No benefit statin use for primary prevention in the elderly
In a secondary analysis of the ALLHAT-LLT trial, mortality and coronary heart disease events were not lower with pravastatin compared to usual care for primary prevention in the elderly.
Effect of Statin Treatment vs Usual Care on Primary Cardiovascular Prevention Among Older AdultsLiterature - Han BH, Sutin D, Williamson JD et al. - JAMA intern med 2017; epub ahead of print
Background
The number of older adults is increasing rapidly, as well is the proportion of older adults that use statins for primary prevention. However, data are limited on the risks and benefits of statins in this age group [1,2]. Until recently, the Framingham Heart Study risk model was used to make decisions regarding statin initiation for primary prevention [3]. However, it has been demonstrated that this risk score is inaccurate for prediction of cardiovascular events among the oldest adults [4,5]. In addition, concerns have been raised about the use of statins in asymptomatic adults, particularly the older patients. Clinical trials evaluating the use of statin in this patient population show contradictive results regarding morbidity. This may be due to the heterogeneity of the effects of statins when used for primary prevention in older age groups [6].
The objective of this study was to conduct secondary data analyses of several important outcomes (primary all-cause mortality) of 2867 older adults (≥65 yrs) without baseline atherosclerotic cardiovascular disease (ASCVD) from the ALLHAT-LLT trial (Antihypertensive and lipid-lowering treatment to prevent heart attach trial – lipid lowering trial)[7], to evaluate the overall benefit for older patients by using pravastatine (conducted from 1994-2002). Patients were categorized into 65-74 years or ≥75 years.
Main results
- Years of follow-up differed significantly between pravastatin-treated patients and usual care patients (4.63 vs. 4.77 years, P=0.04). Also, number of patients above 75 years taking antihypertensive medications and the blood pressure differed significantly between treatment groups at baseline.
- Total cholesterol as well as LDL-c levels were lower at the 2-year, 4-year and 6-year follow-up visits in the pravastatin group compared with the usual care group across all age groups. In the pravastatin group, LDL-c changed from 147.7 to 109.1 mg/dL at year 6, which was 147.6 to 128.8 mg/dL in the usual care group.
- All-cause mortality was higher in the pravastatin group compared with the usual care group in both age groups (65-74yrs HR 1.08 ,95% CI 0.85-1.37, P=0.55 and ≥75yrs 1.34 ,95% CI 0.98-1.84, P=0.07).
- Regarding coronary heart disease, HRs were 0.85 (95% CI 0.62-1.15, P=0.29) and 0.70 (95% CI 0.43-1.13, P=0.14) for patients 65-74yrs and 75 yrs, respectively.
- Also stroke, heart failure and cancer rates were similar between 2 treatment groups for both age groups.
- Using multivariable cox regression, the adjusted HR for all-cause mortality was 1.15 (95% CI 0.94-1.39, P=0.17) for 65 years and older, 1.05 (95% CI 0.82-1.33) for 65-74 years and 1.36 (95% CI 0.98-1.89) for above 75 years (P interaction = 0.24).
Conclusion
Newly administered statin use for primary prevention had no benefit on all-cause mortality of coronary heart disease events compared to usual care in adults older than 65 years with hypertension and moderate hypercholesterolemia in the ALLHAT-LLT trial. In contrast, a non-significant direction towards increased all-cause mortality was noted with the use of pravastatin in patients of 75yrs and older.
Editorial comment
In this editorial [8], Dr. Curfman mentions that the US preventative services task force last year concluded that there is insufficient evidence to conclude about the balance of benefits and harms of statin therapy for the primary prevention of cardiovascular events and mortality in adults older than 75 years. Nevertheless, they are commonly prescribed to these patients and the prevalence of use is increasing. He notes that there is limited data about statin use in the patient group from the PROSPER, JUPITER and HOPE-3 clinical trials, in which is concluded that there is modest benefit on composite cardiovascular outcomes but not on all-cause mortality. He further elaborates on the trend towards increased mortality when using pravastatin in the ALLHAT-LLT trial, in which side effects known for statins may play a role.
References
1. Johansen ME, Green LA. Statin use in very elderly individuals, 1999-2012. JAMA Intern Med.
2015;175(10):1715-1716.
2. Weinberger Y, Han BH. Statin treatment for older adults: the impact of the 2013 ACC/AHA cholesterol guidelines. Drugs Aging. 2015;32(2):87-93.
3. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97(18):1837-1847.
4. de Ruijter W,Westendorp RG, Assendelft WJ, et al. Use of Framingham risk score and new
biomarkers to predict cardiovascular mortality in older people: population based observational
cohort study. BMJ. 2009;338:a3083.
5. Krumholz HM, Seeman TE, Merrill SS, et al. Lack of association between cholesterol and
coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. JAMA. 1994;272(17):1335-1340.
6. Redberg RF, Katz MH. Statins for primary prevention: the debate is intense, but the data are
weak. JAMA Intern Med. 2017;177(1):21-23.
7. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major
outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs
usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
(ALLHAT-LLT). JAMA. 2002;288(23):2998-3007.
8. Curfman G, Risks of Statin Therapy in Older Adults, JAMA intern med 2017, epub ahead of print