43). Interactions with treatments received were not significant. CONCLUSIONS: These results suggest digoxin exposure is not associated with reduced PCSM. Further investigation of other cardiac glycosides that have shown anti-cancer potential may be warranted.

A cohort study of metformin exposure and survival in patients with stage I-III colorectal cancer.

BACKGROUND: Preclinical evidence suggests a beneficial effect of metformin in colorectal cancer. This study aimed to investigate associations between metformin exposure and colorectal cancer-specific survival using population-level data. METHODS: Adult patients with stage I-III colorectal cancer diagnosed from 2001 to 2006 were identified from the National Cancer Registry Ireland. Use of metformin and other antidiabetic medications was determined from a linked national prescription claims database. Multivariate Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for associations between prediagnostic metformin exposure (versus nonmetformin antidiabetic drugs) and colorectal cancer-specific mortality. Models were stratified by antidiabetic drug coprescription and intensity of metformin exposure. RESULTS: The cohort included 207 diabetics who received metformin, 108 diabetics not exposed to metformin, and 3,501 nondiabetic patients. In multivariate analyses, a nonsignificant reduction in colorectal cancer-specific mortality was observed for metformin-exposed patients relative to other treated diabetics (HR, 0.61; 95% CI, 0.37-1.01). In stratified analyses, no significant association was observed for patients receiving low-intensity metformin or metformin in combination with other antidiabetic drugs. High-intensity exclusive metformin use was associated with a significant reduction in colorectal cancer-specific mortality (HR, 0.44; 95% CI, 0.20-0.95). CONCLUSIONS: Significant associations between metformin exposure and colorectal cancer-specific mortality were observed only for high-intensity exclusive metformin use in the diabetic cohort. IMPACT: This study provides moderate evidence of an association between metformin exposure and improved colorectal cancer survival in a diabetic population. Additional studies in larger cohorts, with detailed information on diabetes severity, are required to confirm these results.

Beta-adrenergic blocking drugs in breast cancer: a perspective review.

The purpose of this review is to present the preclinical, epidemiological and clinical data relevant to the association between ß-blockers and breast cancer progression. Preclinical studies have shown that ß-adrenergic receptor (ß-AR) signalling can inhibit multiple cellular processes involved in breast cancer progression and metastasis, including extracellular matrix invasion, expression of inflammatory and chemotactic cytokines, angiogenesis and tumour immune responses. This has led to the hypothesis that the commonly prescribed class of ß-AR antagonist drugs (ß-blockers) may favourably impact cancer progression. A number of recent pharmacoepidemiological studies have examined the association between ß-blocker exposure and breast cancer progression. The results from these studies have suggested a potential role for targeting the ß-AR pathway in breast cancer patients. Larger observational studies are, however, required to confirm these results. Questions regarding the type of ß-blocker, predictive biomarkers or tumour characteristics, appropriate treatment paradigms and, most importantly, efficacy must also be answered in randomized clinical studies before ß-blockers can be considered a therapeutic option for patients with breast cancer.

Beta blockers and breast cancer mortality: a population- based study.

PURPOSE: Preclinical studies have demonstrated that antagonism of ß2-adrenergic signaling inhibits several pathways necessary for breast tumor progression and metastasis. A series of population-based observational studies were conducted to examine associations between beta blocker use and breast tumor characteristics at diagnosis or breast cancer-specific mortality. PATIENTS AND METHODS: Linked national cancer registry and prescription dispensing data were used to identify women with a diagnosis of stage I to IV invasive breast cancer between January 1, 2001, and December 31, 2006. Women taking propranolol (ß1/ß2 antagonist; n = 70) or atenolol (ß1 antagonist; n = 525), in the year before breast cancer diagnosis were matched (1:2) to women not taking a beta blocker (n = 4,738). Associations between use of propranolol or atenolol and risk of local tumor invasion at diagnosis (T4 tumor), nodal or metastatic involvement at diagnosis (N2/N3/M1 tumor), and time to breast cancer-specific mortality were assessed. RESULTS: Propranolol users were significantly less likely to present with a T4 (odds ratio [OR], 0.24, 95% CI, 0.07 to 0.85) or N2/N3/M1 (OR, 0.20; 95% CI, 0.04 to 0.88) tumor compared with matched nonusers. The cumulative probability of breast cancer-specific mortality was significantly lower for propranolol users compared with matched nonusers (hazard ratio, 0.19; 95% CI, 0.06 to 0.60). There was no difference in T4 or N2/N3/M1 tumor incidence or breast cancer-specific mortality between atenolol users and matched nonusers. CONCLUSION: The results provide evidence in humans to support preclinical observations suggesting that inhibiting the ß2-adrenergic signaling pathway can reduce breast cancer progression and mortality.

Early discontinuation of tamoxifen: a lesson for oncologists.

BACKGROUND: Five years of treatment provides the optimum duration of tamoxifen therapy for the prevention of breast cancer recurrence and mortality. Durations of adjuvant tamoxifen therapy less than 5 years are associated with poorer outcomes for breast cancer patients. The purpose of the study was to assess rates of tamoxifen nonpersistence (early discontinuation) in women aged 35 years or older using prescription refill data from a national prescribing database. METHODS: A cohort of 2816 women commencing tamoxifen as initial hormonal therapy was identified between January 2001 and January 2004. The cumulative tamoxifen persistence rate was calculated for these women and the relation between nonpersistence and clinical and demographic variables assessed. RESULTS: Within 1 year of commencing treatment the cumulative tamoxifen nonpersistence rate was 22.1%. This is twice the rate of treatment discontinuation observed in other studies by this time. By the end of follow-up at 3.5 years, the cumulative nonpersistence rate had increased to 35.2%. Determinants of nonpersistence identified included age and a history of antidepressant use. CONCLUSIONS: The rate of nonpersistence with tamoxifen therapy is higher than previously reported. This study demonstrates that persistence with tamoxifen cannot be assumed and raises concerns about persistence with other oral hormonal therapies for breast cancer and oral antineoplastics in general. Oncologists need to identify those at risk of nonpersistence and develop strategies to combat this barrier to treatment success.

Impact of high dose statin trials on hospital prescribers.

BACKGROUND: The PROVE-IT and REVERSAL studies established that an intensive 80 mg/day dose of atorvastatin was superior to pravastatin 40 mg/day for the secondary prevention of coronary heart disease (CHD) following acute coronary syndromes and in limiting the progression of coronary atherosclerosis. We have evaluated the impact of the results from these studies on statin prescribing by hospital doctors in the 2 years following their publication. METHODS AND RESULTS: Using a nationwide database, 18,894 patients receiving a total of 23,750 hospital discharge prescriptions for atorvastatin were identified between September 2002 and December 2005. From this cohort, patients newly commenced on, switched to, or dose titrated on atorvastatin by a hospital prescriber were identified. The mean daily atorvastatin dose on discharge was calculated for each month and the results were analysed using a segmented regression analysis. There was a significant and sustained increase in the mean atorvastatin dose used by hospital prescribers. This resulted in an increase of 12 mg, (95% CI 10.6, 13.4) in the mean dose prescribed by December 2005. This was attributable largely to a 16.4% (95% CI 13.5, 19.3), 17.2% (95% CI 14.0, 20.5) and 8.8% (95% CI 7.4, 10.2) increase in the prescribing of the 20 mg, 40 mg and 80 mg/day dosages, respectively. CONCLUSION: The PROVE-IT and REVERSAL studies have had a significant impact on hospital prescribers' choice of atorvastatin dose. It is likely that this has been the result of both the publication and effective promotion of results from these trials.