Dihydropyridine Calcium Channel Blockers and the Risk of Severe COVID-19

Abstract

and the loss of hypoxic pulmonary vasoconstriction play a pivotal role in the pathophysiology of coronavirus disease 2019 (COVID-19) respiratory distress. 1,2 Dihydropyridine calcium channel blockers (CCBs), frequently prescribed first-line antihypertensive agents, have the potential to disrupt hypoxic pulmonary vasoconstriction 3 and worsen V_/Q_ mismatch that leads to profound hypoxemia in patients with pulmonary disease. 4 We hypothesized that CCBs would be associated with worse respiratory failure in patients with COVID-19. MethodsAmong 444 consecutively hospitalized patients with confirmed COVID-19 (admitted between March 13 and April 7, 2020, at a quaternary referral center and an affiliated community hospital in Massachusetts), 245 patients had hypertension and were included in the analysis. Data elements were abstracted retrospectively from the electronic health record by trained study personnel who followed standardized protocol. The study was approved by the Partners Healthcare Institutional Review Board with a waiver of informed consent.Dihydropyridine CCB exposure status was based on confirmed home medication list at the time of hospital admission. The primary end point was a composite of intubation or death modeled as a time-to-event analysis. 5 For patients who died after intubation, the time of intubation was considered time of primary end point as with previous studies. 5 Cox models were used to evaluate the association between CCBs and the primary end point. Models were adjusted for age, sex, race/ethnicity, BMI, diabetes mellitus, coronary artery disease, heart failure, pulmonary hypertension, chronic kidney disease, asthma/COPD, peripheral arterial disease, Charlson Comorbidity Index, and the following medications: angiotensinconverting enzyme inhibitor/angiotensin receptor blocker, thiazide diuretic, loop diuretic, beta blocker, aspirin, and statin. To further account for potential confounding, an additional analysis was performed with propensity score matching. The propensity score for CCB use was estimated with a logistic regression model that incorporated the same covariates used in the multivariable Cox model.

Clinical outcomes of hypertensive patients with COVID-19 receiving calcium channel blockers: a systematic review and meta-analysis

“…Of these, 30 studies were excluded for reporting no adjusted association estimates, reporting no clinical outcomes, including mixed hypertensive and nonhypertensive patients without subgroup analysis on hypertensive patients, or comparing clinical outcomes between COVID-19 and non-COVID-19 patients. Eventually, nine studies [ 1 , 3 – 10 ] were included in this systematic review and meta-analysis; eight studies [ 3 – 10 ] reported adjusted association estimates for all-cause mortality, while five studies [ 1 , 4 , 6 , 7 , 9 ] reported adjusted association estimates for COVID-19-associated severe illness. The study characteristics are depicted in Table 1 .…”

“…The definition of severe illness varied across studies; in the studies by Choksi et al [ 4 ], Christiansen et al [ 6 ], and Peng et al [ 9 ], it was defined as admission to the intensive care unit; in the studies by Yan et al [ 7 ], it was defined according to the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia by the Chinese National Health Commission. In the study by Mendez et al [ 1 ], it was defined as the use of invasive or noninvasive mechanical ventilation or death. Meta-analysis of four studies [ 4 , 6 , 7 , 9 ] with a total of 2618 patients with COVID-19 revealed a significant reduction in the odds of severe illness with the preadmission/prediagnosis use of CCBs relative to the nonuse of CCBs; the estimated effect indicates a reduction in severe illness (Fig.…”

“…Investigations of the effect of the preadmission/prediagnosis use of comedications in patients with coronavirus disease 2019 (COVID-19) have been a means for researchers to establish their safety and to identify therapeutic agents that could be repurposed for the treatment of COVID-19. However, recently, it has been hypothesized that using calcium channel blockers (CCBs) could disrupt hypoxic pulmonary vasoconstriction and thus worsen ventilation/perfusion mismatch, which can lead to profound hypoxemia in patients with COVID-19 [ 1 ]. Nevertheless, some researchers have also commented that the vasodilatory effects of CCBs in the pulmonary and systemic vasculature could mitigate the effects of inflammation, hypercoagulation, edema, and local vasoconstriction developed as a response to SARS-CoV-2 infection, thus facilitating oxygen delivery and survival of host cells [ 2 ].…”

Pharmacotherapeutic agents for the management of COVID-19 patients with preexisting cardiovascular disease

“…One study [ 71 ] theorizes that CCB use can lead to worsening respiratory failure in COVID-19 patients. Dihydropyridines have been associated with inhibition of hypoxic pulmonary vasoconstriction, and as a consequence can cause severe hypoxemia.…”

“…Dihydropyridines have been associated with inhibition of hypoxic pulmonary vasoconstriction, and as a consequence can cause severe hypoxemia. The study retrospectively analyzed data from 245 hypertensive COVID-19 patients, and concluded that treatment with dihydropyridines may lead to a substantial increase in the risk of intubation and mortality compared to the non-dihydropyridines group [ 71 ]. A limitation of this study is the bias arising from unmeasured confounding variables that likely contribute to the mortality in these patients.…”