Outcomes of Calcium-Channel Blocker Use in Patients With Multiple Myeloma: A Propensity-Matched Study From the Global Federated Health Research Network

TL;DR

This study finds that using calcium-channel blockers in multiple myeloma patients may worsen outcomes like kidney injury and mortality, despite controlling for other factors.

Contribution

The study is the first to explore how specific calcium-channel blockers affect outcomes in multiple myeloma patients using a large, propensity-matched cohort.

Findings

Patients with multiple myeloma not prescribed calcium-channel blockers had lower rates of acute kidney injury and dialysis.

Amlodipine and nifedipine use was associated with increased risks of atrial fibrillation and mortality.

Diltiazem and nicardipine use showed mixed effects, with some CCBs reducing mortality while increasing other risks.

Abstract

Introduction: Multiple myeloma (MM) is a plasma cell hyperproliferative disorder resulting in a classic presentation including anemia, renal dysfunction, bone pain, and hypercalcemia. Many patients with MM also develop unrelated comorbid conditions, such as hypertension or congestive heart failure, that warrant the prescription of calcium-channel blockers (CCBs). Little is known about how MM-associated hypercalcemia could be impacted by CCB use. This study aimed to determine how CCBs could impact outcomes in patients with MM.

Methods: Utilizing TriNetX’s US Collaborative Network and ICD-10 codes, we identified adult patients with MM prescribed CCBs and compared them to patients with MM not prescribed CCBs. Cohorts were propensity-matched according to age, sex, race, and comorbidities. We followed these cohorts for five years to assess rates of acute kidney injury (AKI), dialysis initiation (hemodialysis (HD)), seizures, atrial fibrillation/atrial flutter (AF/AFL), ventricular fibrillation/ventricular tachycardia (VF/VT), ICU admission, and all-cause mortality.

Results: Cohorts were propensity-matched with each CCB cohort compared with a group that was not prescribed any CCB. Compared to any CCBs, the MM no CCB cohort had lower rates of AKI (hazard ratio (HR) 0.937, 95% CI 0.911 - 0.964, p<0.0001), HD (HR 0.587, 95% CI 0.551 - 0.625, p<0.0001), seizures (HR 0.823, 95% CI 0.755 - 0.898, p=0.0002), AF/AFL (HR 0.942, 95% CI 0.905 - 0.98, p<0.0001), and VF/VT (HR 0.981, 95% CI 0.901 - 1.076, p<0.0001). The MM no CCB cohort had higher rates of mortality (HR 1.031, 95% CI 1.004 - 1.059, p<0.0001).

The MM no amlodipine cohort had lower rates of AKI (HR 1.011, 95% CI 0.98 - 1.044, p<0.0001), HD (HR 0.749, 95% CI 0.698 - 0.803, p<0.0001), seizures (HR 1.034, 95% CI 0.939 - 1.139, p<0.0001), and ICU admission (HR 0.159, 95% CI 0.118 - 0.214, p=0.0367) compared to the amlodipine cohort. The MM no amlodipine cohort had increased risk of AF/AFL (HR 1.44, 95% CI 1.371 - 1.513, p<0.0001), VF/VT (HR 1.464, 95% CI 1.322 - 1.62, p<0.0001), and mortality (HR 1.09, 95% CI 1.058 - 1.123, p<0.0001).

The MM no nicardipine cohort had reduced risk of mortality (HR 0.754, 95% CI 0.633 - 0.899, p=0.0002) compared to the nicardipine cohort.

The MM no nifedipine cohort had less risk of HD (HR 0.507, 95% CI 0.402 - 0.639, p=0.0057) and mortality (HR 0.935, 95% CI 0.839 - 1.043, p=0.0395) compared to the nifedipine cohort. The MM no nifedipine cohort had a higher risk of AF/AFL (HR 1.59, 95% CI 1.306 - 1.935, p=0.0003) and VF/VT (HR 1.927, 95% CI 1.326 - 2.799, p=0.0012).

The MM no diltiazem cohort had lower rates of HD (HR 0.941, 95% CI 0.79 - 1.121, p=0.0256), AF/AFL (HR 0.322, 95% CI 0.293 - 0.353, p<0.0001), and mortality (HR 0.775, 95% CI 0.728 - 0.825, p=0.0006) than the diltiazem cohort. The MM no diltiazem cohort demonstrated higher rates of AKI (HR 1.086, 95% CI 1.005-1.174, p=0.0003).

The MM no verapamil cohort had a reduced risk of AF/AFL (HR 0.949, 95% CI 0.798-1.129, p=0.0011) compared to the verapamil cohort. The MM no verapamil cohort had a higher risk of AKI (HR 1.369, 95% CI 1.203 - 1.557, p=0.0001) and HD (HR 1.329, 95% CI 0.985 - 1.795, p=0.0392).

Conclusions: Even after risk stratification and propensity-score matching, there appear to be differences in outcomes between patients with MM on various CCBs. The hypercalcemia in MM may be perpetuated by CCBs, leading to poor outcomes in certain patients. These differences warrant further exploration.