Cardiovascular Effect of an SGLT2i: Case Study

Canagliflozin may decrease blood pressure in patients with treatment resistant hypertension, according to a case study published online in the Journal of the Royal Society of Medicine Open.¹

The cardiovascular effects of SGLT2 inhibitors have been a hot topic lately. Results from the EMPA-REG OUTCOME trial showed that over three years of treatment empagliflozin decreased risk of all-cause mortality by 32%, heart failure hospitalization by 35%, and cardiovascular death by 38%, compared to placebo.²

Based on these results, in June 2016 an FDA advisory committee narrowly voted in favor of expanding the indication of empagliflozin to include prevention of cardiovascular events.³

SGLT2 inhibitors lower blood pressure through osmotic diuresis, via a different site than loop diuretics and thiazides. The mechanism by which SGLT2 inhibitors may improve other cardiovascular parameters, such as atherogenic lipids, is not completely understood.  

The case concerned a 68-year-old man with long-standing hypertension, ischemic heart disease, obesity, T2DM, and rheumatoid arthritis. Despite three antihypertensives (ramipril, felodopine, and atenolol) prescribed at maximum tolerated dosages, the man continued to have uncontrolled hypertension.

In May 2007, he had a blood pressure of 168/99 and was referred to a hypertension clinic, which ruled out secondary causes of hypertension and optimized his antihypertensive regimen. Still, the man’s hypertension continued.

In June 2013, he was admitted to the hospital for direct observation, which ruled out treatment non-adherence. Adherence was re-confirmed on urinary drug screening in 2014. 

In October 2013, the man underwent ablation of the sympathetic nerves surrounding the renal arteries, which had no effect. By June 2014, his blood pressure had reached 181/105 mmHg.

In May 2015, the man was started on canagliflozin 100 mg daily, which was titrated up to 300 mg/day.  Within a month, the man’s blood pressure decreased to 137/80. He tolerated canagliflozin well, except for an increase in creatinine level and a glomerular filtration rate that dropped below 60 mL/min. In response, his dose was decreased to 100 mg daily.

In July 2015, his blood pressure decreased to 121/68, the lowest it had been since 2007. However, due to declining renal function and because it was not thought necessary for diabetes control, the decision was made to stop canagliflozin.

By August 2015, the man’s blood pressure had risen again to 151/86. He was re-started on canagliflozin 100 mg, which resulted in a reduction in blood pressure to 136/83. His blood pressure remained well controlled through November 2015, when it was 136/83.

“It could be argued that sodium glucose co-transporter 2 inhibitors can play a role in the management of such patients [with treatment resistant hypertension] not only for their diabetes but also for their high blood pressure and obesity. However, such medications should be used under close supervision in patients with chronic kidney disease and in those taking a combination of diuretics,” concluded lead author Wasim Hanif, MD, of the Queen Elizabeth Hospital, Birmingham UK, and colleagues.

The authors pointed out that they expect the effect on treatment resistant hypertension in this patient to be a class effect. They advised caution when combining loop diuretics with SGLT2 inhibitors, because of the risk of hypovolemia.

Take-home Points

• A case study of a 68-year-old man with T2DM, treatment resistant hypertension, and multiple medical comorbidities suggests canagliflozin successfully decreased his blood pressure.

• Renal function decreased while on canagliflozin, and the authors urged close supervision when using SGLT2 inhibitors in patients with chronic kidney disease.

• They advised caution when combining SGLT2 inhibitors with loop diuretics, because of the risk for hypovolemia.

Dr Hanif reports travel and research grants as well as consultancy fees from Novo Nordisk, Eli Lilly, Sanofi, MSD, Jansen, Astra Zeneca and BI.

References

1. Obeid A, et al. Sodium glucose co-transporter 2 inhibitors in patients with resistant hypertension: a case study. JRSM Open. 2016 Sep 1;7(9):2054270416649285.

2. Zinman B, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015 Nov 26; 373(22):2117-2128.

3. PR Newswire. FDA Advisory Committee recommends approval of Jardiance® (empagliflozin) for cardiovascular indication in 12-11 vote. Accessed November 4 2016 at http://www.prnewswire.com/news-releases/fda-advisory-committee-recommends-approval-of-jardiance-empagliflozin-for-cardiovascular-indication-in-12-11-vote-300291733.html