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Clinical Scenario

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CLINICAL SCENARIO

As a cost-cutting strategy, your hospital's Phar—macy and Therapeutics Committee is recommending a strategy wherein drugs within the same class can be substituted at the level of the pharmacy for the generic or least costly within-class option. As a physician dealing predominantly with cardiovascular prevention, this would have important implications on your practice. Your clinical team questions the new policy, and several members argue that assuming that drugs with a similar chemical structure exert similar effect on patient-important outcomes without direct evidence is misguided. Statins are the most widely prescribed drug within your practice, and you wonder whether there is a therapeutic class effect for statins.

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Looking for Evidence of a Class Effect

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Determining whether drugs within a class exhibit similar or different therapeutic profiles can be challenging. Typically, a decision on whether a drug acts similarly to other agents with a similar biological makeup is based on an evaluation of the empirical data and pharmacopathophysiologic reasoning. Because of the inadequacies of the former and the subjective nature of the latter, a rigorous and reproducible process is required to support the establishment of whether biologically similar drugs exert a class effect.

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An underlying assumption when examining class effects—an assumption that may or may not be accurate—is that each drug offers similar therapeutic efficacy and safety. However, the methods for determining this are not well established.1 Determining whether a drug is sufficiently similar to another drug should be based on its evidence profile rather than on its name or biological mechanism of action alone.

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Using a series of methodologic questions, we review the clinical example of 3-hydroxymethyl-3-methylglutaryl coenzyme A reductase inhibitors (statins) to determine whether therapeutic substitution offers patients a sufficiently similar efficacy-safety profile to justify interchangeable use of different statins. We chose statins as the example because they have been well evaluated in more than 80 randomized clinical trials (RCTs) addressing patient-important outcomes,2 they are one of the most widely prescribed drugs in the history of modern medicine, and they are used for both primary and secondary cardiovascular disease (CVD) prevention.3,4

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Are the Agents Biologically Similar?

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There is no uniformly accepted definition of a class effect.1 Although the exact mechanism of action of drugs is rarely known, the biological target of a drug may be well established. For example, although all pharmacologic antihypertensives reduce blood pressure, there are several unrelated putative mechanisms involved (such as natriuresis with diuretics, inhibition of vascular cellular calcium influx with calcium channel blockers, and impaired synthesis of the vasoconstrictor angiotensin II with angiotensin-converting enzyme inhibitors). Although these different mechanisms may result in similar changes in blood pressure, their ultimate effect on cardiovascular morbidity and mortality may—and, in this case, do—differ.5,6 Clinical effects may differ even when 2 medications share the same primary pharmacologic action. ...

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