Will this brufen gie me a heart attack doctor

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Will this brufen gie me a heart attack doctor?

• Morag Mahon
• Sept 05

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Risk of myocardial infarction in patients taking
Cox2 inhibitors or conventional NSAIDs

• Hippisley-Cox and Coupland
• BMJ, June 11 2005

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Background

• Recent concerns re cardiovascular safety
• VIGOR study
• Withdrawal of rofecoxib
• Major trials have excluded people with known IHD.

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Methods

• Population-based observational nested
  case-control study
• GP database - gt7 million UK patients
• Study period 1/8/00 to 31/7/04
• Cases - all new MIs (age 25-100)
• Controls - matched for age, sex, practice
• Exposure assessed by prescribing records

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Statistical analysis

• Conditional logistic regression
• Odds ratios with 95 CIs
• Adjusted for confounding factors
• Comorbidity, smoking, deprivation, use of
  aspirin, statins and other NSAIDs
• Repeated with restrictions to certain groups

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Results

• Adjusted odds ratio for MI with use of drug
  within previous 3 months (95 CI)
• Diclofenac 1.55 (1.39 to 1.72) plt0.001
• Rofecoxib 1.32 (1.09 to 1.61) p0.005
• Ibuprofen 1.24 (1.11 to 1.39) plt0.001
• Tendency to increase risk but not significant
• Celecoxib, Naproxen and other selective and
  non-selective NSAIDs

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Results cont.

• No needed to harm (for pt.s gt65yrs) with use of
  drug in previous three months
• Diclofenac 521
• Rofecoxib 695
• Ibuprofen 1005

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Results 3

• Adjusted odds ratio for gt 3 prescriptions
• Diclofenac 1.46 (1.33 1.6)
• Ibuprofen 1.14 (1.03 1.27)
• Naproxen 1.27 (1.06 1.53)

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Strengths

• Large numbers, longer follow-up
• Includes pt.s with coronary heart disease
• Includes younger patients
• Adjusted for comorbidities, aspirin use etc
• No recall bias

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Weaknesses

• Observational study - risk of bias and residual
  confounding factors unadjustable
• Confounding by indication - angina misdiagnosed
  as M/S - Rx with NSAIDs
• Possible misclassification - OTC ibuprofen

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Conclusions of study

• Increased risk of MI with Diclofenac, Rofecoxib
  and Ibuprofen
• No evidence of cardioprotective effect of
  naproxen
• enough concerns exist to warrant a
  reconsideration of the cardiovascular safety of
  all NSAIDs

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Discussion

• The critical analysis bit
• Substantial differences between cases and
  controls
• Retrospective analysis
• No other cause addressed
• The drug or the disease
• Misdiagnosis
• Inflammation increases risk
• ??Increased exercise tolerance
• Warrants attention

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What next?

• Randomised control trial.
• MRHA

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Until then.

• Pills for aches and pains is killer
• (The Sun)
• Ibuprofen increases risk of heart attack by 24
  warn doctors
• (The Independent)

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• Healthy scepticism
• Pragmatic approach
• Any suggestions??