CHD in Moderately Hypercholesterolemic, Hypertensive Patients
Background In previous analyses in ALLHAT, blacks had a significantly lower risk of coronary heart disease (CHD) in the pravastatin group compared to the usual care group, whereas non-blacks had no benefit from pravastatin. No previous statin trial has reported results separately in blacks.
Objectives The study aimed to determine if apparent racial differences in CHD in ALLHAT are explained by differences in baseline characteristics, adherence during the trial, or achieved blood pressure and lipid lowering.
Methods This was a prespecified subgroup analysis of a randomized controlled trial. Hypertensive, moderately hypercholesterolemic participants were assigned to open-label pravastatin (40 mg/d) or usual care. The outcome was a composite of nonfatal myocardial infarction and fatal CHD. We performed intention-to-treat survival analyses using Cox proportional hazards models, adjusting for baseline covariates (age, sex, aspirin use, history of CHD and diabetes, and baseline hypertension treatment) and time-varying levels of blood pressure and total cholesterol.
Results After adjustment for baseline characteristics, there remained a significant interaction between race and treatment group (P = .02). In stratified models, blacks in the pravastatin group had a 29% lower risk of CHD (hazard ratio [HR] 0.71, 95% CI 0.57–0.90, P = .005) compared to those in the usual care group, whereas non-blacks had no benefit (HR 1.00, 95% CI 0.85–1.19, P = .95). With further adjustment for achieved blood pressure and total cholesterol, the HR in blacks was 0.65 (95% CI 0.45–0.96, P = .03) and in non-blacks was 1.07 (95% CI 0.81–1.41, P = .65).
Conclusions Our results suggest that pravastatin is effective in preventing CHD in blacks.
Randomized trials of cholesterol-lowering treatment with statins have shown significant reductions in the risk of myocardial infarction, death, the need for coronary revascularization, stroke, coronary heart disease (CHD) mortality, and all-cause mortality. The effect on major CHD events is proportional to the absolute reduction in low-density lipoprotein (LDL) cholesterol achieved, and does not vary by important participant characteristics such as sex, previous history of CHD, treatment for hypertension, blood pressure (BP), history of diabetes, or level of baseline lipids. However, the effects of cholesterol-lowering treatment in blacks have not been examined, either in single trials or in meta-analyses.
The ALLHAT included a lipid lowering trial (LLT) designed to evaluate the impact of treatment with an HMG coenzyme A reductase inhibitor (pravastatin) on all-cause mortality (primary end point) in a hypertensive cohort with other CHD risk factors. Coronary heart disease was a prespecified secondary end point. A substantial proportion of the participants was black (38%), a group that has been underrepresented in previous studies. The intervention group received pravastatin and the comparison group received usual care from their personal physicians rather than a placebo. We have previously reported that ALLHAT-LLT did not show a significant reduction in either cardiovascular events or mortality, in contrast to other large statin trials. One potential explanation for these findings was diminished power and a smaller than expected reduction in cholesterol resulting from treatment crossovers. In particular, a large proportion of participants in the usual care group (nearly 20% at year 4) began lipid-lowering therapy.
However, these analyses suggested a significant (P = .03) race–treatment group interaction for CHD in the ALLHAT-LLT. Blacks had a significant 27% lower risk of CHD events in the pravastatin group, whereas non-black subjects had no benefit from pravastatin (Figure 1). Because previous analyses did not adjust for potential confounders of the relationship between race and treatment effects, in this article, we explore whether the apparent racial differences in CHD incidence in ALLHAT are explained by differences in baseline risk factors, adherence during the trial, or achieved BP and lipid lowering.
(Enlarge Image)
Figure 1.
Coronary heart disease event rate by race and lipid treatment group. Blacks in the pravastatin group (black line) had a significantly lower risk of CHD events compared to non-black subjects in the pravastatin group (blue line) and both blacks (green line) and non-blacks (red line) in the usual care group.
Abstract and Introduction
Abstract
Background In previous analyses in ALLHAT, blacks had a significantly lower risk of coronary heart disease (CHD) in the pravastatin group compared to the usual care group, whereas non-blacks had no benefit from pravastatin. No previous statin trial has reported results separately in blacks.
Objectives The study aimed to determine if apparent racial differences in CHD in ALLHAT are explained by differences in baseline characteristics, adherence during the trial, or achieved blood pressure and lipid lowering.
Methods This was a prespecified subgroup analysis of a randomized controlled trial. Hypertensive, moderately hypercholesterolemic participants were assigned to open-label pravastatin (40 mg/d) or usual care. The outcome was a composite of nonfatal myocardial infarction and fatal CHD. We performed intention-to-treat survival analyses using Cox proportional hazards models, adjusting for baseline covariates (age, sex, aspirin use, history of CHD and diabetes, and baseline hypertension treatment) and time-varying levels of blood pressure and total cholesterol.
Results After adjustment for baseline characteristics, there remained a significant interaction between race and treatment group (P = .02). In stratified models, blacks in the pravastatin group had a 29% lower risk of CHD (hazard ratio [HR] 0.71, 95% CI 0.57–0.90, P = .005) compared to those in the usual care group, whereas non-blacks had no benefit (HR 1.00, 95% CI 0.85–1.19, P = .95). With further adjustment for achieved blood pressure and total cholesterol, the HR in blacks was 0.65 (95% CI 0.45–0.96, P = .03) and in non-blacks was 1.07 (95% CI 0.81–1.41, P = .65).
Conclusions Our results suggest that pravastatin is effective in preventing CHD in blacks.
Introduction
Randomized trials of cholesterol-lowering treatment with statins have shown significant reductions in the risk of myocardial infarction, death, the need for coronary revascularization, stroke, coronary heart disease (CHD) mortality, and all-cause mortality. The effect on major CHD events is proportional to the absolute reduction in low-density lipoprotein (LDL) cholesterol achieved, and does not vary by important participant characteristics such as sex, previous history of CHD, treatment for hypertension, blood pressure (BP), history of diabetes, or level of baseline lipids. However, the effects of cholesterol-lowering treatment in blacks have not been examined, either in single trials or in meta-analyses.
The ALLHAT included a lipid lowering trial (LLT) designed to evaluate the impact of treatment with an HMG coenzyme A reductase inhibitor (pravastatin) on all-cause mortality (primary end point) in a hypertensive cohort with other CHD risk factors. Coronary heart disease was a prespecified secondary end point. A substantial proportion of the participants was black (38%), a group that has been underrepresented in previous studies. The intervention group received pravastatin and the comparison group received usual care from their personal physicians rather than a placebo. We have previously reported that ALLHAT-LLT did not show a significant reduction in either cardiovascular events or mortality, in contrast to other large statin trials. One potential explanation for these findings was diminished power and a smaller than expected reduction in cholesterol resulting from treatment crossovers. In particular, a large proportion of participants in the usual care group (nearly 20% at year 4) began lipid-lowering therapy.
However, these analyses suggested a significant (P = .03) race–treatment group interaction for CHD in the ALLHAT-LLT. Blacks had a significant 27% lower risk of CHD events in the pravastatin group, whereas non-black subjects had no benefit from pravastatin (Figure 1). Because previous analyses did not adjust for potential confounders of the relationship between race and treatment effects, in this article, we explore whether the apparent racial differences in CHD incidence in ALLHAT are explained by differences in baseline risk factors, adherence during the trial, or achieved BP and lipid lowering.
(Enlarge Image)
Figure 1.
Coronary heart disease event rate by race and lipid treatment group. Blacks in the pravastatin group (black line) had a significantly lower risk of CHD events compared to non-black subjects in the pravastatin group (blue line) and both blacks (green line) and non-blacks (red line) in the usual care group.