While cardiovascular devices are clearly growing in the range of potential applications and therapeutic possibilities, this sector overall still appears to be taking a back seat to the continuing flow of pharmaceuticals being touted as treatment choices. The result is that heart failure patients, or those considered at high risk for cardiovascular disease, will continue to be faced with a growing number of pharmaceutical options – and prescriptions to be filled – in addition to their daily dose of aspirin.

Following are just a few examples from recent research suggesting that this growth will continue.

Antiplatelets. The American College of Cardiology (ACC; Bethesda, Maryland) and American Heart Association (AHA; Dallas, Texas) last month issued updated guidelines recommending the use of Plavix (clopidogrel bisulfate), an antiplatelet drug, to standard therapy for the treatment of heart failure – technically known as unstable angina or non-Q wave myocardial infarction. The guidelines support the use of Plavix for both those either being treated with drug therapy alone or with surgical intervention – that is, balloon angioplasty, with or without stent, or heart bypass surgery. The updated guidelines incorporate the results of the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) study, published in August 2001 in The New England Journal of Medicine. Eugene Braunwald, MD, faculty dean for academic programs at Brigham and Women's Hospital and Massachusetts General Hospital (both Boston, Massachusetts) and head of an ACC/AHA guidelines-developing committee, said the recommendation reflects "an improved understanding of the best treatment for people with unstable angina or mild heart attack" and could save "tens of thousands of lives." The FDA recently cleared an expanded use of Plavix for this treatment indication. Plavix, is co-marketed worldwide by Sanofi-Synthelabo (Paris) and Bristol-Myers Squibb (New York).

ACE inhibitors. Research reported in the March 23 issue of the British Medical Journal indicated that the blood pressure drug ramipril can protect against stroke in high-risk individuals, even if their blood pressure is normal. Rampiril is an ACE inhibitor, and this and other studies indicate this class of drugs reduces the risk of heart attack, stroke and other cardiovascular complications. Their findings come from a large international trial known as the HOPE study, which had previously shown that ramipril can cut the risk of heart attack, stroke and other complications among people with significant risk factors. The study compared the effects of ramipril, vitamin E, the drug and vitamin together, and inactive treatment with a placebo. Nearly 9,300 patients with stroke risk factors such as heart or blood vessel disease were followed for an average of 4.5 years. Ramipril cut the risk of stroke by one-third and the risk of fatal stroke by 61%, the study reported. In the US, ramipril is marketed as Altace by King Pharmaceuticals (Bristol, Tennessee), while in Europe, Aventis (Strasbourg, France) markets it as Tritace and Delix.

Antibiotics. Antiobiotics also have appeared on the horizon for cardiovascular therapy. At this year's ACC meeting, Pfizer (New York) reported on the use of this strategy to treat the bacteria Chlamydia pneumoniae, which is increasingly being found in heart attack patients, and increasingly associated with the development of atherosclerosis. C. pneumoniae is rarely found in normal tissue, but has been detected in up to 60% of artherosclerotic plaques. Pfizer reported that preclinical studies have shown that its antibiotic Zithromax (azithromycin) may affect the progression of atherosclerosis in animals exposed to C. pneumoniae. The company's study results showed that short-term treatment with Zithromax resulted in a 7% reduction in the incidence of recurrent cardiovascular events compared to placebo, a decline that was not considered statistically significant. In 1997, Pfizer began the first large-scale, placebo-controlled study, WIZARD (Weekly Intervention with Zithromax for Atherosclerosis and Related Disorders), to explore the complex link between infection and cardiac events.

Beta-blockers. Though physicians are often accused of prescribing too many pills, a research team at the University of Pittsburgh Medical Center (UPMC; Pittsburgh, Pennsylvania) says they need to do more – in particular the use of beta-blockers, long considered standard therapy. The study, termed a Heart Failure Report Card, indicates many doctors failing to prescribe them as supplements to standard therapy for certain heart failure patients, according to a survey conducted by the Cardiovascular Institute of UPMC. Beta-blockers generally are considered necessary as supplements to standard therapy. The survey polled 400 cardiologists, internists and general practitioners. It reported 87% of respondents saying they understand the benefits of beta-blockers, as shown in clinical trial data, but that they were prescribing them to only one-third of their patients as part of a standard regimen of treatment. The findings indicate that mindset lagging behind clinical evidence in terms of the frequency of beta-blocker prescribing, the researchers said. The Heart Failure Report Card was funded through an educational grant from AstraZeneca (London).

ARBS. Perhaps even better than beta-blockers are a new class of drugs called angiotensin II receptor blockers (ARBs). Researchers last month said Cozaar, from Merck & Co. (Whitehouse Station, New Jersey), outperformed one of the most widely used beta blockers, called atenolol, in a four-year trial. The results could widen use of Cozaar and other members of the new ARB class of drugs. The trial, whose conclusions were released in The Lancet, involved 9,193 people, ages 55-80, with hypertension and diagnosed with an enlarged left ventricle. Both drugs substantially reduced blood pressure to similar levels in the trial, but patients taking Cozaar had a 13% lower combined incidence of heart attack, stroke and death caused by cardiovascular problems than those taking atenolol. Almost 1,200 patients in the trial had already been diagnosed with diabetes when it began. And among them, the death rate was 39% less for those on Cozaar than atenolol. In addition to controlling blood pressure, the study suggests Cozaar works by other yet-unclear mechanisms to protect the heart and cardiovascular system.

Estrogen. Another drug-related strategy, this one for women, may be hormone replacement therapy. The March issue of the Journal of Clinical Endocrinology & Metabolism reported on the use of estrogen as a tactic for decreasing women's risk of developing atherosclerosis. Researchers at the Mayo Clinic (Rochester, Minnesota) examined the relationship between estrogen and atherosclerosis in the coronary arteries of 56 deceased women, ages 19 to 98, and found a strong "negative association between estrogen status in women and both coronary calcium and plaque." Lorraine Fitzpatrick, a professor of medicine at the Mayo Medical School, said the study "suggests that estrogen may slow the progress of coronary calcification and plaque formation."

Aspirin. No matter what pills some cardiovascular patients are prescribed, they probably need to take more aspirin. The Agency for Healthcare Research and Quality (AHRQ; Washington) reported last month that there has been an increase from 59% to 81% in the use of aspirin by heart patients between 1995 and 1999. While saying this reflects "substantial improvement" in this drug regimen, it also said that even more cardiovascular patients could benefit from aspirin. To support this conclusion, researchers at the Duke University Medical Center (Durham, North Carolina), one of seven AHRQ-supported research centers, surveyed more than 25,000 patients from the Duke Databank for Cardiovascular Disease. They found that patients who didn't take aspirin for reasons related to their heart conditions "had nearly twice the risk of dying than those who took the drug regularly."