One important unresolved problem in the management of blood pressure is elevated risk of coronary heart disease (CHD). Dyslipidemia is highly prevalent in hypertensive patients. However, there are a number of patients not deemed dyslipidemic. To date, there have been no major trials addressing the potential impact of lipid lowering on CHD incidence in hypertensives without dyslipidemia.

Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) is a randomized, controlled trial that sought to evaluate the role of cholesterol lowering in hypertensive patients who have normal or mildly elevated cholesterol levels. Recruiting centers included almost 700 general practices in Scandinavian countries and 32 regional centers in the United Kingdom.

The study included almost 20,000 patients with high blood pressure. Investigators randomized the patients to receive 1 of 2 blood pressure lowering regimens: a beta blocker plus a diuretic, or a calcium channel blocker plus an ACE inhibitor.

In addition, 10,305 patients participated in a second part of the study. These patients all had total cholesterol levels less than 250 mg/dL. Current treatment guidelines in the United States and Europe consider 250 mg/dL to be normal or slightly elevated. Investigators randomized these patients to receive atorvastatin 10 mg or placebo. Investigators refer to this second part as the lipid lowering arm of the trial.

The primary endpoint of the lipid lowering arm was non-fatal myocardial infarction or fatal CHD. Investigators expected a 30% relative effect on this endpoint versus placebo.

Of the study participants in the lipid lowering arm, 81% were men, and the mean age was 63 years. All had hypertension and at least three other risk factors for CHD. The Data Safety Monitoring Board stopped the trial early because of a significant reduction in the primary endpoint. At the point of closure, there was a median follow-up of 3.3 years.

Analysis revealed that the patients achieved very good blood pressure control in both the atorvastatin and placebo control group. Blood pressure at follow-up was 138/80 mmHg, down from 164/95 mmHg at baseline. Total cholesterol, similar in the atorvastatin and placebo group at baseline; at 3.3 years, there was a 1.1 mmol/L difference favoring atorvastatin.

Primary endpoint analysis showed a 36% reduction in non-fatal myocardial infarction and fatal CHD at 3.3 years in the atorvastatin arm. Investigators noted that the difference between atorvastatin and placebo emerged earlier than in other major statin trials.

In addition, investigators reported significant reductions in fatal or non-fatal stroke (27%, p=0.0236), all cardiovascular events and procedures (21%, p=0.0005) and all coronary events (29%, p=0.005). There was a trend toward reduction in total mortality favoring atorvastatin, but this did not reach statistical significance.

Investigators performed a number of prespecified subgroup analyses. They found no difference in outcomes. This suggests the benefit of atorvastatin in treated hypertensives applies to a variety of subgroups, including patients with diabetes, smokers, obese individuals, and patients with renal dysfunction.

Safety evaluations showed no significant difference in the number of fatal cancers, serious adverse events or liver enzyme abnormalities between atorvastatin and placebo. There was one case of rhabdomyalysis in the atorvastatin group. However, this occurred in a severely alcoholic patient who had a recent febrile illness.

Investigators said the reductions in major adverse cardiac events they observed are large and notable because they occurred within a relatively short follow-up period. Had follow-up continued to a median of 5 years, investigators expect they would have observed a 50% reduction in CHD events.

Furthermore, the benefit of the statin occurred much earlier than in many other statin trials. It is not clear whether the early benefit occurred because of the lipid lowering effect of the statin or some Investigators believe the bulk of evidence so far suggests early reduction in LDL cholesterol is a very important contributor to this effect.

The challenge for cardiologists is to incorporate a new therapy into the antihypertensive armamentarium. Already, many patients could have better blood poorly controlled blood pressure. This is partly because they do not adhere to potentially effective treatment regimens, and partly because physicians are not treating hypertension aggressively. However, investigators believe doctors should not exclude statins as a potentially effective treatment for primary prevention of CHD in hypertensive patients.