A meta-analysis of randomized controlled trials (RCTs) showed that deaths from all causes were no different between first-line calcium channel blockers (CCBs) and other first-line blood pressure-lowering medications, and comparisons for reducing the incidence of major adverse cardiovascular events were moderate or weak, leaving no strong conclusion regarding the advantages or disadvantages of CCBs. These findings were published in the Cochrane Database of Systematic Reviews.
Researchers sought to determine if the incidence of major adverse cardiovascular events was reduced if CCBs were used as first-line therapy for hypertension vs other classes of antihypertension drugs. Data from 153,849 participants with a history of hypertension were obtained from multiple databases, including the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 1), Ovid MEDLINE, Ovid Embase, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. Researchers found 23 RCTs conducted in Japan, Israel, North America, Oceania, and Europe through September 1, 2020. To be included in the analysis, studies needed to have enrolled at least 100 randomly assigned hypertensive participants, compared CCBs with other classes of antihypertensive drugs, and had a follow-up of at least 2 years. Most of the trials included were multicenter with standardized protocols.
Researchers found all-cause mortality between CCBs and other antihypertensive drug classes to be no different. CCBs may have increased major cardiovascular events compared with diuretics (risk ratio (RR) 1.05; 95% CI, 1.00-1.09; P =.03) and increased congestive heart failure events (RR 1.37; 95% CI, 1.25-1.51; moderate-certainty evidence).
When compared with β-blockers, CCBs decreased outcomes for major cardiovascular events (RR 0.84; 95% CI, 0.77-0.92), stroke (RR 0.77; 95% CI, 0.67-0.88; moderate-certainty evidence), and cardiovascular mortality (RR 0.90; 95% CI, 0.81-0.99; low-certainty evidence). CCBs reduced stroke compared with ACE-inhibitors (RR 0.90; 95% CI, 0.81-0.99; low-certainty evidence) but increased congestive heart failure (RR 1.16; 95% CI, 1.06-1.28; low-certainty evidence). CCBs reduced myocardial infarction compared with angiotensin receptor blockers (ARBs) (RR 0.82; 95% CI, 0.72-0.94; moderate-certainty evidence) but increased congestive heart failure (RR 1.20; 95% CI, 1.06-1.36; low-certainty evidence).
Researchers noted some limitations to the analysis. Data for all of the desired outcomes were not available for every trial. Participants in most trials tended to have advanced or more complicated hypertension, and, in this analysis, those with severe or acute hypertension were excluded. There was also insufficient data for some subgroup comparisons.
Researchers concluded that, for the treatment of hypertension, evidence suggests with moderate certainty that diuretics reduce congestive heart failure and major cardiovascular events more effectively than CCBs. They found low to moderate certainty that CCBs reduced stroke compared with ACE inhibitors and myocardial infarction compared with ARBs, while increasing congestive heart failure compared with both. “Many of the differences found in the current review are not robust, and further trials might change the conclusions,” the investigators wrote. “More well-designed RCTs studying the mortality and morbidity of individuals taking CCBs as compared with other antihypertensive drug classes are needed for patients with different stages of hypertension, different ages, and with different comorbidities such as diabetes.”
Zhu J, Chen N, Zhou M, et al. Calcium channel blockers versus other classes of drugs for hypertension. Cochrane Database Syst Rev. Published online January 9, 2022. doi:10.1002/14651858.CD003654.pub6