A 61-year-old Man with Diabetes and Resistant Hypertension
TD is a 61-year-old man who presents to your clinic for follow-up. His past medical history includes type 2 diabetes (T2DM), hypertension, and hyperlipidemia. His current medications are: metformin XR 2000 mg once daily, glimepiride 8 mg daily, valsartan 320 mg daily, pravastatin 40 mg daily, amlodipine 10 mg daily, chlorthalidone 25mg daily, and aspirin 81 mg daily.
He has been able to keep his diabetes well controlled with the combination of lifestyle modifications and medications for the past 5 years. Laboratory results obtained today are: HbA1c, 7.1%; basic metabolic panel WNL (SCr - 0.9 mg/dL, Na+, 138 mEq/L, K+, 4.0 mEq/L); and urine albumin, 228 µg/mg creatinine. Vitals are: weight, 78 kg; BMI, 28; blood pressure (BP) in clinic, 154/92 and 158/96 mm Hg; pulse, 74 beats/min. Allergies/intolerances include a cough with ace inhibitor therapy. TD checks his BP at home and it ranges from 145/90 to 160/102 mm Hg.
You are most concerned today with his blood pressure.
Most appropriate answer: A. Add spironolactone 25mg daily
Nearly two-thirds of patients with T2DM have hypertension.1 Lowering blood pressure in these patients may help prevent cardiovascular morbidity and mortality, but control is often insufficient in clinical practice.1
Resistant hypertension is defined as elevated blood pressure not controlled with optimally dosed antihypertensives from at least 3 different classes, one of which is an appropriate and optimally dosed diuretic. Resistant hypertension is difficult to treat and especially so in patient with T2DM.
Many different treatment options can be considered in these patients; however, one that is particularly effective is the use of an aldosterone antagonist such as spironolactone. Spironolactone has been shown to be safe and effective in the treatment of resistant hypertension in patients with and without diabetes.2,3 In one double-blind, placebo-controlled study, the addition of spironolactone as a fourth agent initiated at 25 mg/day resulted in significant reductions in daytime, night-time, 24-hour, and office BP. More patients in the spironolactone group also achieved BP control after 16 weeks as compared to placebo. The drug was considered safe with no change in glycemic control and a low incidence of adverse effects (hyperkalemia). In addition BP reduction, the urinary albumin/creatinine ratio also was significantly reduced in the spironolactone group.3
Adding spironolactone to TD’s regimen would require close monitoring of his serum potassium (1 week after initiation and any change in dose) especially since the patient is on concomitant angiotensin receptor blocker (ARB) therapy.
Option B is not recommended. This combination could be considered given this patient’s urinary albumin excretion; however, results of the ALTITUDE trial4 suggest that the combination of aliskiren and an ARB/angiotensin converting enzyme (ACE) inhibitor can result in negative outcomes in diabetic patients and is therefore not recommended as a treatment option.4
Option C is not recommended. Although the patient is older than 60 years of age, JNC 8 recommends maintaining a target goal BP of 140/90 mm Hg in patients with diabetes.5
Option D may be considered but may not be the most appropriate in this patient. Beta-blockers may be considered as a fourth-line agent in this patient; however, there is no clear indication for a beta-blocker that would result in decreased morbidity or mortality in this patient.
Beta-blockers and especially those without vasodilatory effects, such as atenolol, may not result in significant BP reductions in these patients. [Brad: “these patients” meaning those with resistant HTN?] Treatment with beta-blockers, especially non-selective agents, may also result in metabolic adverse effects such as decreased glycemic control.6,7 Lastly, beta-blockers may mask signs and symptoms of hypoglycemia in patients with diabetes who are on therapy such as sulfonylureas or insulin which are more likely to cause hypoglycemia than other agents.8 If a beta-blocker is chosen, an agent such as carvedilol with vasodilatory effects may provide better efficacy and be more appropriate as it may also result in fewer metabolic effects.7
Option E is not recommended. While carvedilol may prove a useful option and a more ideal beta-blocker in this patient with diabetes and hypertension,8 it is not recommended to discontinue the thiazide at this time in the absence of adverse effects (Na+ and K+ are WNL). Diuretic therapy, especially thiazides in those patients without significant chronic kidney disease, is a mainstay in the treatment of resistant hypertension.
- Ferrannini E, Cushman WC. Diabetes and hypertension: the bad companions. Lancet. 2012;380:601-610.
- De Souza F, Muxfeldt E, Fiszman R, Salles G. Efficacy of spironolactone therapy in patients with true resistant hypertension. Hypertension. 2010;55:147-152.
- Oxlund CS, Henriksen JE, Tarnow L, Schousboe K, Gram J, Jacobsen IA. Low dose spironolactone reduces blood pressure in patient with resistant hypertension and type 2 diabetes mellitus: a double blind randomized clinical trial. J Hypertens. 2013;31:2094-2102.
- Parving HH, Brenner BM, McMurray JJ, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med 2012;367:2204-2213
- James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults. report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2013; 311:507-20.
- Jacob S, Rett K, Wicklmayr M, et al. Differential effect of chronic treatment with two beta-blocking agents on insulin sensitivity: the carvedilol-metoprolol study. J Hypertens. 1996;14:489-494.
- Giugliano D, Acampora R, Marfella R, et al. Metabolic and cardiovascular effects of carvedilol and atenolol in non-insulin-dependent diabetes mellitus and hypertension. A randomized, controlled trial. Ann Intern Med. 1997;126:955-959.
- Giorda CB, Ozzello A, Gentile S, et al. Incidence and correlates of hypoglycemia in type 2 diabetes. The Hypos-1 study. Acta Diabetol. 2015 Feb 12. [Epub ahead of print]