High blood pressure is a chronic condition associated with an increased risk of cardiovascular disease and death. Over the last two decades, the Cochrane Hypertension Group has produced numerous reviews of ways to treat it, including one of the effects of a class of drugs called renin inhibitors. The review was updated in April 2017 and we asked the lead author, Vijaya Musini from the University of British Columbia in Vancouver Canada, to tell us about the latest findings.
John: Hello, I'm John Hilton, editor of the Cochrane Editorial unit. High blood pressure is a chronic condition associated with an increased risk of cardiovascular disease and death. Over the last two decades, the Cochrane Hypertension Group has produced numerous reviews of ways to treat it, including one of the effects of a class of drugs called renin inhibitors. The review was updated in April 2017 and we asked the lead author, Vijaya Musini from the University of British Columbia in Vancouver Canada, to tell us about the latest findings.
Vijaya: For patients with established moderate to severe hypertension, blood pressure should first be managed with life-style and behaviour modification, but if these measures prove inadequate, we need to move on to try antihypertensive drugs. There are several classes of these available, acting through different mechanisms to lower blood pressure. Renin inhibitors are a relatively new class that have been developed since the 1990s.
At the moment, only one renin inhibitor has been studied and approved for treatment of hypertension, and that’s aliskiren. We did this review to quantify how effective it is at lowering blood pressure and to explore its adverse effects.
We have added results from five new studies in this update and now include 12 randomized, placebo-controlled studies that recruited nearly seven and a half thousand adults. Most of the patients were Caucasian and the trials evaluated aliskiren at doses ranging from 75 to 600 mg per day, for a mean duration of 8 weeks. All the studies were funded by the drug’s manufacturer, Novartis, and we assessed them all as having a high likelihood of biases related to attrition, reporting and funding.
As well as adding data from recently published studies, we’ve also included in this update extensive detail from nine clinical study reports obtained from the European Medicines Agency. We also included data from an unpublished study that were in a clinical study summary obtained from the Novartis Clinical study Results Database. The clinical study reports allowed us to examine the methods and potential biases in the trials in much more detail, as well as giving us more extensive data on harms.
Turning to the results, there is moderate quality evidence that aliskiren has a dose-related blood pressure lowering effect. A daily dose of 75 mg dose lowered the systolic blood pressure by 3 mmHg and the diastolic blood pressure by 2 mmHg. 150 mg dose lowered these by 6 and 3 mmHg, 300 mg dose by 8 and 5 mmHg, and the falls of 11 and 6 mmHg were found with 600 mg. For adverse effects, we also found that patients allocated to aliskiren were not more likely to stop taking their tablets than those allocated placebo, but there is low-quality evidence that diarrhoea was increased in a dose-dependent manner, with a 7 fold increase with aliskiren 600 mg.
In summary, aliskiren is the only drug of the renin inhibitor class that has been studied and approved for treatment of hypertension at this time. Our systematic review has shown that it is better than placebo at lowering blood pressure, and the effect is similar to that seen with other classes of drugs when the maximum recommended dose is used. In other aspects, such as side effects, aliskiren is not better than other drugs currently available; however diarrhoea was considerably increased with aliskiren 600 mg.
John: If you would like to read more about these benefits and harms of aliskiren, just go online to Cochrane library dot com and search for 'renin inhibitors and hypertension’'