Pravastatin therapy for primary prevention in the elderly did not reduce mortality

1. In this post-hoc analysis of the Lipid-Lowering Trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT) randomized control trial, pravastatin use for patients over 65 years with no evidence of atherosclerotic vascular disease did not reduce all cause or cardiovascular mortality.

2. There was a non-significant trend towards increased mortality in participants 75 years and older, which may highlight the increased risk of statin-related adverse effects in this age group.

Evidence Rating Level: 2 (Good)       

Study Rundown: While evidence supports the use of statins for secondary prevention of cardiovascular morbidity and mortality, the role of statin therapy as primary prevention, particularly in the elderly, is more controversial. Recently, the HOPE-3 trial demonstrated lower rates of cardiovascular outcomes, but not all cause mortality for patients taking rosuvastatin for primary prevention. This study was a post hoc analysis using data from the ALLHAT-LLT trial that evaluated the effect of pravastatin on all-cause mortality when used in a population of older adults (65 years and older) with hypertension and no known baseline atherosclerotic cardiovascular disease (ASCVD). The study found no benefit in cardiovascular or all-cause mortality following 6 years of statin therapy, though there was a trend towards increased mortality in adults over the age of 75 years.

This investigation had a large sample size of a well-studied population from a randomized control trial. The major weaknesses included the post hoc design with unbalanced confounders such as hypertension, as well as significant cross over from the control arm to initiate statin therapy. Additionally, as pravastatin 40mg (goal dose) is a moderate-intensity statin, the effects seen in this study may not reflect the effects of high-intensity statins.

Click to read the study, published in JAMA Internal Medicine

Relevant Reading: Cholesterol lowering in intermediate-risk persons without cardiovascular disease

In-Depth [post-hoc analysis]: This study was a post hoc analysis of the Lipid Lowering Trial (LLT) component of the Hypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) which took place from 1994 to 2002 and evaluated patients 65 years and older with a history of hypertension. Patients were included if they were 65 years or older without evidence of ASCVD (from coronary heart, cerebrovascular, or peripheral vascular disease) and had LDL-C between 120 to 180 mg/dL and triglycerides lower than 350 mg/dL. Participants were excluded if they had baseline lipid-lowering therapy, intolerance of statins, hepatic/renal disease, or secondary causes of hyperlipidemia. Primary outcome was all-cause mortality, while secondary outcomes included cause-specific mortality, and non-fatal myocardial infarction. Intervention was pravastatin titrated up to 40 mg daily, compared to usual care.

A total of 2867 participants were included in the final analysis, with study arms balanced with respect to cholesterol levels, age, sex, race, and smoking status. The pravastatin arm had a lower proportion of patients on antihypertensives (86.7% vs. 92.9%, p = 0.01), and higher systolic blood pressure measurements (p = 0.01). By the 6^th year of follow up, 77.9% of patients in the pravastatin arm remained on statin therapy, while 29.0% of the control arm had started statin treatment. There was no difference in all-cause (p = 0.09) or cause specific mortality between study arms. There was a non-significant trend towards increased mortality in the pravastatin arm for patients 75 years and older (HR 1.34; 95%CI 0.98-1.84; p = 0.07).

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