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Editorial
Statins after acute coronary syndrome: a missed opportunity Gregory A Roth During and immediately following a myocardial infarction, care providers routinely explain the role of statins as a way to reduce the chance of further coronary events and even death. Hospitalised and recalling their recent chest pain, patients are usually highly receptive to this idea of taking a statin medication every day. Some may be reassured that clinical guidelines, supported by large clinical trials, give statins their strongest level of evidence.1 Physicians who follow these patients in clinic might conclude that statin use is widely adopted and well maintained, but these physicians could not possibly know for sure. Statins are among the most effective of medical therapies, but our ability to know if they are actually being used remains severely limited. Into this information gap steps researchers who are able to find and follow the ‘entire denominator’—every patient in a country that has received care for an acute coronary syndrome. The paper by Grey et al2 is an excellent example, and tells the story of New Zealand’s experience delivering statins to acute coronary syndrome (ACS) survivors in fine detail. Using a national data system that links public hospital records, outpatient pharmaceutical claims and death certificates, they were able to identify almost every ACS patient in their country and follow their pharmacy purchases for 3 years. This retrospective analysis included a cohort of over 11 000 individuals, most of whom experienced a non-ST elevation myocardial infarction (MI) or unstable angina. As would be expected for those suffering from coronary artery disease, this was an older population (mean age of 67 years) and predominantly male (63%). As would be expected from this kind of real-world study, the cohort included a distribution of ethnicity and socioeconomic background that looks much like the country as a whole. They found that full adherence to statin therapy was maintained by only 69% of the cohort during the first year following the index event, falling to 66% over the next Correspondence to Dr Gregory A Roth, Division of Cardiology, University of Washington, 2301 5th Avenue, Suite 600, Seattle, WA 98121, USA; [email protected] 752
3 years. Independent predictors of lower adherence included age 35–44 years, female sex, and Maori and Pacific ethnicity, but not a neighbourhood-level measure of socioeconomic deprivation. While data collection is far easier and less costly in this kind of retrospective analysis than in prospective studies, significant challenges remain nonetheless. Grey et al have expertly navigated these methodological challenges and, in doing so, provide an example of careful pharmacoepidemiology. By investigating ACS, they are using administrative ICD10 codes that are well validated against clinical records. This data is recent, covering the years 2007–2010 and, therefore, reflects current clinical practice and public perception. They appropriately excluded those patients who died soon after leaving the hospital, or spent most of their time in a chronic care facility. They also excluded patients at the extremes of the age spectrum where diagnoses, clinical care and patient decision making may differ from common practice. They adopted a simple and widely used metric, the medication possession ratio (MPR), as an outcome measure. MPR divides the number of pills dispensed at pharmacy by the number of days during which they are needed. Attaining an MPR of 80% is a common and accepted outcome that represents a lower bar for adherence in most patients. Perhaps the most important conclusion to draw from this work, considering the current fascination with Big Data and social networks, is the ease with which some countries can link large datasets in order to yield important insights into health and healthcare. Data linkage is an old tool. Beginning in the 1970s, early MONICA (Multinational MONItoring of trends and determinants in CArdiovascular disease) studies manually linked hospital care to death certificates.3 In the USA in the 1990s, the Cooperative Cardiovascular Project laboriously abstracted over 16 000 patient charts from billing records that reported ACS.4 In the present study, these intensive efforts have been replaced by an encrypted and unique national identifier that was used to connect data managed by different government departments. This
kind of record linkage is becoming a new standard for population studies of pharmacotherapy. For example, with the advent of a government-sponsored prescription drug benefit in the USA, the pharmacy data of 60 million patients can now be studies.5 While Grey et al demonstrate the power of linking national health data systems, they mostly substantiate the poor adherence to statins found in prior studies. Phase Z of the A to Z trial randomised patients with ACS to placebo followed by 20 mg versus 40 mg, followed by 80 mg doses of simvastatin for 2 years.6 This study went so far as to assume a 15% discontinuation rate in their sample size calculations. In fact, treatment was discontinued by 32% and 34%, respectively. PROVE-IT 22 randomised patients following ACS to pravastatin 40 mg versus atorvastatin 80 mg, and found discontinuation rates of 21–23%.7 More directly relevant to the question of adherence in a real-world setting was the recent MI-FREEE (Mi-freee PostMyocardial Infarction Free Rx Event and Economic Evaluation) trial, which randomised patients with myocardial infarction to standard or waived copayment for their cardiovascular prescriptions. Over the following 3 years, patients only achieved an 80% MPR for statins of 31.6% and 38.6%, respectively (p
Editorial
Statins after acute coronary syndrome: a missed opportunity Gregory A Roth During and immediately following a myocardial infarction, care providers routinely explain the role of statins as a way to reduce the chance of further coronary events and even death. Hospitalised and recalling their recent chest pain, patients are usually highly receptive to this idea of taking a statin medication every day. Some may be reassured that clinical guidelines, supported by large clinical trials, give statins their strongest level of evidence.1 Physicians who follow these patients in clinic might conclude that statin use is widely adopted and well maintained, but these physicians could not possibly know for sure. Statins are among the most effective of medical therapies, but our ability to know if they are actually being used remains severely limited. Into this information gap steps researchers who are able to find and follow the ‘entire denominator’—every patient in a country that has received care for an acute coronary syndrome. The paper by Grey et al2 is an excellent example, and tells the story of New Zealand’s experience delivering statins to acute coronary syndrome (ACS) survivors in fine detail. Using a national data system that links public hospital records, outpatient pharmaceutical claims and death certificates, they were able to identify almost every ACS patient in their country and follow their pharmacy purchases for 3 years. This retrospective analysis included a cohort of over 11 000 individuals, most of whom experienced a non-ST elevation myocardial infarction (MI) or unstable angina. As would be expected for those suffering from coronary artery disease, this was an older population (mean age of 67 years) and predominantly male (63%). As would be expected from this kind of real-world study, the cohort included a distribution of ethnicity and socioeconomic background that looks much like the country as a whole. They found that full adherence to statin therapy was maintained by only 69% of the cohort during the first year following the index event, falling to 66% over the next Correspondence to Dr Gregory A Roth, Division of Cardiology, University of Washington, 2301 5th Avenue, Suite 600, Seattle, WA 98121, USA; [email protected] 752
3 years. Independent predictors of lower adherence included age 35–44 years, female sex, and Maori and Pacific ethnicity, but not a neighbourhood-level measure of socioeconomic deprivation. While data collection is far easier and less costly in this kind of retrospective analysis than in prospective studies, significant challenges remain nonetheless. Grey et al have expertly navigated these methodological challenges and, in doing so, provide an example of careful pharmacoepidemiology. By investigating ACS, they are using administrative ICD10 codes that are well validated against clinical records. This data is recent, covering the years 2007–2010 and, therefore, reflects current clinical practice and public perception. They appropriately excluded those patients who died soon after leaving the hospital, or spent most of their time in a chronic care facility. They also excluded patients at the extremes of the age spectrum where diagnoses, clinical care and patient decision making may differ from common practice. They adopted a simple and widely used metric, the medication possession ratio (MPR), as an outcome measure. MPR divides the number of pills dispensed at pharmacy by the number of days during which they are needed. Attaining an MPR of 80% is a common and accepted outcome that represents a lower bar for adherence in most patients. Perhaps the most important conclusion to draw from this work, considering the current fascination with Big Data and social networks, is the ease with which some countries can link large datasets in order to yield important insights into health and healthcare. Data linkage is an old tool. Beginning in the 1970s, early MONICA (Multinational MONItoring of trends and determinants in CArdiovascular disease) studies manually linked hospital care to death certificates.3 In the USA in the 1990s, the Cooperative Cardiovascular Project laboriously abstracted over 16 000 patient charts from billing records that reported ACS.4 In the present study, these intensive efforts have been replaced by an encrypted and unique national identifier that was used to connect data managed by different government departments. This
kind of record linkage is becoming a new standard for population studies of pharmacotherapy. For example, with the advent of a government-sponsored prescription drug benefit in the USA, the pharmacy data of 60 million patients can now be studies.5 While Grey et al demonstrate the power of linking national health data systems, they mostly substantiate the poor adherence to statins found in prior studies. Phase Z of the A to Z trial randomised patients with ACS to placebo followed by 20 mg versus 40 mg, followed by 80 mg doses of simvastatin for 2 years.6 This study went so far as to assume a 15% discontinuation rate in their sample size calculations. In fact, treatment was discontinued by 32% and 34%, respectively. PROVE-IT 22 randomised patients following ACS to pravastatin 40 mg versus atorvastatin 80 mg, and found discontinuation rates of 21–23%.7 More directly relevant to the question of adherence in a real-world setting was the recent MI-FREEE (Mi-freee PostMyocardial Infarction Free Rx Event and Economic Evaluation) trial, which randomised patients with myocardial infarction to standard or waived copayment for their cardiovascular prescriptions. Over the following 3 years, patients only achieved an 80% MPR for statins of 31.6% and 38.6%, respectively (p
