Untreated hypertension contributes to stroke, heart disease, and kidney disease and is a strong predictor of death associated with these conditions.1–3 Lowering blood pressure, regardless of the medication used, has been shown to reduce the risk of major cardiovascular events. Many experts believe that the most important determinant for risk reduction is how much the blood pressure is lowered. Amlodipine has been shown to be effective at lowering blood pressure and the risk of many cardiovascular events.4–7
The CAMELOT study, a randomized control study of 1,991 patients with angiographically proven coronary artery disease but normal blood pressure (average blood pressure 129/78 at baseline) compared efficacy of amlodipine at 10 mg per day or enalapril at 20 mg per day with placebo in preventing cardiovascular events.8 The 663 patients taking amlodipine had fewer cardiovascular events compared with placebo (16.6% versus 23.1%, odds ratio [OR] 0.69, 95% confidence interval [CI] [0.54 – 0.88, p=0.003). Specifically, amlodipine reduced non-fatal myocardial infarction by 26% and stroke or transient ischemic attacks by 50% compared to placebo.9
One large meta-analysis (n = 80,483) demonstrated that amlodipine lowers the risk of stroke when compared to other major anti-hypertensive therapies including beta-blockers, diuretics, angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers (17% lower risk of stroke, relative risk [RR] 0.83, 95% CI [0.72 – 0.97], p<0.009).10 The risk of developing myocardial infarction was lower among amlodipine users as well, but not significantly. In this same analysis, amlodipine therapy was shown to be associated with a 25% higher risk of heart failure compared to other anti-hypertensives (RR 1.25, 95% CI [1.05 – 1.49], p<0.019).
A 2009 meta-analysis of 27 trials (n=175,634) demonstrated that long-acting calcium channel blockers (CCBs), including amlodipine, reduce the risk of all-cause mortality compared with other therapies (OR 0.96,95% CI [0.93 – 0.99], p=0.026).11 The risk of heart failure was increased with CCBs compared with angiotensin-converting enzyme inhibitors, diuretics, or beta blockers (OR 1.17, 95% CI [1.11 – 1.24], p=0.0001), but it was decreased when comparing CCBs with placebo (OR 0.72, 95% CI [0.59 – 0.87], comparison p=0.001).
In a more recent meta-analysis (n = 87,257) that included many of the same trials as the 2009 analysis, but added newer data, the risk of heart failure was higher with amlodipine-based regimens compared with non-CCB-based regimens, but the difference was marginally significant (OR 1.14, 95% CI [0.98 – 1.31], p=0.08).12 The same analysis found that cardiovascular disease events, which combined CHD, stroke, CHF, and other cardiovascular disease mortalities, were lower with amlodipine-based regimens (OR 0.90, 95% CI [0.82 – 0.99], p=0.02).
A recent Cochrane analysis of available evidence supported the conclusion that first-line therapy with CCBs appeared to reduce stroke risk (3.4% with placebo or no treatment versus 1.9% with treatment, RR 0.58, 95% CI [0.41 – 0.84]).13 The same analysis found insufficient evidence that CCB therapy reduced coronary heart disease or mortality compared to placebo or no treatment.
References
- Staessen JA, Li Y, Thijs L, Wang J-G. Blood pressure reduction and cardiovascular prevention: an update including the 2003-2004 secondary prevention trials. Hypertens Res 2005; 28 (5): 385-407.
- Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Hypertens 2014; 32 (1): 3-15.
- Xie X, Atkins E, Lv J, et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet 2016; 387 (10017): 435-443.
- Byrd JB, Bakris G, Jamerson K. The contribution of the ACCOMPLISH trial to the treatment of stage 2 hypertension. Curr Hypertens Rep 2014; 16 (3).
- Dahlöf B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian cardiac outcomes trial-blood pressure lowering arm (ASCOT-B). Lancet 2005; 366 (9489): 895-906.
- Furberg CD, Wright JT, Davis BR, et al. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288 (23): 2981-2997.
- Park CG. Is amlodipine more cardioprotective than other antihypertensive drug classes? Korean J Intern Med 2014; 29 (3): 301-304.
- Nissen SE, Tuzcu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure. JAMA 2004; 292 (18): 2217.
- Fares H, DiNicolantonio JJ, O’Keefe JH, Lavie CJ. Amlodipine in hypertension: a first-line agent with efficacy for improving blood pressure and patient outcomes. Open Hear 2016; 3 (2): 1-7.
- Sandip C, Yangchen SL, Amir S, Rezza JKS, Hisatomi A. Effects of long- and intermediate-acting dihydropyridine calcium channel blockers in hypertension: a systematic review and meta-analysis of 18 prospective, randomized, actively controlled trials. J Cardiovasc Pharmacol Ther January 2018.
- Costanzo P, Perrone-Filardi P, Petretta M, et al. Calcium channel blockers and cardiovascular outcomes: a meta-analysis of 175 634 patients. J Hypertens 2009; 27 (6): 1136-1151.
- Lee SA, Choi HM, Park HJ, Ko SK, Lee HY. Amlodipine and cardiovascular outcomes in hypertensive patients: meta-analysis comparing amlodipine-based versus other antihypertensive therapy. Korean J Intern Med 2014; 29 (3): 315-324.
- Wright J, Musini V, Gill R. First-line drugs for hypertension (review). Cochrane Database Syst Rev 2018; (4).
