Statins After Stroke: What is the effect on mortality and morbidity?

Statins (cholesterol lowering drugs such as Lipitor or Crestor and others) have been shown to reduce major cardiovascular events after stroke and are considered the standard of therapy in patients with stroke. Most patients with new stroke are prescribed one of the statins when discharged from hospital. However, whether the beneficial effects of statins seen in strict clinical trials settings are also present in non-clinical trial settings remains to be seen. In other words, while it is established that statins have efficacy (work in clinical trials) it remains to be seen whether statin have effectiveness (work in usual delivery of healthcare).

The distinction between efficacy and effectiveness is an important one. A clinical trial has inclusion (and exclusion) criteria which limit enrollment to only a certain group of individuals. Patients who volunteer for clinical trials are also known to be more compliant and receptive to medical advice. Furthermore, patients in clinical trial are closely followed (and observed) and, therefore, perhaps get better care. Thus, results seen in a clinical trial setting may not hold true in the usual healthcare delivery environment where all sort of patients get drugs (or interventions), compliance may be an issue, and patients are not as closely followed. This necessitates effectiveness studies, which are not commonly performed, although thought to be quite important. Perhaps the biggest reason is that such studies are not required for a drug approval by FDA and perhaps drug companies fear that effectiveness studies may show that a particular drug (or intervention) is not as effective as shown in the clinical trial (or not effective at all).

It is then no surprise that effectiveness studies for statins in stroke (one of the commonly prescribed drug class) have not been done, that is until now. O’Brien et al report in this issue of circulation such an effectiveness study. Investigators linked data from Get With The Guidelines (GWTG)-Stroke register with the Medicare data and followed patients 2-year post-discharge for major cardiovascular events, time spent at home (out of hospital or nursing home), all cause mortality, readmissions to hospitals, and hemorrhagic stroke. Investigators report that from 2007–2011, 77,468 patients who were not taking statins at the time of admission were hospitalized with ischemic stroke. Of these 77K patients, 71% were discharged on some form of statin therapy; 31% on high-intensity statin therapy.

What they found was that the rates were lower for major adverse cardiovascular events (9% lower), mortality (16% lower), and readmission (7% lower) within two years of hospital discharge were lower for patients who were taking statins as compared with those not taking a statin. On average, patients also spent 28 more days at home. Of note, these results were adjusted for risk factors. There were no differences in rates of hemorrhagic stroke, ischemic stroke, or cardiovascular readmission by statin therapy.

Now contrast this data with the results from clinical trials of statins that showed a 20% reduction in major adverse cardiovascular events, 16% reduction in risk of ischemic stroke, and as high as 32% reduced risk of mortality. Obviously, as expected, the benefits are much larger in a clinical trial setting. This example, among others, highlights the need for effectiveness trials. Of note, this trial was funded through PCORI (a tax-payer funded program) and not by a drug company.