Peer Reviewed
Primary Prevention of Cardiovascular Disease: Aspirin or Statin?
Aspirin has been a mainstay of treatment for a very long time and because many are comfortable with it, it continues to be used routinely now. However, for those of us who have thoroughly consumed the 2013 American College of Cardiology/American Heart Association (ACC/AHA Cholesterol Guidelines—and followed the hard-to-overlook controversy that it generated, both in the medical and lay press, the debate has escalated. Though the FDA has started to provide guidance that aspirin likely should not be used as widely as it currently is as the bleeding risk outweighs the potential benefits, many clinicians are not still unaware of the evidence for each agent. In our clinical practice, however, this fight of aspirin versus statins in primary prevention is something that we see on a daily basis. To help primary care and other healthcare providers gain a better understanding of the pros and cons of both, we present this hypothetical case along with supporting information on the impact of both aspirin and statins on patients.
Information Gathering
A 64-year-old white female presents to your office for a visit asking about treatment options to reduce future risk for heart attack. Though she has a past history of hypertension (HTN) that is well controlled with 5 mg of indapamide daily, she does not take any other medications, does not smoke, and does not have any additional medical comorbidities. Her sudden concern over the possibility of a heart attack arose after a close personal friend recently suffered such an event. She would like your opinion on aspirin and cholesterol-lowering medications as she has read numerous media reports providing conflicting information regarding the benefits and risks of these agents. Blood pressure at the time of her visit was 142/85 mm Hg with lab results from blood drawn that day showing a high-density lipoprotein of 40 mg/dL and total cholesterol of 205 mg/dL.
Clinical Question
The big question on your mind is: Should this patient, who is otherwise healthy, be started on therapy to reduce her future risk of cardiovascular (CV) events? If so, which therapy (or therapies) would be considered optimal? Apart from addressing other risk factors (such as controlling HTN and encouraging exercise, proper diet, and smoking cessation), 2 therapies are likely to be considered: aspirin and statins. In order to fully define their optimal role, an understanding of the absolute risks and benefits of each therapy is necessary.
Evidence
The release of the 2013 ACC /AHA Cholesterol Guidelines in late 2013 has dramatically changed the overall approach to primary prevention of CV events and the clinical use of lipid modifying agents, most notably statins. Initially controversial (and still controversial for some), the 2013 ACC/AHA guidelines recommended risk assessment using the Pooled Cohort Risk Calculator to determine the 10-year risk for atherosclerotic cardiovascular disease (ASCVD) events. Statin therapy was recommended for those between the age of 40 to 75 years with a baseline low-density lipoprotein (LDL) of 70 to 189 mg/dL and an estimated ASCVD risk of 7.5% or higher who had no history of ASCVD. Although the selection of the 7.5% cutoff may seem arbitrary, the guideline committee believed this cutoff represented a reasonable point in which the benefits of statin therapy outweigh the potential risks.1
The use of this calculator and the risk assessment cutoff has been received with significant skepticism. Many question the risk calculator’s ability to predict future risk and how well it compares to previous methods of risk estimation, such as using Framingham risk calculator. The Framingham risk assessment was based on a cohort of patients from the 1940s that were followed through time to determine the association between baseline characteristics (such as lipid parameters, risk factors such as HTN, smoking, family history, age) to predict future risk of CV events.2 Although used clinically for many years, the assessment tool had several limitations that required the development of a novel risk calculator. Most importantly, Framingham was done in a predominantly white population, thus limiting its applicability to patients of other races and ethnicities. Second, it only predicted the future risk of coronary heart disease events such as unstable angina or myocardial infarction (MI); the Framingham calculator does not estimate such events as ischemic stroke.
Although not initially validated, and suspected to overestimate future risk for ASCVD events, the risk calculator was subsequently validated in a primary prevention population and was shown to accurately assess future risk.3 While the risk cutoff of 7.5% may seem arbitrary, meta-analyses have reported that the benefits of statin therapy outweighs the risk of adverse effects in patients with an estimated 10-year risk as low as 2.5%. Evaluation of the potential risks and benefits combined with a thorough discussion with the patient should be employed in all cases prior to beginning therapy, an exercise that is highly suggested by the ACC/AHA guidelines.
Statins: Benefits and Risks
Statins (or HMG-CoA reductase inhibitors) work to inhibit the synthesis of lipoproteins and lower LDL. Independent of their LDL lowering effects, statins also have additional unique benefits, most notably plaque stabilization and anti-inflammatory effects. In large-scale randomized trials in patients without a history of ASCVD (primary prevention) statins have been shown to have a relative risk reduction of 30 to 40%; these events include MI, stroke, coronary revascularization, and unstable angina. The absolute reduction in these events is on the order of 1% to 2% (number needed to treat 50-100). Importantly, this reduction in events is seen consistently in patients of all ages, sexes, and racial ethnicities.4
These benefits have to be considered in the context of risk, of which rhabdomyolysis is likely the most concerning. However, this outcome occurs at an estimated incidence of 3.4 events per 100,000 patient-years. Myopathy and cost are other important considerations: myopathy is more common than rhabdomyolysis but is not associated with such negative sequlae; all statins except rosuvastatin and pitavastatin are now generically available, making them affordable and accessible to most patients.5
Aspirin: Benefits and Risks
Through its antiplatelet effects, aspirin leads to a relative risk reduction for serious vascular events of approximately 20% in the setting of primary prevention. However, this relative risk reduction translates into an absolute risk reduction of approximately 0.1%. Furthermore, aspirin does not seem to have the same efficacy in all populations, as noted in 2009 by the United States Preventive Services Task Force (USPSTF). Their recommendations note that aspirin will only reduce the risk of MI in men and the risk of stroke in women— both sexes do not receive the same risk reduction for the same outcome.5
Bleeding is the biggest concern with aspirin therapy, most notably GI and intracranial hemorrhage (the most devastating adverse event). Estimates suggest the absolute risk of major bleeding is increased by 0.1% (number needed to harm 1000). Given the long history of aspirin use, this risk seems acceptable to many clinicians.6
Clinical Application
Based on this patient's age, blood pressure, and lipid results her estimated 10-year risk for ASCVD is 9.6%, suggesting a sufficient risk to warrant consideration of statin therapy based on the 2013 ACC/AHA guidelines. What about aspirin?
As noted in the USPSTF Guidelines, aspirin in this patient would only serve to reduce her future risk of stroke—no benefit is offered in terms of reducing the risk for MI, which was her main concern. Although the absolute risk for bleeding appears low with aspirin, so does the absolute benefit: on average a reduction of 0.1% (number needed to treat of 1000). On the other hand, statins offer a stronger degree of benefit (absolute reduction on the order of 1% to 2%, number needed to treat 50-100). Furthermore, statins will reduce the risk of both MI and stroke (along with other ASCVD events). Statins also carry a very low risk for severe adverse events (approximately 3 cases of rhabdomyolysis per 100,000 patient years).
Based on the available evidence, statins appear to have a more favorable risk-benefit profile. Upon review with the patient regarding potential risks and benefits, if she elects to begin therapy, we would suggest initiation of atorvastatin 20 mg daily in order to reduce her risk for future ASCVD events such as MI and stroke. This would be in addition to appropriate lifestyle modifications, always top of mind when advising patients on how to improve their health. ν
Eric A. Dietrich, PharmD, BCPS, graduated from UF College of Pharmacy in 2011 and completed a 2-year fellowship in family medicine where he was in charge of a coumadin clinic. He now works for UF Colleges of Pharmacy and Medicine.
Kyle Davis, PharmD, BCPS, is a clinical pharmacy specialist in internal medicine at Jackson Memorial Hospital in Miami, FL. A graduate of UF College of Pharmacy in 2011, he completed 2 years of internal medicine training at Jackson Memorial Hospital and Indiana University Health/Butler College of Pharmacy.
References:
1. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: a Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S1-S45.
2.Oppenheimer GM. Becoming the Framingham Study 1947–1950. Am J Public Health. 2005;95(4):602-610.
3.Muntner P, Colantonio LD, Cushman M, et al. Validation of the atherosclerotic cardiovascular disease Pooled Cohort risk equations. JAMA. 2014;311(14):1406-1415.
4. Dietrich E, Davis K. A statin a day to keep the doctor away? Comparing aspirin and statins for primary prevention of cardiovascular disease. Ann Pharmacother.2014;48(9):1238-1241.
5. US Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;150(6):396-404.