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Vale N, Nordmann AJ, Schwartz GG, de Lemos J, Colivicchi F, den Hartog F, Ostadal P, Macin SM, Liem AH, Mills E, Bhatnagar N, Bucher HC, Briel M. Statins for acute coronary syndrome. Cochrane Database Syst Rev. 2011 Jun 15;(6):CD006870. Review. PubMed PMID: 21678362.

Efficacy Endpoints

Death, heart attack, stroke, acute heart failure, unstable angina

Harm Endpoints

Myopathy, rhabdomyolysis

Narrative

Patients are at highest risk of severe adverse events in the early period after an episode of acute coronary syndrome (ACS). Beyond their cholesterol lowering properties, some experimental data suggests that statins may improve endothelial function, decrease platelet aggregation, and reduce inflammation. It has been hypothesized that these effects may reduce adverse outcomes if initiated soon after an episode of ACS.

The Cochrane review identified 18 randomized control trials with useable data comparing treatment with early administration of statins following an episode of ACS to placebo or standard treatment. The studies included 14,303 patients, had a population with ages ranging from 53-69 and were predominantly male (59-88%). This large, systematic review concluded that early initiation of statin therapy (within 14 days of MI) did not significantly decrease the risk of subsequent MI, death, revascularization, heart failure or stroke at 4 months follow up. The authors of the review do note, however, that there was a small decrease in episodes of hospitalization for unstable angina at 4 months, amounting to an approximately 1.5% absolute reduction, and suggesting a NNT of 67.

Caveats

Early addition of statins is a Level 1A recommendation by the ACC/AHA and guidelines state that statins should be started prior to hospital discharge regardless of baseline LDL level. This analysis and systematic review does not support these recommendations.

While the eventual addition of statin therapy for patients with established elevations in LDL cholesterol who have suffered a prior MI has been shown to improve long-term outcomes, giving statins in the acute or subacute period following a heart attack without attention to cholesterol levels appears to provide no benefit for virtually any major patient-important outcomes. Presumably because patient-level data was not available the Cochrane authors did not perform subgroup analysis based on entry LDL levels, thus it remains possible that those with elevated cholesterol may benefit in the short term.

There was a small decrease in rehospitalization for unstable angina and some may note that at 12 months there was a decrease in the secondary outcome of ‘revascularization’ procedures (ARR = 5%, NNT = 20). As we have noted in prior reviews, since the condition that led to these hospitalizations and procedures was not an MI, did not result in death, and is based on clinician judgment rather than anatomic disease or objective pathology, the need for these measures is questionable and does not meet our standard for a patient-important outcome or clinically important end-point.

Finally, it is a point of interest that this review, like many other Cochrane reviews, notes important and large discrepancies in the results of trials performed with lesser and greater methodologic rigor. As one may expect, statistical benefits of statin medications were considerably and consistently greater in trials that did not explicitly use methods such as blinding and allocation concealment. This finding suggests that benefits of these medications may be strongly exaggerated, or in some cases created, by methods that potentially introduce bias into the conduct of randomized trials. This highlights the importance of these methods in maximizing validity, and also supports the Cochrane Collaboration practice of routinely including subgroup analyses examining results separately from trials that do and do not employ these methods.

Author

Viral Patel, MD and Daniel Runde, MD

Published/Updated

September 28, 2011