British Journal of Clinical Pharmacology
Br J Clin Pharmacol (2016) 82 892–894
892
LETTER TO THE EDITOR Statins for primary prevention in practice: clinical use in Wales and the NICE guideline effect Correspondence Dr Majd B Protty, MSc MRCP MAcadMEd, Cardiff University, Wales, UK. Tel.: +44 (0)16 3323 4234; E-mail: [email protected]
Received 10 December 2015; revised 4 May 2016; accepted 15 May 2016
Majd B. Protty1, Arron Lacey2, Jamie Hayes3 and Phillip Freeman1 1
Cardiff University, Cardiff, Wales, UK, 2Swansea University, Cardiff, Wales, UK, and 3Welsh Medicines Resource Centre, Cardiff, Wales, UK
Cardiovascular disease is the biggest killer in the UK, with mortality rates being above average in Wales [1]. Statins are used for, and have a proven benefit in, the prevention of cardiovascular disease [2] but are known to have variable patient compliance in clinical trials, with limited data on typical clinical use [3]. There is wide variation in the comparative cost-effectiveness of different statins within different groups of patients. This was made more complex by a multitude of large clinical trials investigating different groups, statins and doses. This resulted in heterogeneous prescribing practices across the UK, leading to potential reduced cost-effectiveness at a population level. In 2008, the National Institute for Health and Care Excellence (NICE) published guidance for statin prescription in the UK to maximize the cost–benefit ratio [4]. To investigate the typical clinical (‘real-life’) use of statins for primary prevention of cardiovascular disease in Wales, a retrospective longitudinal study was performed using the Secure Anonymised Information Linkage (SAIL) databank – a national Welsh database that links person-based data from primary and secondary healthcare records using robust anonymization techniques [5]. A total of 152 781 patients who were prescribed a first statin for the primary prevention of cardiovascular disease between 2000 and 2014 were identified from general practice records by excluding all secondary prevention indications. This group was followed up for five years to examine the choice of statins prescribed, adherence rates in typical clinical practice and the effect of the NICE guidelines (CG67, 2008) on prescribing patterns [4]. Simvastatin was the most commonly initiated statin (74.8%) for the primary prevention of cardiovascular disease in Wales, with most patients remaining on their initial statin type at one-, three- and five-year follow-up. The discontinuation rates of all statins were 26.8%, 32.6% and 36.0% at one-, three- and five-year follow up, respectively. Following the introduction of the NICE CG67 guidelines in 2008, 85.5% of participants were initiated on guideline-recommended DOI:10.1111/bcp.13014
therapy with low-acquisition-cost statins at the time (simvastatin 40 mg/20 mg, pravastatin 40 mg; see Table 1). The present study revealed that in the last 15 years, simvastatin has been the most commonly initiated statin in the primary prevention of cardiovascular disease, although prior to the NICE guidelines there had been no specific pattern in the use of statins. The percentage of patients initiated on low-acquisition-cost statins was 50.5% compared with a majority of 85.5% following the publication of the guidelines. Atorvastatin, which was far more expensive at the time, was the second most commonly initiated statin, at 24.1% prior to the implementation of the guidelines. The choice of statin dose varied (Table 1). Indeed, a large proportion of patients were on doses that were lower than recommended by the guidelines and than clinical trial-proven doses. It is difficult to pinpoint what led to this but it is likely that patient factors (e.g. prejudice by the media) and prescriber factors (e.g. minimizing side effects) have influenced the choice of statin and dose. The cost implications of statins on health resources in Wales are significant. Atorvastatin came off patent in 2011; prior to that, the cost of a 28-tablet pack of atorvastatin cost in excess of £25, ten times more than it cost after 2011 [6]. Taking this into consideration, there would have been a potential saving within NHS Wales of £550 000 per month or £6.6 million per annum had all 22 000 patients who were started on atorvastatin for primary prevention prior to the implementation of the guidelines used simvastatin instead. Indeed, a number of studies have suggested that physicians may be unaware of the costs of many commonly used drugs, and it was found to be common to underestimate the costs of expensive drugs, and vice versa [7]. To address this, NHS Wales publishes monthly prescription cost analyses that reveal the actual cost of all medications dispensed in Wales. In addition, all health boards across Wales utilize ScriptSwitch (Optum, London), a digital aid that advises general practitioners of cost-effective alternatives at the time of prescribing, in order to promote national guidelines and © 2016 The British Pharmacological Society
Letter to the Editor
Table 1 Initial choice of statins for primary prevention in Wales
Type of statin and dose Atorvastatin
Total n
Pre-May 2008 %
n
May 2008 onwards %
n
%
26 935
17.6
22 000
24.1
4935
8.0
10 mg
17 808
66.1
15 697
71.4
2111
42.8
20 mg
7049
26.2
5210
23.7
1839
37.3
40 mg
1847
6.9
1020
4.6
827
16.8
80 mg
231
0.9
73
0.3
158
3.2
Fluvastatin
2033
1.3
1999
2.2
34
0.1
20 mg
1215
59.8
1200
60.0
15
44.1
40 mg
753
37.0
744
37.2
9
26.5
80 mg
65
3.2
55
2.8
10
29.4
Pravastatin
5890
3.9
5222
5.7
668
1.1
10 mg
2531
43.0
2352
45.0
179
26.8
20 mg
2047
34.8
1771
33.9
276
41.3
40 mg
1312
22.3
1099
21.0
213
31.9
3672
2.4
3066
3.4
606
1.0
5 mg
232
6.3
71
2.3
161
26.6
10 mg
3214
87.5
2869
93.6
345
56.9
20 mg
205
5.6
117
3.8
88
14.5
40 mg
21
0.6
9
0.3
12
2.0
Simvastatin
114 252
74.8
59 108
64.7
55 144
89.8
10 mg
16 588
14.5
13 801
23.3
2787
5.1
20 mg
46 342
40.6
29 029
49.1
17 313
31.4
40 mg
51 156
44.8
16 187
27.4
34 969
63.4
80 mg
166
0.1
91
0.2
75
0.1
Rosuvastatin
cost information. However, further interventions to encourage the use of these resources by physicians need to be considered. Nevertheless, the current study suggested that the NICE guidelines have played a pivotal role in resource management in Wales. Discontinuation rates were higher than the previously described estimates published by NICE [8] of 13% at three years for primary prevention. It was not possible to ascertain the reasons for discontinuation of statins using our current methodology. This is because discontinuation reasons are not routinely coded into primary and secondary care patient records using standardized codes. Instead, they tend to be entered in free-text format, which makes its upload into SAIL and subsequent extraction for analysis difficult to achieve. One way to improve this is by encouraging the use of the standardized 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10; e.g. Z91.1 – noncompliance with medication) or READ codes (e.g. U60CA – adverse reaction to statin). Scandinavian countries have improved the accuracy of coding by linking it to outcome-based payment schemes [9]. The main strengths of the present study were the large number of typical clinical practice participants in the analysis, which provided a robust and comprehensive analysis of a representative sample of the population in Wales over a number of years. Furthermore, the typical clinical
practice nature of this sample population limited the possibilities for selection bias, which may be an issue with carefully selected clinical trial sample populations, and included factors that affect the typical clinical effectiveness of statin therapy which may not have been experienced by trial participants. Finally, the present study demonstrated the feasibility of using and linking anonymized, routinely collected data in the form of the SAIL databank to avoid bias, protect patient confidentiality and include all patients, thus minimizing attrition and greatly reducing costs. Indeed, clinicians and policy makers may view it as a robust method for national therapeutic audits and quality improvement across Wales.
Competing Interests All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; JH declares receiving a one-off consultancy fee from Optum in May 2015 for delivering a communications workshop. Br J Clin Pharmacol (2016) 82 892–894
893
Letter to the Editor
References 1 British Heart Foundation. Coronary heart disease statistics 2012 [online]. Available at http://www.bhf.org.uk/publications/viewpublication.aspx?ps=1002097 (last accessed 26 May 2014). 2 Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013; 1: CD004816. 3 Phan K, Gomez YH, Elbaz L, Daskalopoulou SS. Statin treatment non-adherence and discontinuation: clinical implications and potential solutions. Curr Pharm Des 2014; 20: 6314–24. 4 National Institute for Health and Care Excellence. Guideline 67: Lipid modification 2010 [online]. Available at http://guidance. nice.org.uk/CG67/QuickRefGuide/pdf/English (last accessed 22 May 2014).
894
Br J Clin Pharmacol (2016) 82 892–894
5 Ford DV, Jones KH, Verplancke JP, Lyons RA, John G, Brown G, et al. The SAIL databank: building a national architecture for ehealth research and evaluation. BMC Health Serv Res 2009; 9: 157. 6 NHS Business Services Authority. Drug Tariff 2015 [online]. Available at http://www.ppa.org.uk/edt/February_2015/mindex. htm (last accessed 1 February 2015). 7 Allan GM, Lexchin J, Wiebe N. Physician awareness of drug cost: a systematic review. PLoS Med 2007; 4: e283. 8 National Institute for Health and Clinical Excellence. Technology Appraisal 94: Statins for the prevention of cardiovascular events 2006 [online]. Available at https://www.nice.org.uk/guidance/ ta94/history (last accessed 22 May 2014). 9 Schmidt M, Schmidt SA, Sandegaard JL, Ehrenstein V, Pedersen L, Sorensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol 2015; 7: 449–90.
Br J Clin Pharmacol (2016) 82 892–894
892
LETTER TO THE EDITOR Statins for primary prevention in practice: clinical use in Wales and the NICE guideline effect Correspondence Dr Majd B Protty, MSc MRCP MAcadMEd, Cardiff University, Wales, UK. Tel.: +44 (0)16 3323 4234; E-mail: [email protected]
Received 10 December 2015; revised 4 May 2016; accepted 15 May 2016
Majd B. Protty1, Arron Lacey2, Jamie Hayes3 and Phillip Freeman1 1
Cardiff University, Cardiff, Wales, UK, 2Swansea University, Cardiff, Wales, UK, and 3Welsh Medicines Resource Centre, Cardiff, Wales, UK
Cardiovascular disease is the biggest killer in the UK, with mortality rates being above average in Wales [1]. Statins are used for, and have a proven benefit in, the prevention of cardiovascular disease [2] but are known to have variable patient compliance in clinical trials, with limited data on typical clinical use [3]. There is wide variation in the comparative cost-effectiveness of different statins within different groups of patients. This was made more complex by a multitude of large clinical trials investigating different groups, statins and doses. This resulted in heterogeneous prescribing practices across the UK, leading to potential reduced cost-effectiveness at a population level. In 2008, the National Institute for Health and Care Excellence (NICE) published guidance for statin prescription in the UK to maximize the cost–benefit ratio [4]. To investigate the typical clinical (‘real-life’) use of statins for primary prevention of cardiovascular disease in Wales, a retrospective longitudinal study was performed using the Secure Anonymised Information Linkage (SAIL) databank – a national Welsh database that links person-based data from primary and secondary healthcare records using robust anonymization techniques [5]. A total of 152 781 patients who were prescribed a first statin for the primary prevention of cardiovascular disease between 2000 and 2014 were identified from general practice records by excluding all secondary prevention indications. This group was followed up for five years to examine the choice of statins prescribed, adherence rates in typical clinical practice and the effect of the NICE guidelines (CG67, 2008) on prescribing patterns [4]. Simvastatin was the most commonly initiated statin (74.8%) for the primary prevention of cardiovascular disease in Wales, with most patients remaining on their initial statin type at one-, three- and five-year follow-up. The discontinuation rates of all statins were 26.8%, 32.6% and 36.0% at one-, three- and five-year follow up, respectively. Following the introduction of the NICE CG67 guidelines in 2008, 85.5% of participants were initiated on guideline-recommended DOI:10.1111/bcp.13014
therapy with low-acquisition-cost statins at the time (simvastatin 40 mg/20 mg, pravastatin 40 mg; see Table 1). The present study revealed that in the last 15 years, simvastatin has been the most commonly initiated statin in the primary prevention of cardiovascular disease, although prior to the NICE guidelines there had been no specific pattern in the use of statins. The percentage of patients initiated on low-acquisition-cost statins was 50.5% compared with a majority of 85.5% following the publication of the guidelines. Atorvastatin, which was far more expensive at the time, was the second most commonly initiated statin, at 24.1% prior to the implementation of the guidelines. The choice of statin dose varied (Table 1). Indeed, a large proportion of patients were on doses that were lower than recommended by the guidelines and than clinical trial-proven doses. It is difficult to pinpoint what led to this but it is likely that patient factors (e.g. prejudice by the media) and prescriber factors (e.g. minimizing side effects) have influenced the choice of statin and dose. The cost implications of statins on health resources in Wales are significant. Atorvastatin came off patent in 2011; prior to that, the cost of a 28-tablet pack of atorvastatin cost in excess of £25, ten times more than it cost after 2011 [6]. Taking this into consideration, there would have been a potential saving within NHS Wales of £550 000 per month or £6.6 million per annum had all 22 000 patients who were started on atorvastatin for primary prevention prior to the implementation of the guidelines used simvastatin instead. Indeed, a number of studies have suggested that physicians may be unaware of the costs of many commonly used drugs, and it was found to be common to underestimate the costs of expensive drugs, and vice versa [7]. To address this, NHS Wales publishes monthly prescription cost analyses that reveal the actual cost of all medications dispensed in Wales. In addition, all health boards across Wales utilize ScriptSwitch (Optum, London), a digital aid that advises general practitioners of cost-effective alternatives at the time of prescribing, in order to promote national guidelines and © 2016 The British Pharmacological Society
Letter to the Editor
Table 1 Initial choice of statins for primary prevention in Wales
Type of statin and dose Atorvastatin
Total n
Pre-May 2008 %
n
May 2008 onwards %
n
%
26 935
17.6
22 000
24.1
4935
8.0
10 mg
17 808
66.1
15 697
71.4
2111
42.8
20 mg
7049
26.2
5210
23.7
1839
37.3
40 mg
1847
6.9
1020
4.6
827
16.8
80 mg
231
0.9
73
0.3
158
3.2
Fluvastatin
2033
1.3
1999
2.2
34
0.1
20 mg
1215
59.8
1200
60.0
15
44.1
40 mg
753
37.0
744
37.2
9
26.5
80 mg
65
3.2
55
2.8
10
29.4
Pravastatin
5890
3.9
5222
5.7
668
1.1
10 mg
2531
43.0
2352
45.0
179
26.8
20 mg
2047
34.8
1771
33.9
276
41.3
40 mg
1312
22.3
1099
21.0
213
31.9
3672
2.4
3066
3.4
606
1.0
5 mg
232
6.3
71
2.3
161
26.6
10 mg
3214
87.5
2869
93.6
345
56.9
20 mg
205
5.6
117
3.8
88
14.5
40 mg
21
0.6
9
0.3
12
2.0
Simvastatin
114 252
74.8
59 108
64.7
55 144
89.8
10 mg
16 588
14.5
13 801
23.3
2787
5.1
20 mg
46 342
40.6
29 029
49.1
17 313
31.4
40 mg
51 156
44.8
16 187
27.4
34 969
63.4
80 mg
166
0.1
91
0.2
75
0.1
Rosuvastatin
cost information. However, further interventions to encourage the use of these resources by physicians need to be considered. Nevertheless, the current study suggested that the NICE guidelines have played a pivotal role in resource management in Wales. Discontinuation rates were higher than the previously described estimates published by NICE [8] of 13% at three years for primary prevention. It was not possible to ascertain the reasons for discontinuation of statins using our current methodology. This is because discontinuation reasons are not routinely coded into primary and secondary care patient records using standardized codes. Instead, they tend to be entered in free-text format, which makes its upload into SAIL and subsequent extraction for analysis difficult to achieve. One way to improve this is by encouraging the use of the standardized 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10; e.g. Z91.1 – noncompliance with medication) or READ codes (e.g. U60CA – adverse reaction to statin). Scandinavian countries have improved the accuracy of coding by linking it to outcome-based payment schemes [9]. The main strengths of the present study were the large number of typical clinical practice participants in the analysis, which provided a robust and comprehensive analysis of a representative sample of the population in Wales over a number of years. Furthermore, the typical clinical
practice nature of this sample population limited the possibilities for selection bias, which may be an issue with carefully selected clinical trial sample populations, and included factors that affect the typical clinical effectiveness of statin therapy which may not have been experienced by trial participants. Finally, the present study demonstrated the feasibility of using and linking anonymized, routinely collected data in the form of the SAIL databank to avoid bias, protect patient confidentiality and include all patients, thus minimizing attrition and greatly reducing costs. Indeed, clinicians and policy makers may view it as a robust method for national therapeutic audits and quality improvement across Wales.
Competing Interests All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; JH declares receiving a one-off consultancy fee from Optum in May 2015 for delivering a communications workshop. Br J Clin Pharmacol (2016) 82 892–894
893
Letter to the Editor
References 1 British Heart Foundation. Coronary heart disease statistics 2012 [online]. Available at http://www.bhf.org.uk/publications/viewpublication.aspx?ps=1002097 (last accessed 26 May 2014). 2 Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013; 1: CD004816. 3 Phan K, Gomez YH, Elbaz L, Daskalopoulou SS. Statin treatment non-adherence and discontinuation: clinical implications and potential solutions. Curr Pharm Des 2014; 20: 6314–24. 4 National Institute for Health and Care Excellence. Guideline 67: Lipid modification 2010 [online]. Available at http://guidance. nice.org.uk/CG67/QuickRefGuide/pdf/English (last accessed 22 May 2014).
894
Br J Clin Pharmacol (2016) 82 892–894
5 Ford DV, Jones KH, Verplancke JP, Lyons RA, John G, Brown G, et al. The SAIL databank: building a national architecture for ehealth research and evaluation. BMC Health Serv Res 2009; 9: 157. 6 NHS Business Services Authority. Drug Tariff 2015 [online]. Available at http://www.ppa.org.uk/edt/February_2015/mindex. htm (last accessed 1 February 2015). 7 Allan GM, Lexchin J, Wiebe N. Physician awareness of drug cost: a systematic review. PLoS Med 2007; 4: e283. 8 National Institute for Health and Clinical Excellence. Technology Appraisal 94: Statins for the prevention of cardiovascular events 2006 [online]. Available at https://www.nice.org.uk/guidance/ ta94/history (last accessed 22 May 2014). 9 Schmidt M, Schmidt SA, Sandegaard JL, Ehrenstein V, Pedersen L, Sorensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol 2015; 7: 449–90.
