|
||||||
|
|
|
|
|||||||||||
|
|||||||||||||
| ||||||||||||||||||||||||||||||||||||
Intensive statin therapy to lower LDL cholesterol well below the current target recommended for patients with stable coronary heart disease (CHD) reduces the risk of major cardiovascular events by 22% compared with moderate-dose statin therapy.1
This was just one highlight among news stories stemming from late-breaking clinical trials presented March 6–9 in Orlando, Fla., as part of the American College of Cardiology (ACC) Annual Scientific Session 2005. The gathering offered a wealth of interventional cardiology updates in addition to practical prevention and risk-reduction news for primary care providers.
Other important findings showed that a blood pressure–lowering drug regimen of a calcium-channel blocker (CCB) and an angiotensin-converting enzyme (ACE) inhibitor cuts stroke risk by 25% and heart complications by 15% compared with the older treatment of a beta-blocker and a diuretic. These results have not yet been published.
And investigators for the Women's Health Study of almost 40,000 women reported that daily low-dose aspirin therapy over 10 years does not prevent first heart attacks, although it does reduce stroke risk by 17%.2
BENEFITS OF AGGRESSIVE STATIN THERAPY
Current guidelines recommend an LDL cholesterol <100 mg/dl as the goal of therapy for patients with stable CHD and <70 mg/dl for patients with especially high risk, such as those who have CVD with multiple risk factors (especially diabetes), smokers, or those with metabolic syndrome. Investigators for the Treating to New Targets (TNT) trial wanted to find out if intensive statin therapy to reach the high-risk goal would be safe and beneficial even for patients with stable CHD.
TNT started with about 15,500 patients with stable CHD and a mean LDL cholesterol level at baseline between 130 mg/dl and 250 mg/dl who were treated daily with 10 mg of atorvastatin (Lipitor, Pfizer). After this 8-week run-in phase, 10,000 patients with LDL cholesterol levels <130 mg/dl were randomly assigned to two groups. One group continued to receive 10 mg of atorvastatin per day while the other received 80 mg of atorvastatin per day.
After 5 years, the high-dose statin group had an average LDL of 77 mg/dl, and the moderate-dose group had an average LDL of 101 mg/dl. Patients getting intensive atorvastatin treatment had a 22% lower risk of suffering a major cardiovascular event, including heart attack, stroke, and sudden cardiac arrest, compared with patients receiving 10 mg of atorvastatin.
"This was not an equivocal result," says lead investigator John C. LaRosa, MD, president of the State University of New York Downstate Medical Center in Brooklyn. "We have entered a new era in the treatment of established coronary heart disease."
Results were published online by the New England Journal of Medicine while LaRosa presented the data in Orlando. Pfizer funded the study.
LaRosa notes that the study was not designed to detect differences in overall mortality between the two groups, something Bertram Pitt, MD, takes issue with in an editorial accompanying the published study.3 Pitt also questions the lack of conclusive data explaining the slightly higher number of deaths from non-cardiovascular causes associated with the 80-mg dose of atorvastatin.
LaRosa says the researchers looked at every death and found "no pattern whatsoever." He says prescribing 80 mg of atorvastatin daily is "absolutely safe."
"We saw essentially no toxicity, no negative effects, and a very positive and robust effect on events," LaRosa says. "Morbidity is an important end point. If I said you had 5 years to live, and you could choose to live those 5 years with a debilitating stroke or with all your faculties, you wouldn't have any trouble making that choice."
CHALLENGING BETA-BLOCKER TREATMENT
Presenting the preliminary results from the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm (ASCOT-BPLA), investigators reported that the superior cardiovascular effects of a CCB/ACE inhibitor–based strategy for treating hypertension may signal the end of the era of beta-blockers as an initial treatment for high blood pressure.
The trial involved more than 19,000 hypertensive patients randomized to receive either the CCB amlodipine (Norvasc, Pfizer) with or without the ACE inhibitor perindopril (Aceon, CV Therapeutics/Solvay Pharmaceuticals; Coversyl, Servier) or the beta-blocker atenolol (Tenormin, AstraZeneca) with or without a diuretic.
The study's steering committee halted the trial early, in November 2004, after observing that patients in the amlodipine/perindopril arm had about a 15% reduction in all-cause mortality and determining that patients in the beta-blocker arm were disadvantaged. Amlodipine/perindopril also cut the risk of stroke by 25% and the risk of serious heart complications by 15%.
"What we expect, at least in the U.K., is a meeting of the guideline committee to reevaluate the future place of beta-blockers as first-line treatment of hypertension," says Peter S. Sever, MD, of Imperial College in London, who led the presentation.
He acknowledged that beta-blockers are indicated for patients with a prior myocardial infarction or symptomatic CHD. But in cases of uncomplicated hypertension, "I think the ASCOT data raise serious questions about the future position of beta-blockers," he says.
Confirming findings from previous studies, the trial also showed treatment with a beta-blocker and a diuretic increased the risk of developing new diabetes by one-third more than treatment with a CCB and an ACE inhibitor.
"It's clear that patients on any regime containing a beta-blocker and, even worse, a diuretic, are 30% more likely to develop diabetes," Sever says. "Something about this drug induces diabetes, and this is not good news."
|
The ASCOT-BPLA results presented at the ACC sessions are preliminary, Sever notes, but they represent about 95% of the data, and he says he does not expect them to change substantially before the final results are presented in September.
Commenting on the results, Richard B. Devereux, MD, of Weill Medical College of Cornell University in New York, points out that 20 years of research show that the older regimen of a beta-blocker and diuretic is effective in reducing blood pressure by 18% to 40%. "It is not by any means a placebo," Devereux says.
Co-investigator Bjorn Dahof, MD, of Sahlgrenska University Hospital in Oslo, Norway, says the results cannot be attributed to any particular drug. "It's a strategy of a drug combination," Dahof says. Reconsidering the role of beta-blockers will have to be cautiously approached, he adds.
SEX-BASED DIFFERENCES IN ASPIRIN THERAPY
The Women's Health Study, funded by the National Heart, Lung, and Blood Institute, enrolled almost 40,000 healthy women aged 45 to 80. Half the women were randomized to receive 100 mg of aspirin on alternate days while the other half received placebo. Results were presented March 7 at the ACC meeting and published simultaneously in the New England Journal of Medicine.
After 10 years, the regular low-dose aspirin therapy did not prevent first heart attacks or death from heart disease in women, but it did reduce the incidence of stroke by 17%.
Co-investigator Julie E. Buring, ScD, of Brigham and Women's Hospital in Boston notes that the finding on stroke is particularly relevant to women. She points to 2002 figures from the American Heart Association (AHA) that show women have 10% more strokes than heart attacks, while men have 40% fewer strokes than heart attacks.
The most consistent benefit was seen in a subgroup of women over age 65, for whom aspirin reduced the risk of major cardiovascular events by 26%.
"From a clinical standpoint, the new data suggest that many women, particularly over age 65, are likely to attain a net benefit from preventive aspirin therapy," says co-investigator Paul Ridker, MD, a cardiologist at Brigham and Women's Hospital.
The American Diabetes Association recommends aspirin therapy (75–162 mg/day) as a primary prevention strategy in those with type 2 diabetes at increased cardiovascular risk, including those who are >40 years of age or who have additional risk factors, such as a history of hypertension, smoking, dyslipidemia, albuminuria or a family history of cardiovascular disease (CVD). Diabetes was present in 2.6%, or about 1,000, study participants. Almost 31% of the subjects had a body mass index (BMI) between 25 and 30, and 18% had a BMI >30.
The AHA published guidelines in February 2004 for reducing CVD in women that include recommendations for aspirin use by varying levels of risk. But those guidelines do not recommend regular use of low-dose aspirin for low-risk women, pending the results of ongoing trials.
In a media advisory, AHA president Alice Jacobs, MD, stresses that it is well established that aspirin therapy helps reduce heart attacks and strokes among women with known CVD and that, unless contraindicated, these women should receive aspirin therapy.
Buring says the recommendations of the Women's Health Study researchers are the same for women as for men: The decision to use aspirin to prevent heart disease or stroke should be made individually with the help of a physician.
"It's a true risk-to-benefit ratio, for a man or a woman."
References
2. Ridker PM, Cook NR, Lee IM, et al.: A randomized trial of low-dose
aspirin in the primary prevention of cardiovascular disease in women.
N Engl J Med 352:1293–1304, 2005.
3. Pitt B: Low-density lipoprotein cholesterol in patients with stable
coronary heart disease—is it time to shift our goals? N Engl
J Med 352:1483–1484, 2005.
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
| ||||||||||||||||||||||||||||||||||||
|
||||||
|
| DOC News | Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |
