**Background:** Cardiovascular diseases (CVDs) account for 17.9 million deaths annually (31% of all deaths globally) and are projected to remain the leading cause of mortality through 2030. Medication non-adherence is a leading preventable cause of mortality in over 60% of cardiovascular patients. Despite substantial resources allocated to developing new treatment regimens, non-adherence persists as a major public health problem. Mobile health (mHealth) interventions—using mobile phones, SMS, apps, and voice calls—have emerged as potentially cost-effective tools to improve adherence, given the global reach of mobile technology (5.3 billion mobile broadband subscribers in 2018). However, evidence for their effectiveness specifically in CVD medication adherence remained unclear, prompting this systematic review.
**Methods:** The review followed PRISMA guidelines and searched PubMed, MEDLINE, ProQuest, and Google Scholar databases for primary studies published between August 2000 and July 2021. Inclusion criteria were: (1) clinical trials comparing mHealth interventions to standard care or control, (2) peer-reviewed full-text articles, (3) studies on mHealth interventions for CVD medication adherence, and (4) interventions meeting the WHO or ATA definition of mHealth. Exclusion criteria included non-original research, studies without adherence as a primary or secondary outcome, non-CVD populations, non-randomized designs, non-English studies, and prematurely terminated trials. The search used MeSH terms with Boolean operators including "Reminder Systems," "Text Messaging," "mobile app," "SMS," "phone call," "digital health," and "Medication Adherence." Quality was assessed using Cochrane's risk-of-bias tool across seven domains, with studies scored on a 2-point Likert scale and categorized as good quality (score >4), moderate quality (score 3–4), or poor quality (score <2).
**Key Results:** The initial search identified 1,254 studies; after screening, 23 randomized controlled trials with 34,915 participants met the inclusion criteria. Studies originated from the USA (7 studies), Canada (2), China (3), Pakistan (2), South Africa (1), the United Kingdom (1), Australia (1), France (1), Malaysia (1), Iran (1), and New Zealand (1). Sample sizes ranged from 50 to 21,750 participants, with study durations from 1 month to 12 months. mHealth interventions varied widely: single SMS interventions, SMS combined with Micro Letter platforms, interactive voice interventions, multifaceted interventions (medication reconciliation, patient education, collaborative care, voice messaging), interactive text messages, wireless self-monitoring devices, web-based apps, reminder alarms, talking treatment interventions (SMS + voice calls), WeChat with BlackBerry reminder apps, electronic pill bottle reminders with automated messages, and advanced mobile apps. Nine trials used the Morisky Medication Adherence Scale-8 (MMAS-8), one used MMAS-4, three used proportion of days covered (PDC), and others used various methods including electronic pill bottles, wireless pill bottles, self-report, and prescription records. Regarding medication adherence outcomes, 17 studies (73.9%) reported significant improvement in medication adherence, while 6 studies (26%) failed to show a substantial impact. Among nine studies measuring blood pressure, three showed significant decreases alongside improved adherence, while six did not. For ischemic heart disease (14 trials), 10 showed significant adherence improvement and 4 did not. The single heart failure study (n=60, 28 days) found no improvement. Two stroke studies from Pakistan showed mixed results (one positive, one negative). One trial in patients with CVD and comorbid type 2 diabetes found interactive voice recognition phone calls improved adherence by 2.2 percentage points (95% CI, 1.1–3.4) and enhanced calls by 3.0 percentage points (95% CI, 1.9–4.2) versus usual care. Quality assessment: 15 trials were high-quality (good scores across ≥5 domains), 6 were moderate quality, and 2 were poor quality.
**Clinical Implications:** This review provides moderate support for mHealth interventions as effective tools for improving medication adherence in CVD patients, with nearly three-quarters of included RCTs showing positive results. The heterogeneity of interventions, populations, and outcome measures limits the ability to recommend a specific mHealth approach. SMS-based interventions were most common and appear promising, particularly in resource-limited settings where they can be implemented at low cost (e.g., approximately USD 0.02 per SMS, or roughly USD 1 per patient annually). However, the contradictory findings across studies—particularly the 26% that showed no benefit—indicate that mHealth is not universally effective and may depend on patient characteristics, disease type, intervention design, and outcome measurement tools. The review highlights the need for more refined, standardized, and validated mHealth applications; attention to message timing, frequency, and language; alternative approaches for patients with sensory or literacy limitations; and long-term follow-up studies to assess durability of behavioral change. Cost-effectiveness studies are also needed to guide policymakers in targeting resource-intensive interventions to patients most likely to benefit.