Abstract
Aims
Little is known about the occurrence of potassium disturbances in relation to combination therapy in hypertension. Using data from Danish electronic registries, we investigated the association between different combinations of antihypertensive therapy and potassium imbalances, in 22,060 individuals, between 1995–2012.
Methods
Using incidence density matching, two comparison patients without hypokalemia were matched to each corresponding patient with hypokalemia on age, gender, renal function, time from HTN date to date of potassium measurement. The same approach was applied to identify matches for patients with hyperkalemia. The ten most common antihypertensive drug combinations in our population were: (1) Beta-blockers + Angiotensin converting enzyme inhibitors, (2) Angiotensin converting enzyme inhibitors + Thiazides, (3) Angiotensin converting enzyme inhibitors + Thiazides + Potassium supplement, (4) Angiotensin receptor blockers + Other diuretics, (5) Beta-blockers + Angiotensin converting enzyme inhibitors + Potassium supplement (ATC: A12B), (6) Beta-blockers + Calcium channel blockers, (7) Beta-blockers + Thiazides + Potassium supplement, (8) Calcium channel blockers + Angiotensin converting enzyme inhibitors, (9) Calcium channel blockers + Thiazides + Potassium supplement, (10) Other antihypertensive drug combinations. We used conditional logistic regression analysis to examine the risk of developing hypo- and hyperkalemia in relation to different combinations of antihypertensive drugs within one year. The multivariable model was adjusted for serum sodium, malignancy, inflammatory bowel disease, diabetes, alcoholism and beta2-agonists.
Results
The multivariable analysis showed 10.5 times increased odds for developing hypokalemia if administered Calcium channel blockers + Thiazides + Potassium supplement (95% CI 4.97–22.06) compared to Angiotensin converting enzyme inhibitors + Beta blockers. Other drug combinations significantly associated with increased hypokalemia risk were: Angiotensin converting enzyme inhibitors + Thiazides (OR 5.01, 95% CI 2.32–10.79), Angiotensin converting enzyme inhibitors + Loop + Potassium supplement (A12B) (OR 4.03, 95% CI 1.69–9.62), Angiotensin converting enzyme inhibitors + Thiazides + Potassium supplement (OR 4.16, 95% CI 2.01–8.64) and Calcium channel blockers + Angiotensin converting enzyme inhibitors (OR 4.04, 95% CI 1.72–9.50). None of the ten groups were associated with increased odds for developing hyperkalemia in the multivariable analysis.
Cumulative incidence curves for hypokale
Conclusion
Thiazide diuretics in combination with angiotensin converting enzyme inhibitors or calcium channel blockers were strongly associated with hypokalemia risk within one year from treatment initiation.
Acknowledgement/Funding
None
Has the Use of Angiotensin Converting Enzyme Inhibitors and Calcium Channel Blockers Improved the Outcome for Hypertensive Patients?
