Ranexa^® (ranolazine) Clinical Evidence

The efficacy and safety of Ranexa^® (ranolazine) is supported by a number of randomised controlled trials and real-world data

CARISA¹

CARISA was a randomised, 3-group parallel, double-blind, placebo- controlled trial involving 832 eligible adults with symptomatic chronic angina. The primary endpoint of the trial was change in exercise treadmill time and trough levels vs the baseline. The main outcome measures included; change in exercise duration, time to onset of angina and ischemia, nitroglycerin use and the number of angina attacks. In this study, Ranexa^® was added to a beta-blocker or a calcium channel blocker.

Key findings

After a 12 week follow-up period, trough exercise duration increased by 115.6 seconds from baseline in both Ranexa^® groups, vs 91.7 seconds in the placebo group (P=0.01). It was also found that the use of Ranexa^® resulted in an additional 42% reduction in weekly angina attacks over and above that offered by first line therapy (baseline) and 14% reduction compared to placebo.

CARISA Sub-Study: Use of Ranexa^® in diabetic patients^1,2

The effects of Ranexa^® in diabetic and non-diabetic patients were studied in a sub-analysis of the phase 3 CARISA trial. HbA1c levels, serum glucose and serum lipid levels during the trial were evaluated with HbA1c levels from the long-term open-label extension study to identify if Ranexa^® had specific effects on diabetic patients.

Key findings

Without the need for dose adjustment, Ranexa^® was found to be equally effective in reducing angina frequency in stable angina patients with type 2 diabetes, compared with non-diabetic patients. The number of weekly angina attacks and nitroglycerin consumption were reduced in the Ranexa^® group vs the placebo, and a reduction in HbA1c concentration was also observed in diabetic patients taking Ranexa^® vs the placebo.²

The Manolis Systematic Review³

A systematic review by Manolis et al. (2016) set out to answer questions around the evidence for categorising antianginal drugs as first and second- line therapy, with the goal of identifying possibilities for individualising patients and tailoring treatments.

Key findings

The review found that all antianginals had a similar level of evidence but proposed a systematic therapeutic approach that could offer a more patient tailored approach, based on a patient’s cardiovascular profile, comorbidities, risk factors and haemodynamic status. The algorithm is based on heart rate and blood pressure, recommending Ranexa^® as the optimal choice for second line treatment, after beta blockers (BB) or calcium channel blockers (CCB) in all circumstances except where patients have a low heart rate and low blood pressure. For these patients, Ranexa^® is recommended as first line treatment due to it haemodynamic independence.¹

ARETHA⁴

ARETHA was an observational, open, non-interventional, real-world evidence study which evaluated the use of Ranexa^® for treating stable angina symptoms in daily practice. 1,537 patients across 790 centres were given Ranexa^® as an add on therapy to their first line anti-anginal treatment. Patient’s Ranexa^® dose was uptitrated from 500mg bd as considered appropriate. The study had a 3 month follow up period and endpoints included changes in the number of angina attacks per week, short acting nitrate use per week and change in physical impairment classification and quality of life.

Key findings

At the end of the 3 months, patients on Ranexa^® experienced 74.5% fewer angina attacks per week compared to baseline, and Ranexa^® significantly reduced the use of short-acting nitrates by 76.5%. 69% of patients on Ranexa^® also benefited from an improved physical impairment classification and 43.6% from an improvement in quality of life (as rated by their physician.) 98.6% of patients did not experience any adverse drug reactions and the side effects that were experienced by patients were all mild to moderate in incidence. They were all resolved or close to resolving at the end of the 3 months, which highlighted that Ranexa^® was generally well tolerated.

References

1. Chaitman BR et al, JAMA 2004; 291(3):309–316
2. Timmis AD et al, Eur Hear J 2006; 27(1): 42-48
3. Manolis AJ et al, Int J Cardiol 2016; 220:445-453
4. Diedrichs et al, J Clin Exp Cardiolog 2015, 6(12): 1000412