POTENTIAL LIFE-THREATENING DRUG INTERACTION IN PATIENTS WITH HIGH CARDIOVASCULAR RISK: LESSON FROM HOPE-TOO TRIAL IN SLOVAKIA

Introduction. Prospective trials provide knowledge for evidence-based medicine, however, their application in real-life medicine often provide different  data.  
Patients.  Prospective randomised trial HOPE TOO in Slovakia involved  849 high risk CV pts (435 males – 51.2% and 414 females - 48,8%) aged 67,2 yrs (55– 88 yrs) followed for 5 yrs. Randomly allocated therapy with multivitamins/placebo failed to affect CV or total mortality (TM) and morbidity.
Method. All drugs were reported according to brand names (follow-up was not part of HOPE-TOO trial protocol, but was approved by Steering Committee). Potential drug interaction (PDI) were analysed according to Magulova at al  (2003) and only degree 3 (serious health-threatening – PDI3) and degree 4 (life-threatening- PDI4) were considered.
Results. Pts were treated with PDI3 in 40.4% and with PDI4 in 35.9% (combined PDI3 and PDI4 in 52.3%). The most common combinations of PDI4 were digoxin – furosemid (34,3% PDI yrl), ACEI – K-sparring diuretics (28,1 % PDI yrl) and  digoxin – tiazide diuretics (16,4% PDI yrl). Total mortality during the trial was 24,7%. Therapy with  PDI4 was associated with high risk of TM (OR=1,83, [1,33–2,51]; p<0.01) and with increased risk of  CV hospitalization (OR=2,15  [1,61– 2,87]; p<0.001). PDI4 with digoxine increased TM in all pts (OR=2,34 [1,67–3,28]; p<0.001), in pts with heart failure (OR=1,82 [1,08–3,06]; p<0.01) and in pts without heart failure (OR=2,34 [1,46–3,77]; p<0.001) as compare to digoxin treated  pts without PDI4 combination.
Conclusion. High risk CV pts treated in real-life medicine with combination of drugs with high potential for serious interaction had increased mortality and morbidity. Especially interactions with digoxin and K-sparring diuretics should be monitored and prevented.

Ref. Magulová et al . (2003): Interakcie liečiv v klinickej praxi, SAP, 2003.