A meta-analysis of randomized, controlled trials (RCTs) disclosed that deaths from all causes were no different between first-line CCBs and other first-line antihypertensives, and comparisons for decreasing the prevalence of major adverse cardiovascular events (MACEs) were moderate or weak, leaving no robust conclusion regarding the advantages or disadvantages of CCBs.
In the meta-analysis published in the Cochran Database of Systematic Reviews, 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.
The 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 heightened MACE 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 beta-blockers, CCBs decreased outcomes for MACEs (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 angiotensin-converting enzyme (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).
The 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 were also insufficient data for some subgroup comparisons.
The researchers concluded that with regard to the treatment of hypertension, there is moderate-certainty evidence that diuretics diminish MACEs and congestive heart failure more than CCBs. There is low-to-moderate certainty evidence, they noted, that CCBs decrease MACEs more than beta-blockers. They also found that there is low-to-moderate certainty evidence that CCBs reduce stroke compared with ACE inhibitors and reduce myocardial infarction compared with ARBs but augmented congestive heart failure compared with ACE inhibitors and ARBs. They wrote, "Many of the differences found in the current review are not robust, and further trials might change the conclusions. 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."
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