In general, randomized clinical trials in CS are difficult to perform and only three randomized trials adequately powered to detect differences in clinical outcomes achieved completion of the required number of patients.

Based on the SHOCK trial, early revascularization has been adopted into clinical practice leading to a relevant reduction in mortality.

The IABP-SHOCK II and CULPRIT-SHOCK trials challenged common assumptions and led to rapid changes in guideline recommendations.

However, despite major advances in PCI technique and antithrombotic pharmacology during the approximately 20 years between the SHOCK trial and these two trials the 30-day mortality of CS remained nearly unchanged in the range of 40–50%.

Obviously, this is disappointing and research efforts and also public and industry funding should be directed more rigorously to CS.

Despite indisputable complexities of performing clinical studies in CS, it has now been repeatedly shown that such trials can be successfully performed.

International activities may be required to build large CS research networks to answer the multiple open questions in treatment as reflected by the high number of recommendations with a level of evidence C in current guidelines.

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