New Combo Treatment for Hypertension Reduces Side Effects

A new study – termed Prevention and Treatment of Resistant Hypertension with Algorithm Guided Therapy (PATHWAY-3) – has found that by administering half doses of two commonly prescribed diuretics, blood pressure can be significantly reduced without the usual side effects these medications cause when they’re taken on their own. The results were reported at the 2015 (European Society of Cardiology) ESC Congress.

According to the study, these findings, “support first-line use of this combination in patients requiring diuretic therapy for hypertension.” Morris J. Brown, FMedSci, and lead investigator of the study from the University of Cambridge, in Cambridge UK said, “The British Hypertension Society investigators will be recommending this combination.”

Brown explained that diuretics such as hydrochlorothiazide (HCTZ) – a member of the thiazide class of diuretic drugs – have been used for decades as a first-line treatment for hypertension. In recent years however, they have been linked to an increased risk of diabetes, which has reduced their usage.

Thiazides are known to deplete potassium levels, which may account for the elevated possibility that a patient will develop diabetes. While non-potassium-depleting diuretics such as amiloride are available, they carry an increased risk of potentially high potassium levels, which may require additional monitoring.

The true win-win is in the combination of both diuretics at half doses, which cancels-out any potential changes in potassium levels. These drugs are also capable of working in tandem to make sodium excretion by the kidneys more efficient, thereby reducing blood pressure. Researchers involved in the study call this type of drug interaction “natriuretic synergism” because neither pharmaceutical has the same powerful anti-hypertension ability on its own.

“That matched doses of the two classes of diuretics could neutralize undesirable effects while potentiating the desirable is an important discovery,” said Brown. The study authors also noted, “It is probable therefore, that it is the prevention of potassium depletion combined with effective blood pressure reduction, which underpins the success of amiloride-HCTZ in the present study.”

A total of 399 participants with an average age of 61-63, who were categorized as being obese and hypertensive, were a part of the PATHWAY-3 study. These patients were candidates for diuretic treatment and at a minimum, they had another component of metabolic syndrome such as high cholesterol, or a fasting glucose level of 100 mg/dL or higher.

Patients were randomly and equally assigned to one of three trial groups; Group 1 received 10 mg of amiloride alone, Group 2 received 25 mg of HCTZ alone, and Group 3 received a combination of both diuretics at half dose. The treatment spanned a total of 24 weeks; for 12 weeks patients were given the drugs at the concentrations listed above, followed by an additional 12 weeks at double the above doses.

Following the study period, the patients in each treatment group were tested on two parameters; the change from baseline in an oral glucose tolerance test (OGTT), and blood pressure controlling ability. There was a significant difference between the amiloride and HCTZ treatment groups in the results of the OGTT, with lower glucose levels in the former, and higher glucose levels in the latter. The mean difference in blood glucose levels between treatment Groups 1 and 2 was 0.55 mmol/L. Importantly, blood glucose levels remained stable in patients receiving the combo treatment in Group 3, with a 0.42 mmol/L difference in blood sugar, compared to the HCTZ group.

Patients in Groups 1 and 2 saw near identical anti-hypertensive effects of the drugs, with a drop of 14.7 mmHg and 14.0 mmHg in Groups 1 and 2, respectively. Patients receiving both drugs received the most anti-hypertensive impact, with a drop of 17.4 mmHg.

“Our study shows that amiloride itself is a very good drug — at least as effective as HCTZ; and that combining a half-dose of it with half-dose of HCTZ is a ‘win-win’ — producing better blood pressure, lower glucose and no change in potassium,” said Brown. This study joins PATHWAY-2 – a trial investigating the best therapy for resistant hypertension – which was conducted by academic researchers who are members of the British Hypertension Society.

Sources:

• Half-dose combo of common diuretics a ‘win-win’ for hypertension – http://www.sciencedaily.com/releases/2015/08/150831085606.htm
• High Blood Pressure and Metabolic Syndrome – http://www.heart.org/HEARTORG/Conditions/HighBloodPressure/AboutHighBloodPressure/High-Blood-Pressure-and-Metabolic-Syndrome_UCM_301801_Article.jsp
• PATHWAY Project – http://www.bhsoc.org/research/pathway-project/