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To the heart of the matter: cardiac safety of non-cardiac drugs

Cardiovascular Pharmacotherapy

This session focused on safety for body systems that are not the therapeutic focus of specific drugs/biologicals.

Raymond Lipicky indicated that low exposure minima required for drug approval effectively preclude adverse event rates needed to confidently assess absolute risk/risk-benefit relations. He decried arbitrary adverse event threshold rates as bases for drug approval: adversity must be judged in relation to benefit to determine appropriateness for human use. He proposed specific study designs to enable exploration of full dose-response relations.

Dr. G. Calvo Rojas argued against surrogate end points for judging drug safety, noting the relatively poor predictive value for adversity of now-required ECG QT interval measurements. He supported defining drug approval policies based on optimal long-term impact rather than short-term results and political pressures.

Dr. Steven Nissen reviewed data related to antidiabetic drugs, decrying the “glucocentric” regulatory approach at the expense of cardiovascular outcomes, the reduction of which is one primary basis for diabetic therapy. He suggested selecting study populations to enhance adverse events, maximizing potential for confident risk-benefit analyses.

Dr. Frank Ruschitzka discussed the problem of agents featuring effects beneficial in one organ system but detrimental in another: in his example, macular degeneration was minimized by anti-VEGF while coronary artery events were increased. Dr. Ruschitzka debunked the “class effect myth”, the tendency to ascribe common clinical effects to different agents that share single pharmacological actions or structural features, unsupported by clinical outcomes.

Dr. Henry Krum extended this argument, citing non-steroidal anti-inflammatory drugs, some of which, at certain doses, are therapeutic for arthritides but adverse for cardiovascular outcomes. He highlighted the fallacy of inferring effects from putative mechanisms of action.

In summary, assessment of therapeutics requires measurement of clinical events, not surrogates; dose-response relations should be fully explored; confident risk-benefit relations require collection of sufficient events for unambiguous statistical evaluation.




To the heart of the matter: cardiac safety of non-cardiac drugs
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.