#67 How does high dose statin compare to low dose in people with heart disease?

CLINICAL QUESTION

QUESTION CLINIQUE

In patients with coronary heart disease (like previous myocardial infarction), what are the benefits and harms of prescribing high dose compared to low dose statins?

BOTTOM LINE

RÉSULTAT FINAL

In patients with coronary heart disease, using high dose statins (compared to low-moderate dose) prevents one coronary heart disease (CHD) event for every 91 patients but results in one in 47 patients discontinuing therapy due to adverse events. However, low-moderate dose statin (compared to placebo) provides 2-3 times greater benefit than increasing to high dose statin. Therefore, getting and keeping patients on any statin is key, with dose adjusted up to tolerable levels.

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EVIDENCE

DONNÉES PROBANTES

There at least six meta-analyses^1-6 :

Most recent: Ten trials, 41,778 patients with CHD. Mean trial duration 2.5 years.
- High dose is usually atorvastatin 80mg. Low-moderate dose varies: pravastatin 40 mg to lovastatin 5mg.
- Outcomes:
  - No difference in death, cardiovascular death, or fatal myocardial infarction (MI).
  - High dose reduced the combined endpoint of non-fatal MI and CHD death: 9.4% vs 10.5%, Number Needed to Treat (NNT) =91 over 2.5 years.
Other meta-analyses have similar results. High dose statins:
- Reduced mortality in patients with acute coronary syndrome: ^1,3 NNT=91 over two years.
- Increased adverse events leading to stopping therapy: Number Needed to Harm (NNH) =47.

Context

In patients with CHD, low-moderate dose statin (like 40mg pravastatin or 20-40mg simvastatin) compared to placebo:⁷
- Reduced CHD: NNT=27.
- Reduced mortality: NNT=56.
Benefits of low-moderate dose over placebo (relative benefit 25% for CHD⁷ ) are larger than the benefits of high dose over low-moderate dose (only 10% incremental benefit¹ ).
Adherence to statin therapy in the community is poor (worse than trials):
- Up to 50% discontinue statin by 3 years with adverse events often cited as a reason for stopping.^8-10
- Post-marketing data^11,12 indicates muscle-related side effects and transaminase abnormalities increase four-five fold when increasing atorvastatin from 40 mg to 80 mg.