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[Clinical study of the month. The ALLHAT-LLT trial]
1Service de Diabétologie, Nutrition et Maladies métaboliques et de Médecine interne générale, CHU, Sart Tilman.
Insights
Pravastatin did not significantly reduce all-cause mortality or coronary heart disease events in older hypertensive patients compared to usual care. The small cholesterol reduction difference likely explains these findings in this large trial.
Area of Science:
- Cardiovascular Medicine
- Clinical Trials
- Pharmacology
Background:
- The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) investigated the efficacy of various treatments for cardiovascular disease prevention.
- The ALLHAT-LLT (Lipid-Lowering Treatment) component specifically assessed the role of pravastatin in a high-risk population.
Purpose of the Study:
- To determine if pravastatin, compared to usual care, reduces all-cause mortality in older, hypertensive patients with hypercholesterolemia and at least one coronary heart disease (CHD) risk factor.
Main Methods:
- 10,355 ambulatory patients (≥55 years) with specific cholesterol and triglyceride levels were randomized to pravastatin (40 mg/d) or usual care.
- Follow-up averaged 4.8 years, with lipid-lowering drug use monitored in the usual care group.
- All-cause mortality and CHD event rates were the primary endpoints.
Main Results:
- Pravastatin reduced total cholesterol by 17.2% and LDL-C by 28% compared to baseline; usual care reduced them by 7.6% and 11%, respectively.
- All-cause mortality was similar between groups (14.9% vs. 15.3% at 6 years; RR 0.99).
- CHD event rates were also not significantly different (9.3% vs. 10.4% at 6 years; RR 0.91).
Conclusions:
- Pravastatin did not demonstrate a significant benefit in reducing all-cause mortality or CHD events in this patient population.
- The limited differential in LDL-C reduction between pravastatin and usual care, due to the open-label design and statin use in the usual care group, likely contributed to the observed results.
- These findings suggest that the magnitude of LDL-C lowering may be a critical factor in achieving mortality benefits with statin therapy in such trials.
Abstract:
ALLHAT-LLT was part of the ALLHAT study. The purpose was to determine whether pravastatin compared with usual care reduces all-cause mortality in older, moderately hypercholesterolaemic, hypertensive patients with at least one additional coronary heart disease (CHD) risk factor. 10,355 ambulatory patients, aged 55 years or more, with LDL cholesterol of 120-189 mg/dl (or, 100-129 mg/dl if known CHD) and triglycerides < 350 mg/dl, were randomised to pravastatin (40 mg/d; n = 5,170), or usual care (n = 5,185). Mean age was 66 years; 49% were women; 38% were black and 23% hispanic; 14% had a history of CHD and 35%, type 2 diabetes. Baseline mean total cholesterol was 224 mg/dl; LDL-C, 146 mg/dl; HDL-C, 48 mg/dl, and triglycerides, 152 mg/dl. Mean follow-up was 4.8 years. Among usual care patients, 32% of those with known CHD and 29% of those without CHD started taking lipid-lowering drugs. At year 4, total cholesterol was reduced by 17.2% with pravastatin and by 7.6% with usual care. A random sample had their LDL-C levels assessed: there was a reduction of 28% with pravastatin and of 11% with usual care. All-cause mortality was similar in the two groups (RR, 0.99; 95% CI, 0.89-1.11; p = 0.88), with 6-year mortality rates of 14.9% (pravastatin) and 15.3% (usual care). CHD event-rates were not different between the two groups (RR, 0.91; 95% CI, 0.79-1.04; p = 0.16); 6-year CHD event rates were 9.3% (pravastatin) and 10.4% (usual care), respectively. These results are likely due to the small differential in total cholesterol (9.6%) and LDL-C (16.7%) between pravastatin and usual care, compared with prior statin trials. Such an unusual differential essentially results from the open table of the study and from the possibility of prescribing a statin in the usual care group.