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Since the introduction of warfarin over 50 years ago, the indications for anticoagulants have changed considerably. For many years warfarin has been the standard treatment for venous thrombosis and pulmonary embolus, and it has been used to prevent thrombosis in people with mechanical heart valves. Practice changed in the 1990s when studies showed that anticoagulants reduced the risk of stroke in people with atrial fibrillation (AF) by approximately 64%.[[1,2]] This led to a steady growth in warfarin use, and by 2010 approximately 60% of people on anticoagulants were taking it for stroke prevention in AF. Despite the clear benefit, studies at the time from the UK and the US showed that anticoagulants were underutilised, with over 50% of patients who could benefit from treatment not prescribed with anticoagulants.[[3,4]] Approximately 1% of the New Zealand population have AF, with the prevalence increasing with age to greater than 10% over the age of 70yrs. In New Zealand, this equates to approximately 55,000 people;[[5]] however, in 2011 only 27,000 were taking warfarin for stroke prevention in AF.

In the last 10 years, there have been further changes following the introduction of direct oral anticoagulants (DOACs). In July 2011, dabigatran became available in New Zealand. It was initially approved for the prevention of stroke in AF and for prophylaxis in orthopaedic surgery. Approval was widened in July 2014 to include the prevention and treatment of deep vein thrombosis and pulmonary embolus. It remained the only fully funded DOAC in New Zealand until August 2018, when rivaroxaban was approved for stroke prevention in AF and for the treatment of venous thromboembolic disease. In the last few years, the use of DOACs has widened further and replaced low molecular weight heparin for prophylaxis in some orthopaedic surgery, and rivaroxaban is used for the treatment of thrombosis related to malignancy.

The DOACs are more convenient, and have a better safety profile than warfarin with a lower incidence of intracranial haemorrhage. Therefore, since 2011, we have seen a shift from warfarin to the DOACs and an increase in the total number of patients on anticoagulants, as patients who were previously deterred from using warfarin by the frequent testing would find these drugs more acceptable. One potential barrier to the rapid up take of dabigatran was the lack of a reversal agent prior to September 2016. Since then, funding for idarucizumab has been approved by The Pharmaceutical Management Agency (PHARMAC), enabling this reversal agent to be used in New Zealand public hospitals. A reversal agent for rivaroxaban is not available.

Another factor that may have influenced the shift from warfarin to the DOACs was a potential change in practice during the COVID-19 pandemic. In April 2020, the Thrombosis & Haemostasis Society of Australia and New Zealand (THANZ) produced a statement on the management of warfarin monitoring during the COVID-19 pandemic. One of their suggestions was for doctors to consider changing patients from warfarin to DOACs to reduce laboratory visits.[[6]]

The primary aim of this study is to assess the impact of the introduction of DOACs on anticoagulant use in New Zealand over the last 10 years. A secondary consideration is to see if the advice given during lockdown altered practice with a trend away from warfarin use.

Methods

Data source

Data were collected from the Ministry of Health pharmaceuticals database from 1 January 2011 to 31 March 2021. Data on all prescriptions issued in New Zealand are recorded in this database. The following information was obtained for each prescription during the study period; the date the medication was dispensed, the patient’s national identification number (encrypted), the medication dispensed (dabigatran, rivaroxaban or warfarin), the dose prescribed, the patient’s gender and age at time of dispensing.

Data analysis

Data were analysed using Microsoft Excel power pivot software. Data analysis models were developed to calculate the total number of patients who received at least one prescription each month and the mean age at time of dispensing grouped by gender for warfarin, dabigatran and rivaroxaban. The prescription data were summarised as total counts for each drug plotted over time. The population data is presented as a proportion of total population as a percentage.

Patient numbers

Warfarin

Warfarin patients fill prescriptions irregularly, as their dose can change frequently based on the INR. A patient on continuous warfarin therapy can fill a prescription anywhere between monthly and every six months. To estimate the total number of patients on warfarin at a specific time we looked at the number of people who received at least one prescription over various intervals (three months, four months, five months and six months); the three-month interval is likely to underestimate the total as it fails to include patients collecting a script every four to six months; and the six-month total is likely to overestimate the total as it will include patients on short term treatment (for example, a patient who started three months treatment in January will still be counted as being on treatment in June). Based on our assessment, we concluded that using an interval of four months between prescriptions gives a reasonable estimate of the total number of people on warfarin.

We have assumed that an interval between prescriptions of four months or less implies the patient is on anticoagulants the whole time between prescriptions. If the interval is longer than four months, we have assumed the patient has discontinued anticoagulant therapy and restarted later. We have also assumed that a patient has continued treatment for three months after their last prescription (unless they had a new prescription for dabigatran or rivaroxaban).

Dabigatran and rivaroxaban

For dabigatran and rivaroxaban patients the interval between prescriptions is usually less than for warfarin as the drug is dispensed monthly, but patients on continuous treatment do not necessarily fill a prescription every month.

To calculate the estimated number of patients on treatment at a specific time, we have assumed that an interval between prescriptions of two months or less implies the patient is on anticoagulants the whole time between prescriptions. If the interval is longer than two months, we have assumed the patient has discontinued anticoagulant therapy and restarted later. We have also assumed that a patient has stopped treatment the month of their last prescription, as the DOACs are only dispensed monthly.

The following estimates were calculated for dabigatran, rivaroxaban and warfarin each month: (1) The total number of patients on treatment; (2) the total number starting treatment; (3) the total number stopping treatment; and (4) the total number changing between treatments.

The study was approved by the National Ethics committee; ref 14/CEN/135.

Results

Prescriptions

Seven point five million prescriptions for oral anticoagulants were issued during the 10-year study period. A total of 237,218 people received at least one prescription of an oral anticoagulant: Warfarin – 109,416; Dabigatran – 126,108; and Rivaroxaban – 61,918 (over 60,000 received more than one medication).

Warfarin

The number of patients filling warfarin prescriptions dropped by approximate 2,100 (~10%) at the time that dabigatran was introduced (July 2011). The mean number of patients filling at least one prescription each month for the first six months of 2011 (before dabigatran) was 20,530; the mean for the second six months of 2011 was 18,423. There has been a steady fall in prescription numbers over the last 10 years. The mean for six months from October 2020 to March 2021 was 11,308; a fall of 45% from before the introduction of dabigatran and 38.6% since 2012 (Figure 1).  

Dabigatran

The number of patients filling prescription for dabigatran had increased steadily since August 2011, until the introduction of rivaroxaban. Approximately 7,000 patients filled prescriptions for dabigatran each month immediately after its introduction. This has increased by approximately 2% each month since then to approximately 40,000 per month by July 2018, when rivaroxaban was introduced, and has increased more slowly since; the mean of six months from October 2020 to March 2021 was 53,000 (Figure 1).

Rivaroxaban

The number of patients filling prescriptions for rivaroxaban has increased steadily since its introduction in August 2018. We have assumed that patients who had a single prescription for 10mg were receiving treatment for surgical prophylaxis. An increasing number are receiving long term therapy at 10mg. In March 2021, 23,000 prescriptions were dispensed (Figure 2).

View Figures 1 & 2.

Patient numbers

Approximately 46,500 people were taking warfarin at the time dabigatran was introduced. The number dropped to approximately 41,600 within six months (~10%). The number of patients on warfarin remained constant until mid-2014, and subsequently the number fell to 36,000 by March 2017; 29,500 by March 2019; and 23,200 by March 2021—a fall of 50% since April 2011 (before dabigatran).

The number of patients on dabigatran rose to approximately 8000 in August 2011, and has shown a consistent increase to mid-2015, and faster growth to mid-2018 to a total of 51,000 patients. Dabigatran numbers only increased by a further 3,000 between July 2018 and March 2021.

In August 2018, rivaroxaban was fully funded and use has grown rapidly since with approximately 30,000 people prescribed treatment by March 2021. The total number of patients on anticoagulants has risen consistently since the introduction of dabigatran from 46,000 to approximately 105,000; an increase of 140% over 10 years (Figure 3).

Changing anticoagulants

During the first month after the introduction of dabigatran, approximately 5,000 people switched from warfarin to dabigatran; however, a large proportion of these changed back to warfarin over the next six months.

From 2012 to 2014, the number of people starting dabigatran each month has risen steadily and the majority are new to the medication, with only a small number switching from warfarin to dabigatran (<100 per month) and a similar number changing the other way. From 2014 to 2018, the number of people starting dabigatran increased more rapidly and more people switch from warfarin to dabigatran, but the latter group are still only a small proportion of the total (<10%).

The number of people who discontinue dabigatran every month is high, and almost half as many discontinue treatment as start each month. These are either people who stop dabigatran completely and have no further prescriptions, or people who have an interval of more than three months between prescriptions.  

Following the introduction of rivaroxaban in August 2018, approximately 300 people each month changed from dabigatran to rivaroxaban and the growth in dabigatran use has declined (Figure 4).

View Figures 3 & 4.

Patient age

The mean age for people on warfarin has risen progressively from 2011 to 2018 and has subsequently shown a slight fall. The age of people on dabigatran has been stable over the whole study period, but since 2018 there has been a trend to use the drug in older patients. Rivaroxaban was initially used in younger patients as it was probably primarily used to manage venous thrombosis but shows a similar trend to dabigatran (Figure 5).

Impact of lockdown

On 23 March 2020, the Government announced that New Zealand would go into Level 4 lockdown on 25 March. The country reverted to Level 3 on 27 April 2020. Our data shows that during the week immediately prior to lockdown the number of prescriptions increased. During lockdown there was a brief reduction in dispensing. There was no clear evidence that the number of warfarin prescriptions dropped following lockdown (Figure 6).

View Figures 5 & 6.

Estimates of anticoagulant use

Historical audit data prior to 2011 showed that approximately 60% of patients are on warfarin for AF, 20% for VTE treatment and prevention, 12% for prosthetic heart valves and 8% for other reasons.[[7,8]] On this basis, we estimate that approximately 27,500 patients were on anticoagulants for AF prior to the introduction of dabigatran.

The total number of patients on warfarin for mechanical heart valves and “other” indications would be expected to remain constant over time. Also, the total number of patients on treatment for acute VTE is likely to remain stable, although from July 2014 treatment would be split between dabigatran and warfarin. The management of the prevention of recurrent VTE has changed with more patients being advised to remain on long term anticoagulants especially with the convenience of the DOACs. We have estimated that anticoagulants for VTE could have doubled over 10 years.

Based on our estimates, the number of patients on anticoagulants for AF has increased 2.8 times from 27,500 in July 2011 to 78,000 by 2021.

Proportion of patients in New Zealand on anticoagulants

The number of people in New Zealand on anticoagulants presented by age group is shown in Table 2. This is based on population data from Statistics New Zealand (data for 2020).[[9]]

View Tables 1 & 2.

Discussion

The most striking finding is that the total number of people on oral anticoagulants in New Zealand has more than doubled over 10 years; from 46,000 in 2011 to over 100,000 by 2021 (Figure 3). Although we do not have clinical details of the patients, our estimates suggest that most new cases are likely to be receiving anticoagulants for stroke prevention in AF; approximately 27,000 people were on anticoagulants for AF in 2011 and this has increased to over 70,000 by 2021 (Table 1). This is in line with data from other countries which show that 90% of patients on DOACs are taking them for stroke prevention in AF.  This marked increase in use means approximately 12% of people over the age of 70yrs in New Zealand are on anticoagulants, and this rises to 17% in those over 80yrs (Table 2).

It was predicted that the introduction of the DOACs would lead to a move away from warfarin, as the new anticoagulants are more convenient and have a better safety profile with a lower incidence of intracranial bleeding; however, the transition has been slower than many expected. One explanation is that there was some nervousness around the risk of bleeding soon after dabigatran was introduced. In July 2011, approximately 5,000 people switched to dabigatran, but within weeks cases of serious bleeding were reported[[10]] which led to a large proportion changing back to warfarin. Nonetheless, this initial enthusiasm for a new anticoagulant led to a 12% drop (46,500 to 41,300) in patients on warfarin by the end of 2011. The concern around bleeding led to a change in practice with both clinicians[[11]] and the dabigatran manufacturers, recommending that patients stable on warfarin should remain on treatment and that dabigatran should be primarily used for new patients. This would explain why the warfarin numbers remained relatively stable between 2012 and 2015 (Figure 3), supported by the data that shows only a small proportion of patients change from warfarin to dabigatran each month (Figure 4). The steady increase in the median age over time is also in keeping with the warfarin population being relatively stable (Figure 5).

The more rapid decline in warfarin since 2015 is probably due to dabigatran being approved for venous thromboembolic disease; the DOACs are now largely used as first line treatment for venous thrombosis and pulmonary embolus. Warfarin use is likely to reach a plateau as patients with mechanical heart valves, lupus anticoagulant or unusual thromboses need to remain on warfarin and there are some people who cannot tolerate either of the available DOACs. The baseline level is hard to predict, as warfarin use continues to fall steadily and there is currently no sign of a plateau.

During the COVID-19 pandemic in 2020, our results showed there had been no change in warfarin use despite the advice from THANZ. In March 2020, there was an increase in the number of prescriptions dispensed immediately prior to lockdown which subsequently dropped during lockdown itself. However, by May 2020 the number of prescriptions for all three medications had recovered to the pre-lockdown level, and there has been no clear evidence of a more rapid move away from warfarin use since (Figure 6).

The uptake of DOACs has steadily increased and continues to rise. The number of people on dabigatran exceeded those on warfarin by the end of 2016, and currently over 50,000 people take this medication. Practice changed following the introduction of rivaroxaban in 2018, and rivaroxaban appeared to have become the preferred DOAC. It has the advantage of being a “once daily” medication, and can be used for the treatment of DVT and PE from diagnosis without the need for a low molecular weight heparin; hence, it has become the drug of choice for managing acute venous thrombosis.

The clinical impact of these changes is uncertain, but it potentially has both positive and negative effects. The expected benefit is that a higher proportion of people with AF are receiving anticoagulants, and therefore the incidence of embolic stroke should be reduced. This is yet to be confirmed and is part of an ongoing study.

The downside to the wider use of anticoagulants is the increased risk of bleeding. The long-term use of both warfarin and DOACs has been associated with a higher incidence of bleeding complications particularly in the elderly.[[12–14]] This can be problematic for those admitted to hospital, especially if they require urgent surgery. Patients on anticoagulants admitted with trauma have a higher complication rate with more requiring surgical intervention.[[15]]

Anticoagulants are used directly as preventative medicine to reduce the risk of stroke in AF and to prevent recurrence in DVT and PE. It is appropriate that all patients who are likely to benefit have access to these drugs. However, the increase in anticoagulant use has been dramatic over the last 10 years, and it is important that clinicians have the necessary knowledge to use these drugs safely, are aware of the potential complications and the impact these have on our health system.

Summary

Abstract

Aim

To assess the change in the use of oral anticoagulants in New Zealand over 10 years since the introduction of dabigatran and rivaroxaban.

Method

Data were collected from the National Pharmaceutical database from January 2011 to March 2021. Seven and a half million prescriptions for oral anticoagulants were analysed.

Results

The total number of people taking oral anticoagulants increased from 46,000 in July 2011 to 105,000 by March 2021. The growth was predominantly from the increased use of direct oral anticoagulants (DOACs). Initially, dabigatran was the only funded DOAC in New Zealand; approximately 50,000 people were taking this medication by August 2018, when rivaroxaban was introduced. Subsequent growth has predominantly been from rivaroxaban, with 23,000 users by March 2021. Warfarin use has dropped by 50% over the last 10 years.

Conclusion

The introduction of the DOACs was expected to reduce the use of warfarin. However, the rapid rise in DOAC use was not predicted. The increase is most likely in patients with atrial fibrillation with the positive benefit of reducing the incidence of embolic stroke. However, having a high proportion of the elderly population (15% of people over 75-years) on anticoagulants has implications for the health sector, making hospital admissions and surgery more complex.

Author Information

Dr Paul Harper: Consultant Haematologist, Dept. of Clinical Haematology, Palmerston North Hospital, Palmerston North. Dr Alison Chang: Haematology Registrar, Dept. of Clinical Haematology, Palmerston North Hospital, Palmerston North. Dr Matt Stephens: Consultant Haematologist, Dept. of Clinical Haematology, Palmerston North Hospital, Palmerston North.

Acknowledgements

The Ministry of Health for provision of the pharmaceutical database data.

Correspondence

Dr Paul Harper: Consultant Haematologist, Dept. of Clinical Haematology, Palmerston North Hospital, Palmerston North. 021 852235.

Correspondence Email

Paul.harper@midcentraldhb.govt.nz

Competing Interests

Nil.

1) Preliminary report of the Stroke Prevention in Atrial Fibrillation Study. N Engl J Med. 1990;322:863-8.

2) Petersen P, Godtfredsen J, Boysen G, et al. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: The Copenhagen AFASAK Study. The Lancet. 1989;333:175-9.

3) Ogilvie IM, Newton N, Welner SA, et al. Underuse of Oral Anticoagulants in Atrial Fibrillation: A Systematic Review. Am J Med. 2010;123:638-645.e4.

4) Pechlaner C. Anticoagulation for atrial fibrillation: Underuse? Am J Med. 2011;124:e11.

5) Tomlin A, Lloyd H, Tilyard M. Atrial fibrillation in New Zealand primary care: Prevalence, risk factors for stroke and the management of thromboembolic risk. Eur. J. Prev. Cardiol. 2017;24:311-9.

6) THANZ [Internet]. [cited 2021 Jul 26]. Available from: https://www.thanz.org.au/news/outpatient-inr-monitoring-for-patients-receiving-warfarin-during-covid-19-pandemic

7) Young L, Ockelford P, Harper P. Audit of community-based anticoagulant monitoring in patients with thromboembolic disease: is frequent testing necessary? Intern Med J. 2004;34:639-41.

8) Kirley K, Qato DM, Kornfield R, et al. National Trends in Oral Anticoagulant Use in the United States, 2007 to 2011. Circ Cardiovasc Qual Outcomes. 2012;5:615-21.

9) Statistics New Zealand. [accessed 2021 Jul 26]. Available from: http://infoshare.stats.govt.nz/ViewTable.aspx?pxID=83faf750-e860-4102-877d-9e6baedadd1c

10) Harper P, Young L, Merriman E. Bleeding Risk with Dabigatran in the Frail Elderly. N Engl J Med. 2012;366:864-6.

11) Baker R, Harper P, McLintock C. Avoiding adverse events with dabigatran by careful selection of eligible patients. Med J Aust. 2012;196:431-2.

12) Khan F, Tritschler T, Kimpton M et al. Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism. Ann Intern Med. 2021;174:1420-1429.

13) Gunasekaran K, Rajasurya V, Devasahayam J et al. Review of the Incidence Diagnosis and Treatment of Spontaneous Hemorrhage in Patients Treated with Direct Oral Anticoagulants. J. Clin. Med. 2020, 9, 2984.

14) Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use: a prevalent adverse effect resulting in regulatory action. Arch Intern Med. 2007;167:1414-9.

15) Bläsius FM, Laubach M, Andruszkow H, et al. Impact of anticoagulation and antiplatelet drugs on surgery rates and mortality in trauma patients. Sci Rep. 2021;11:15172.

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Since the introduction of warfarin over 50 years ago, the indications for anticoagulants have changed considerably. For many years warfarin has been the standard treatment for venous thrombosis and pulmonary embolus, and it has been used to prevent thrombosis in people with mechanical heart valves. Practice changed in the 1990s when studies showed that anticoagulants reduced the risk of stroke in people with atrial fibrillation (AF) by approximately 64%.[[1,2]] This led to a steady growth in warfarin use, and by 2010 approximately 60% of people on anticoagulants were taking it for stroke prevention in AF. Despite the clear benefit, studies at the time from the UK and the US showed that anticoagulants were underutilised, with over 50% of patients who could benefit from treatment not prescribed with anticoagulants.[[3,4]] Approximately 1% of the New Zealand population have AF, with the prevalence increasing with age to greater than 10% over the age of 70yrs. In New Zealand, this equates to approximately 55,000 people;[[5]] however, in 2011 only 27,000 were taking warfarin for stroke prevention in AF.

In the last 10 years, there have been further changes following the introduction of direct oral anticoagulants (DOACs). In July 2011, dabigatran became available in New Zealand. It was initially approved for the prevention of stroke in AF and for prophylaxis in orthopaedic surgery. Approval was widened in July 2014 to include the prevention and treatment of deep vein thrombosis and pulmonary embolus. It remained the only fully funded DOAC in New Zealand until August 2018, when rivaroxaban was approved for stroke prevention in AF and for the treatment of venous thromboembolic disease. In the last few years, the use of DOACs has widened further and replaced low molecular weight heparin for prophylaxis in some orthopaedic surgery, and rivaroxaban is used for the treatment of thrombosis related to malignancy.

The DOACs are more convenient, and have a better safety profile than warfarin with a lower incidence of intracranial haemorrhage. Therefore, since 2011, we have seen a shift from warfarin to the DOACs and an increase in the total number of patients on anticoagulants, as patients who were previously deterred from using warfarin by the frequent testing would find these drugs more acceptable. One potential barrier to the rapid up take of dabigatran was the lack of a reversal agent prior to September 2016. Since then, funding for idarucizumab has been approved by The Pharmaceutical Management Agency (PHARMAC), enabling this reversal agent to be used in New Zealand public hospitals. A reversal agent for rivaroxaban is not available.

Another factor that may have influenced the shift from warfarin to the DOACs was a potential change in practice during the COVID-19 pandemic. In April 2020, the Thrombosis & Haemostasis Society of Australia and New Zealand (THANZ) produced a statement on the management of warfarin monitoring during the COVID-19 pandemic. One of their suggestions was for doctors to consider changing patients from warfarin to DOACs to reduce laboratory visits.[[6]]

The primary aim of this study is to assess the impact of the introduction of DOACs on anticoagulant use in New Zealand over the last 10 years. A secondary consideration is to see if the advice given during lockdown altered practice with a trend away from warfarin use.

Methods

Data source

Data were collected from the Ministry of Health pharmaceuticals database from 1 January 2011 to 31 March 2021. Data on all prescriptions issued in New Zealand are recorded in this database. The following information was obtained for each prescription during the study period; the date the medication was dispensed, the patient’s national identification number (encrypted), the medication dispensed (dabigatran, rivaroxaban or warfarin), the dose prescribed, the patient’s gender and age at time of dispensing.

Data analysis

Data were analysed using Microsoft Excel power pivot software. Data analysis models were developed to calculate the total number of patients who received at least one prescription each month and the mean age at time of dispensing grouped by gender for warfarin, dabigatran and rivaroxaban. The prescription data were summarised as total counts for each drug plotted over time. The population data is presented as a proportion of total population as a percentage.

Patient numbers

Warfarin

Warfarin patients fill prescriptions irregularly, as their dose can change frequently based on the INR. A patient on continuous warfarin therapy can fill a prescription anywhere between monthly and every six months. To estimate the total number of patients on warfarin at a specific time we looked at the number of people who received at least one prescription over various intervals (three months, four months, five months and six months); the three-month interval is likely to underestimate the total as it fails to include patients collecting a script every four to six months; and the six-month total is likely to overestimate the total as it will include patients on short term treatment (for example, a patient who started three months treatment in January will still be counted as being on treatment in June). Based on our assessment, we concluded that using an interval of four months between prescriptions gives a reasonable estimate of the total number of people on warfarin.

We have assumed that an interval between prescriptions of four months or less implies the patient is on anticoagulants the whole time between prescriptions. If the interval is longer than four months, we have assumed the patient has discontinued anticoagulant therapy and restarted later. We have also assumed that a patient has continued treatment for three months after their last prescription (unless they had a new prescription for dabigatran or rivaroxaban).

Dabigatran and rivaroxaban

For dabigatran and rivaroxaban patients the interval between prescriptions is usually less than for warfarin as the drug is dispensed monthly, but patients on continuous treatment do not necessarily fill a prescription every month.

To calculate the estimated number of patients on treatment at a specific time, we have assumed that an interval between prescriptions of two months or less implies the patient is on anticoagulants the whole time between prescriptions. If the interval is longer than two months, we have assumed the patient has discontinued anticoagulant therapy and restarted later. We have also assumed that a patient has stopped treatment the month of their last prescription, as the DOACs are only dispensed monthly.

The following estimates were calculated for dabigatran, rivaroxaban and warfarin each month: (1) The total number of patients on treatment; (2) the total number starting treatment; (3) the total number stopping treatment; and (4) the total number changing between treatments.

The study was approved by the National Ethics committee; ref 14/CEN/135.

Results

Prescriptions

Seven point five million prescriptions for oral anticoagulants were issued during the 10-year study period. A total of 237,218 people received at least one prescription of an oral anticoagulant: Warfarin – 109,416; Dabigatran – 126,108; and Rivaroxaban – 61,918 (over 60,000 received more than one medication).

Warfarin

The number of patients filling warfarin prescriptions dropped by approximate 2,100 (~10%) at the time that dabigatran was introduced (July 2011). The mean number of patients filling at least one prescription each month for the first six months of 2011 (before dabigatran) was 20,530; the mean for the second six months of 2011 was 18,423. There has been a steady fall in prescription numbers over the last 10 years. The mean for six months from October 2020 to March 2021 was 11,308; a fall of 45% from before the introduction of dabigatran and 38.6% since 2012 (Figure 1).  

Dabigatran

The number of patients filling prescription for dabigatran had increased steadily since August 2011, until the introduction of rivaroxaban. Approximately 7,000 patients filled prescriptions for dabigatran each month immediately after its introduction. This has increased by approximately 2% each month since then to approximately 40,000 per month by July 2018, when rivaroxaban was introduced, and has increased more slowly since; the mean of six months from October 2020 to March 2021 was 53,000 (Figure 1).

Rivaroxaban

The number of patients filling prescriptions for rivaroxaban has increased steadily since its introduction in August 2018. We have assumed that patients who had a single prescription for 10mg were receiving treatment for surgical prophylaxis. An increasing number are receiving long term therapy at 10mg. In March 2021, 23,000 prescriptions were dispensed (Figure 2).

View Figures 1 & 2.

Patient numbers

Approximately 46,500 people were taking warfarin at the time dabigatran was introduced. The number dropped to approximately 41,600 within six months (~10%). The number of patients on warfarin remained constant until mid-2014, and subsequently the number fell to 36,000 by March 2017; 29,500 by March 2019; and 23,200 by March 2021—a fall of 50% since April 2011 (before dabigatran).

The number of patients on dabigatran rose to approximately 8000 in August 2011, and has shown a consistent increase to mid-2015, and faster growth to mid-2018 to a total of 51,000 patients. Dabigatran numbers only increased by a further 3,000 between July 2018 and March 2021.

In August 2018, rivaroxaban was fully funded and use has grown rapidly since with approximately 30,000 people prescribed treatment by March 2021. The total number of patients on anticoagulants has risen consistently since the introduction of dabigatran from 46,000 to approximately 105,000; an increase of 140% over 10 years (Figure 3).

Changing anticoagulants

During the first month after the introduction of dabigatran, approximately 5,000 people switched from warfarin to dabigatran; however, a large proportion of these changed back to warfarin over the next six months.

From 2012 to 2014, the number of people starting dabigatran each month has risen steadily and the majority are new to the medication, with only a small number switching from warfarin to dabigatran (<100 per month) and a similar number changing the other way. From 2014 to 2018, the number of people starting dabigatran increased more rapidly and more people switch from warfarin to dabigatran, but the latter group are still only a small proportion of the total (<10%).

The number of people who discontinue dabigatran every month is high, and almost half as many discontinue treatment as start each month. These are either people who stop dabigatran completely and have no further prescriptions, or people who have an interval of more than three months between prescriptions.  

Following the introduction of rivaroxaban in August 2018, approximately 300 people each month changed from dabigatran to rivaroxaban and the growth in dabigatran use has declined (Figure 4).

View Figures 3 & 4.

Patient age

The mean age for people on warfarin has risen progressively from 2011 to 2018 and has subsequently shown a slight fall. The age of people on dabigatran has been stable over the whole study period, but since 2018 there has been a trend to use the drug in older patients. Rivaroxaban was initially used in younger patients as it was probably primarily used to manage venous thrombosis but shows a similar trend to dabigatran (Figure 5).

Impact of lockdown

On 23 March 2020, the Government announced that New Zealand would go into Level 4 lockdown on 25 March. The country reverted to Level 3 on 27 April 2020. Our data shows that during the week immediately prior to lockdown the number of prescriptions increased. During lockdown there was a brief reduction in dispensing. There was no clear evidence that the number of warfarin prescriptions dropped following lockdown (Figure 6).

View Figures 5 & 6.

Estimates of anticoagulant use

Historical audit data prior to 2011 showed that approximately 60% of patients are on warfarin for AF, 20% for VTE treatment and prevention, 12% for prosthetic heart valves and 8% for other reasons.[[7,8]] On this basis, we estimate that approximately 27,500 patients were on anticoagulants for AF prior to the introduction of dabigatran.

The total number of patients on warfarin for mechanical heart valves and “other” indications would be expected to remain constant over time. Also, the total number of patients on treatment for acute VTE is likely to remain stable, although from July 2014 treatment would be split between dabigatran and warfarin. The management of the prevention of recurrent VTE has changed with more patients being advised to remain on long term anticoagulants especially with the convenience of the DOACs. We have estimated that anticoagulants for VTE could have doubled over 10 years.

Based on our estimates, the number of patients on anticoagulants for AF has increased 2.8 times from 27,500 in July 2011 to 78,000 by 2021.

Proportion of patients in New Zealand on anticoagulants

The number of people in New Zealand on anticoagulants presented by age group is shown in Table 2. This is based on population data from Statistics New Zealand (data for 2020).[[9]]

View Tables 1 & 2.

Discussion

The most striking finding is that the total number of people on oral anticoagulants in New Zealand has more than doubled over 10 years; from 46,000 in 2011 to over 100,000 by 2021 (Figure 3). Although we do not have clinical details of the patients, our estimates suggest that most new cases are likely to be receiving anticoagulants for stroke prevention in AF; approximately 27,000 people were on anticoagulants for AF in 2011 and this has increased to over 70,000 by 2021 (Table 1). This is in line with data from other countries which show that 90% of patients on DOACs are taking them for stroke prevention in AF.  This marked increase in use means approximately 12% of people over the age of 70yrs in New Zealand are on anticoagulants, and this rises to 17% in those over 80yrs (Table 2).

It was predicted that the introduction of the DOACs would lead to a move away from warfarin, as the new anticoagulants are more convenient and have a better safety profile with a lower incidence of intracranial bleeding; however, the transition has been slower than many expected. One explanation is that there was some nervousness around the risk of bleeding soon after dabigatran was introduced. In July 2011, approximately 5,000 people switched to dabigatran, but within weeks cases of serious bleeding were reported[[10]] which led to a large proportion changing back to warfarin. Nonetheless, this initial enthusiasm for a new anticoagulant led to a 12% drop (46,500 to 41,300) in patients on warfarin by the end of 2011. The concern around bleeding led to a change in practice with both clinicians[[11]] and the dabigatran manufacturers, recommending that patients stable on warfarin should remain on treatment and that dabigatran should be primarily used for new patients. This would explain why the warfarin numbers remained relatively stable between 2012 and 2015 (Figure 3), supported by the data that shows only a small proportion of patients change from warfarin to dabigatran each month (Figure 4). The steady increase in the median age over time is also in keeping with the warfarin population being relatively stable (Figure 5).

The more rapid decline in warfarin since 2015 is probably due to dabigatran being approved for venous thromboembolic disease; the DOACs are now largely used as first line treatment for venous thrombosis and pulmonary embolus. Warfarin use is likely to reach a plateau as patients with mechanical heart valves, lupus anticoagulant or unusual thromboses need to remain on warfarin and there are some people who cannot tolerate either of the available DOACs. The baseline level is hard to predict, as warfarin use continues to fall steadily and there is currently no sign of a plateau.

During the COVID-19 pandemic in 2020, our results showed there had been no change in warfarin use despite the advice from THANZ. In March 2020, there was an increase in the number of prescriptions dispensed immediately prior to lockdown which subsequently dropped during lockdown itself. However, by May 2020 the number of prescriptions for all three medications had recovered to the pre-lockdown level, and there has been no clear evidence of a more rapid move away from warfarin use since (Figure 6).

The uptake of DOACs has steadily increased and continues to rise. The number of people on dabigatran exceeded those on warfarin by the end of 2016, and currently over 50,000 people take this medication. Practice changed following the introduction of rivaroxaban in 2018, and rivaroxaban appeared to have become the preferred DOAC. It has the advantage of being a “once daily” medication, and can be used for the treatment of DVT and PE from diagnosis without the need for a low molecular weight heparin; hence, it has become the drug of choice for managing acute venous thrombosis.

The clinical impact of these changes is uncertain, but it potentially has both positive and negative effects. The expected benefit is that a higher proportion of people with AF are receiving anticoagulants, and therefore the incidence of embolic stroke should be reduced. This is yet to be confirmed and is part of an ongoing study.

The downside to the wider use of anticoagulants is the increased risk of bleeding. The long-term use of both warfarin and DOACs has been associated with a higher incidence of bleeding complications particularly in the elderly.[[12–14]] This can be problematic for those admitted to hospital, especially if they require urgent surgery. Patients on anticoagulants admitted with trauma have a higher complication rate with more requiring surgical intervention.[[15]]

Anticoagulants are used directly as preventative medicine to reduce the risk of stroke in AF and to prevent recurrence in DVT and PE. It is appropriate that all patients who are likely to benefit have access to these drugs. However, the increase in anticoagulant use has been dramatic over the last 10 years, and it is important that clinicians have the necessary knowledge to use these drugs safely, are aware of the potential complications and the impact these have on our health system.

Summary

Abstract

Aim

To assess the change in the use of oral anticoagulants in New Zealand over 10 years since the introduction of dabigatran and rivaroxaban.

Method

Data were collected from the National Pharmaceutical database from January 2011 to March 2021. Seven and a half million prescriptions for oral anticoagulants were analysed.

Results

The total number of people taking oral anticoagulants increased from 46,000 in July 2011 to 105,000 by March 2021. The growth was predominantly from the increased use of direct oral anticoagulants (DOACs). Initially, dabigatran was the only funded DOAC in New Zealand; approximately 50,000 people were taking this medication by August 2018, when rivaroxaban was introduced. Subsequent growth has predominantly been from rivaroxaban, with 23,000 users by March 2021. Warfarin use has dropped by 50% over the last 10 years.

Conclusion

The introduction of the DOACs was expected to reduce the use of warfarin. However, the rapid rise in DOAC use was not predicted. The increase is most likely in patients with atrial fibrillation with the positive benefit of reducing the incidence of embolic stroke. However, having a high proportion of the elderly population (15% of people over 75-years) on anticoagulants has implications for the health sector, making hospital admissions and surgery more complex.

Author Information

Dr Paul Harper: Consultant Haematologist, Dept. of Clinical Haematology, Palmerston North Hospital, Palmerston North. Dr Alison Chang: Haematology Registrar, Dept. of Clinical Haematology, Palmerston North Hospital, Palmerston North. Dr Matt Stephens: Consultant Haematologist, Dept. of Clinical Haematology, Palmerston North Hospital, Palmerston North.

Acknowledgements

The Ministry of Health for provision of the pharmaceutical database data.

Correspondence

Dr Paul Harper: Consultant Haematologist, Dept. of Clinical Haematology, Palmerston North Hospital, Palmerston North. 021 852235.

Correspondence Email

Paul.harper@midcentraldhb.govt.nz

Competing Interests

Nil.

1) Preliminary report of the Stroke Prevention in Atrial Fibrillation Study. N Engl J Med. 1990;322:863-8.

2) Petersen P, Godtfredsen J, Boysen G, et al. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: The Copenhagen AFASAK Study. The Lancet. 1989;333:175-9.

3) Ogilvie IM, Newton N, Welner SA, et al. Underuse of Oral Anticoagulants in Atrial Fibrillation: A Systematic Review. Am J Med. 2010;123:638-645.e4.

4) Pechlaner C. Anticoagulation for atrial fibrillation: Underuse? Am J Med. 2011;124:e11.

5) Tomlin A, Lloyd H, Tilyard M. Atrial fibrillation in New Zealand primary care: Prevalence, risk factors for stroke and the management of thromboembolic risk. Eur. J. Prev. Cardiol. 2017;24:311-9.

6) THANZ [Internet]. [cited 2021 Jul 26]. Available from: https://www.thanz.org.au/news/outpatient-inr-monitoring-for-patients-receiving-warfarin-during-covid-19-pandemic

7) Young L, Ockelford P, Harper P. Audit of community-based anticoagulant monitoring in patients with thromboembolic disease: is frequent testing necessary? Intern Med J. 2004;34:639-41.

8) Kirley K, Qato DM, Kornfield R, et al. National Trends in Oral Anticoagulant Use in the United States, 2007 to 2011. Circ Cardiovasc Qual Outcomes. 2012;5:615-21.

9) Statistics New Zealand. [accessed 2021 Jul 26]. Available from: http://infoshare.stats.govt.nz/ViewTable.aspx?pxID=83faf750-e860-4102-877d-9e6baedadd1c

10) Harper P, Young L, Merriman E. Bleeding Risk with Dabigatran in the Frail Elderly. N Engl J Med. 2012;366:864-6.

11) Baker R, Harper P, McLintock C. Avoiding adverse events with dabigatran by careful selection of eligible patients. Med J Aust. 2012;196:431-2.

12) Khan F, Tritschler T, Kimpton M et al. Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism. Ann Intern Med. 2021;174:1420-1429.

13) Gunasekaran K, Rajasurya V, Devasahayam J et al. Review of the Incidence Diagnosis and Treatment of Spontaneous Hemorrhage in Patients Treated with Direct Oral Anticoagulants. J. Clin. Med. 2020, 9, 2984.

14) Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use: a prevalent adverse effect resulting in regulatory action. Arch Intern Med. 2007;167:1414-9.

15) Bläsius FM, Laubach M, Andruszkow H, et al. Impact of anticoagulation and antiplatelet drugs on surgery rates and mortality in trauma patients. Sci Rep. 2021;11:15172.

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Since the introduction of warfarin over 50 years ago, the indications for anticoagulants have changed considerably. For many years warfarin has been the standard treatment for venous thrombosis and pulmonary embolus, and it has been used to prevent thrombosis in people with mechanical heart valves. Practice changed in the 1990s when studies showed that anticoagulants reduced the risk of stroke in people with atrial fibrillation (AF) by approximately 64%.[[1,2]] This led to a steady growth in warfarin use, and by 2010 approximately 60% of people on anticoagulants were taking it for stroke prevention in AF. Despite the clear benefit, studies at the time from the UK and the US showed that anticoagulants were underutilised, with over 50% of patients who could benefit from treatment not prescribed with anticoagulants.[[3,4]] Approximately 1% of the New Zealand population have AF, with the prevalence increasing with age to greater than 10% over the age of 70yrs. In New Zealand, this equates to approximately 55,000 people;[[5]] however, in 2011 only 27,000 were taking warfarin for stroke prevention in AF.

In the last 10 years, there have been further changes following the introduction of direct oral anticoagulants (DOACs). In July 2011, dabigatran became available in New Zealand. It was initially approved for the prevention of stroke in AF and for prophylaxis in orthopaedic surgery. Approval was widened in July 2014 to include the prevention and treatment of deep vein thrombosis and pulmonary embolus. It remained the only fully funded DOAC in New Zealand until August 2018, when rivaroxaban was approved for stroke prevention in AF and for the treatment of venous thromboembolic disease. In the last few years, the use of DOACs has widened further and replaced low molecular weight heparin for prophylaxis in some orthopaedic surgery, and rivaroxaban is used for the treatment of thrombosis related to malignancy.

The DOACs are more convenient, and have a better safety profile than warfarin with a lower incidence of intracranial haemorrhage. Therefore, since 2011, we have seen a shift from warfarin to the DOACs and an increase in the total number of patients on anticoagulants, as patients who were previously deterred from using warfarin by the frequent testing would find these drugs more acceptable. One potential barrier to the rapid up take of dabigatran was the lack of a reversal agent prior to September 2016. Since then, funding for idarucizumab has been approved by The Pharmaceutical Management Agency (PHARMAC), enabling this reversal agent to be used in New Zealand public hospitals. A reversal agent for rivaroxaban is not available.

Another factor that may have influenced the shift from warfarin to the DOACs was a potential change in practice during the COVID-19 pandemic. In April 2020, the Thrombosis & Haemostasis Society of Australia and New Zealand (THANZ) produced a statement on the management of warfarin monitoring during the COVID-19 pandemic. One of their suggestions was for doctors to consider changing patients from warfarin to DOACs to reduce laboratory visits.[[6]]

The primary aim of this study is to assess the impact of the introduction of DOACs on anticoagulant use in New Zealand over the last 10 years. A secondary consideration is to see if the advice given during lockdown altered practice with a trend away from warfarin use.

Methods

Data source

Data were collected from the Ministry of Health pharmaceuticals database from 1 January 2011 to 31 March 2021. Data on all prescriptions issued in New Zealand are recorded in this database. The following information was obtained for each prescription during the study period; the date the medication was dispensed, the patient’s national identification number (encrypted), the medication dispensed (dabigatran, rivaroxaban or warfarin), the dose prescribed, the patient’s gender and age at time of dispensing.

Data analysis

Data were analysed using Microsoft Excel power pivot software. Data analysis models were developed to calculate the total number of patients who received at least one prescription each month and the mean age at time of dispensing grouped by gender for warfarin, dabigatran and rivaroxaban. The prescription data were summarised as total counts for each drug plotted over time. The population data is presented as a proportion of total population as a percentage.

Patient numbers

Warfarin

Warfarin patients fill prescriptions irregularly, as their dose can change frequently based on the INR. A patient on continuous warfarin therapy can fill a prescription anywhere between monthly and every six months. To estimate the total number of patients on warfarin at a specific time we looked at the number of people who received at least one prescription over various intervals (three months, four months, five months and six months); the three-month interval is likely to underestimate the total as it fails to include patients collecting a script every four to six months; and the six-month total is likely to overestimate the total as it will include patients on short term treatment (for example, a patient who started three months treatment in January will still be counted as being on treatment in June). Based on our assessment, we concluded that using an interval of four months between prescriptions gives a reasonable estimate of the total number of people on warfarin.

We have assumed that an interval between prescriptions of four months or less implies the patient is on anticoagulants the whole time between prescriptions. If the interval is longer than four months, we have assumed the patient has discontinued anticoagulant therapy and restarted later. We have also assumed that a patient has continued treatment for three months after their last prescription (unless they had a new prescription for dabigatran or rivaroxaban).

Dabigatran and rivaroxaban

For dabigatran and rivaroxaban patients the interval between prescriptions is usually less than for warfarin as the drug is dispensed monthly, but patients on continuous treatment do not necessarily fill a prescription every month.

To calculate the estimated number of patients on treatment at a specific time, we have assumed that an interval between prescriptions of two months or less implies the patient is on anticoagulants the whole time between prescriptions. If the interval is longer than two months, we have assumed the patient has discontinued anticoagulant therapy and restarted later. We have also assumed that a patient has stopped treatment the month of their last prescription, as the DOACs are only dispensed monthly.

The following estimates were calculated for dabigatran, rivaroxaban and warfarin each month: (1) The total number of patients on treatment; (2) the total number starting treatment; (3) the total number stopping treatment; and (4) the total number changing between treatments.

The study was approved by the National Ethics committee; ref 14/CEN/135.

Results

Prescriptions

Seven point five million prescriptions for oral anticoagulants were issued during the 10-year study period. A total of 237,218 people received at least one prescription of an oral anticoagulant: Warfarin – 109,416; Dabigatran – 126,108; and Rivaroxaban – 61,918 (over 60,000 received more than one medication).

Warfarin

The number of patients filling warfarin prescriptions dropped by approximate 2,100 (~10%) at the time that dabigatran was introduced (July 2011). The mean number of patients filling at least one prescription each month for the first six months of 2011 (before dabigatran) was 20,530; the mean for the second six months of 2011 was 18,423. There has been a steady fall in prescription numbers over the last 10 years. The mean for six months from October 2020 to March 2021 was 11,308; a fall of 45% from before the introduction of dabigatran and 38.6% since 2012 (Figure 1).  

Dabigatran

The number of patients filling prescription for dabigatran had increased steadily since August 2011, until the introduction of rivaroxaban. Approximately 7,000 patients filled prescriptions for dabigatran each month immediately after its introduction. This has increased by approximately 2% each month since then to approximately 40,000 per month by July 2018, when rivaroxaban was introduced, and has increased more slowly since; the mean of six months from October 2020 to March 2021 was 53,000 (Figure 1).

Rivaroxaban

The number of patients filling prescriptions for rivaroxaban has increased steadily since its introduction in August 2018. We have assumed that patients who had a single prescription for 10mg were receiving treatment for surgical prophylaxis. An increasing number are receiving long term therapy at 10mg. In March 2021, 23,000 prescriptions were dispensed (Figure 2).

View Figures 1 & 2.

Patient numbers

Approximately 46,500 people were taking warfarin at the time dabigatran was introduced. The number dropped to approximately 41,600 within six months (~10%). The number of patients on warfarin remained constant until mid-2014, and subsequently the number fell to 36,000 by March 2017; 29,500 by March 2019; and 23,200 by March 2021—a fall of 50% since April 2011 (before dabigatran).

The number of patients on dabigatran rose to approximately 8000 in August 2011, and has shown a consistent increase to mid-2015, and faster growth to mid-2018 to a total of 51,000 patients. Dabigatran numbers only increased by a further 3,000 between July 2018 and March 2021.

In August 2018, rivaroxaban was fully funded and use has grown rapidly since with approximately 30,000 people prescribed treatment by March 2021. The total number of patients on anticoagulants has risen consistently since the introduction of dabigatran from 46,000 to approximately 105,000; an increase of 140% over 10 years (Figure 3).

Changing anticoagulants

During the first month after the introduction of dabigatran, approximately 5,000 people switched from warfarin to dabigatran; however, a large proportion of these changed back to warfarin over the next six months.

From 2012 to 2014, the number of people starting dabigatran each month has risen steadily and the majority are new to the medication, with only a small number switching from warfarin to dabigatran (<100 per month) and a similar number changing the other way. From 2014 to 2018, the number of people starting dabigatran increased more rapidly and more people switch from warfarin to dabigatran, but the latter group are still only a small proportion of the total (<10%).

The number of people who discontinue dabigatran every month is high, and almost half as many discontinue treatment as start each month. These are either people who stop dabigatran completely and have no further prescriptions, or people who have an interval of more than three months between prescriptions.  

Following the introduction of rivaroxaban in August 2018, approximately 300 people each month changed from dabigatran to rivaroxaban and the growth in dabigatran use has declined (Figure 4).

View Figures 3 & 4.

Patient age

The mean age for people on warfarin has risen progressively from 2011 to 2018 and has subsequently shown a slight fall. The age of people on dabigatran has been stable over the whole study period, but since 2018 there has been a trend to use the drug in older patients. Rivaroxaban was initially used in younger patients as it was probably primarily used to manage venous thrombosis but shows a similar trend to dabigatran (Figure 5).

Impact of lockdown

On 23 March 2020, the Government announced that New Zealand would go into Level 4 lockdown on 25 March. The country reverted to Level 3 on 27 April 2020. Our data shows that during the week immediately prior to lockdown the number of prescriptions increased. During lockdown there was a brief reduction in dispensing. There was no clear evidence that the number of warfarin prescriptions dropped following lockdown (Figure 6).

View Figures 5 & 6.

Estimates of anticoagulant use

Historical audit data prior to 2011 showed that approximately 60% of patients are on warfarin for AF, 20% for VTE treatment and prevention, 12% for prosthetic heart valves and 8% for other reasons.[[7,8]] On this basis, we estimate that approximately 27,500 patients were on anticoagulants for AF prior to the introduction of dabigatran.

The total number of patients on warfarin for mechanical heart valves and “other” indications would be expected to remain constant over time. Also, the total number of patients on treatment for acute VTE is likely to remain stable, although from July 2014 treatment would be split between dabigatran and warfarin. The management of the prevention of recurrent VTE has changed with more patients being advised to remain on long term anticoagulants especially with the convenience of the DOACs. We have estimated that anticoagulants for VTE could have doubled over 10 years.

Based on our estimates, the number of patients on anticoagulants for AF has increased 2.8 times from 27,500 in July 2011 to 78,000 by 2021.

Proportion of patients in New Zealand on anticoagulants

The number of people in New Zealand on anticoagulants presented by age group is shown in Table 2. This is based on population data from Statistics New Zealand (data for 2020).[[9]]

View Tables 1 & 2.

Discussion

The most striking finding is that the total number of people on oral anticoagulants in New Zealand has more than doubled over 10 years; from 46,000 in 2011 to over 100,000 by 2021 (Figure 3). Although we do not have clinical details of the patients, our estimates suggest that most new cases are likely to be receiving anticoagulants for stroke prevention in AF; approximately 27,000 people were on anticoagulants for AF in 2011 and this has increased to over 70,000 by 2021 (Table 1). This is in line with data from other countries which show that 90% of patients on DOACs are taking them for stroke prevention in AF.  This marked increase in use means approximately 12% of people over the age of 70yrs in New Zealand are on anticoagulants, and this rises to 17% in those over 80yrs (Table 2).

It was predicted that the introduction of the DOACs would lead to a move away from warfarin, as the new anticoagulants are more convenient and have a better safety profile with a lower incidence of intracranial bleeding; however, the transition has been slower than many expected. One explanation is that there was some nervousness around the risk of bleeding soon after dabigatran was introduced. In July 2011, approximately 5,000 people switched to dabigatran, but within weeks cases of serious bleeding were reported[[10]] which led to a large proportion changing back to warfarin. Nonetheless, this initial enthusiasm for a new anticoagulant led to a 12% drop (46,500 to 41,300) in patients on warfarin by the end of 2011. The concern around bleeding led to a change in practice with both clinicians[[11]] and the dabigatran manufacturers, recommending that patients stable on warfarin should remain on treatment and that dabigatran should be primarily used for new patients. This would explain why the warfarin numbers remained relatively stable between 2012 and 2015 (Figure 3), supported by the data that shows only a small proportion of patients change from warfarin to dabigatran each month (Figure 4). The steady increase in the median age over time is also in keeping with the warfarin population being relatively stable (Figure 5).

The more rapid decline in warfarin since 2015 is probably due to dabigatran being approved for venous thromboembolic disease; the DOACs are now largely used as first line treatment for venous thrombosis and pulmonary embolus. Warfarin use is likely to reach a plateau as patients with mechanical heart valves, lupus anticoagulant or unusual thromboses need to remain on warfarin and there are some people who cannot tolerate either of the available DOACs. The baseline level is hard to predict, as warfarin use continues to fall steadily and there is currently no sign of a plateau.

During the COVID-19 pandemic in 2020, our results showed there had been no change in warfarin use despite the advice from THANZ. In March 2020, there was an increase in the number of prescriptions dispensed immediately prior to lockdown which subsequently dropped during lockdown itself. However, by May 2020 the number of prescriptions for all three medications had recovered to the pre-lockdown level, and there has been no clear evidence of a more rapid move away from warfarin use since (Figure 6).

The uptake of DOACs has steadily increased and continues to rise. The number of people on dabigatran exceeded those on warfarin by the end of 2016, and currently over 50,000 people take this medication. Practice changed following the introduction of rivaroxaban in 2018, and rivaroxaban appeared to have become the preferred DOAC. It has the advantage of being a “once daily” medication, and can be used for the treatment of DVT and PE from diagnosis without the need for a low molecular weight heparin; hence, it has become the drug of choice for managing acute venous thrombosis.

The clinical impact of these changes is uncertain, but it potentially has both positive and negative effects. The expected benefit is that a higher proportion of people with AF are receiving anticoagulants, and therefore the incidence of embolic stroke should be reduced. This is yet to be confirmed and is part of an ongoing study.

The downside to the wider use of anticoagulants is the increased risk of bleeding. The long-term use of both warfarin and DOACs has been associated with a higher incidence of bleeding complications particularly in the elderly.[[12–14]] This can be problematic for those admitted to hospital, especially if they require urgent surgery. Patients on anticoagulants admitted with trauma have a higher complication rate with more requiring surgical intervention.[[15]]

Anticoagulants are used directly as preventative medicine to reduce the risk of stroke in AF and to prevent recurrence in DVT and PE. It is appropriate that all patients who are likely to benefit have access to these drugs. However, the increase in anticoagulant use has been dramatic over the last 10 years, and it is important that clinicians have the necessary knowledge to use these drugs safely, are aware of the potential complications and the impact these have on our health system.

Summary

Abstract

Aim

To assess the change in the use of oral anticoagulants in New Zealand over 10 years since the introduction of dabigatran and rivaroxaban.

Method

Data were collected from the National Pharmaceutical database from January 2011 to March 2021. Seven and a half million prescriptions for oral anticoagulants were analysed.

Results

The total number of people taking oral anticoagulants increased from 46,000 in July 2011 to 105,000 by March 2021. The growth was predominantly from the increased use of direct oral anticoagulants (DOACs). Initially, dabigatran was the only funded DOAC in New Zealand; approximately 50,000 people were taking this medication by August 2018, when rivaroxaban was introduced. Subsequent growth has predominantly been from rivaroxaban, with 23,000 users by March 2021. Warfarin use has dropped by 50% over the last 10 years.

Conclusion

The introduction of the DOACs was expected to reduce the use of warfarin. However, the rapid rise in DOAC use was not predicted. The increase is most likely in patients with atrial fibrillation with the positive benefit of reducing the incidence of embolic stroke. However, having a high proportion of the elderly population (15% of people over 75-years) on anticoagulants has implications for the health sector, making hospital admissions and surgery more complex.

Author Information

Dr Paul Harper: Consultant Haematologist, Dept. of Clinical Haematology, Palmerston North Hospital, Palmerston North. Dr Alison Chang: Haematology Registrar, Dept. of Clinical Haematology, Palmerston North Hospital, Palmerston North. Dr Matt Stephens: Consultant Haematologist, Dept. of Clinical Haematology, Palmerston North Hospital, Palmerston North.

Acknowledgements

The Ministry of Health for provision of the pharmaceutical database data.

Correspondence

Dr Paul Harper: Consultant Haematologist, Dept. of Clinical Haematology, Palmerston North Hospital, Palmerston North. 021 852235.

Correspondence Email

Paul.harper@midcentraldhb.govt.nz

Competing Interests

Nil.

1) Preliminary report of the Stroke Prevention in Atrial Fibrillation Study. N Engl J Med. 1990;322:863-8.

2) Petersen P, Godtfredsen J, Boysen G, et al. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: The Copenhagen AFASAK Study. The Lancet. 1989;333:175-9.

3) Ogilvie IM, Newton N, Welner SA, et al. Underuse of Oral Anticoagulants in Atrial Fibrillation: A Systematic Review. Am J Med. 2010;123:638-645.e4.

4) Pechlaner C. Anticoagulation for atrial fibrillation: Underuse? Am J Med. 2011;124:e11.

5) Tomlin A, Lloyd H, Tilyard M. Atrial fibrillation in New Zealand primary care: Prevalence, risk factors for stroke and the management of thromboembolic risk. Eur. J. Prev. Cardiol. 2017;24:311-9.

6) THANZ [Internet]. [cited 2021 Jul 26]. Available from: https://www.thanz.org.au/news/outpatient-inr-monitoring-for-patients-receiving-warfarin-during-covid-19-pandemic

7) Young L, Ockelford P, Harper P. Audit of community-based anticoagulant monitoring in patients with thromboembolic disease: is frequent testing necessary? Intern Med J. 2004;34:639-41.

8) Kirley K, Qato DM, Kornfield R, et al. National Trends in Oral Anticoagulant Use in the United States, 2007 to 2011. Circ Cardiovasc Qual Outcomes. 2012;5:615-21.

9) Statistics New Zealand. [accessed 2021 Jul 26]. Available from: http://infoshare.stats.govt.nz/ViewTable.aspx?pxID=83faf750-e860-4102-877d-9e6baedadd1c

10) Harper P, Young L, Merriman E. Bleeding Risk with Dabigatran in the Frail Elderly. N Engl J Med. 2012;366:864-6.

11) Baker R, Harper P, McLintock C. Avoiding adverse events with dabigatran by careful selection of eligible patients. Med J Aust. 2012;196:431-2.

12) Khan F, Tritschler T, Kimpton M et al. Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism. Ann Intern Med. 2021;174:1420-1429.

13) Gunasekaran K, Rajasurya V, Devasahayam J et al. Review of the Incidence Diagnosis and Treatment of Spontaneous Hemorrhage in Patients Treated with Direct Oral Anticoagulants. J. Clin. Med. 2020, 9, 2984.

14) Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use: a prevalent adverse effect resulting in regulatory action. Arch Intern Med. 2007;167:1414-9.

15) Bläsius FM, Laubach M, Andruszkow H, et al. Impact of anticoagulation and antiplatelet drugs on surgery rates and mortality in trauma patients. Sci Rep. 2021;11:15172.

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