Exploring the association between stroke and acute myocardial infarction and statins adherence following a medicines co-payment increase

ObjectivesPatient contributions (co-payments) for one months' supply of a publicly-subsidised medicine in Australia were increased by 21% in January 2005 (US$2.73-$3.31 for social security recipients and $17.05-$20.58 for others). This study investigates the relationship between patients’ use of statin medication and hospitalisation for acute coronary syndrome and stroke, following this large increase in co-payments.MethodsWe designed a retrospective cohort study of all patients in Western Australia who were dispensed statin medication between 2004 and 05. Data for the cohort was obtained from State and Federal linked databases. We divided the cohort into those who discontinued, reduced or continued statin therapy in the first six months after the co-payment increase. The primary outcome was two-year hospitalisation for acute coronary syndrome or stroke-related event. Analysis was conducted using Fine and Gray competing risk methods, with death as the competing risk.ResultsThere were 207,066 patients using statins prior to the co-payment increase. Following the increase, 12.5% of patients reduced their use of statin medication, 3.3% of patients discontinued therapy, and 84.2% continued therapy. There were 4343 acute coronary syndrome and stroke-related hospitalisations in the two-year follow-up period. Multivariate analysis demonstrated that discontinuing statins increased the risk of hospitalisation for acute coronary syndrome or stroke-related events by 18% (95%CI = 0.1%–40%) compared to continuing therapy. Subgroup analysis showed that men aged <70 years were at increased risk of 54–63% after discontinuing statins compared to those continuing, but that women and older men were not.ConclusionDiscontinuing statin medication after a large increase patient cost contribution was associated with higher rates of acute coronary syndrome and stroke-related hospitalisation in men under 70 years. The findings highlight the importance of continued adherence to prescribed statin medication, and that discontinuing therapy for non-clinical reasons (such as cost) can possibly have negative consequences particularly for younger men.     

Statins do not Increase the Rate of Bleeding Among Warfarin Users

Clinical significance of potential interaction between warfarin and statins is unclear. Our objective was to determine whether use of statins as a class or use of simvastatin modulates the rate of bleeding requiring hospitalization among new warfarin users. Using Finnish healthcare databases, we identified a cohort of 101,588 warfarin initiators between 1 January 2009 and 30 June 2012. By the end of 2012, these patients accumulated 92,695 person‐years of exposure to warfarin‐only and 60,253 years of exposure to warfarin‐with‐statin. The outcome was a composite of gastrointestinal, intracranial or other bleeding leading to hospitalization. A Poisson generalized estimating equation model was employed to estimate rate ratios (RR) and their 95% confidence intervals (CI) for exposure to warfarin‐with‐statin compared to warfarin‐only and to allow multiple episodes per patient and time‐dependent covariates. In multivariable models, we found no difference in the bleeding rate in association with exposure to any statin (multivariable‐adjusted RR = 0.98, 95% CI 0.89–1.07) or to simvastatin (RR = 1.01, 95% CI 0.91–1.11) with warfarin compared to exposure to warfarin‐only. We conclude that concomitant use of statins and warfarin was not associated with an increased rate of bleeding requiring hospitalization.     

Risk of insulin resistance with statin therapy in individuals without dyslipidemia: A propensity-matched analysis in a registry population

Several studies suggest the higher vulnerability of individuals with lower low-density lipoprotein cholesterol (LDL-C) levels to diabetes mellitus. However, the discordance between high and low baseline LDL-C levels shown by statin-induced insulin resistance is not fully understood. This study aimed to explore the relationship between baseline LDL-C levels and the risk of statin-induced insulin resistance during statin therapy. In total, 2660 (451 with dyslipidemia and 2209 without dyslipidemia) consecutive patients were enrolled. Their baseline clinical data were adjusted using a propensity score matching analysis, using the logistic regression model. Insulin resistance index was based on the homeostatic model assessment-insulin resistance (HOMA-IR) and was monitored for a median of 2 years. Among the individuals who received statin therapy, those with and without dyslipidemia showed significantly decreased LDL-C levels (all P < .0001) and significantly increased fasting plasma insulin levels (Δ = +24.1%, P = .0230; Δ = +30.1%, P < .0001); however, their glycated haemoglobin A1c and fasting blood glucose levels did not change (all P > .05). Although HOMA-IR was positively associated with statin therapy in individuals with and without dyslipidemia, statistically significant difference during follow-ups was observed only in individuals without dyslipidemia (Δ = +15.6%, P = .1609; Δ = 24.0%; P = .0001). Insulin resistance was higher in statin users without baseline dyslipidemia than in those with dyslipidemia. Thus, statin therapy could increase the risk of statin-induced insulin resistance in individuals with normal baseline cholesterol levels.     

Safety and efficacy of fibrate–statin combination therapy compared to fibrate monotherapy in patients with dyslipidemia: A meta-analysis

BackgroundDyslipidemia is a major risk factor for the development of cardiovascular disease. Treatment with fibrate, statins, or other lipid-lowering drugs prevents primary or recurrent cardiovascular events. However, all lipid-lowering drugs have side effects, which may become more severe if combination therapy is prescribed.MethodsWe performed a meta-analysis of published data to compare the safety and efficacy of fibrates alone, compared to fibrate–statin combinations, in patients with dyslipidemia. Six articles were assessed in terms of the efficacy of therapy and nine from the viewpoint of therapeutic safety.ResultsIn terms of efficacy, fibrate–statin combinations afforded significantly greater reductions in the levels of total cholesterol (SE = −2.248; 95% CI 1.986–2.510), LDL cholesterol (SE = −2.274; 95% CI 2.015–2.533), and triglycerides (SE = −0.465; 95% CI 0.272–0.658) compared to fibrate alone. In terms of safety, treatment with fibrate alone was associated with a significant decrease in the number of kidney-related adverse events (RR = −0.547; 95% CI 0.368–0.812), compared to treatment with fibrate–statin combinations.ConclusionWe suggest that treatment with a fibrate–statin combination affords clinical benefits that are superior to treatment with fibrate alone, but increases the risk of side effects (particularly renal). Therapy should thus be carefully monitored.     

Physicians' perceptions and beliefs on the current dyslipidemia management practices within Saudi Arabia

BackgroundLimited reports addressing physicians’ understanding of the various low-density lipoprotein cholesterol (LDL-C) targets/statin intensity required for treating the various dyslipidemia patient populations in Saudi Arabia are available. Therefore, the current study assessed the perceptions and beliefs of practicing clinicians in Saudi Arabia regarding the current practice for management of dyslipidemia and potential perceived barriers to adherence to lipid guidelines encountered in their regular clinical practice. Knowledge of different clinical practices and beliefs could have a positive impact on improving the quality of future care provided by physicians.MethodsA survey questionnaire was designed to assess physicians’ familiarity, usage, and adherence to seven different international guidelines and used to evaluate the management of dyslipidemia, practice of patient treatment, and perceived obstacles to adhering to lipid guidelines related to specific patients, doctors, and practice issues.ResultsA total of 467 physicians were recruited for the study: (1) 57.2% were primary care physicians (PCPs) and (2) 42.8% were specialists. About 90.8% of them followed lipid guidelines of which the most common set were based on those by the American College of Cardiology/American Heart Association. The most utilized risk assessment tool was the atherosclerotic cardiovascular disease (ASCVD) risk calculator. About 60% of the physicians set an LDL-C target for their patients based on a combination of patients’ risk factors and lipid profiles. In all, 42.1% of the physicians chose not to change existing therapy among patients with dyslipidemia to attain a non-high-density lipoprotein goal with controlled LDL-C level. Atorvastatin accounted for the greatest percentage of primary and secondary prevention choices (71.9% and 69.6%, respectively). Rosuvastatin was mostly preferred by physicians for patients with familial hypercholesterolemia. About two-thirds of the physicians (77.9%) prescribed statins to diabetic patients aged 40–75 years. Statin intolerance was encountered by 62.9% of the physicians in ≤ 10% of patients by 62.9%. Therapeutic strategies included switching to an alternative statin (40.1%) followed by reducing the statin dose (35.3%). Ezetimibe was prescribed by most physicians (77.9%) as an add-on to statin if the LDL-C target was not achieved. Fibrate was most preferred by physicians (62.7%) for hypertriglyceremia treatment followed by statins (28.7% of the physicians). Sixty-six percent reported not using proprotein convertase subtilisin/kexin type 9 serine protease inhibitors in their clinical practice due to unavailability at their institute (51.8%), high costs (26.3%), and/or lack of knowledge (20.6%). Perceived barriers to guideline adherence identified by physicians were lack of familiarity and knowledge of the guidelines, patient non-adherence, medication costs, and lack of timely follow-up appointments and educational tools. Multiple similarities and differences were observed after comparisons were made between specialists and PCPs in terms of guideline preference, clinical practice, and perceived barriers.ConclusionDifferent perceptions and attitudes among physicians in Saudi Arabia were found due to variable recommendations by international lipid guidelines. Perceived barriers that included the patient, physician, and practice were identified by physicians at multiple levels. Multiple challenges and different action gaps were observed when comparing specialists to PCPs. It is recommended that standardized practices be followed by clinicians in Saudi Arabia, and actions to address the outlined barriers are essential for optimizing health outcomes and ASCVD prevention.     

Five-year follow-up of drug utilization for secondary prevention in coronary artery disease

Objective Despite the availability of various prevention guidelines on coronary artery disease, secondary prevention practice utilizing aspirin, beta-blockers, angiotensin converting enzyme inhibitors and statins still can be sub-optimal. In this study, we aimed to assess the guideline adherence of secondary prevention prescribing and the continuity of adherence for a 5-year period in a small cohort of patients angiographically diagnosed to have coronary artery disease. Method In this prospective study, 73 patients who were angiographically diagnosed to have CAD were followed up for 5 years. The baseline demographic and clinical data were collected just before angiography. The baseline drug data were collected at the day of discharge. The fifth year data were taken from the patients via face-to-face consultations or phone interviews. Results The ‘initial prescribing rate’ at discharge was found to be 82% for aspirin, 49% for statins, 44% for ACE inhibitors and 55% for beta-blockers. ‘Continuity of prescribing’ for 5 years was 45% for aspirin, 26% for statins, 17% for ACE inhibitors and 20% for beta-blockers. Conclusions Besides the sub-optimal prescribing of secondary prevention drugs, absence of continuity of prescribing seems to be a challenging issue in pharmaceutical care of coronary artery disease patients.     

GPs’ views on patient drug use and the pharmacist’s role in DRP management

Objective The aim of this study was to examine general practitioners’ (GPs’) views on (1) patients’ drug-related problems (DRPs) and noncompliance and (2) the role of pharmacy practitioners in DRP management. Method A brief questionnaire was designed and distributed to 224 GPs in Sweden. Results Totally 152 GPs responded (68%). Most felt that pharmacy practitioners could improve patients’ drug use by identifying DRPs. A majority of the GPs also found presentations and analyses of their local pharmacies’ DRP documentation valuable. According to the GPs’ experiences, adverse drug effects and therapy failure were the most salient problems in patients’ drug use. Half of the doctors believed that 50–75% of their patients were compliant with their prescribed drug treatments. A majority of the GPs found a 75–95% degree of compliance acceptable. Conclusion The surveyed GPs demonstrated very positive attitudes towards the role of pharmacy practitioners in improving patients’ drug use and managing DRPs. The GPs realised that many patients were not compliant with their prescribed drug treatments and accepted an imperfect compliance.     

Lipid-lowering drug use in Italian primary care: effects of reimbursement criteria revision

Objective To assess whether the prescribing pattern of lipid-lowering drugs (LLD) changed after reimbursement criteria revision in a general practice in southern Italy. Methods From the Caserta-1 Local Health Service database, 93 general practitioners (GPs) who had consistently sent data about their patients during the years 2003-2005 were recruited. Prevalence of use and incidence of new treatments were calculated for each year, stratified by three drug cohorts: statins, omega-3 fatty acids, and fibrates. Subanalyses by gender, age, and indication of use were performed. Results Overall, 1-year prevalence of LLD use increased from 2003 to 2004. After reimbursement criteria revision (November 2004), a slight decrease was observed for statins, from 41.1 (95% CI: 39.9–42.2) per 1,000 inhabitants in 2004 to 40.3 (39.2–41.5) in 2005, while omega-3 utilization fell markedly: 14.6 (13.9–15.3) vs. 5.4 (5.0–5.8). The use of both statins and omega-3 fatty acids was reduced particularly for primary prevention. On the other hand, utilization of statins increased in diabetic patients and as secondary prevention from 2004 to 2005. Concerning individual molecules, 1-year prevalence of use of any statin declined from 2004 to 2005, except for rosuvastatin. Conclusions Revision of reimbursement criteria led to significant changes in the trend in LLD use in general practice in southern Italy: (1) statin utilization was slightly reduced in 2005, although it increased in certain categories, such as diabetic patients, and (2) omega-3 fatty acid use was strongly reduced even though a higher use in post-infarction cases was reported.