Use of lipid-lowering drugs from 1990 to 1994: an international comparison among Australia, Finland, Italy (Emilia Romagna Region), Norway and Sweden

Objective: To compare the overall utilisation patterns of lipid-lowering drugs between 1990 and 1994 in Australia, Finland, Italy, Norway and Sweden as well as the pattern of use with respect to age and gender in Italy and Sweden. Methods: Data were retrieved from regulatory authorities in each country for the 5-year period and analysed according to the ATC/DDD methodology (Anatomical Therapeutic Chemical classification/Defined Daily Doses). Utilisation was calculated as the DDDs for 1000 inhabitants per day for all drugs of the ATC category B04 (serum lipid-reducing agents). Data from Sweden and Italy were also compared with respect to gender and age. Results: In 1994, Australia demonstrated the highest degree of utilisation (11.9 DDD) and the Nordic Countries the lowest (Sweden 5.6; Norway 4.9; Finland 4.0). In all countries except Italy, a steady increase was observed; in Italy, utilisation of these drugs reached a maximum in 1992 (11.5 DDD), but then underwent a reduction which was caused by restrictions in the reimbursement status in 1993 (10.4) and 1994 (6.7). Administration of statins increased in all countries, becoming the most used group of the B04 class. In 1988, the number of different drugs listed by each national health service ranged from 4 (Norway) to 16 (Italy); in 1994 it ranged from 6 (Norway) to 9 (Sweden). Analysis with respect to gender showed the opposite pattern in Sweden (males 4.6 and females 3.3 in 1992; 6.2 and 4.5, respectively, in 1994) than in Italy (males 10.8 and females 17.8 in 1992; 6.4 and 9.2, respectively, in 1994). Exposure was highest in people aged 60–69 years in both countries, followed by age group 50–59 in Sweden and 70–79 in Italy. Conclusions: Large variations in the utilisation of lipid-lowering drugs exist between countries, with Australia and Italy much higher than others. Of the drugs in the ATC category B04, the use of statins predominates in all countries, but to varying degrees. The large difference in the degree of drug utilisation with respect to age and gender between Italy and Sweden suggests major deviations from evidence-based medicine. Received: 12 February 1997 / Accepted in revised form: 6 March 1997     

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.     

Trends in prescribing and utilization of statins and other lipid lowering drugs across Europe 1997-2003

AIMS: To describe trends in utilization and prescribing of statins and other lipid lowering drugs across Europe from data in routine administrative databases. METHODS: Observational study in EU member states and Norway. Comparison of annual utilization data for lipid lowering agents by class and drug from national administrative databases for reimbursement over the period 1997-2003, measured in DDDs per 1000 inhabitants/day. Prescribed daily doses (PDD) of statins obtained from a commercial database (IMS Health) for 2000 and 2003, and used to calculate numbers of "patient treatment days" (PTD) in each country in each year. Analysis of PTD to explain increased utilization of statins. RESULTS: Use of lipid lowering agents varied among countries (in 2003, highest in Ireland and Norway, and lowest in Italy), but increased in all countries studied (between 2000 and 2003 by 274% in Ireland and by 56% in France). This increase was entirely due to increases in statin use. Prescribed daily doses of statins increased in all countries for which data was available between 2000 and 2003, but still usually fell below the doses used in the major trials of statins. As a result, the numbers of PTDs increased to a lesser extent than suggested by utilization (e.g. by 192% in Ireland and by 35% in France). One-third of the total rise in utilization was explained by increased PDD, and two-thirds by an increase in numbers of PTDs. Statins dominated the markets in all countries, although fibrates remained strong in France and Belgium (approximately 25% of all lipid lowering agents) and to a lesser extent Germany (10%). CONCLUSIONS: Use of statins across Europe has increased hugely over the study period. Some of the increase in use is due to higher prescribed daily doses, but two-thirds is due to increases in numbers of patient days of treatment, either due to more patients treated or less likely to better compliance.     

急性ST段抬高型心肌梗死患者口服药物变化的分析

目的 探讨近15年循证医学的发展对阿司匹林、β受体阻滞剂、他汀类药物、血管紧张素转换酶抑制剂(ACEI)/血管紧张素Ⅱ受体拈抗剂(ARB)在急性ST段抬高型心肌梗死(STEMI)患者住院期间使用比率的影响.方法 从1994年1月到2009年12月宣武医院心脏科住院的STEMI患者中选取初发且发病时限在24 h内的患者879例,按时间分为4组:1994年1月～1995年12月(A组)、1999年1月～2000年12月(B组)、2004年1月～2005年12月(C组)、2009年1月～12月(D组),分别对其临床诊治资料做回顾性分析.结果 近15年STEMI患者住院期间的阿司匹林使用率一直维持在97%以上,是4种药物中使用率最高的.β受体阻滞剂、他汀类药物、ACEI/ARB的使用率有了明显的上升,分别从1994年的37.9%、7.2%、25.3%上升为2009年的90.2%、95.5%、93.2%.结论 近15年,在循证医学的规范和指导下,阿司匹林、β受体阻滞剂、他汀类药物、血管紧张素转换酶抑制剂(ACEI)/血管紧张素Ⅱ受体拮抗剂(ARB)在STEMI中使用地位日益巩固.

Abstract：

Objective To investigate the results of evidence-based medicine on use of aspirin, beta blockers, statin, angiotensin-converting enzyme inhibitors (ACEIs) /angiotensin receptor blockers (ARBs) in hospitalized patients with ST-segment elevation (STEMI) during 15 years. Methods Selected four groups of patients with acute myocardial infarction admitted to cardiology department of Xuanwu hospital between January 1994 and December 2009:1994. 1-1995.12 (group A), 1999. 1-2000. 12 (group B), 2004. 1 2005. 12-(group C), 2009. 12( group D). A total of 879 patients with STEMI whose emergency time within 24 hours were retrospectively analyzed. Results The utilization rate of aspirin in STEMI patients remained more than 97%, the highest utilization among four kinds of medicine. The in-hospital utilization rates of Beta blockers, statins, ACEI/ARB rose significantly: from 7.2%, 25.3%, 37.9% to 93.2%, 90.2%, 95.5% respectively during 15 years. Conclusion With the development of evidence-based medicine, the used status of aspirin, beta blockers, statins, ACEI/ARB in STEMI patients haveconsolidated in recently 15 years.     

Statins and the risk of pneumonia: a population-based, nested case-control study

STUDY OBJECTIVE: To determine if the use of statins affects pneumonia-related outpatient visits, hospitalizations with survival, and deaths. DESIGN: Population-based, retrospective, nested case-control analysis. DATA SOURCE: United Kingdom-based General Practice Research Database. PARTICIPANTS: The study population (134,262 patients aged > or = 30 yrs) consisted of 55,118 patients who took statins and/or fibrates, 29,144 patients with hyperlipidemia not taking lipid-lowering agents, and 50,000 randomly selected patients without hyperlipidemia and without lipid-lowering treatment. MEASUREMENTS AND MAIN RESULTS: We identified 1253 patients with pneumonia and matched them with 4838 control subjects based on age, sex, general practice, and index date. After adjusting for comorbidity and frequency of visits to general practitioners, we calculated the risks (odds ratios with 95% confidence intervals) of uncomplicated pneumonia, hospitalization for pneumonia with survival, and fatal pneumonia in participants who used statins compared with those who did not. Current statin users had a significantly reduced risk of fatal pneumonia (adjusted odds ratio 0.47, 95% confidence interval 0.25-0.88) and slightly but not significantly reduced risks of uncomplicated pneumonia and pneumonia hospitalization with survival. Recent or past statin use and fibrate use at any time were not associated with a reduced risk of pneumonia. CONCLUSION: Current use of statins was associated with a reduced risk of pneumonia. The risk reduction was particularly strong in the subgroup of patients with fatal pneumonias.     

Concomitant use of clopidogrel and statins and risk of major adverse cardiovascular events following coronary stent implantation

AIMS

To examine whether CYP3A4-metabolizing statin use modified the association between clopidogrel use and major adverse cardiovascular events (MACE) after coronary stent implantation, using time-varying drug exposure ascertainment.

METHODS

We conducted this population-based cohort study in Western Denmark (population: 3 million) using medical databases. We identified all 13 001 patients with coronary stent implantation between 2002 and 2005 and their comorbidities. During 12 months of follow-up, we tracked the use of clopidogrel and CYP3A4-metabolizing statins and the rate of MACE. We used Cox regression to compute hazard ratios (HRs) controlling for potential confounders.

RESULTS

The rate of MACE per 1000 person years was 104 for concomitant clopidogrel and statin use, 130 for clopidogrel without statin use, 108 for statin without clopidogrel use and 446 for no use of either drug. The adjusted HR comparing clopidogrel use with non-use was 0.68 (95% confidence interval (CI) 0.58, 0.79) among statin users and 0.34 (95% CI 0.29, 0.40) among statin non-users, yielding an interaction effect (i.e. relative rate increase) of 1.97 (95% CI 1.59, 2.44). The adjusted HR for MACE comparing statin use with non-use was 0.97 (95% CI 0.83, 1.13) among clopidogrel users and 0.49 (95% CI 0.42, 0.57) among clopidogrel non-users.

CONCLUSIONS

Clopidogrel and CYP3A4-metabolizing statin use were each associated with a substantially reduced rate of MACE within 12 months after coronary stent implantation. Although we observed an interaction between use of clopidogrel and statins, statin use vs. non-use was not associated with an increased rate of MACE in patients using clopidogrel after coronary stent implantation.     

Impact of SLCO1B1 (OATP1B1) and ABCG2 (BCRP) genetic polymorphisms and inhibition on LDL-C lowering and myopathy of statins

Statins are the preferred class of drugs for treating patients with atherosclerosis and related coronary heart disease. Treatment with statins leads to significant low-density lipoprotein cholesterol (LDL-C) lowering, resulting in reductions in major coronary and vascular events. Statins are generally well tolerated and safe; however, their use is complicated by infrequent, but often serious, muscular adverse events. For many statins, both efficacy and risk of adverse muscle events can be influenced by membrane transporters, which are important determinants of statin disposition. Genetic polymorphisms and drug-drug interactions (DDIs) involving organic anion-transporting polypeptide 1B1 and breast cancer resistance protein have shown the capacity to reduce the activity of these transporters, resulting in changes in LDL-C lowering by statins, as well as changes in the frequency of adverse muscle events associated with their use. This review presents evidence for how reduced transporter activity impacts the safety and pharmacology of statins. It expands on the scope of other recent statin reviews by providing recommendations on in vitro evaluation of statin interaction potential, discussing how reduced transporter activity impacts statin management during drug development, and proposing ideas on how to evaluate the impact of DDI on statin efficacy during clinical trials. Furthermore, the potential clinical consequences of perturbing statin efficacy via DDI are discussed.     

Safety of statin therapy in patients with preexisting liver disease

Cardiovascular disease is the leading cause of mortality in the United States. In high-risk patients, statin therapy has become the standard of care. In fact, statins are the most efficacious drugs for decreasing low-density lipoprotein cholesterol levels; they reduce both primary and secondary cardiovascular risk in the general population. However, less is known about the safety of statin use in patients with liver disease. Results from studies of statin therapy in patients with elevated liver enzyme levels, nonalcoholic fatty liver disease, hepatitis C, cirrhosis, liver transplants, and hepatocellular carcinoma show benefit without increased risk of adverse effects. Thus, based on available evidence, statin therapy should not be withheld in this patient population; however, more robust, prospective clinical trials are needed to confirm the safety and efficacy.