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Reinhold Kreutz, MD, PhD, is a professor of clinical pharmacology and hypertension and director of the Department of Clinical Pharmacology and Toxicology at the Charité University Medical Centre in Berlin, Germany. He has served as president of the European Society of Hypertension.
What factors should be considered when choosing antihypertensive drugs?
Reinhold Kreutz, MD, PhD: This is a very important, clinically relevant question. First of all, most factors are patient-, condition-associated, comorbidities are important, and also some laboratory tests are important when selecting blood pressure–lowering antihypertensive drugs.
First of all, I should say that the core drug treatment algorithm, which I will summarize in a minute, applies to many, many patients, including younger patients, old patients, patients with diabetes, patients after stroke. We have a common strategy on how to select the drugs and use the core treatment algorithm. The major drugs are renin-angiotensin system (RAS) inhibitors, either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), in combination with either a calcium channel blocker (CCB) or thiazide-like diuretics.
We recommend actually for most of the patients to start already with the dual combination, always having—if that’s not contraindicated—a RAS blocker plus either a CCB or a thiazide-like diuretic. Now, the question is, should I select the CCB or the thiazide-like diuretic? There is more or less the same evidence for both, but clinical conditions may guide the therapy. What will call for or support the selection of a thiazide-like diuretic would be heart failure, edema. Other than that, you have both options.
Then, it’s important to look into the comorbidities, and they are where you can deviate from the core treatment algorithm. For instance, in patients with coronary artery disease, angina, ischemic problems, we can also use a beta-blocker, depending on the condition, or comorbidity; or in a patient who has a high resting heart rate or has atrial fibrillation with a high heart rate—another indication to use a beta-blocker. So, we have also the beta-blocker as an alternative.
In terms of laboratory tests, it is important… I am also a clinical pharmacologist and I always teach the students: when you select drugs, you have to be aware and consider the renal function, because depending on renal function you have contraindications, drugs you cannot use. Particularly in severe kidney disease, advanced chronic kidney disease (CKD) stage 4, or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, you cannot use several drugs—they are contraindicated or you have to adjust the dose. In terms of antihypertensive treatment, renal function is important because we have to select the diuretics based on renal function. We can use thiazide-like diuretics down to an eGFR of 45 mL/min/1.73 m2; between 45 and 30 mL/min/1.73 m2 we may switch; definitely <30 mL/min/1.73 m2 we may prefer a loop diuretic in most of the patients.
Potassium is also the key parameter that impacts the selection of drugs. We have to be aware… obviously we know that all the RAS inhibitors would increase potassium. Hyperkalemia could be a problem. Definitely if we use a mineralocorticoid receptor antagonist (MRA), such as spironolactone, in patients with resistant hypertension, difficult to control, we have to check renal function and also potassium. We should be cautious; if potassium was already >4.5 mmol/L when starting, we can still start, but we should be cautious and monitor. If the baseline potassium is already ≥5.0 mmol/L, we maybe should not use an MRA in the first place.
