Perindopril heart failure

Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease Trial... 

With the data included in the overview of Garg et al. (316), it is possible to calculate that 18 patients need to be treated for 90 days to avoid one death or one hospitalization for congestive heart failure (95% confidence interval [Cl] 16-23). This meta-analysis includes 32 trials with the ACE inhibitors captopril, enalapril, lisinopril, quinapril, ramipril, and perindopril. It is likely that high doses (for instance, lisinopril 35 mg daily) are more effective than low doses (lisinopril 5 mg daily) (302). Treating 30 patients for 4 years with a high dose of lisinopril (95% Cl 16-509) will avoid one hospitalization for cardiovascular reasons or one death in comparison with a low dose, without increasing the number of adverse effects requiring withdrawal from treatment. 

Perindopril is a prodrug ester of perindoprilat, an ACE inhibitor that has been used in patients with hypertension and heart failure. An updated review of its use in hypertension has appeared (1). 

More recent data suggest that all patients with CAD, not just ACS or heart failure patients, benefit from an ACE inhibitor. In the Heart Outcome Prevention Evaluation (HOPE) trial, ramipril significantly reduced the risk of death, MI, or stroke in high-risk patients aged 55 years or older with chronic CAD or with diabetes and one cardiovascular risk factor. The more recent European trial On Reduction Of Cardiac Events With Perindopril In Stable Coronary Artery Disease (EUROPA) extended the benefit of chronic therapy with ACE inhibitors to patients with stable CAD at lower risk of cardiovascular events compared with patients from the HOPE trial. In the EUROPA trial, patients randomized to perindopril experienced a lower risk of the combined end point of cardiovascular death, MI, or cardiac arrest compared with patients randomized to placebo. Therefore, based on the extensive benefit of ACE inhibitors in patients with CAD, their routine use should be considered in all patients following an ACS in the absence of a contraindication. 

Based on these results treatment with an ACE inhibitor was recommended for patients with CAD and/or diabetes in addition to those indicated by the SAVE and SOLVD trials. The EUROPA trial (84) confirmed the HOPE results by demonstrating that ACE inhibitors were of benefit in the treatment of stable, low-risk patients with CAD as well. A 2% absolute risk reduction in the composite endpoint of cardiovascular mortality, nonfatal MI, and cardiac arrest was achieved using perindopril over a mean of 4.2 years. Patients with clinical heart failure were excluded and ejection fraction was not assessed. 

There is some evidence that in patients with heart failure the incidence of marked orthostatic hypotension requiring treatment discontinuation in the first 36 hours was lower with perindopril 2 mg once daily than captopril 6.25 mg three times daily (6 of 357 cases versus 16 of 368 cases, respectively). ... 

Hmat R, Piot O, Gallois H, Hanania G. Blood pressure response to the first 36 hours of heart failure Aerapy widi perindopril versus captopm. French General Hospitals National College of Cardiologists. J Cardiovasc Pharmacol (1999) 33,953-9. 

Perindopril 2 to 4 mg daily for a month had no effect on the steady-state serum digoxin levels of 10 patients with mild chronic heart failure. ... 

ACE inhibitors can raisie lithium levels, and in some individuals two to fourfold increases have been recorded. Cases of lithium toxicity have been reported in patients when given captopril, enal-april or lisinopril (and possibly perindopril). One analysis found an increased relative risk of 7.6 for lithium toxicity requiring hos-pitaUsation in elderly patients newly started on an ACE inhibitor. Risk factors for this interaction seem to be poor renal function, heart failure, volume depletion, and increased age. 

Risk factors for increased lithium toxicity include advanced age, " congestive heart failure, "" renal insufficiency " and volume depletion. " Some consider these to be contraindications to the use of lithi-um. " " Only captopril, enalapril, lisinopril (and possibly perindopril) have been reported to interact, but it seems likely, given the proposed mechanism, that this interaction will occur with any other ACE inhibitor. 

A potential case of an interaction between quinidine and flucloxacillin was demonstrated in a 63-year-old patient with recently diagnosed dilated cardiomyopathy who was admitted to the hospital with polymorphic ventricular tachycardia and ventricular fibrillation episodes induced by bradycardia. The patient was on a heart failure regimen of furosemide, spironolactone and perindopril, and was initiated on oral quinidine in the hospital for the prevention of ventricular arrhythmias. The patient s temporary pacemaker lead was removed and an implantable cardioverter-defibrillator was placed due to continued ventricular fibrillation. The next day, the patient became febrile. Culture of pacemaker lead tip and blood cultures were positive for S. aureus. Flucloxacillin and rifampin were initiated, but rifampin was discontinued due to the development of renal insufficiency and liver test abnormalities. These were normalised after rifampin was discontinued. The patient required continuous pacing to prevent ventricular tachycardia episodes, and quinidine was increased to 2800 mg per day (maximum daily dose). Quinidine plasma levels were subtherapeutic at 1.1 mg/L. The authors speculate that this interaction was due to quinidine being a substrate of Pgp and CYP3A4, and flucloxacillin s ability to induce these enzymes. While this may be a potential mechanism, the authors do not comment on how long the patient received rifampin. Rifampin is also a CYP3A4 inducer and could have been parf of fhe reason for fhe decrease in quinidine level [46 ]. 

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