Hypertension, But not "Prehypertension," Increases Stroke Risk -- and Should Combination Therapy Include a Calcium Antagonist?

March 16, 2004

In This Article

Combination Therapies More Effective in Acute Coronary Syndromes – More Support for the Polypill?

According to the results of a retrospective analysis of patients with ACS, survival was increased among those patients simultaneously given recommended medical therapies. Patients who received combination, evidence-based therapy consisting of antiplatelet, antihypertensive, and cholesterol-lowering agents showed a 72% to 87% reduction in mortality compared with those who did not, researchers from the University of Michigan (Ann Arbor) reported in Circulation.[9]

Clinical, demographic, management, and outcome data were abstracted from the medical charts of 1358 consecutive patients admitted to or discharged from the University of Michigan Medical Center between January 1999 and March 2002 with a diagnosis of unstable angina or MI. Data on management included the use of beta-blockers, aspirin, ACE inhibitors or ARBs, and lipid lowering agents. (The study predated current recommendations for dual therapy for aspirin and clopidogrel.)

An appropriateness algorithm for the use of each of the secondary pharmacologic prevention strategies was devised based on the current clinical practice guidelines of the American College of Cardiology and the American Heart Association.[10,11,12,13] A composite appropriateness score was calculated for each patient based on the number of drugs used at discharge divided by the number of drugs indicated. The impact of the score on 6-month mortality was analyzed using a risk-adjusted logistic regression model. These calculations showed that for patients who were on all 4 types of medications, the odds ratio for mortality was 0.0 compared with 0.10 for patients who receive none of the medications. For those using 3 of 4 indicated medications, the odds of mortality were 0.17, 0.18 when 2 of 3 or 4 medications were used, and 0.36 if only 1 medication of 3 or 4 was being used.

"We already know that these drugs work well individually. Our results indicate that the drugs work even better when they are used together in appropriate patients," said Debabrata Mukherjee, MD, commenting on the results of the analysis. He noted that secondary prevention therapies continue to be underutilized, despite "strong and unequivocal benefits of these agents." The investigators found that although about 95% of these patients received antiplatelet therapy, 82% beta-blockers, and 84% lipid-lowering agents, 40% did not receive ACE inhibitors, possibly because the recommendations for them are more recent, they suggest.

In an accompanying editorial, Harvey D White, DSc (Green Lane Hospital, Auckland, New Zealand) and James T Willerson, MD (St Luke's Episcopal Hospital/Texas Heart Institute, Houston) urged physicians to use current knowledge about proven therapies to reduce mortality in patients with ACS.[14] They note that although the cumulative risk reduction with all 4 therapies in the University of Michigan study might have been expected to be 68%, based on their each reducing mortality by 25%, the actual risk reduction seen by Dr Mukherjee and colleagues was 90%. Professor White and Dr Willerson believe that by application of current knowledge, mortality after an acute coronary syndrome could be reduced by as much as 80%. They say that "it is not sufficient to simply add 1 therapy in patients at high risk of future ischemic events. Instead, wherever clinically possible, patients should be started simultaneously on as many as 4 evidence-based therapies while they are still in hospital, combined with nonpharmacologic approaches to risk prevention such as smoking cessation, achievement of ideal weight, and graded exercise programs.

Professor White and Dr Willerson raise the possibility of simultaneous administration of these drugs in the form of a "polypill." This concept was first proposed for use in patients over the age of 55 years and patients with vascular disease last year by researchers from the United Kingdom.[15] Professor White and Dr Willerson suggest that a polypill for ACS patients would contain aspirin, a statin, a beta-blocker, and an ACE inhibitor. This would improve patient compliance, simultaneously reduce multiple risk factors, and would encourage physicians to prescribe 4 evidence therapies instead of 1 or 2, they reason. However, difficulty in identifying the component in the event of adverse events would be a major concern.

According to Anthony Rodgers, MD, PhD (University of Auckland, New Zealand), speaking at the 20th Scientific Meeting of the International Society of Hypertension, held February 15-19 in São Paulo, Brazil, the polypill represents "plain common sense" for people with vascular disease.[16] Dr Rodgers predicted that numerous formulations of the polypill, based on a cholesterol-lowering drug, 2 low-dose blood-pressure-lowering agents, and low-dose aspirin, with various other drugs added, will become available within 10 years. Side effects with the polypill are likely to be rare, with most coming from the low-dose aspirin, Dr Rodgers believes.

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