Effect of Statin Treatment vs Usual Care on Primary Cardiovascular Prevention Among Older Adults

Abstract

IMPORTANCE While statin therapy for primary cardiovascular prevention has been associated with reductions in cardiovascular morbidity, the effect on all-cause mortality has been variable. There is little evidence to guide the use of statins for primary prevention in adults 75 years and older. OBJECTIVES To examine statin treatment among adults aged 65 to 74 years and 75 years and older when used for primary prevention in the Lipid-Lowering Trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). DESIGN, SETTING, AND PARTICIPANTS Post hoc secondary data analyses were conducted of participants 65 years and older without evidence of atherosclerotic cardiovascular disease; 2867 ambulatory adults with hypertension and without baseline atherosclerotic cardiovascular disease were included. The ALLHAT-LLT was conducted from February 1994 to March 2002 at 513 clinical sites. INTERVENTIONS Pravastatin sodium (40 mg/d) vs usual care (UC). MAIN OUTCOMES AND MEASURES The primary outcome in the ALLHAT-LLT was all-cause mortality. Secondary outcomes included cause-specific mortality and nonfatal myocardial infarction or fatal coronary heart disease combined (coronary heart disease events). RESULTS There were 1467 participants (mean [SD] age, 71.3 [5.2] years) in the pravastatin group (48.0% [n = 704] female) and 1400 participants (mean [SD] age, 71.2 [5.2] years) in the UC group (50.8% [n = 711] female). The baseline mean (SD) low-density lipoprotein cholesterol levels were 147.7 (19.8) mg/dL in the pravastatin group and 147.6 (19.4) mg/dL in the UC group; by year 6, the mean (SD) low-density lipoprotein cholesterol levels were 109.1 (35.4) mg/dL in the pravastatin group and 128.8 (27.5) mg/dL in the UC group. At year 6, of the participants assigned to pravastatin, 42 of 253 (16.6%) were not taking any statin; 71.0% in the UC group were not taking any statin. The hazard ratios for all-cause mortality in the pravastatin group vs the UC group were 1.18 (95% CI, 0.97-1.42; P = .09) for all adults 65 years and older, 1.08 (95% CI, 0.85-1.37; P = .55) for adults aged 65 to 74 years, and 1.34 (95% CI, 0.98-1.84; P = .07) for adults 75 years and older. Coronary heart disease event rates were not significantly different among the groups. In multivariable regression, the results remained nonsignificant, and there was no significant interaction between treatment group and age. CONCLUSIONS AND RELEVANCE No benefit was found when pravastatin was given for primary prevention to older adults with moderate hyperlipidemia and hypertension, and a nonsignificant direction toward increased all-cause mortality with pravastatin was observed among adults 75 years and older. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00000542

Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study

“…In a recently published post hoc analysis of the ALLHAT-LLT study,12 which included patients with both hyperlipidaemia and hypertension, the authors performed a subanalysis including 726 people aged 75 years or older (375 receiving pravastatin and 351 receiving usual care) and found no reduction in all cause mortality or in CVD. Our results in participants without type 2 diabetes are in line with those of the ALLHAT-LLT study.…”

Statin Use and Adverse Effects Among Adults >75 Years of Age: Insights From the Patient and Provider Assessment of Lipid Management (PALM) Registry

“…Similarly, a recent observational study suggests a significant survival advantage exists among older adults with ASCVD treated with high‐ versus moderate‐intensity statins, amplified at maximal doses of high‐intensity statins 20. On the other hand, a recent post hoc analysis from the ALLHAT‐LLT (Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial) found a signal ( P =0.07) for possible increased all‐cause mortality among older adults treated with statins 7. These findings highlight the necessity for clinical trials to evaluate the efficacy and safety of statin therapy, including high‐intensity therapy, for both primary and secondary prevention of cardiovascular disease, specifically in older adults.…”

“…In addition, concerns have been raised about the adverse effects of statins and polypharmacy as a reason not to treat older patients as aggressively as younger patients 1, 6. Although data are mixed for primary prevention after the age of 75 years,7 studies in older patients with atherosclerotic cardiovascular disease (ASCVD) suggest no attenuation of benefit. The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults acknowledges the limitations of existing data on older individuals and recommends individualizing the decision to initiate statins for primary prevention in adults >75 years 1.…”

Judging the benefits and harms of medicines

“…7 The report says that future controversies could be prevented through better communication and, among other things, better access to data. But the debate about statins in people at low risk has not gone away, [8][9][10][11] and the anonymised trial data remain inaccessible. The academy could have put its weight behind calls for an independent review of the evidence, 12 similar to the review on breast cancer screening commissioned by the UK's cancer tsar in 2012.…”