Effect of Prepublication Results on Trends in Prescribing of Antihypertensive Medication: Impact of the ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Disease Endpoints) Trial on Aliskiren Prescribing.

Although published randomized trial evidence can reduce prescribing of less efficacious or potentially harmful medications,1,2 prepublication alerts are often released before the clinical trial results are published. It is unknown whether prepublication alerts can effectively impact population-based prescribing of medications by both primary care physicians and specialists. In this study, we explored the trends in prescribing of aliskiren, the first orally active direct renin inhibitor, in relation to drug policy decisions, prepublication alerts, and availability of evidence from randomized controlled trials. Aliskiren was approved by the Food and Drug Administration as an antihypertensive agent in 20073 and received a notice of compliance by Health Canada in November 2007 for the treatment of hypertension.4 Before listing aliskiren on the Ontario Drug Benefit (ODB) formulary, it was reviewed by the Canadian Agency for Drugs and Technology in Health (a national expert panel) and the Committee to Evaluate Drugs (a provincial expert panel), who identified the absence of long-term studies, insufficient safety data, and lack of evidence supporting a reduction in clinically important outcomes, such as stroke, myocardial infarction, and chronic kidney disease.5,6 The drug was ultimately approved for listing on the Ontario provincial pharmacare formulary in December 2008, for use in patients with hypertension who have not achieved adequate blood pressure reduction with the combination of a thiazide-diuretic with either an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker.7 It is estimated that 15% to 20% of hypertensive people have uncontrolled blood pressure despite being treated with this combination of antihypertensive medications.8,9 A large postmarketing trial, ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Disease Endpoints), was initiated October 2007 and terminated early, after interim analysis showed increased frequency of nonfatal strokes, serious renal complications, hyperkalemia, and hypotension in …